• Title/Summary/Keyword: Copy Numbers

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Factors that Predict Clinical Benefit of EGFR TKI Therapy in Patients with EGFR Wild-Type Lung Adenocarcinoma

  • Kim, Seo Yun;Myung, Jae Kyung;Kim, Hye-Ryoun;Na, Im Il;Koh, Jae Soo;Baek, Hee Jong;Kim, Cheol Hyeon
    • Tuberculosis and Respiratory Diseases
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    • v.82 no.1
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    • pp.62-70
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    • 2019
  • Background: Epidermal growth factor receptor (EGFR) mutations in non-small cell lung cancers have emerged as key predictive biomarkers in EGFR tyrosine kinase inhibitor (TKI) treatment. However, a few patients with wild-type EGFR also respond to EGFR TKIs. This study investigated the factors predicting successful EGFR TKI treatment in lung adenocarcinoma patients with wild-type EGFR. Methods: We examined 66 patients diagnosed with lung adenocarcinoma carrying wide-type EGFR who were treated with EGFR TKIs. The EGFR gene copy number was assessed by silver in situ hybridization (SISH). We evaluated the clinical factors and EGFR gene copy numbers that are associated with a favorable clinical response to EGFR TKIs. Results: The objective response rate was 12.1%, while the disease control rate was 40.9%. EGFR SISH analysis was feasible in 23 cases. Twelve patients tested EGFR SISH-positive, and 11 were EGFR SISH-negative, with no significant difference in tumor response and survival between EGFR SISH-positive and -negative patients. The overall median progression-free survival (PFS) and overall survival (OS) of 66 patients were 2.1 months and 9.7 months, respectively. Female sex and Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0-1 were independent predictors of PFS. ECOG PS 0-1 and a low tumor burden of extrathoracic metastasis were independent predictors of good OS. Conclusion: Factors such as good PS, female sex, and low tumor burden may predict favorable outcomes following EGFR TKI therapy in patients with EGFR wild-type lung adenocarcinoma. However, EGFR gene copy number was not predictive of survival.

Genome-wide Copy Number Variation in a Korean Native Chicken Breed (한국 토종닭의 전장 유전체 복제수변이(CNV) 발굴)

  • Cho, Eun-Seok;Chung, Won-Hyong;Choi, Jung-Woo;Jang, Hyun-Jun;Park, Mi-Na;Kim, Namshin;Kim, Tae-Hun;Lee, Kyung-Tai
    • Korean Journal of Poultry Science
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    • v.41 no.4
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    • pp.305-311
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    • 2014
  • Copy number variation (CNV) is a form of structural variation that shows various numbers of copies in segments of the DNA. It has been shown to account for phenotypic variations in human diseases and agricultural production traits. Currently, most of chicken breeds in the poultry industry are based on European-origin breeds that have been mostly provided from several international breeding companies. Therefore, National Institute of Animal Science, RDA has been trying to restore and improve Korean native chicken breeds (12 lines of 5 breeds) for about 20 years. Thanks to the recent advance of sequencing technologies, genome-wide CNV can be accessed in the higher resolution throughout the genome of species of interest. However, there is no systematic study available to dissect the CNV in the native chicken breed in Korea. Here, we report genome-wide copy number variations identified from a genome of Korean native chicken (Line L) by comparing between the chicken reference sequence assembly (Gallus gallus) and a de novo sequencing assembly of the Korean native chicken (Line L). Throughout all twenty eight chicken autosomes, we identified a total of 501 CNVs; defined as gain and loss of duplication and deletion respectively. Furthermore, we performed gene ontology (GO) analysis for the putative CNVs using DAVID, leading to 68 GO terms clustered independently. Of the clustered GO terms, genes related to transcription and gene regulation were mainly detected. This study provides useful genomic resource to investigate potential biological implications of CNVs with traits of interest in the Korean native chicken.

