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Thymidylate Synthase Polymorphisms and Risk of Lung Cancer among the Jordanian Population: a Case Control Study

  • Qasem, Wiam Al;Yousef, Al-Motassem;Yousef, Mohammad;Manasreh, Ihab
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.18
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    • pp.8287-8292
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    • 2016
  • Background: Thymidylate synthase (TS) catalyzes the methylation of deoxyuridylate to deoxythymidylate and is involved in DNA methylation, synthesis and repair. Two common polymorphisms have been reported, tandem repeats in the promoter-enhancer region (TSER), and 6bp ins/del in the 5'UTR, that are implicated in a number of human diseases, including cancer. The association between the two polymorphisms in risk for lung cancer (LC) was here investigated in the Jordanian population. Materials and Methods: An age, gender, and smoking-matched case-control study involving 84 lung cancer cases and 71 controls was conducted. The polymerase chain reaction/restriction fragment length polymorphism (PCR-RFLP) technique was used to detect the polymorphism of interest. Results: Individuals bearing the ins/ins genotype were 2.5 times more likely to have lung cancer [(95%CI: 0.98-6.37), p=0.051]. Individuals who were less than or equal to 57 years and carrying ins/ins genotype were 4.6 times more susceptible to lung cancer [OR<57 vs >57years: 4.6 (95%CI: 0.93-22.5), p=0.059)]. Genotypes and alleles of TSER were distributed similarly between cases and controls. Weak linkage disequilibrium existed between the two loci of interest (Lewontin's coefficient [D']) (LC: D' =0.03, r2: 0. 001, p=0.8; Controls: D' =0.29, r2: 0.08, p=0.02). Carriers of the "3 tandem repeats_insertion" haplotype (3R_ins) were 2 times more likely to have lung cancer [2 (95%CI: 1.13-3.48), p=0.061]. Conclusions: Genetic polymorphism of TS at 3 'UTR and its haplotype analysis may modulate the risk of lung cancer in Jordanians. The 6bp ins/del polymorphism of TS at 3 'UTR is more informative than TSER polymorphism in predicting increased risk.

A Study of the PDCA and CAPD Economic Designs of the $\bar{x}$ Control Chart

  • Sun, Jing;Tsubaki, Michiko;Matsui, Masayuki
    • Industrial Engineering and Management Systems
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    • v.6 no.1
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    • pp.11-21
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    • 2007
  • The PDCA (Plan, Do, Check and Act) cycle is often used in the field of quality management. Recently, business environments have become more competitive, and the due time of products has shortened. In a short production run process, to increase efficiency of management, the necessity for distinguishing the PDCA design that starts with PLAN and the CAPD design that starts with CHECK has been clarified. Starting from Duncan (1956), there have been a number of papers dealing with the economic design of control charts from the viewpoint of production run. Some authors (Gibra, 1971; Ladany and Bedi, 1976; etc.) have studied the economic design for finite-length runs; other authors (Crowder, 1992; Del Castillo and Montgomery, 1996; etc.) have studied the economic design for short runs. However, neither the PDCA nor the CAPD design of control charts has been considered. In this paper, both the PDCA and CAPD designs of the $\bar{\x}$ chart are defined based on Del Castillo and Montgomery's design (1996), and their mathematical formulations are shown. Then from an economic viewpoint, the optimal values of the sample size per each sampling, control limits width, and the sampling interval of the two designs are studied. Finally, by numerically analyzing the relations between the key parameters and the total expected cost per unit time, the comparisons between the two designs are considered in detail.

Evaluation of Delamination for Fiber Reinforced Composite Material without Crack (균열이 발생하지 않는 섬유강화 복합재료의 층간분리 평가법)

  • 송삼홍;김철웅;황진우
    • Proceedings of the Korean Society of Precision Engineering Conference
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    • 2003.06a
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    • pp.1349-1353
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    • 2003
  • Previous researches for fiber reinforced composite material(FRCM) have been evaluated the fatigue delamination behavior using the traditional fracture mechanics parameters. Therefore. previous researches for FRCM have not generally been firmed yet. Because delamination growth behavior in FRCM should be consider relationship between delamination area, A$\sub$D/ and crack length, a instead of traditional fracture mechanics parameters. Especially, in case of delamination behavior for FRCM without crack should be considering equivalent crack, i.e., pseudo crack, a$\sub$p/, using the fracture behavior of FRCM with crack. The major purpose of this study was to evaluate the delamination for FRCM without crack. The details of the studies are as follow : 1) Relationship between crack growth rate, da/dN and stress intensity factor, ΔK in FRCM containing a saw-cut and circular hole with crack. 2) Propose of PSEUDO CRACK MODEL for the delamination in FRCM without crack. 3) Analysis of crack propagation energy, E$\sub$crack/ using a total energy, E$\sub$total/ and delamination growth energy, E$\sub$del/.

