• Title/Summary/Keyword: Combinatorial synthesis

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Therapeutic aptamers: developmental potential as anticancer drugs

  • Lee, Ji Won;Kim, Hyun Jung;Heo, Kyun
    • BMB Reports
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    • v.48 no.4
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    • pp.234-237
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    • 2015
  • Aptamers, composed of single-stranded DNA or RNA oligonucleotides that interact with target molecules through a specific three-dimensional structure, are selected from pools of combinatorial oligonucleotide libraries. With their high specificity and affinity for target proteins, ease of synthesis and modification, and low immunogenicity and toxicity, aptamers are considered to be attractive molecules for development as anticancer therapeutics. Two aptamers - one targeting nucleolin and a second targeting CXCL12 - are currently undergoing clinical trials for treating cancer patients, and many more are under study. In this mini-review, we present the current clinical status of aptamers and aptamer-based cancer therapeutics. We also discuss advantages, limitations, and prospects for aptamers as cancer therapeutics. [BMB Reports 2015; 48(4): 234-237]

An Enhanced Genetic Algorithm for Global and Local Optimization Search (전역 및 국소 최적화탐색을 위한 향상된 유전 알고리듬의 제안)

  • Kim, Young-Chan;Yang, Bo-Suk
    • Transactions of the Korean Society of Mechanical Engineers A
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    • v.26 no.6
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    • pp.1008-1015
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    • 2002
  • This paper proposes a combinatorial method to compute the global and local solutions of optimization problem. The present hybrid algorithm is the synthesis of a genetic algorithm and a local concentrate search algorithm (simplex method). The hybrid algorithm is not only faster than the standard genetic algorithm, but also gives a more accurate solution. In addition, this algorithm can find both the global and local optimum solutions. An optimization result is presented to demonstrate that the proposed approach successfully focuses on the advantages of global and local searches. Three numerical examples are also presented in this paper to compare with conventional methods.

Progressive Compression of 3D Mesh Geometry Using Sparse Approximations from Redundant Frame Dictionaries

  • Krivokuca, Maja;Abdulla, Waleed Habib;Wunsche, Burkhard Claus
    • ETRI Journal
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    • v.39 no.1
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    • pp.1-12
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    • 2017
  • In this paper, we present a new approach for the progressive compression of three-dimensional (3D) mesh geometry using redundant frame dictionaries and sparse approximation techniques. We construct the proposed frames from redundant linear combinations of the eigenvectors of a combinatorial mesh Laplacian matrix. We achieve a sparse synthesis of the mesh geometry by selecting atoms from a frame using matching pursuit. Experimental results show that the resulting rate-distortion performance compares favorably with other progressive mesh compression algorithms in the same category, even when a very simple, sub-optimal encoding strategy is used for the transmitted data. The proposed frames also have the desirable property of being able to be applied directly to a manifold mesh having arbitrary topology and connectivity types; thus, no initial remeshing is required and the original mesh connectivity is preserved.

Optimum Design of High-Speed, Short Journal Bearings by Enhanced Artificial Life Algorithm (향상된 인공생명 알고리듬에 의한 고속, 소폭 저널 베어링의 최적설계)

  • Yang, Bo-Suk;Song, Jin-Dae
    • Proceedings of the KSME Conference
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    • 2001.11a
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    • pp.698-702
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    • 2001
  • This paper presents a combinatorial method to compute the solutions of optimization problem. The present hybrid algorithm is the synthesis of an artificial life algorithm and the random tabu search method. The hybrid algorithm is not only faster than the conventional artificial life algorithm, but also gives a more accurate solution. In addition, this algorithm can find all global optimum solutions. And the enhanced artificial life algorithm is applied to optimum design of high-speed, short journal bearings and the usefuless is verified through this example.

