• The Korean Journal of Nuclear Medicine
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• v.37 no.6
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• pp.382-392
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• 2003

Purpose: Uptakes of Tc-99m MIBI (MIBI) and Tc-99m tetrofosmin (tetrofosmin) in human non-small cell lung cancer A549, multidrug-resistance associated protein (MRP) expressing cell, were investigated in vitro and in vivo. Materials and Methods: Western blot analysis and immunohistochemistry were used for detection of MRP in A549 cells with anti-MRPr1 antibody. Cellular uptakes of two tracers were evaluated at $100{\mu}M$ of verapamil (Vrp), $50{\mu}M$ of cyclosporin A (CsA) and $25{\mu}M$ of butoxysulfoximide (BSO) after incubation with MIBI and tetrofosmin for 30 and 50 min at $37^{\circ}C$, using single cell suspensions at $1{\times}10^6cells/ml$. Radioactivities in supernatants and pellets were measured with gamma well counter. A549 cells were inoculated in each flanks of 24 nude mice. Group 1 (Gr1) and Gr3 mice were treated with only MIBI or tetrofosmin, and Gr2 and Gr4 mice were treated with 70mg/kg of CsA i.p. for 1 hour before injection of 370KBq of MIBI or tetrofosmin. Mice were sacrificed at 10, 60 and 240 min. Radioactivities of organs and tumors were expressed as percentage injected dose per gram of tissue (%ID/gm). Results: Western blot analysis of the A549 cells detected expression of MRPr1 (190 kDa) and immunohistochemical staining of tumor tissue for MRPr1 revealed brownish staining in cell membrane but not P-gp. Upon incubating A549 cells for 60 min with MIBI and tetrofosmin, cellular uptake of MIBI was higher than that of tetrofosmin. Coincubation with modulators resulted in an increase in cellular uptakes of MIBI and tetrofosmin. Percentage increase of MIBI was higher than that of tetrofosmin with Vrp by 623% and 427%, CsA by 753% and 629% and BSO by 219% and 140%, respectively. There was no significant difference in tumoral uptakes of MIBI and tetrofosmin between Gr1 and Gr3. Percentage increases in MIBI (114% at 10 min, 257% at 60 min, 396% at 240 min) and tetrofosmin uptake (110% at 10 min, 205% at 60 min, 410% at 240 min) were progressively higher by the time up to 240 min with CsA. Conclusion: These results indicate that MIBI and tetrofosmin are suitable tracers for imaging MRP-mediated drug resistance in A549 tumors. MIBI may be a better tracer than tetrofosmin for evaluating MRP reversal effect of modulators.

• Tuberculosis and Respiratory Diseases
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• v.53 no.5
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• pp.519-529
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• 2002

Background : The therapeutic effects of surfactants on acute lung injury derive not only from their recruiting action on collapsed alveoli but also from their anti-inflammatory action in the alveolar sapce. This study evaluated the anti-inflammatory action of a surfactant in an acute lung injury model of rats by neutrophils were recollected from the BAL fluid and the NF-${\kappa}B$ activity of the neutrophilic nuclear protein was evaluated. Methods : Male Sprague-Dawley rats weighing approximately 300 gram were divided into 3 groups, which consisted of 6 rats respectively. In the control group, normal saline(3ml/kg) was instilled into the trachea twice with 30 minute interval. In two other groups, acute lung injury was induced by the intra-tracheal instillation of LPS(5mg/kg). Thirty minutes later, either a surfactant(ST group; 30mg/kg) or normal saline(NT group: 3ml/kg) was instilled via the trachea. Twenty-four hours after the LPS instillation, the BAL fluid was retrieved to measure the WBC count and cytokine(IL-$1{\beta}$ and IL-6) levels. The neutrophils were isolated from the BAL fluid and the nuclear protein was extracted to evaluate the NF-${\kappa}B$ activity using a eletrophoretic mobility shift assay(EMSA). Results : The WBC count of the BAL fluid of the ST group($3,221{\pm}1,914{\times}10^3/{\mu}l$) was higher than that of the control group($356{\pm}275{\times}10^3/{\mu}l$)(p<0.05) and lower than that of the NT group($5,561{\pm}1,757{\times}10^3/{\mu}l$)(p<0.05)). The BAL fluid level of IL-$1{\beta}$ from the NT group($2,064{\pm}1,082pg/ml$) was higher than those of the ST group($360{\pm}234pg/ml$)(p<0.05) and the control group(0pg/ml)p<0.05) and control group($49{\pm}62pg/ml$)(p<0.05). The NF-${\kappa}B$ activity of the neutrophilic nuclear protein in the ST group and NT group was similar. Conclusion : The surfactant, attenuates the alveolar inflammation in the acute lung injury of rats model. However, its anti-inflammatory action does no't appear to be mediated by the inhibition of NF-${\kappa}B$ activity.