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Correlation Between Primary Tuberculous Pleurisy and NRAMP1 Genetic Polymorphism (결핵성 흉막염 환자에서 NRAMP1 유전자 다형성에 대한 연구)

  • Kim, Je-Hyeong;Kim, Byung-Gyu;Jung, Ki-Hwan;Park, Sang-Myun;Lee, Sang-Youb;Lee, Sin-Hyung;Sin, Cheol;Cho, Jae-Youn;Shim, Jae-Jeong;In, Kwang-Ho;Yoo, Se-Hwa;Kang, Kyung-Ho
    • Tuberculosis and Respiratory Diseases
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    • v.48 no.2
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    • pp.155-165
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    • 2000
  • Background: The phagolysosomal function of alveolar macrophage against M. tuberculosis infection is influenced by Nramp1, which is encoded by the NRAMP1 gene. There are several genetic polymorphisms in NRAMP1, and these polymorphisms affect the innate host resistance through the defect in production and function of Nramp1. To investigate this relationship, the NRAMP1 genetic polymorphism in patients with primary tuberculous pleurisy was determined. Methods: Fifty-six primary tuberculous pleurisy patient, who were diagnosed by pleural biopsy, were designated to the pleurisy group and 45 healthy adults were designated to the healthy control group. Three genetic polymorphisms of NRAMP1, such as a single point mutation in intron 4(469+14G/C, INT4), a nonconservative single-base substitution at codon 543 that changes aspartic acid to asparagine(D543N) and a TGTG deletion in the 3' untranslated region(1729+55delI4, 3'UTR), were determined. Polymerase chain reaction(PCR) and polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP) were used. Results: The frequencies of mutant genotypes of INT4 and 3'UTR were significantly high in pleurisy group(p=0.001, p=0.023). But the frequencies of D543N were not significantly different between the two groups(p=0.079). The odds ratios, which are a comparison with wild genotype for determining mutant genotypes, were 8. 022(95% confidence interval=2.422-26.572) for INT4 and 5.733(95% confidence interval = 1.137~28.916) for 3'UTR ; these were statistically significant But the ratio for D543N was not significant In the combined analysis of the INT4 and 3'UTR polymorphisms, the odds ratios were 6.000(95% confidence interval = 1.461~24.640) for GC/++ genotype and 14.000(95% confidence interval=1.610~121.754) for GC/+del when compared with GG/++ homozygotes ; these were statistically significant. Conclusion: Among the NRAMP1 genetic polymorphisms, a single point mutation in intron 4(469+14G/C, INT4) and a TGTG deletion in the 3' untranslated region(1729+55del4, 3'UTR) were closely related to the primary tuberculous pleurisy.

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Morphological variability of intertidal Eisenia arborea (Laminariales, Ochrophyta) at Punta Eugenia, Baja California Sur

  • Parada, Gloria M.;Riosmena-Rodriguez, Rafael;Martinez, Enrique A.;Hernandez-Carmona, Gustavo
    • ALGAE
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    • v.27 no.2
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    • pp.109-114
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    • 2012
  • Water motion is one of the main drivers in morphological variability in species within de order Laminariales, and most of our current knowledge is based on subtidal populations. $Eisenia$ $arborea$ is a dominant kelp species in the North Pacific, widely distributed along the Baja California Peninsula from mid intertidal down to subtidal areas. This species presents great variability in the intertidal zone but it has not been yet evaluated such variability according to wave exposure. The present work also identifies the spatial / temporal variation, particularly respect to the presence of stipes without medulla (hollow stipes) a feature common among other brown seaweeds. We evaluated the effects of wave action in morphological variation of intertidal $Eisenia$ $arborea$ (Laminariales, Ochrophyta) at Punta Eugenia. The spatial and temporal variation sampling was surveyed between February, May, July, and August 2004 in the intertidal of Punta Eugenia, Baja California Sur. Our results have shown that exposed sites correlate with increased length and width of stipes as compared to more protected sites. Hollow stipes frequency changed more in association with temporal variation than with spatial heterogeneity suggesting nutrient limitation for thalli development. Our results suggest that $Eisenia$ $arborea$ compensate by morphological modifications the stress of living in the intertidal zone by showing larger stipes. Hollow stipes might be are also a mechanical adaptation to increase survival in high energy environments.

