• Title/Summary/Keyword: Target Throughput

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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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Enhancement of Sensitivity in Interferometric Biosensing by Using a New Biolinker and Prebinding Antibody

  • Park, Jae-Sook;Lim, Sung-Hyun;Sim, Sang-Jun;Chae, Hee-Yeop;Yoon, Hyun-C.;Yang, Sang-Sik;Kim, Byung-Woo
    • Journal of Microbiology and Biotechnology
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    • v.16 no.12
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    • pp.1968-1976
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    • 2006
  • Recombinant E. coli ACV 1003 (recA:: lacZ) was used to measure low concentrations of DNA-damaging chemicals, which produce $\beta$-galactosidase via an SOS regulon system. Very low $\beta$-galactosidase activities of less than 0.01 unit/ml, $\beta$-galactosidase produced through an SOS response corresponding to the 10 ng/ml (ppb) of DNA damaging chemicals in the environment, can be rapidly determined by using an alternative interferometric biosensor with optically flat thin films of porous silicon rather than by the conventional time-consuming Miller's enzyme assay as well as the ELISA method. fu order to enhance the sensitivity in the interferometry, it needs to obtain more uniform distribution and higher biolinking efficiency, whereas interferometric sensing is rapid, cheap, and advantageous in high throughput by using a multiple-well-type chip. In this study, pore size adjusted to 60 nm for the target enzyme $\beta$-galactosidase to be bound on both walls of a Si pore and a calyx crown derivative was apllied as a more efficient biolinker. Furthermore, anti-$\beta$-galactosidase was previously functionalized with the biolinker for the target $\beta$-galactosidase to be specifically bound. When anti-$\beta$-galactosidase was bound to the calyx-crown derivative-linked surface, the effective optical thickness was found to be three times as high as that obtained without using anti-$\beta$-galactosidase. The resolution obtained was very similar to that afforded by the time-consuming ELISA method; however, the reproducibility was still unsatisfactory, below 1 unit $\beta$-galactosidase/ml, owing to the microscopic non-uniform distribution of the pores in the etched silicon surface.

Service Class-Aided Scheduling for LTE (LTE를 위한 서비스 클래스를 고려한 스케줄링 기법)

  • Hung, Pham;Hwang, Seung-Hoon
    • Journal of the Institute of Electronics Engineers of Korea TC
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    • v.48 no.11
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    • pp.60-66
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    • 2011
  • LTE (Long Term Evolution) supports QoS (Quality of Service) with several service classes. For each class of traffic, a big difference exists on BER (Bit Error Rate) requirement. This leads to a considerable difference in transmission power for various classes of traffic. In this paper, a novel scheduler is designed and proposed for LTE which supports CoS (Class of Service) with the consideration of priority as well as target BER. By the CQI (Channel Quality Indicator) and QCI (QoS Class Identifier), a minimum transmission power is assigned from the target BER for each class of traffic per each user. Hence, with the other information such as user's used rate in the past and the priority of traffic, the probability of occupying channels is determined. The simulation results of Service Class scheduling are compared with that of Maximum Rate and Proportional Fair. The results show that the service class-aided scheduling can improve the throughput of whole system significantly.

Small RNA Transcriptome of Hibiscus Syriacus Provides Insights into the Potential Influence of microRNAs in Flower Development and Terpene Synthesis

  • Kim, Taewook;Park, June Hyun;Lee, Sang-gil;Kim, Soyoung;Kim, Jihyun;Lee, Jungho;Shin, Chanseok
    • Molecules and Cells
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    • v.40 no.8
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    • pp.587-597
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    • 2017
  • MicroRNAs (miRNAs) are essential small RNA molecules that regulate the expression of target mRNAs in plants and animals. Here, we aimed to identify miRNAs and their putative targets in Hibiscus syriacus, the national flower of South Korea. We employed high-throughput sequencing of small RNAs obtained from four different tissues (i.e., leaf, root, flower, and ovary) and identified 33 conserved and 30 novel miRNA families, many of which showed differential tissuespecific expressions. In addition, we computationally predicted novel targets of miRNAs and validated some of them using 5' rapid amplification of cDNA ends analysis. One of the validated novel targets of miR477 was a terpene synthase, the primary gene involved in the formation of disease-resistant terpene metabolites such as sterols and phytoalexins. In addition, a predicted target of conserved miRNAs, miR396, is SHORT VEGETATIVE PHASE, which is involved in flower initiation and is duplicated in H. syriacus. Collectively, this study provides the first reliable draft of the H. syriacus miRNA transcriptome that should constitute a basis for understanding the biological roles of miRNAs in H. syriacus.

