• 제목/요약/키워드: Gene Modeling

검색결과 98건 처리시간 0.024초

Prediction of Lung Cancer Based on Serum Biomarkers by Gene Expression Programming Methods

  • Yu, Zhuang;Chen, Xiao-Zheng;Cui, Lian-Hua;Si, Hong-Zong;Lu, Hai-Jiao;Liu, Shi-Hai
    • Asian Pacific Journal of Cancer Prevention
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    • 제15권21호
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    • pp.9367-9373
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    • 2014
  • In diagnosis of lung cancer, rapid distinction between small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC) tumors is very important. Serum markers, including lactate dehydrogenase (LDH), C-reactive protein (CRP), carcino-embryonic antigen (CEA), neurone specific enolase (NSE) and Cyfra21-1, are reported to reflect lung cancer characteristics. In this study classification of lung tumors was made based on biomarkers (measured in 120 NSCLC and 60 SCLC patients) by setting up optimal biomarker joint models with a powerful computerized tool - gene expression programming (GEP). GEP is a learning algorithm that combines the advantages of genetic programming (GP) and genetic algorithms (GA). It specifically focuses on relationships between variables in sets of data and then builds models to explain these relationships, and has been successfully used in formula finding and function mining. As a basis for defining a GEP environment for SCLC and NSCLC prediction, three explicit predictive models were constructed. CEA and NSE are requentlyused lung cancer markers in clinical trials, CRP, LDH and Cyfra21-1 have significant meaning in lung cancer, basis on CEA and NSE we set up three GEP models-GEP 1(CEA, NSE, Cyfra21-1), GEP2 (CEA, NSE, LDH), GEP3 (CEA, NSE, CRP). The best classification result of GEP gained when CEA, NSE and Cyfra21-1 were combined: 128 of 135 subjects in the training set and 40 of 45 subjects in the test set were classified correctly, the accuracy rate is 94.8% in training set; on collection of samples for testing, the accuracy rate is 88.9%. With GEP2, the accuracy was significantly decreased by 1.5% and 6.6% in training set and test set, in GEP3 was 0.82% and 4.45% respectively. Serum Cyfra21-1 is a useful and sensitive serum biomarker in discriminating between NSCLC and SCLC. GEP modeling is a promising and excellent tool in diagnosis of lung cancer.

Utilizing cell-free DNA to validate targeted disruption of MYO7A in rhesus macaque pre-implantation embryos

  • Junghyun Ryu;Fernanda C. Burch;Emily Mishler;Martha Neuringer;Jon D. Hennebold;Carol Hanna
    • 한국동물생명공학회지
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    • 제37권4호
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    • pp.292-297
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    • 2022
  • Direct injection of CRISPR/Cas9 into zygotes enables the production of genetically modified nonhuman primates (NHPs) essential for modeling specific human diseases, such as Usher syndrome, and for developing novel therapeutic strategies. Usher syndrome is a rare genetic disease that causes loss of hearing, retinal degeneration, and problems with balance, and is attributed to a mutation in MYO7A, a gene that encodes an uncommon myosin motor protein expressed in the inner ear and retinal photoreceptors. To produce an Usher syndrome type 1B (USH1B) rhesus macaque model, we disrupted the MYO7A gene in developing zygotes. Identification of appropriately edited MYO7A embryos for knockout embryo transfer requires sequence analysis of material recovered from a trophectoderm (TE) cell biopsy. However, the TE biopsy procedure is labor intensive and could adversely impact embryo development. Recent studies have reported using cell-free DNA (cfDNA) from embryo culture media to detect aneuploid embryos in human in vitro fertilization (IVF) clinics. The cfDNA is released from the embryo during cell division or cell death, suggesting that cfDNA may be a viable resource for sequence analysis. Moreover, cfDNA collection is not invasive to the embryo and does not require special tools or expertise. We hypothesized that selection of appropriate edited embryos could be performed by analyzing cfDNA for MYO7A editing in embryo culture medium, and that this method would be advantageous for the subsequent generation of genetically modified NHPs. The purpose of this experiment is to determine whether cfDNA can be used to identify the target gene mutation of CRISPR/Cas9 injected embryos. In this study, we were able to obtain and utilize cfDNA to confirm the mutagenesis of MYO7A, but the method will require further optimization to obtain better accuracy before it can replace the TE biopsy approach.