Elevated folic acid results in contrasting cancer cell line growth with implications for mandatory folic acid fortification

  • Yates, Zoe;Lucock, Mark;Veysey, Martin;Choi, Jeong-hwa
    • Journal of Nutrition and Health
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    • v.49 no.2
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    • pp.72-79
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    • 2016
  • Purpose: The initiation of mandatory folic acid fortification using pteroylmonoglutamic acid (PteGlu) has reduced the rate of congenital malformations. However, it also appears to be responsible for several adverse effects, including increased cancer incidence. This may be related to physicho-chemical characteristics of PteGlu. This study examines the potential effect of high concentrations of PteGlu on a population subjected to mandatory folic acid fortification using an in vitro model. Methods: Caco-2 (colorectal cancer) and MCF7 (breast cancer) cell lines were cultured at 6 different PteGlu concentrations (0, 0.1, 1, 50, 250, and $500{\mu}g/ml$) for 6 days. Cell growth was determined using thiazolyl blue tetrazolium bromide assay. The genotype of dihydrofolate reductase 19bp deletion/insertion (DHFR 19-del) was also scored in cell lines using a restriction fragment length polymorphism technique to examine whether genetic variations may factor in cell proliferation. Results: PteGlu exhibited differential growth promoting properties between cell lines. Caco-2 cells did not show a significant growth difference at low concentrations compared to control, however, at higher concentrations, the growth showed a contrasting trend in the early experimental period, while MCF7 showed enhanced cell growth at all concentrations. The DHFR 19-del genotype differed in the two cell lines. Conclusions: Altered response to PteGlu by Caco-2 and MCF7 may reflect a tissue specific disease aetiology or genotype specific differential enzyme activity, for example by DHFR, to critical levels of PteGlu. As folic acid fortification is a blanket intervention, and DHFR and other enzyme activities vary between individuals, PteGlu intake may have an as yet undefined effect on health. These findings may be relevant when considering mandatory folic acid fortification for disease prevention.

Polymorphisms in the Thymidylate Synthase Gene and Risk of Colorectal Cancer

  • Gao, Chang-Ming;Ding, Jian-Hua;Li, Su-Ping;Liu, Yan-Ting;Cao, Hai-Xia;Wu, Jian-Zhong;Tajima, Kazuo
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.8
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    • pp.4087-4091
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    • 2012
  • To evaluate the relationship between polymorphisms (28 bp repeated sequences in 5'-UTR and 6-bp ins/del in 3'-UTR) in then thymidylate synthetase gene (TS) and risk of colorectal, colon and rectal cancers, we conducted a case-control study with 315 cases of colorectal cancer and 439 population-based controls in Jiangsu province, China. TS genotypes were identified using PCR.RFLP (restriction fragment length polymorphism) methods. Odds ratios (ORs) were estimated with an unconditional logistic regression model. We found that the distributions of 5'-UTR genotypes in TS were significantly different between controls and male colon cases (${\chi}^2$=8.25, P = 0.016). Compared with 3R/3R genotype, individuals with the 2R allele were at an increased risk of colon cancer (age-, BMI-, smoking- and alcohol drinking-adjusted OR=1.98, 95%CI: 1.11-3.53) among men. In ccontrast, the 6-bp ins/del polymorphism at the TS 3'- UTR did not influence risk of the colorectal, colon and rectal cancers. When combined genotypes for both TS 5'-UTR and 3'-UTR polymorphisms were evaluated, individuals with the 5'-UTR 2R allele had a OR of 3.61 (95%CI: 1.38-9.49) for colon cancer among men with the 3'-UTR .6bp/-6bp genotype. These results show that the polymorphism of the 28 bp repeated sequences in TS 5'-UTR could influence susceptibility to colon cancer and that there was a coordinated effect between TS 3'-UTR and 5'-UTR polymorphisms in increasing risk of colon cancer among Chinese men.