Real-Time Implementation of Active Classification Using Cumulative Processing (누적처리기법을 이용한 능동표적식별 시스템의 실시간 구현)

  • Park, Gyu-Tae;Bae, Eun-Hyon;Lee, Kyun-Kyung
    • The Journal of the Acoustical Society of Korea
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    • v.26 no.2
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    • pp.87-94
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    • 2007
  • In active sonar system, aspect angle and length of a target can be estimated by calculating the cross-correlation between left and right split-beams of a LFM(Linear Frequency Modulated) signal. However, high-resolution performances in bearing and range are required to estimate the information of a remote target. Because a certain higher sampling frequency than the Nyquist sampling frequency is required in this performance, an over-sampling process through interpolation method should be required. However, real-time implementation of split-beam processing with over-sampled split-beam outputs on a COTS(commercial off-the-shelf) DSP platform limits its performance because of given throughput and memory capacity. This paper proposes a cumulative processing algorithm for split-beam processing to solve the problems. The performance of the proposed method was verified through some simulation tests. Also, the proposed method was implemented as a real-time system using an ADSP-TS101.

Continuous Photolithography by Roll-Type Mask and Applications (롤타입 마스크를 이용한 연속 포토리소그래피 기술과 그 응용)

  • Kwak, Moon-Kyu
    • Transactions of the Korean Society of Mechanical Engineers B
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    • v.36 no.10
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    • pp.1011-1017
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    • 2012
  • We report the development of an optical micro-nanolithography method by using a roll-type mask. It includes phase-shift lithography and photolithography for realizing various target dimensions. For sub-wavelength resolution, a structure is achieved using the near-field exposure of a photoresist through a cylindrical phase-mask, allowing high-throughput continuous patterning. By using a film-type metal mask, continuous photolithography was achieved, and this method could be used to control the period of resultant patterns in real time by changing the rotating speed of the cylinder mask. As an application, we present the fabrication of a transparent electrode in the form of a metallic mesh by using the developed roll-type photolithography process. As a result, a transparent conductor with good properties was achieved by using a recently built cylindrical phase-shift lithography prototype, which was designed for patterning on 100-mm2 substrates.

AFSO: An Adaptative Frame Size Optimization Mechanism for 802.11 Networks

  • Ge, Xiaohu;Wang, Cheng-Xiang;Yang, Yang;Shu, Lei;Liu, Chuang;Xiang, Lin
    • KSII Transactions on Internet and Information Systems (TIIS)
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    • v.4 no.3
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    • pp.205-223
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    • 2010
  • In this paper, we analyze the impact of different frame types on self-similarity and burstiness characteristics of the aggregated frame traffic from a real 802.11 wireless local area network. We find that characteristics of aggregated frame traffic are affected by both mean frame size and the proportion of specified frame types. Based on this new knowledge, an adaptative frame size optimization (AFSO) mechanism is proposed to improve the transmission efficiency by adaptively adjusting data frame size according to the proportions of different frame types. Simulation results show that our proposed mechanism can effectively regulate the burstiness of aggregated frame traffic and improve the successful delivery rate of data frames when a fixed throughput target is set for 802.11 wireless networks.

