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Synthesis and Biodistribution of Flumazenil Derivative [F-18](3-(2-Fluoro) flumazenil for Imaging Benzodiazepine Receptor (벤조디아제핀 수용체 영상용 양전자 방출 핵종 표지 플루마제닐 유도체 [F-18](3-(2-Fluoro)flumazenil의 합성과 생체 내 분포)

  • Hong, Sung-Hyun;Jeong, Jae-Min;Chang, Young-Soo;Lee, Dong-Soo;Chung, June-Key;Cho, Jung-Hyuck;Lee, Sook-Ja;Kang, Sam-Sik;Lee, Myung-Chul
    • The Korean Journal of Nuclear Medicine
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    • v.33 no.6
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    • pp.527-536
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    • 1999
  • Purpose: Radiotracers that bind to the central benzodiazepine receptor are useful for the investigation of various neurological and psychiatric diseases. [C-11]Flumazenil, a benzodiazepine antagonist, is the most widely used radioligand for central benzodiazepine receptor imaging by PET. We synthesized 3-(2-[F-18]fluoro)flumazenil, a new fluorine-18 ($t_{1/2}$= 110 min) labeled analogue of benzodiazepine receptor imaging agent, and evaluated in vivo for biodistribution in mice. Materials and Methods: Flumazenil (Ro 15-1788) was synthesized by a modification of the reported method. Precursor of 3-(2-[F-18]fluoro)flumazenil, the tosylated flumazenil derivative was prepared by the tosylation of the ethyl ester by ditosylethane. [F-18] labeling of tosyl substitued flumazenil precursor was performed by adding F-18 ion at $85^{\circ}C$ in the hot ceil for 20 min. The reaction mixture was trapped by C18 cartridge, washed with 10% ethanol, and eluted by 40% ethanol. Bidistribution in mice was determined after intravenous injection. Results: The total chemical yield of tosylated flumazenil derivative was ${\sim}40%$. The efficiency of labeling 3-(2-[F-18]fluoro)flumazenil was 66% with a total synthesis time of 50 min. Brain uptakes of 3-(2-[F-18]fluoro)flumazenil at 10, 30, 60 min after injection, were $2.5{\pm}0.37,\;2.2{\pm}0.26,\;2.1{\pm}0.11$ and blood activities were $3.7{\pm}0.43,\;3.3{\pm}0.07,\;3.3{\pm}0.09%ID/g$, respectively. Conclusion: We synthesized a tosylated flumazenil derivative which was successfully labeled with no-carrier-added F-18 by nucleophilic substitution.

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Effect of Breads Containing Trans Fat, Soybean or Rice on Plasma Lipid and Fatty Acid Composition in Healthy Korean Adults (Trans 지방과 쌀, 콩을 첨가한 빵의 섭취가 건강한 성인 남녀의 혈장 지질 및 지방산 조성에 미치는 영향)

  • Noh, Kyung-Hee;Huh, Young;Jang, Ji-Hyun;Kim, Soo-Hee;Shin, Jin-Hyuk;Kim, Do-Hoon;Lee, Seong-Hwan;Lee, Kyung-Sik;Park, Yong-Kyu;Cho, Kyung-Hwan;Song, Young-Sun
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.38 no.8
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    • pp.1042-1049
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    • 2009
  • It has been reported that trans fat (tFA) may have adverse or beneficial effect depending upon the position and number of double bonds. The presence of tFA in human tissues and fluids is related to dietary intake, intestinal absorption, metabolism and storage, exchanges among compartments. This study investigated the effect of breads containing tFA, soybean or rice on postprandial plasma fatty acid and lipid composition. 33 healthy volunteers were divided into 3 groups and fed soybean bread, rice bread or wheat bread groups containing equivalent amounts of tFA (elaidic acid rich, 3.75 g/day), respectively. Postprandial lipid profiles at 0, 1, 2, 3 and 4 hours after a respective meal were studied. Plasma fatty acid was extracted by the method of Folch and methyl ester of fatty and prepared by acid transmethylation and analyzed by Gas Chromatography. Peaks were identified using pure reference compounds and quantified. Postprandial data indicated that consumption of soybean and rice breads with 3.75 g tFA retarded the appearance of C18:1 and C18:2 tFA in plasma lipid compared to that of wheat bread. Futhermore, soybean and rice bread groups showed lower plasma saturated fatty acid levels than wheat bread group. Postprandial TG level was significantly lowered in soybean bread group compared to that of rice and wheat bread groups. These results imply that soybean bread with high dietary fiber content and biologically active substances may inhibit or delay lipid absorption.