Development of Cellobiose-utilizing Recombinant Yeast for Ethanol Production from Cellulose Hydrolyzate

  • Pack, Seung-Pil;Cho, Kwang-Myung;Kang, Hyen-Sam;Yoo, Young-Je
    • Journal of Microbiology and Biotechnology
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    • 제8권5호
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    • pp.441-448
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    • 1998
  • A cellobiose-utilizing recombinant yeast having $\beta$-glucosidase activity was developed for ethanol production from a mixture of glucose and cellobiose. Using $\delta$-sequences of Tyl transposon of yeast as target sites for homologous recombination, a heterologous gene of $\beta$-glucosidase was integrated into the chromosome of Saccharomyces cerevisiae. The $\delta$-integrated recombinant yeast, Saccharomyces cerevisiae L2612 (Pb-BGL), showed perfect mitotic stability even in nonselective media and showed ca. 1.5 fold higher $\beta$-glucosidase activity than the recombinant yeast harboring the $2\mu$-based plasmid vector system. A mathematical model was developed to describe the $\beta$-glucosidase formation and ethanol production from the Saccharomyces cerevisiae L2612 ($p\delta-BGL$). The model newly described that the heterologous $\beta$-glucosidase production mediated by ADH1 promoter is regulated by glucose and repressed by ethanol.

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이산 경로 시스템에서 유전알고리듬을 이용한 최적음향탐색경로 전략 (Optimal Acoustic Search Path Planning Based on Genetic Algorithm in Discrete Path System)

  • 조정홍;김정해;김재수;임준석;김성일;김영선
    • 한국해양공학회지
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    • 제20권1호
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    • pp.69-76
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    • 2006
  • The design of efficient search path to maximize the Cumulative Detection Probability(CDP) is mainly dependent on experience and intuition when searcher detect the target using SONAR in the ocean. Recently with the advance of modeling and simulation method, it has been possible to access the optimization problems more systematically. In this paper, a method for the optimal search path calculation is developed based on the combination of the genetic algorithm and the calculation algorithm for detection range. We consider the discrete system for search path, space, and time, and use the movement direction of the SONAR for the gene of the genetic algorithm. The developed algorithm, OASPP(Optimal Acoustic Search Path Planning), is shown to be effective, via a simulation, finding the optimal search path for the case when the intuitive solution exists. Also, OASPP is compared with other algorithms for the measure of efficiency to maximize CDP.

2차원 수리해석을 위한 범용 Mesh Generator의 개발(Ⅴ) (Development of Mesh Generator for 2D Hydraulic Analysis(Ⅴ))

  • 김유진;이승현;오정환;김홍식
    • 한국수자원학회:학술대회논문집
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    • 한국수자원학회 2009년도 학술발표회 초록집
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    • pp.815-821
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    • 2009
  • 하천의 2차원 흐름 및 하상변동, 오염확산 해석을 위한 유체의 수치해석법에는 유한요소법, 유한차분법, 유한차분법의 변형인 유한체적법, 경계적분법 등이 있으며, 국내의 경우 비구조적 요소망(unstructured mesh)을 이용하여 복잡한 형상을 표현하기가 상대적으로 용이한 유한요소법이 널리 사용되고 있다. 하천을 유한 요소화 하는 전처리 과정은 전체 해석 과정을 자동화 하는데 있어 필수적인 요소이며, 주로 삼각 요소망 또는 사각 요소망을 이용하여 해석을 수행하게 된다. 삼각 요소망의 경우 상대적으로 자동화하기 쉬운 반면 사각 요소망의 생성은 절점 생성 자체가 삼각 요소망 보다 더 많은 기하학적 제한 요소를 가지고 있기 때문에 상대적으로 완성도 높은 알고리즘을 구현하기가 어렵다 할 수 있다. 이에 따라 본 연구에서는 2차원 상에서 사각 요소망(quadrilateral elements)을 생성할 수 있는 Paving method를 중심으로 한 요소망 생성 알고리즘에 대해 고찰하고, 국내 최초의 범용 수치해석 모형인 RAMS(River Analysis and Modeling System)에 적용하였다. Paving method는 1990년에 Blacker and Stephenson에 의해 제안되었으며, Sandia National Laboratories에 의해 완성되었다. Paving Method는 advancing front style의 요소망을 생성하게 되고, 바깥쪽에서 안쪽으로 element layer를 생성하면서 채워나간다. 본 연구에서는 기존의 요소망 생성 프로세스에서 element 삽입 전의 검증 기능을 강화한 새로운 버전의 paving method를 적용하엿다.

