• Title/Summary/Keyword: combinatorial

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A Preliminary Study on the Inhibitory Effect of Chunghyul-dan on Stroke Recurrence on Patients with Small Vessel Disease

  • Cho, Ki-Ho;Jee, Nam-gue;Jung, Woo-Sang;Park, Seong-Uk;Moon, Sang-Kwan;Ko, Chang-Nam;Kim, Young-Suk;Jung, Woo-Sang
    • The Journal of Korean Medicine
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    • v.28 no.1 s.69
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    • pp.224-236
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    • 2007
  • Background : Chunghyul-dan is a combinatorial herbal medicine; previous studies reported it had therapeutic effects for microangiopathy, a major part in the progression of small vessel disease, as well as having anti-hypertensive, anti-hyperlipidemic, anti-apoptotic, anti-oxidative, and anti-inflammatory activities. Therefor, we examined the inhibitory effect of Chunghyul-dan on stroke recurrence in patients with small vessel disease. Methods : We prescribed Chunghyul-dan at 600 mg a day to patients with small vessel disease, and monitored stroke recurrence, drug compliances, and adverse effect for 1 year. We then performed follow-up brain MRI to find new vascular lesions after 1 year of Chunghyul-dan medication. For the subjects lost to follow-up, we assessed their prognosis after 1 year by telephone. Results : There were 73 subjects treated with Chunghyul-dan for 1 year; new vascular events were found in 3. Of the 85 subjects lost to follow-up, fifty four could be contacted, and eight of them had stroke recurrence. One year of Chunghyul-dan medication reduced the odds ratio of stroke recurrence by 75% compared to the subjects lost to follow-up and the rate increased to 88%, when adjusted for other relevant risk factors for stroke recurrence. These reductions were much higher than those of aspirin and other kinds of conventional anti-platelets. There was no adverse effect in any of the study subjects. Conclusions : We suggest Chunghyul-dan could be useful for inhibition of stroke recurrence. Further study with a randomized controlled trial is needed to confirm this suggestion.

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Chunghyul-dan acts as an anti-inflammatory agent in endothelial cells by regulating gene expression

  • Jung, Woo-Sang;Cho, Jin-Gu;In, Kyung-Min;Kim, Jong-Min;Cho, Ki-Ho;Park, Jung-Mi;Moon, Sang-Kwan;Kim, Kyung-Wook;Park, Seong-Uk;Pyee, Jae-Ho;Park, Sang-Gyu;Jeong, Yoon-Hwa;Park, Heon-Yong;Ko, Chang-Nam
    • Animal cells and systems
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    • v.14 no.4
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    • pp.275-282
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    • 2010
  • Chunghyul-dan (CHD) is a combinatorial drug known to exert anti-inflammatory effects in endothelial cells. In this study, we employed global transcriptional profiling using cDNA microarrays to identify molecular mechanisms responsible for the anti-inflammatory activity of CHD in endothelial cells. An analysis of the microarray data revealed that transcript levels of monocyte chemotactic protein-1 (MCP-1), vascular cell-adhesion molecule-1 (VCAM-1) and activated leukocyte cell-adhesion molecule were dramatically altered in CHD-treated endothelial cells. These changes in gene expression were confirmed by RT-PCR, Western blotting and ELISA. Chronic CHD treatment also appeared to decrease MCP-1 secretion, probably as a result of decreased MCP-1 expression. In addition, we determined that chronic CHD treatment inhibited lipopolysaccharide-stimulated adhesion of THP-1 leukocytes to endothelial cells. The inhibitory effect of CHD on LPS-stimulated adhesion resulted from downregulation of VCAM-1 expression. Transmigration of THP-1 leukocytes through endothelial cells was also inhibited by chronic CHD treatment. In conclusion, CHD controls a variety of inflammatory activities by regulating MCP-1 and VCAM-1 gene expression.

Culture Conditions of Garlic Resistant Lactic Acid Bacteria for Feed Additives (사료첨가용 생균제 개발을 위한 마늘 내성 유산균의 배양 조건)