Effects of Linoleic Acid and Serum Albumin Concentrations on Lipid Metabolism in HepG2 Cells (간세포 배양에서 Linoleic Acid와 혈청알부민의 첩가가 지질대사에 미치는 영향)

  • Cha, Jae-Young;Cho, Young-Su
    • Applied Biological Chemistry
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    • v.42 no.3
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    • pp.229-234
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    • 1999
  • The effects of linoleic acid(LA, 18 : 2) and/or bovine serum albumin(BSA) on the lipid metabolism in human hepatoma cell line HepG2 cells were evaluated. HepG2 cells were cultured in basal Dulbecco's modified Eagle's(DME) medium(Basal medium), DME medium containing 0.2 mM LA(LA medium), or DME medium containing both 0.2 mM LA and 0.2-1.0% BSA(LA+BSA medium). $[^{14}C]Acetate(0.3\;{\mu}Ci/ml\;medium)$ was added as a radioactive lipid precursor and the cells were incubated for 6 hours. An addition of LA to basal medium resulted in a decrease in the incorporation of $[^{14}C]acetate$ into total cholesterol fraction. In contrast, an addition of BSA to LA-containing medium tended to increase the incorporation of $[^{14}C]acetate$ into total cholesterol. The alteration of cholesterol metabolism in HepG2 cells incubated in LA+BSA medium was attributed by an increase in the incorporation of $[^{14}C]acetate$ into free cholesterol, but not cholesteryl ester fraction. In addition, the secretion of cholesterol was increased by LA+BSA medium, suggesting that BSA stimulates cholesterol secretion. No significant change in the incorporation of $[^{14}C]acetate$ into cellular total lipids was observed among the experimental groups. However, an increased incorporation of $[^{14}C]-labelled$ fatty acid into cellular triacylglycerol and decreased incorporation into phospholipid were observed in cells incubated with LA+BSA medium as compared to those of LA medium. The secretions of $[^{14}C]-labelled$ triacylglycerol, phospholipid, and free fatty acid were also stimulated in HepG2 cells incubated with LA+BSA medium. In conclusion, the present study suggests that in human hepatocytes, LA and BSA influence lipid metabolism, and BSA enhances the secretion of lipids.

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Effects of Nitric Oxide Scavenger and Inhibitor on the Development of Bovine IVM/IVF Embryos (Nitric Oxide 화합물 첨가가 소 체외수정란의 체외발육에 미치는 효과)