PCR-based markers to select plastid genotypes of Solanum acaule (Solanum acaule 색소체 유전자형 선발을 위한 특이적 분자마커 개발)

  • Park, Tae-Ho
    • Journal of Plant Biotechnology
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    • v.49 no.3
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    • pp.178-186
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    • 2022
  • The tetraploid Solanum acaule is a wild potato species from Bolivia widely used for potato breeding because of its diverse attractive traits, including resistance to frost, late blight, potato virus X, potato virus Y, potato leafroll virus, potato spindle tuber viroid, and cyst nematode. However, the introgression of useful traits into cultivated potatoes via crossing has been limited by differences in endosperm balance number between species. Somatic fusion could be used to overcome sexual reproduction barriers and the development of molecular markers is essential to select proper fusion products. The chloroplast genome of S. acaule was sequenced using next-generation sequencing technology and specific markers for S. acaule were developed by comparing the obtained sequence with those of seven other Solanum species. The total length of the chloroplast genome is 155,570 bp, and 158 genes were annotated. Structure and gene content were very similar to other Solanum species and maximum likelihood phylogenetic analysis with 12 other species belonging to the Solanaceae family revealed that S. acaule is very closely related to other Solanum species. Sequence alignment with the chloroplast genome of seven other Solanum species revealed four InDels and 79 SNPs specific to S. acaule. Based on these InDel and SNP regions, one SCAR marker and one CAPS marker were developed to discriminate S. acaule from other Solanum species. These results will aid in exploring evolutionary aspects of Solanum species and accelerating potato breeding using S. acaule.

Development of PCR-based markers for selecting plastid genotypes of Solanum hjertingii (Solanum hjertingii 색소체 유전자형 선발을 위한 PCR 기반 분자마커 개발)

  • Tae-Ho Park
    • Journal of Plant Biotechnology
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    • v.50
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    • pp.34-44
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    • 2023
  • The tetraploid Solanum hjertingii, a wild tuber-bearing species from Mexico is a relative of potato, S. tuberosum. The species has been identified as a potential source of resistance to blackening for potato breeding. It does not exhibit enzymatic browning nor blackspot which are physiological disorders. However, due to their sexual incompatibility, somatic hybridization between S. hjertingii and S. tuberosum must be used to introduce various traits from this wild species into potato. After somatic hybridization, molecular markers are essential for selecting fusion products. In this study, the chloroplast genome of S. hjertingii was sequenced by next-generation sequencing technology and compared with those of other Solanum species to develop specific markers for S. hjertingii. The chloroplast genome has a total sequence length of 155,545 bp, and its size, gene content, order and orientation are similar to those of the other Solanum species. Phylogenic analysis including 15 other Solanaceae species grouped S. hjertingii with S. demissum, S. hougasii, and S. stoloniferum. After detailed comparisons of the chloroplast genome sequence with eight other Solanum species, we identified one InDel and seven SNPs specific to S. hjertingii. Based on these, five PCR-based markers were developed for discriminating S. hjertingii from other Solanum species. The results obtained in this study will aid in exploring the evolutionary aspects of Solanum species and accelerating breeding using S. hjertingii.

Implementation of an Efficient Wavelet Based Audio Data Retrieval System (효율적인 웨이블렛 기반 오디오 데이터 검색 시스템 구현)

  • 이배호;조용춘;김광희
    • The Journal of the Acoustical Society of Korea
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    • v.21 no.1
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    • pp.82-88
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    • 2002
  • In this paper, we proposed a audio indexing method that is used wavelet transform for audio data retrieval. It is difficult for audio data to make a efficient audio data index because of its own particular properties, such as requirement of large storage, real time to transfer and wide bandwidth. An audio data in del using wavelet transform make it possible to index and retrieval by using the particular wavelet transform properties. Our proposed indexing method doesn't separate data to several blocks. Therefore we use both high-pass and low-pass parts of last level coefficient of wavelet transform. Audio data indexing is made by applying the string matching algorithm to high-pass part and zero-crossing histogram to low-pass part. These are transformed to the continued strings, Through this method, we described a retrieval efficiency. The retrieval method is done by comparing the database index string to the query string and then data of minimum values is chosen to the result. Our simulation decided proper comparative coefficient and made known changing of retrieval efficiency versus audio data length. The results show that the proposed method improves retrieval efficiency compared to conventional method.