  • Kim, Yu-Jin;Jang, Seo-Jung;Park, Jung-Min;Kim, Chang-Uk;Park, Young-Seo
    • Food Engineering Progress
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    • v.14 no.1
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    • pp.65-74
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    • 2010
  • Culture conditions of L. plantarum TJ-LP-002, the garlic resistant strain isolated from pakimchi (green onion kimchi), were investigated for the use of feed additives. Acetic acid, citric acid, lactic acid, and tartaric acid were detected in the culture supernatant, and especially the concentrations of lactic acid and acetic acid significantly increased during cultivation. The antimicrobial activity of L. plantarum TJ-LP-002 was not affected by proteases, calatase or cellulase, which showed that the antimicrobial activity might be due to the production of acids rather than proteinaceous antimicrobial substances. L. plantarum TJ-LP-002 was resistant to neomycin sulfate, spectinomycin dihydrochloride, and lincomycin hydrochloride, sensitive to streptomycin sulfate, and intermediate resistant to ampicillin trihydrate, chloramphenicol, erythromycin, tetracycline hydrochloride, and kanamycin sulfate. The optimum initial pH of medium, fermentation temperature and time for the cell growth and antibacterial activity were pH 7.0, 30${^{\circ}C}$ and 24hr, respectively. The optimal composition of culture medium for the cell growth and antimicrobial activity was 3%(w/v) glucose as a carbon source, 3%(w/v) yeast extract as a nitrogen source, and manganese sulfate and ammonium citrate as inorganic salts. The combinatorial supplementation of these inorganic salts, rather than sole addition as an inorganic salt, resulted in better antibacterial activity.

Image Processing of Pseudo-rate-distortion Function Based on MSSSIM and KL-Divergence, Using Multiple Video Processing Filters for Video Compression (MSSSIM 및 쿨백-라이블러 발산 기반 의사 율-왜곡 평가 함수와 복수개의 영상처리 필터를 이용한 동영상 전처리 방법)

  • Seok, Jinwuk;Cho, Seunghyun;Kim, Hui Yong;Choi, Jin Soo
    • Journal of Broadcast Engineering
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    • v.23 no.6
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    • pp.768-779
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    • 2018
  • In this paper, we propose a novel video quality function for video processing based on MSSSIM to select an appropriate video processing filter and to accommodate multiple processing filters to each pixel block in a picture frame by a mathematical selection law so as to maintain video quality and to reduce the bitrate of compressed video. In viewpoint of video compression, since the properties of video quality and bitrate is different for each picture of video frames and for each areas in the same frame, it is difficult for the video filter with single property to satisfy the object of increasing video quality and decreasing bitrate. Consequently, to maintain the subjective video quality in spite of decreasing bitrate, we propose the methodology about the MSSSIM as the measure of subjective video quality, the KL-Divergence as the measure of bitrate, and the combination method of those two measurements. Moreover, using the proposed combinatorial measurement, when we use the multiple image filters with mutually different properties as a pre-processing filter for video, we can verify that it is possible to compress video with maintaining the video quality under decreasing the bitrate, as possible.

Generation of single stranded DNA with selective affinity to bovine spermatozoa

  • Vinod, Sivadasan Pathiyil;Vignesh, Rajamani;Priyanka, Mani;Tirumurugaan, Krishnaswamy Gopalan;Sivaselvam, Salem Nagalingam;Raj, Gopal Dhinakar
    • Animal Bioscience
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    • v.34 no.10
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    • pp.1579-1589
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    • 2021
  • Objective: This study was conducted to generate single stranded DNA oligonucleotides with selective affinity to bovine spermatozoa, assess its binding potential and explore its potential utility in trapping spermatozoa from suspensions. Methods: A combinatorial library of 94 mer long oligonucleotide was used for systematic evolution of ligands by exponential enrichment (SELEX) with bovine spermatozoa. The amplicons from sixth and seventh rounds of SELEX were sequenced, and the reads were clustered employing cluster database at high identity with tolerance (CD-HIT) and FASTAptamer. The enriched nucleotides were predicted for secondary structures by Mfold, motifs by Multiple Em for Motif Elicitation and 5' labelled with biotin/6-FAM to determine the binding potential and binding pattern. Results: We generated 14.1 and 17.7 million reads from sixth and seventh rounds of SELEX respectively to bovine spermatozoa. The CD-HIT clustered 78,098 and 21,196 reads in the top ten clusters and FASTAptamer identified 2,195 and 4,405 unique sequences in the top three clusters from the sixth and seventh rounds, respectively. The identified oligonucleotides formed secondary structures with delta G values between -1.17 to -26.18 kcal/mol indicating varied stability. Confocal imaging with the oligonucleotides from the seventh round revealed different patterns of binding to bovine spermatozoa (fluorescence of the whole head, spot of fluorescence in head and mid- piece and tail). Use of a 5'-biotin tagged oligonucleotide from the sixth round at 100 pmol with 4×106 spermatozoa could trap almost 80% from the suspension. Conclusion: The binding patterns and ability of the identified oligonucleotides confirms successful optimization of the SELEX process and generation of aptamers to bovine spermatozoa. These oligonucleotides provide a quick approach for selective capture of spermatozoa from complex samples. Future SELEX rounds with X- or Y- enriched sperm suspension will be used to generate oligonucleotides that bind to spermatozoa of a specific sex type.