  • Jang H. Y.;Kim J. T.;Park C. K.;Cheong H. T.;Kim C. I.;Yang B. K.
    • Reproductive and Developmental Biology
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    • v.28 no.3
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    • pp.161-166
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    • 2004
  • This study was designed to evaluate the effects of nitric oxide scavenger (hemoglobin) and inhibitor (L-nitro-L-arginine methyl ester; L-NAME) with or without cumulus cell on the development of bovine IVM/IVF embryos. When CR/sub 1aa/ medium were supplemented with different dosage (lug/m, 5ug/m and 10ug/ml) of hemoglobin at 48hrs for in vitro culture, the proportion of embryos developing beyond morulae stage in 0, 1ug/ml and 5ug/ml with or without cumulus cell were 23.8%, 33.3 % and 26.8%, and 39.5%, 54.8% and 48.8%, respectively. There was a significantly difference the developmental rate of 1ug/ml hemoglobin intact cumulus cells to any other groups (P<0.05). On the other hand, when added to hemoglobin at 96 hrs, 1 ug/ml hemoglobin with cumulus cell group was significantly increased the percentage of developing into morulae and blastocysts to any other groups (P<0.05), and similar trend that of added at 48hrs. The overall means of the percentage of developing into morulae and blstocysts in 1ug/ml hemoglobin group was significantly increased than those of any other groups (P<0.05) and cumulus co-culture with hemoglobin was increased the in vitro developing rate of IVM/IVF embryos. In CR/sub 1aa/ medium treated with L-NAME 0, 10, 50 and 100mM, the developmental rate of morula plus blastocysts were 55.6%, 64.9%, 58.8% and 66.7%, respectively. The L-NAME did not affect the developmental rate and the cell numbers of blastocysts in all treated groups. These results indicate that hemoglobin and cumulus co-culture can increase the proportion of embryos that developed into morulae and blastocysts, but cell numbers of blastocysts were not affect in all groups.

Effects of the Combination Feeding of β-glucan and Multi-species Probiotics on Growth Performance and Microflora in Broiler Chickens (효모변이균주 유래 β-글루칸과 복합균종 생균제의 혼합급여가 육계의 생산성 및 장내 균총에 미치는 영향)

  • Cho, B.I.;You, S.J.;Kim, E.J.;Ahn, B.K.;Paik, H.D.;Yun, C.W.;Chang, H.I.;Kim, S.W.;Kang, C.W.
    • Journal of Animal Science and Technology
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    • v.50 no.1
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    • pp.89-98
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    • 2008
  • This experiment was carried out to investigate the combination feeding of β-glucan and multi-species probiotics on growth performance, various lipid concentrations of serum, antibody production and cecal microbial profiles in broiler chicks. A total of six hundred 1-d-old male broiler chicks were divided into five groups, placed into four pens per group(30 birds per pen) and fed one of five non-medicated experimental diets(T1, 0.15% multi-species probiotics; T2, 0.1% β-glucan+0.15% multi-species probiotics; T3, 0.3% multi-species probiotics; T4, 0.1% β-glucan+0.3% probiotics or devoid them as control) for 5 wk. There was no significant difference in feed intake among the groups. The average weight gains and FCR in groups fed diet containing 0.3% probiotics were significantly improved(p<0.05) than control in finisher period(22-35d). The concentration of serum cholesterol ester in groups fed 0.3% probiotics were significantly lowered(p<0.05) as compared to that of the control. Relative weights of liver, spleen, bursa of Fabricius, breast and leg were not influenced by the dietary treatments. The average ND or IB antibody titers in groups fed diets containing β-glucan and probiotics were tended to be increased, but not significantly. The number of cecal lactic acid bacteria was significantly increased(p<0.05) by the dietary β- glucan and probiotics. These results indicated that dietary β-glucan and probiotics exerted a growth- promoting and immune-enhancing effects on broiler chicks. In addition, yeast derived β-glucan, and multi-species probiotics modulated the profiles of cecal microflora, reflecting potential alternative substances to replace antibiotics for feeding broiler.