Effect of PVA-Encapsulation on Hydrogen Production and Bacterial Community Structure (수소 생산과 세균 군집구조에 미치는 PVA-포괄고정화의 영향)

  • Yun, Jeonghee;Kim, Tae Gwan;Cho, Kyung-Suk
    • Microbiology and Biotechnology Letters
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    • v.42 no.1
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    • pp.41-50
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    • 2014
  • In this study, the performances of PVA-encapsulation and non-encapsulation in a fed-batch bioreactor system were compared for biohydrogen production. Hydrogen production in the PVA-encapsulation bioreactor was not significantly different in comparison to the non-encapsulation bioreactor. However, the hydrogen gas in the encapsulation bioreactor could be stably produced when it was exposed to environmental difficulties such as pH impact by the accumulation of organic acids as fermentative metabolic products. Bacterial communities by DGGE analysis were differently shifted between the PVA-encapsulation and non-encapsulation bioreactors from the initial sludge. The community of hydrogen producing bacteria was stable during the experimental period in the PVA-encapsulation bioreactor compared to the non-encapsulation method. The absolute quantitation of the DNA copy number by a high-throughput droplet digital PCR system for six genera contributed to hydrogen production showing that the numbers of dominant bacteria existed at similar levels in the two bioreactors regardless of encapsulation. In both of two bioreactors, not only Clostridium and Enterobacter, which are known as anaerobic hydrogen producing bacteria, but also Firmicutes, Ruminococcus and Escherichia existed with $1{\times}10^5-1{\times}10^6$ copy numbers of ml-samples exhibiting rapid growth during the initial operation period.

A Garbage Collection Method for Flash Memory Based on Block-level Buffer Management Policy

  • Li, Liangbo;Shin, Song-Sun;Li, Yan;Baek, Sung-Ha;Bae, Hae-Young
    • Journal of Korea Multimedia Society
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    • v.12 no.12
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    • pp.1710-1717
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    • 2009
  • Flash memory has become the most important storage media in mobile devices along with its attractive features such as low power consumption, small size, light weight, and shock resistance. However, a flash memory can not be written before erased because of its erase-before-write characteristic, which lead to some garbage collection when there is not enough space to use. In this paper, we propose a novel garbage collection scheme, called block-level buffer garbage collection. When it is need to do merge operation during garbage collection, the proposed scheme does not merge the data block and corresponding log block but also search the block-level buffer to find the corresponding block which will be written to flash memory in the next future, and then decide whether merge it in advance or not. Our experimental results show that the proposed technique improves the flash performance up to 4.6% by reducing the unnecessary block erase numbers and page copy numbers.

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Expression of the Transgene is Consistently Inherited to High Numbers of Generations and Independent on Its Source

  • Zheng, Zhen-Yu;Oh, Keon-Bong;Koo, Deog-Bon;Han, Yong-Mahn;Lee, Kyung-Kwang
    • Reproductive and Developmental Biology
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    • v.32 no.1
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    • pp.39-43
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    • 2008
  • Most studies on transgenic bioreactors have focused on expression levels of interest genes. In this study we examined whether transgenic bioreactors would inherit expression level of the Oansgene to long-term generations independently of transgene sources. We employed three transgenic mice, which were separately reported, carrying different transgenes and copy numbers, 27 kb of hLF and 22 kb of hIL-10 genomic sequences, and 1.3 kb of hTPO cDNA, respectively. Three females of the transgenic lineages crossbred with a wild-type male up to 20 generations to test transgenic frequencies of their progenies and to determine expression levels of the transgenes. Ultimately, transmission rates of kLF, hIL-10, and hTPO were $64.3{\pm}7.0$, $59.3{\pm}9.8$, and $56.1{\pm}9.7$, respectively, appeared following Mendelian pattern of inheritance. Notably, we found that levels of expressions of hLF, hIL-10, and hTPO in milk were sustained to high numbers of generations. No transgene silencing of expression was observed in every generations of all transgenic mice. In conclusion, we suggest that once established animal bioreactors could consistently transmit the transgene to continual generations, without loss of expressional activity, independently of transgene sources.

Production and characterization of ultra-high-molecular weight poly(3-hydroxybutyrate) by recombinant Escherichia coli

  • Park, Jong-Pil;Park, Si-Jae;Lee, Sang-Yeop
    • 한국생물공학회:학술대회논문집
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    • 2001.11a
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    • pp.731-734
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    • 2001
  • An efficient fermentation strategy for the high level production of ultra-high-molecular weight poly(3-hdyroxybutyrate) (PHB) was developed. Although the cell and PHA concentrations obtained by flask cultures at different initial pH (6.0 or 6.9) were almost same level, the molecular mass of PHB produced were quite different along with the initial pH. When a recombinant Escherichia coli XL1-Blue harboring pJC2 containing the Alcaligenes latus PHB biosynthesis genes was cultivated in flask culture (pH 6.0), the PHB having a very high molecular weight of 22 MDa could be produced while only below 1 MDa at initial pH 6.9. The ultra-high-molecular weight PHB could be synthesized to high concentration of 89.8 g/L resulting in the PHB productivity of 2.07 g/L-h by simple fed-batch culture. In this study, we report that PHB having various molecular mass can be produced by employing metabolically engineered E. coli strains harboring the plasmids of different copy numbers containing the A. latus phbCAB genes.