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신약개발 환경의 변화와 대응책

  • 유성은
    • Proceedings of the Korean Society of Applied Pharmacology
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    • 2000.04a
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    • pp.1-2
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    • 2000
  • 일반적인 신약 개발 방법으로는 천연물로부터 선도화합물이 발견되었을 때 의약화학자들은 그 물질의 화학구조식 중에서 약리 작용에 필수 요건이 되는 구조 요소를 규정하고, 체계적인 분자변형을 통하여 약리 작용의 최적화 작업을 추진한다. 그러나 분자 내에 여러 가지 치환기를 도입할 수 있는 경우 수많은 유도체가 합성 가능하며, 실제로 이와 같은 많은 수의 유도체를 합성한다는 것은 현실적으로 불가능하다. 통계적으로 하나의 신약 개발에 드는 시간과 경비는 약 10년 이상의 기간과 3,000 억원 이상의 경비가 소요된다. 따라서 시간과 경비를 줄이는 노력의 하나로 실험분야에서는 조합 화학합성 (Combinatorial Chemical Synthesis, CCS) 기술인 새로운 개념의 고효율 합성 기술이나 이를 대량 검색할 수 있는 초고속 활성 검색법 (High Through-put Screening, HTS) 기술이 1990년대 초에 본격적으로 각광 받게되었고, 정보관리 시스템을 통한 library 구축, 컴퓨터를 이용한 구조-활성 관계 및 분자 설계 기법이 급속히 발전하게 되었다. 따라서 기존의 random screening에 의한 신약개발 방법으로부터 탈피하여 새로운 차원의 신의약 개발 방법의 필요성이 절실히 요구되고 있다.

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Mathematical Model Development of Whole-body Vertical Vibration, Using a Simulated Annealing Method (Simulated Annealing 기법을 이용한 인체 수직 전신 진동 모델의 파라미터 선정)

  • Choi, Jun-Hee;Kim, Young-Eun;Baek, Kwang-Hyun
    • Proceedings of the KSME Conference
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    • 2000.11a
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    • pp.381-386
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    • 2000
  • Simple spring-damper-mass models have been widely used to understand whole-body vertical biodynamic response characteristics of the seated vehicle driver. However, most previous models have not considered about the non-rigid masses(wobbling masses). A simple mechanical model of seated human body developed in this study included the torso represented by a rigid and a wobbling mass. Within the 0.5-20Hz frequency range and for excitation amplitudes maintained below $5ms^{-2}$, this 4-degree-of-freedom driver model is proposed to satisfy the measured vertical vibration response characteristics defined from a synthesis of published data for subjects seated erect without backrest support. The parameters are identified by using the combinatorial optimization technique, simulated annealing method. The model response was found to be provided a closer agreement with the response characteristics than previously published models.

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Shape invariant recognition of korean characters with noise using wavelet SDF filter (웨이브릿 SDF 필터를 이용한 잡음을 갖는 한글의 모양불변 인식)

  • 김용규;김철수;김정우;이하운;도양회;김수중
    • Journal of the Korean Institute of Telematics and Electronics B
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    • v.33B no.7
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    • pp.147-153
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    • 1996
  • For shape invariant recognitin of korean characters iwth noise, an optical wavelet SDF filter is proposed To preserve the features of a reference image and inimize effects of a random noise in the inpt image wavelet transformed images with different dialation parameters are used. And to adapt to divese variations in the combinatorial form, eCP-SDF filter synthesis algorithm is used. The proposed optical wavelet SDF filter is the type of the matched filter so that it can use the structure of 4f optical correlation system. The computer simulation results show that the proposed filter is useful in the noisy input.