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Prediction of the bond strength of ribbed steel bars in concrete based on genetic programming

  • Golafshani, Emadaldin Mohammadi;Rahai, Alireza;Kebria, Seyedeh Somayeh Hosseini
    • Computers and Concrete
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    • 제14권3호
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    • pp.327-345
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    • 2014
  • This paper presents the application of multi-gene genetic programming (MGP) technique for modeling the bond strength of ribbed steel bars in concrete. In this regard, the experimental data of 264 splice beam tests from different technical papers were used for training, validating and testing the model. Seven basic parameters affecting on the bond strength of steel bars were selected as input parameters. These parameters are diameter, relative rib area and yield strength of steel bar, minimum concrete cover to bar diameter ratio, splice length to bar diameter ratio, concrete compressive strength and transverse reinforcement index. The results show that the proposed MGP model can be alternative approach for predicting the bond strength of ribbed steel bars in concrete. Moreover, the performance of the developed model was compared with the building codes' empirical equations for a complete comparison. The study concludes that the proposed MGP model predicts the bond strength of ribbed steel bars better than the existing building codes' equations. Using the proposed MGP model and building codes' equations, a parametric study was also conducted to investigate the trend of the input variables on the bond strength of ribbed steel bars in concrete.

노인의 이미지와 노인차별경험 간의 인과관계에 관한 연구 (Relation of Cause and Effect between the Elderly's Image and Ageism Experience)

  • 신학진;전상남
    • 한국생활과학회지
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    • 제18권6호
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    • pp.1169-1179
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    • 2009
  • The purpose of this study was to explore the effects of the elderly's image or appearance to ageism. In this study, image included factors such as image management, external image and self and other's acceptance. To investigate the cause and effect of image to ageism, we purposely collected 315 samples from 4 senior welfare centers in Jeonju and exploited SEM (Structural equation modeling) for 297 cases excluding some cases with missing values. According to the results, first, we found that oneself and others' acceptance of the elderly's external image decreases the experience of ageism. Second, the behavior for image management resulted in oneself and others' acceptance of the image. Third, the behavior for image management positively influenced the external image. Fourth, the elderly's external image caused positive effects on oneself and others' acceptance of the image. Fifth, behavior for image management showed decreasing effects of the ageism experience.

Characterization and Cofactor Binding Mechanism of a Novel NAD(P)H-Dependent Aldehyde Reductase from Klebsiella pneumoniae DSM2026