Mechanism of Inhibitory Effect of Imipramine on Isolated Rat Detrusor Muscle in Relation to Calcium Modulation (흰쥐 적출 방광 배뇨근의 수축성에 대한 Imipramine의 작용과 Calcium동원 기전과의 관계)

  • Lee, Jong-Bum;Yoo, Kae-Joon;Ha, Jeoung-Hee;Kwon, Oh-Cheol;Lee, Kwang-Youn;Kim, Won-Joon
    • The Korean Journal of Pharmacology
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    • v.28 no.1
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    • pp.81-89
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    • 1992
  • Enuresis is a common voiding disorder among children. There are several therapeutic regimens for the disorder available today; behavioral therapies, psychotherapy, bladder training, sleep interruption, hypnosis and drug therapy. Recently, the efficacy of drug therapy has been acknowledged, particularly of antidepressants. Among the tricyclic antidepressants, imipramine is most frequently employed for the treatment of enuresis. Present study was undertaken to investigate the mechanism of imipramine on the contractility of urinary bladder in relation to the calcium modulation using isolated strips of rat detrusor urinae. 1. The electric fileld stimulation-induced contraction was abolished by imipramine, but partially inhibited by atropine. 2. Imipramine reduced the basal tone and diminished the phasic activity of detrusor muscle concentration-dependently, which was similar to that of diltiazem, a calcium channel blocker. 3. Imipramine suppressed the maximal responses and shifted the concentration-response curves of bethanechol and ATP to right. 4. Imipramine inhibited the calcium-induced recovery of tension in calcium-free physiologic salt solution (PSS) with a mode of action similar to that of diltizaem. 5. A23187, a calcium ionophore recovered the basal tone which had been reduced by imipramine in normal PSS. 6. In calcium-free PSS, A23187 could recover the abolished basal tone with the pretreatment of imipramine, but it exerted a partial recovery with the pretreatment of TMB-8, an inhibitor of intracellular calcium release. Based on these results, it is suggested that the inhibitory action of imipramine on the detrusor muscle exerted in part by blockade of the muscarinic and purinergic receptors, and interference with the influx of extracellular calcium, but not with the release of intracellular stored calcium, is involved in its mechanism of action.

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Lipid Composition of Roe, Muscle and Viscus of Liza Carinata, a Species of the Mugilidae Family (등줄숭어의 알, 근육 및 내장의 지질조성에 관한 연구)

  • Joh, Yong-Goe;Lee, Kyeng-Hee;Cho, Yon-Joo
    • Korean Journal of Food Science and Technology
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    • v.20 no.5
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    • pp.674-682
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    • 1988
  • Total lipids from the roe, muscle and viscus of L. carinata were analyzed for lipid composition by column chromatography, thin-layer chromatography and gas-liquid chromatography. The roe lipids were characterized by a high level of wax esters (63.1%) and a low proportion of trigiycerides (9.9%). The viscus lipids also contained wax esters (32.8%) as its main component, followed by free fatty alcohols and acids (23.5%). On the other hand, the muscle lipids were found to contain a large amount of triglycerides (66.1%) with a trace of wax esters. The main fatty alcohol component of roe and viscus wax esters was C16:0 alcohol (53.0%; 61.7%), accompanied by C18:1 alcohol (10.2%) in the former and by C15:0 alcohol (8.8%) in the latter. Considerable amounts of odd-numbered fatty alcohols were found in both wax esters. On the other hand, the fatty acids of the roe and viscus wax esters contained a high percentage of monounsaturated (49.7%-56.6%) consisting of C16:1, C18:1 and C17:1 acid, and a significant amount of polyunsaturated (41.2%-32.9%), particularly C20:5${\omega}$3. The fatty acid components of triglycerides and phospholipids were different among the tissues tested, especially between roe and muscle or viscus. The fatty acid compositions of free fatty acids from the muscle and viscus were characterized by a higher level of polyunsaturated fatty acids (46.0-34.3%) compared to those of triglycerides 'in the roe, muscle and viscus (28.4%, 19.4% and 19.2%).