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Design, Combinatorial Library Synthesis and Biological Evaluation of Nonpeptide Scaffold for Beta Turns

  • Im, I-Sak;Thomas R.Webb;Dona Chianelli;Kim, Yong-Chul
    • Proceedings of the PSK Conference
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    • 2003.10a
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    • pp.91-91
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    • 2003
  • The beta-turn has been implicated as an important conformation for biological recognition of peptides or proteins. We adapted the concept of general Ca atom positioning from the cluster analysis and recombination of each ideal beta-turn conformation pattern by Garland and Dean (1. Computer-Aided Molecular Design, 1999, 13, 469) as one strategy of designing non-peptide beta-turn scaffolds. (omitted)

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High Throughput Screening for Natural Products to Find Biologically Active Compounds : Natural Products versus Combinatorial Chemistry

  • Sankawa, Ushio
    • Proceedings of the Korean Society of Applied Pharmacology
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    • 1997.11a
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    • pp.47-50
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    • 1997
  • Drug development began with the finding of biologically active compounds which are obtained by chemical synthesis or from natural sources. The advent of Combinatorial Chemistry is recognized as a strategy which has a potential to change the methodology of research and development(R&D) of new drugs. Drug development has been carried out with diverse strategies. In the past several decades a variety of new methodology have been introduced in R&D. Random screening of accumulated synthetic samples which had been synthesized for development of other drugs led to the discovery of new drugs. The typical examples are anti-asthma drug trimethoquinol and calcium antagonist diltiazem. (herbesser). In particular the latter drug has been used as a calcium antagonist worldwide, however it was first synthesized to find new tranquilizer and this is the reason why diltiazem has benzodiazepam skeleton. The random screening contributed in the finding of new drugs were carried out with whole animal test and it is a standard methodology in R&D of new drugs. Aspirin is the first synthetic non-steroidal antiinflammatory drug(NSAID) and has been used for more than one hundred years. It is the first example of drug developed from natural product. Salicin is the main constituent of willow bark which had been used in Europe for a long time to treat arthritis and aspirin was developed from salicin. Most of NSAID used clinically were developed from the structure of aspirin, however it took 70 years to clarify why aspirin exhibits its antiinflammatory, analgesic and antipyretic activities. The target of aspirin is cyclooxygenase(COX)which is the first enzyme involved in arachidonate cascade leading to the production of prostaglandins(PG) and thromboxan(TX). Side effect of aspirin causing ulcer in stomach is rather serious problem, since aspirin is so popular drug easily obtained in drug store(OTP). This problem is now going to be solved by a new finding on COX, which have two different types, one is constitutionally expressed COX 1 in almost all organs and the other is inducible COX 2. COX 2 is the responsible enzyme in inflammation etc and now the search of COX 2 specific inhibitors is the target of R&D of next generation NSAID.

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Combinatorial Methylerythritol Phosphate Pathway Engineering and Process Optimization for Increased Menaquinone-7 Synthesis in Bacillus subtilis

  • Chen, Taichi;Xia, Hongzhi;Cui, Shixiu;Lv, Xueqin;Li, Xueliang;Liu, Yanfeng;Li, Jianghua;Du, Guocheng;Liu, Long
    • Journal of Microbiology and Biotechnology
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    • v.30 no.5
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    • pp.762-769
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    • 2020
  • Vitamin K2 (menaquinone) is an essential vitamin existing in the daily diet, and menaquinone-7 (MK-7) is an important form of it. In a recent work, we engineered the synthesis modules of MK-7 in Bacillus subtilis, and the strain BS20 could produce 360 mg/l MK-7 in shake flasks, while the methylerythritol phosphate (MEP) pathway, which provides the precursor isopentenyl diphosphate for MK-7 synthesis, was not engineered. In this study, we overexpressed five genes of the MEP pathway in BS20 and finally obtained a strain (BS20DFHG) with MK-7 titer of 415 mg/l in shake flasks. Next, we optimized the fermentation process parameters (initial pH, temperature and aeration) in an 8-unit parallel bioreactor system consisting of 300-ml glass vessels. Based on this, we scaled up the MK-7 production by the strain BS20DFHG in a 50-l bioreactor, and the highest MK-7 titer reached 242 mg/l. Here, we show that the engineered strain BS20DFHG may be used for the industrial production of MK-7 in the future.