Factors Influencing Innovation Performance through Industry-Research Institute Cooperation of Researchers at Government-Funded Research Institutes in Daedeok Innopolis: An fsQCA Approach (대덕연구개발특구 정부출연연연구기관 연구자의 산연협력 혁신성과 결정요인 분석: 퍼지집합 질적 비교분석 접근)

  • Hwang, Kyung-Yun;Sung, Eul-Hyun
    • Journal of the Korea Convergence Society
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    • v.12 no.7
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    • pp.221-233
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    • 2021
  • The purpose of this study is to analyze the effects of determinants of innovation performance on innovation performance in industry-research institute(IR) cooperation for researchers of government-funded research institutes in Daedeok Innopolis. We reviewed the existing literature on the determinants of innovation performance through cooperation, and established a conceptual framework to analyze the combinatorial effect of the determinants of innovation performance on innovation performance in IR cooperation. Data for empirical analysis were collected through a questionnaire survey targeting researchers at a government-funded research institute in Daedeok Innopolis. The fuzzy-set qualitative comparative analysis (fsQCA) was used to analyze the combined effect of determinants of innovation performance. The fsQCA results show that the configuration of high motivation, high trust, high commitment and high satisfaction of researchers of government-funded research institutes improve innovation performance. On the other hand, it shows that the configuration of high motivation, high trust, low commitment and low satisfaction of the researcher improves innovation performance.

Impact of Microbiota on Gastrointestinal Cancer and Anticancer Therapy (미생물 균총이 위장관암과 항암제에 미치는 영향)

  • Kim, Sa-Rang;Lee, Jung Min
    • Journal of Life Science
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    • v.32 no.5
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    • pp.391-410
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    • 2022
  • Human microbiota is a community of microorganisms, including bacteria, fungi, and viruses, that inhabit various locations of the body, such as the gut, oral, and skin. Along with the development of metabolomic analysis and next-generation sequencing techniques for 16S ribosomal RNA, it has become possible to analyze the population for subtypes of microbiota, and with these techniques, it has been demonstrated that bacterial microbiota are involved in the metabolic and immunological processes of the hosts. While specific bacteria of microbiota, called commensal bacteria, positively affect hosts by producing essential nutrients and protecting hosts against other pathogenic microorganisms, dysbiosis, an abnormal microbiota composition, disrupts homeostasis and thereby has a detrimental effect on the development and progression of various types of diseases. Recently, several studies have reported that oral and gut bacteria of microbiota are involved in the carcinogenesis of gastrointestinal tumors and the therapeutic effects of anticancer therapy, such as radiation, chemotherapy, targeted therapy, and immunotherapy. Studying the complex relationships (bacterial microbiota-cancer-immunity) and microbiota-related carcinogenic mechanisms can provide important clues for understanding cancer and developing new cancer treatments. This review provides a summary of current studies focused on how bacterial microbiota affect gastrointestinal cancer and anticancer therapy and discusses compelling possibilities for using microbiota as a combinatorial therapy to improve the therapeutic effects of existing anticancer treatments.

Multi-objective Genetic Algorithm for Variable Selection in Linear Regression Model and Application (선형회귀모델의 변수선택을 위한 다중목적 유전 알고리즘과 응용)

  • Kim, Dong-Il;Park, Cheong-Sool;Baek, Jun-Geol;Kim, Sung-Shick
    • Journal of the Korea Society for Simulation
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    • v.18 no.4
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    • pp.137-148
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    • 2009
  • The purpose of this study is to implement variable selection algorithm which helps construct a reliable linear regression model. If we use all candidate variables to construct a linear regression model, the significance of the model will be decreased and it will cause 'Curse of Dimensionality'. And if the number of data is less than the number of variables (dimension), we cannot construct the regression model. Due to these problems, we consider the variable selection problem as a combinatorial optimization problem, and apply GA (Genetic Algorithm) to the problem. Typical measures of estimating statistical significance are $R^2$, F-value of regression model, t-value of regression coefficients, and standard error of estimates. We design GA to solve multi-objective functions, because statistical significance of model is not to be estimated by a single measure. We perform experiments using simulation data, designed to consider various kinds of situations. As a result, it shows better performance than LARS (Least Angle Regression) which is an algorithm to solve variable selection problems. We modify algorithm to solve portfolio selection problem which construct portfolio by selecting stocks. We conclude that the algorithm is able to solve real problems.