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Atypical Correlation between CTG Repeat Size Variation and Clinical Manifestation in Brothers of Myotonic Dystrophy (임상양상과 유전자수가 비전형적인 연관관계를 갖는 근긴장성 이영양증 형제 1례)

  • Kim, Jung-Mee;Cho, Eun-Kyoung;Cho, Jeong-Seon;Choi, Yong-Suk;Han, Young-Su;Han, Jeong-Ho;Kim, Doo-Eung
    • Annals of Clinical Neurophysiology
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    • v.6 no.1
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    • pp.61-63
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    • 2004
  • The copy numbers of the CTG repeats are known to relate to the severity of clinical symptoms for myotonic dystrophy. The positive correlation between clinical manifestations and CTG repeat size has been demonstrated previously. A genetically confirmed myotonic dystrophy patient with 90 CTG repeat number had more severe clinical manifestation than brother with 120 CTG repeats, in adulthood.

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Development of a Denaturing High-Performance Liquid Chromatography (DHPLC) Assay to Detect Parasite Infection in Grass Shrimp Palaemonetes pugio

  • Cho, Sang-Man
    • Fisheries and Aquatic Sciences
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    • v.15 no.2
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    • pp.107-115
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    • 2012
  • In developing a useful tool to detect parasitic dynamics in an estuarine ecosystem, a denaturing high-performance liquid chromatography (DHPLC) assay was optimized by cloning plasmid DNA from the grass shrimp Palaemonetes pugio, and its two parasites, the trematode Microphallus turgidus and bopyrid isopod Probopyrus pandalicola. The optimal separation condition was an oven temperature of $57.9^{\circ}C$ and 62-68% of buffer B gradient at a flow rate of 0.45 mL/min. A peptide nucleic acid blocking probe was designed to clamp the amplification of the host gene, which increased the amplification efficiency of genes with low copy numbers. Using the DHPLC assay with wild-type genomic, the assay could detect GC Gram positive bacteria and the bopyrid isopod (P. pandalicola). Therefore, the DHPLC assay is an effective tool for surveying parasitic dynamics in an estuarine ecosystem.

Genetic Diversity and Phylogenetic Analysis of the mtDNA D-loop Region in Tibetan Sheep

  • Wang, X.;Chen, H.;Lei, C. Z.
    • Asian-Australasian Journal of Animal Sciences
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    • v.20 no.3
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    • pp.313-315
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    • 2007
  • Seventeen haplotypes were detected from the complete mitochondrial DNA control region sequences analyzed from eighty individuals of two Tibetan domestic sheep breeds. The nucleotide composition of all the sequences was 33.0% A, 29.7%T, 22.9%C and 14.4%G; G+C was 37.3%. The length of the sequences ranged from 1,107 bp to 1,259 bp. The difference between them was primarily due to 3-5 copy numbers of a 75 bp tandem repeat sequence. The NJ phylogenetic tree (the number of replications of bootstrap test is 1,000) presented three major domestic sheep lineages, which suggested that modern Tibetan sheep breeds are derived from three maternal sources.

Secretion of Human Growth Hormone from Mammary Gland of Transgenic Mice (형질전환동물의 유선조직으로부터 인간 성장호르몬의 분비)

  • 구덕본;최강덕;정형민;이상민;이경광;이훈택;정길생
    • Korean Journal of Animal Reproduction
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    • v.17 no.4
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    • pp.375-383
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    • 1994
  • The human growth hormone (hGH) gene uder the control of the rat $\beta$-casein promoter gene was designed to produce transgenic mouse expressed hGH gene in only mammary gland. One hundred seventy two eggs microinjected were transferred to the oviducts of pseudopregnants and 43 offspring were delivered. By Southern blotting hybridization, 3 were transgenic with rat $\beta$-casein/hGH gene. The copy numbers of three transgenic founder were 1, 5, and 15, respectively. A radioimmunoassay was developed to quantitate the amount of expression of the hGH gene in mammary gland of transgenic mice. The amount of hGH was 13.3ng/ml in the lactating milk of one transgenic line, showing predominantly higher than 3.0ng/ml in milk of control mice. Therefore, our findings suggested that $\beta$-casein promoter may induce the tissue specific expression of structural gene.

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