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Characterization of Platycodon grandiflorum Seeds Oil Extracted by Supercritical Carbon Dioxide (초임계 이산화탄소를 이용하여 추출된 도라지 종자유의 특성)

  • Kim, Yangji;Imm, Jee-Young;Kim, Seok Joong
    • Journal of the Korean Applied Science and Technology
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    • v.35 no.1
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    • pp.99-110
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    • 2018
  • In this study, oil of Platycodon grandiflorum seeds was prepared using supercritical carbon dioxide extraction (SCE) and its physicochemical indices as a new edible oil were investigated. Compared to Soxhlet solvent extraction, SCE under the condition of 6,000 psi at $40^{\circ}C$ produced more oil, especially from the roasted seeds to 32.7%. TLC analysis showed triacylglycerols accounted for most of the oil obtained from roasted Platycodon grandiflorum seeds by SCE similarly to commercial soybean oil or perilla seeds oil. The oil had highly unsaturated lipid with considerable amount of linoleic acid(73.27%) much more than two commercial oils followed by oleic acid(13.16%). Physicochemical properties of the oil were as follows; specific gravity, 0.92; dynamic viscosity, 45.37 cP; refractive index, 1.48; color, L=47.30, a=-3.69, b=25.72; iodine value, 141.57 g $I_2/100g$ oil; saponification value, 191.21 mg of KOH/g of oil; acid value, 2.60 mg of KOH/g of oil. Among those, refractive index, viscosity and iodine value, which were related to unsaturation degree of lipid, were ranged between those of two commercial oils. The oxidation stability of oil(2.03 hr) was also ranged between less stable perilla seeds oil(1.79 hr) and more stable soybean oil(2.94 hr) based on the induction time measured by Rancimat assay. In addition to extraction yield increase, seeds roasting provided further benefits such as reductions of cholesterol ester content and acid value without change in fatty acid composition. In conclusion, oil was extracted from the roasted Platycodon grandiflorum seeds at high yield by supercritical carbon dioxide and it seemed to have proper characteristics as a edible oil.