  • Ma, Cheng-Wei;Zhang, Le;Dai, Jian-Ying;Xiu, Zhi-Long
    • Journal of Microbiology and Biotechnology
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    • 제23권12호
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    • pp.1699-1707
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    • 2013
  • During the fermentative production of 1,3-propanediol under high substrate concentrations, accumulation of intracellular 3-hydroxypropionaldehyde will cause premature cessation of cell growth and glycerol consumption. Discovery of oxidoreductases that can convert 3-hydroxypropionaldehyde to 1,3-propanediol using NADPH as cofactor could serve as a solution to this problem. In this paper, the yqhD gene from Klebsiella pneumoniae DSM2026, which was found encoding an aldehyde reductase (KpAR), was cloned and characterized. KpAR showed broad substrate specificity under physiological direction, whereas no catalytic activity was detected in the oxidation direction, and both NADPH and NADH can be utilized as cofactors. The cofactor binding mechanism was then investigated employing homology modeling and molecular dynamics simulations. Hydrogen-bond analysis showed that the hydrogen-bond interactions between KpAR and NADPH are much stronger than that for NADH. Free-energy decomposition dedicated that residues Gly37 to Val41 contribute most to the cofactor preference through polar interactions. In conclusion, this work provides a novel aldehyde reductase that has potential applications in the development of novel genetically engineered strains in the 1,3-propanediol industry, and gives a better understanding of the mechanisms involved in cofactor binding.

Silibinin Inhibits LPS-Induced Macrophage Activation by Blocking p38 MAPK in RAW 264.7 Cells

  • Youn, Cha Kyung;Park, Seon Joo;Lee, Min Young;Cha, Man Jin;Kim, Ok Hyeun;You, Ho Jin;Chang, In Youp;Yoon, Sang Pil;Jeon, Young Jin
    • Biomolecules & Therapeutics
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    • 제21권4호
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    • pp.258-263
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    • 2013
  • We demonstrate herein that silibinin, a polyphenolic flavonoid compound isolated from milk thistle (Silybum marianum), inhibits LPS-induced activation of macrophages and production of nitric oxide (NO) in RAW 264.7 cells. Western blot analysis showed silibinin inhibits iNOS gene expression. RT-PCR showed that silibinin inhibits iNOS, TNF-${\alpha}$, and $IL1{\beta}$. We also showed that silibinin strongly inhibits p38 MAPK phosphorylation, whereas the ERK1/2 and JNK pathways are not inhibited. The p38 MAPK inhibitor abrogated the LPS-induced nitrite production, whereas the MEK-1 inhibitor did not affect the nitrite production. A molecular modeling study proposed a binding pose for silibinin targeting the ATP binding site of p38 MAPK (1OUK). Collectively, this series of experiments indicates that silibinin inhibits macrophage activation by blocking p38 MAPK signaling.

Discovery of Anticancer Activity of Amentoflavone on Esophageal Squamous Cell Carcinoma: Bioinformatics, Structure-Based Virtual Screening, and Biological Evaluation

  • Chen, Lei;Fang, Bo;Qiao, Liman;Zheng, Yihui
    • Journal of Microbiology and Biotechnology
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    • 제32권6호
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    • pp.718-729
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    • 2022
  • Esophageal squamous cell carcinoma (ESCC) is the most common primary esophageal malignancy with poor prognosis. Here, due to the necessity for exploring potential therapies against ESCC, we obtained the gene expression data on ESCC from the TCGA and GEO databases. Venn diagram analysis was applied to identify common targets. The protein-protein interaction network was constructed by Cytoscape software, and the hub targets were extracted from the network via cytoHubba. The potential hub nodes as drug targets were found by pharmacophore-based virtual screening and molecular modeling, and the antitumor activity was evaluated through in vitro studies. A total of 364 differentially expressed genes (DEGs) in ESCC were identified. Pathway enrichment analyses suggested that most DEGs were mainly involved in the cell cycle. Three hub targets were retrieved, including CENPF, CCNA2 (cyclin A), and CCNB1 (cyclin B1), which were highly expressed in esophageal cancer and associated with prognosis. Moreover, amentoflavone, a promising drug candidate found by pharmacophore-based virtual screening, showed antiproliferative and proapoptotic effects and induced G1 in esophageal squamous carcinoma cells. Taken together, our findings suggested that amentoflavone could be a potential cell cycle inhibitor targeting cyclin B1, and is therefore expected to serve as a great therapeutic agent for treating esophageal squamous cell carcinoma.