Message in a Bottle: Chemical Biology of Induced Disease Resistance in Plants

  • Schreiber, Karl;Desveaux, Darrell
    • The Plant Pathology Journal
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    • v.24 no.3
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    • pp.245-268
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    • 2008
  • The outcome of plant-pathogen interactions is influenced significantly by endogenous small molecules that coordinate plant defence responses. There is currently tremendous scientific and commercial interest in identifying chemicals whose exogenous application activates plant defences and affords protection from pathogen infection. In this review, we provide a survey of compounds known to induce disease resistance in plants, with particular emphasis on how each compound was originally identified, its putative or demonstrated mechanism of defence induction, and the known biological target(s) of each chemical. Larger polymeric structures and peptides/proteins are also discussed in this context. The quest for novel defence-inducing molecules would be aided by the capability for high-throughput analysis of candidate compounds, and we describe some issues associated with the development of these types of screens. Subsequent characterization of hits can be a formidable challenge, especially in terms of identifying chemical targets in plant cells. A variety of powerful molecular tools are available for this characterization, not only to provide insight into methods of plant defence activation, but also to probe fundamental biological processes. Furthermore, these investigations can reveal molecules with significant commercial potential as crop protectants, although a number of factors must be considered for this potential to be realized. By highlighting recent progress in the application of chemical biology techniques for the modulation of plant-pathogen interactions, we provide some perspective on the exciting opportunities for future progress in this field of research.

Steroid Hormone Receptor/Reporter Gene Transcription Assay for Food Additives and Contaminants

  • Jeong Sang-Hee;Cho Joon-Hyoung;Park Jong-Myung
    • Toxicological Research
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    • v.22 no.1
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    • pp.15-22
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    • 2006
  • Many of endocrine disrupting chemicals induce effects via interaction with hormone receptors and responsive elements in target cells. We investigated endocrine disrupting effects of some food additives and contaminants including BHA, BHT, ethoxyquin, propionic acid, sorbic acid, benzoic acid, CPM, aflatoxin B1, cadmium chloride, genistein, TCDD and PCBs in yeast transformants expressing human steroid hormone receptors along with steroid responsive elements. The response limit of genetically recombinant yeast to $17{\beta}$-estradiol, testosterone and progesterone was $1{\times}10^{-16},\;1{\times}10^{-12}\;and\;1{\times}10^{-13}M$, respectively. BHT induced weak transcriptional activity in estrogen sensitive yeast, while BHA and sorbic acid interacted weakly with androgen receptor/responsive element. CPM induced transcriptional activities in all types of yeasts sensitive to steroid hormones. Zearalenone and genistein induced high transcriptional activation in estrogen sensitive yeast with relative potencies almost $10^8$ folds lower than $17{\beta}$-estradiol. TCDD induced transcriptional activation weakly in estrogen- and progesterone- sensitive yeasts. This study elucidated that recombinant yeast is a sensitive and high-throughput system and can be used for the direct assessment on chemical interactions with steroid receptors and responsive elements. Also, the present study raises the requirement of evaluation on the endocrine disrupting effects of BHT, BHA, sorbic acid, CPM and TCDD for their transcription activity in yeast screening system though weak in intensity.

Tyrosine Kinase Inhibitors in Ph+ Chronic Myeloid Leukemia Therapy: a Review

  • Shah, Krupa;Parikh, Sonia;Rawal, Rakesh
    • Asian Pacific Journal of Cancer Prevention
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    • v.17 no.7
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    • pp.3025-3033
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    • 2016
  • Chronic myeloid leukaemia (CML) is a clonal myeloproliferative hematopoietic stem cell disorder. Deregulated BCR-ABL fusion tyrosine kinase activity is the main cause of CML disease pathogenesis, making BCR-ABL an ideal target for inhibition. Current tyrosine kinase inhibitors (TKIs) designed to inhibit BCR-ABL oncoprotein activity, have completely transformed the prognosis of CML. Interruption of TKI treatment leads to minimal residual disease reside (MRD), thought to reside in TKI-insensitive leukaemia stem cells which remain a potential reservoir for disease relapse. This highlights the need to develop new therapeutic strategies for CML either as small molecule master TKIs or phytopharmaceuticals derived from nature to achieve chronic molecular remission. This review outlines the past, present and future therapeutic approaches for CML including coverage of relevant mechanisms, whether ABL dependent or independent, and epigenetic factors responsible for developing resistance against TKIs. Appearance of mutant clones along the course of therapy either pre-existing or induced due to therapy is still a challenge for the clinician. A proposed in-vitro model of generating colony forming units from CML stem cells derived from diagnostic samples seems to be achievable in the era of high throughput technology which can take care of single cell genomic profiling.