ATHEROSCLEROSIS, CHOLESTEROL AND EGG - REVIEW -

  • Paik, I.K.;Blair, R.
    • Asian-Australasian Journal of Animal Sciences
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    • v.9 no.1
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    • pp.1-25
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    • 1996
  • The pathogenesis of atherosclerosis can not be summarized as a single process. Lipid infiltration hypothesis and endothelial injury hypothesis have been proposed and investigated. Recent developments show that there are many points of potential interactions between them and that they can actually be regarded as two phases of a single, unifying hypothesis. Among the many risk factors of atherosclerosis, plasma homocysteine and lipoprotein(a) draw a considerable interest because they are independent indicators of atherogenicity. Triglyceride (TG)-rich lipoproteins (chylomicron and VLDL) are not considered to be atherogenic but they are related to the metabolism of HDL cholesterol and indirectly related to coronary heart disease (CHD). LDL can of itself be atherogenic but the oxidative products of this lipoprotein are more detrimental. HDL cholesterol has been considered to be a favorable cholesterol. The so-called 'causalist view' claims that HDL traps excess cholesterol from cellular membranes and transfers it to TG-rich lipoproteins that are subsequently removed by hepatic receptors. In the so-called 'noncausalist view', HDL does not interfere directly with cholesterol deposition in the arterial wall but instead reflects he metabolism of TG-rich lipoproteins and their conversion to atherogenic remnants. Approximately 70-80% of the human population shows an effective feedback control mechanism in cholesterol homeostasis. Type of dietary fat has a significant effect on the lipoprotein cholesterol metabolism and atherosclerosis. Generally, saturated fatty acids elevate and PUFA lower serum cholesterol, whereas MUFA have no specific effect. EPA and DHA inhibit the synthesis of TG, VLDL and LDL, and may have favourable effects on some of the risk factors. Phospholipids, particularly lecithin, have an antiatherosclerotic effect. Essential phospholipids (EPL) may enhance the formation of polyunsaturated cholesteryl ester (CE) which is less sclerotic and more easily dispersed via enhanced hydrolysis of CE in the arterial wall. Also, neutral fecal steroid elimination may be enhanced and cholesterol absorption reduced following EPL treatment. Antioxidants protect lipoproteins from oxidation, and cells from the injury of toxic, oxidized LDL. The rationale for lowering of serum cholesterol is the strong association between elevation of plasma or serum cholesterol and CHD. Cholesterol-lowing, especially LDL cholesterol, to the target level could be achieved using diet and combination of drug therapy. Information on the link between cholesterol and CHD has decreased egg consumption by 16-25%. Some clinical studies have indicated that dietary cholesterol and egg have a significant hypercholesterolemic effect, while others have indicated no effect. These studies differed in the use of purified cholesterol or cholesterol in eggs, in the range of baseline and challenge cholesterol levels, in the quality and quantity of concomitant dietary fat, in the study population demographics and initial serum cholesterol levels, and clinical settings. Cholesterol content of eggs varies to a certain extent depending on the age, breed and diet of hens. However, egg yolk cholesterol level is very resistant to change because of the particular mechanism involved in yolk formation. Egg yolk contains a factor of factors responsible for accelerated cholesterol metabolism and excretion compared with crystalline cholesterol. One of these factors could be egg lecithin. Egg lecithin may not be as effective as soybean lecithin in lowering serum cholesterol level due probably to the differences of fatty acid composition. However, egg lecithin may have positive effects in hypercholesterolemia by increasing serum HDL level and excretion of fecal cholesterol. The association of serum cholesterol with egg consumption has been widely studied. When the basal or control diet contained little or no cholesterol, consumption of 1 or 2 eggs daily increased the concentration of plasma cholesterol, whereas that of the normolipemic persons on a normal diet was not significantly influenced by consuming 2 to 3 eggs daily. At higher levels of egg consumption, the concentration of HDL tends to increase as well as LDL. There exist hyper-and hypo-responders to dietary (egg) cholesterol. Identifying individuals in both categories would be useful from the point of view of nutrition guidelines. Dietary modification of fatty acid composition has been pursued as a viable method of modifying fat composition of eggs and adding value to eggs. In many cases beneficial effects of PUFA enriched eggs have been demonstrated. Generally, consumption of n-3 fatty acids enriched eggs lowered the concentration of plasma TG and total cholesterol compared to the consumption of regular eggs. Due to the highly oxidative nature of PUFA, stability of this fat is essential. The implication of hepatic lipid accumulation which was observed in hens fed on fish oils should be explored. Nutritional manipulations, such as supplementation with iodine, inhibitors of cholesterol biosynthesis, garlic products, amino acids and high fibre ingredients, have met a limited success in lowering egg cholesterol.

A Hierarchical Grid Alignment Algorithm for Microarray Image Analysis (마이크로어레이 이미지 분석을 위한 계층적 그리드 정렬 알고리즘)

  • Chun Bong-Kyung;Jin Hee-Jeong;Lee Pyung-Jun;Cho Hwan-Gue
    • Journal of KIISE:Software and Applications
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    • v.33 no.2
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    • pp.143-153
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    • 2006
  • Microarray which enables us to obtain hundreds and thousands of expression of gene or genotype at once is an epoch-making technology in comparative analysis of genes. First of all, we have to measure the intensity of each gene in an microarray image from the experiment to gain the expression level of each gene. But it is difficult to analyze the microarray image in manual because it has a lot of genes. Meta-gridding method and various auto-gridding methods have been proposed for this, but thew still have some problems. For example, meta-gridding requires manual-work due to some variations in spite of experiment in same microarray, and auto-gridding nay not carried out fully or correctly when an image has a lot of noises or is lowly expressed. In this article, we propose Hierarchical Grid Alignment algorithm for new methodology combining meta-gridding method with auto-gridding method. In our methodology, we necd a meta-grid as an input, and then align it with the microarray image automatically. Experimental results show that the proposed method serves more robust and reliable gridding result than the previous methods. It is also possible for user to do more reliable batch analysis by using our algorithm.