Deletion Timing of Cic Alleles during Hematopoiesis Determines the Degree of Peripheral CD4+ T Cell Activation and Proliferation

  • Guk-Yeol Park;Gil-Woo Lee;Soeun Kim;Hyebeen Hong;Jong Seok Park;Jae-Ho Cho;Yoontae Lee
    • IMMUNE NETWORK
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    • v.20 no.5
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    • pp.43.1-43.11
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    • 2020
  • Capicua (CIC) is a transcriptional repressor that regulates several developmental processes. CIC deficiency results in lymphoproliferative autoimmunity accompanied by expansion of CD44hiCD62Llo effector/memory and follicular Th cell populations. Deletion of Cic alleles in hematopoietic stem cells (Vav1-Cre-mediated knockout of Cic) causes more severe autoimmunity than that caused by the knockout of Cic in CD4+CD8+ double positive thymocytes (Cd4-Cre-mediated knockout of Cic). In this study, we compared splenic CD4+ T cell activation and proliferation between whole immune cell-specific Cic-null (Cicf/f;Vav1-Cre) and T cell-specific Cic-null (Cicf/f;Cd4-Cre) mice. Hyperactivation and hyperproliferation of CD4+ T cells were more apparent in Cicf/f;Vav1-Cre mice than in Cicf/f;Cd4-Cre mice. Cicf/f;Vav1-Cre CD4+ T cells more rapidly proliferated and secreted larger amounts of IL-2 upon TCR stimulation than did Cicf/f;Cd4-Cre CD4+ T cells, while the TCR stimulation-induced activation of the TCR signaling cascade and calcium flux were comparable between them. Mixed wild-type and Cicf/f;Vav1-Cre bone marrow chimeras also exhibited more apparent hyperactivation and hyperproliferation of Cic-deficient CD4+ T cells than did mixed wild-type and Cicf/f;Cd4-Cre bone marrow chimeras. Taken together, our data demonstrate that CIC deficiency at the beginning of T cell development endows peripheral CD4+ T cells with enhanced T cell activation and proliferative capability.

A prognosis discovering lethal-related genes in plants for target identification and inhibitor design (식물 치사관련 유전자를 이용하는 신규 제초제 작용점 탐색 및 조절물질 개발동향)

  • Hwang, I.T.;Lee, D.H.;Choi, J.S.;Kim, T.J.;Kim, B.T.;Park, Y.S.;Cho, K.Y.
    • The Korean Journal of Pesticide Science
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    • v.5 no.3
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    • pp.1-11
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    • 2001
  • New technologies will have a large impact on the discovery of new herbicide site of action. Genomics, combinatorial chemistry, and bioinformatics help take advantage of serendipity through tile sequencing of huge numbers of genes or the synthesis of large numbers of chemical compounds. There are approximately $10^{30}\;to\;10^{50}$ possible molecules in molecular space of which only a fraction have been synthesized. Combining this potential with having access to 50,000 plant genes in the future elevates tile probability of discovering flew herbicidal site of actions. If 0.1, 1.0 or 10% of total genes in a typical plant are valid for herbicide target, a plant with 50,000 genes would provide about 50, 500, and 5,000 targets, respectively. However, only 11 herbicide targets have been identified and commercialized. The successful design of novel herbicides depends on careful consideration of a number of factors including target enzyme selections and validations, inhibitor designs, and the metabolic fates. Biochemical information can be used to identify enzymes which produce lethal phenotypes. The identification of a lethal target site is an important step to this approach. An examination of the characteristics of known targets provides of crucial insight as to the definition of a lethal target. Recently, antisense RNA suppression of an enzyme translation has been used to determine the genes required for toxicity and offers a strategy for identifying lethal target sites. After the identification of a lethal target, detailed knowledge such as the enzyme kinetics and the protein structure may be used to design potent inhibitors. Various types of inhibitors may be designed for a given enzyme. Strategies for the selection of new enzyme targets giving the desired physiological response upon partial inhibition include identification of chemical leads, lethal mutants and the use of antisense technology. Enzyme inhibitors having agrochemical utility can be categorized into six major groups: ground-state analogues, group specific reagents, affinity labels, suicide substrates, reaction intermediate analogues, and extraneous site inhibitors. In this review, examples of each category, and their advantages and disadvantages, will be discussed. The target identification and construction of a potent inhibitor, in itself, may not lead to develop an effective herbicide. The desired in vivo activity, uptake and translocation, and metabolism of the inhibitor should be studied in detail to assess the full potential of the target. Strategies for delivery of the compound to the target enzyme and avoidance of premature detoxification may include a proherbicidal approach, especially when inhibitors are highly charged or when selective detoxification or activation can be exploited. Utilization of differences in detoxification or activation between weeds and crops may lead to enhance selectivity. Without a full appreciation of each of these facets of herbicide design, the chances for success with the target or enzyme-driven approach are reduced.

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