• Korean journal of applied entomology
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• v.9 no.2
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• pp.57-74
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• 1970

These experiments were conducted to investigate the :actors influencing the systemic action of Dimethoate (O,O-dimethyl-S-(N-methylcarhamoylmethyl) photphorodithioate) to rice seeds and the phytotoxic effects on the seed germination. Dimethoate $(Roxion^{(R)})$ $40\%$ emulsion was used. The varieties tested were Jinheung. Nongkwang,Suwon #82, Norm #6, Paltal, Shirogane, Suseong, Pungkwang, Shin #2, Fujisaka #5, Kwanok, and Jaekeun. The permeated Dimethoate was extracted from the treated seeds by chloroform and quantities were determined by Spectrophotometer. The phytotoxicity was evaluated from the effects on the germination of the treated seeds which were kept in an incubator. The oxygen consumption was measured by Warburg Manometer at $30^{\circ}C$ for 60 minutes. Indices of KOH disintegration of seeds and chemical composition of the seeds were also determined. The results obtained were as followings; 1) The amount of permeated Dimethoate in the seeds showed remarkable differences with varieties. The amount of Dimethoate per 100 grains was greater as in the ascending order of Suseong, Kwanok, Nongkwang, Jinheung, Paltal, Fujisaka #5, Suwon #82, Norm #6, Shirogane, Shin #2, Pungkwang and Jaekeun. 2) It was observed that the total amount of Dimethoate in the seeds(mg./100 grains) were greater among the varieties with large grain than those with small grains, while reverse cases were true in the amount of Dimethoate in a gramme of seeds, probably because of the greater surface areas In a small grains for a gramme weight. 3) There was no significant correlation between the permeated amount of Dimethoate and amount of absorbed water by the seeds when the seeds were treated with $0.1\%$ Dimethoate for 24 and 48 hours. 4) The permeability of Dimethoate to seeds significantly increased in the prolonged soaking periods, higher concentration, and higher temperature. 5) When the seeds were treated with $0.1\%$ Dimethoate for 24 and 48 hours at $15^{\circ},\;20^{\circ},\; 20^{\circ},\; and \;30^{\circ}C$, the permeated amount of Dimethoate were increased at higher temperature. It seems to be that the more active penetration of Dimethoate was involved at the higher temperature. 6) The phytotoxic effects of Dinethoate on the seed germination varied with the varieties. An descending order of varietal tolerance of seeds was as followings: Jinheung, Fujisaka #5, Suwon #82, Paltal, Nongkwang, Jaekeun, Shin #2, Kwanok, Shirogane, Pungkwang, Suseong, and Norm #6. 7) There was a positive correlation between the amount of Dimethoate permeated into the seeds (mg./gram. of seeds) and phytotoxicity of seeds. 8) The Phytotoxic effects of Dimethoate showed close correlation with the degree of KOH disintegration of seeds, average germination periods, and oxygen respiration of seeds. 9) It was observed that higher protein contents of the seeds decreased the phytotoxic effects of Dimethoate. 10) Relatively high negative correlation between the degree of KOH disintegration of seeds and crude protein content of the seeds was observed. 11) The average germination period was delayed for about 2 days when the seeds were treated with $0.2\%$ Dimethoate for 24 hours at $30^{\circ}C$. 12) The oxygen consumption of the seeds treated with $0.2\%$ Dimethoate for 24 hours at $30^{\circ}C$ was greatly decreased when compared with that of the normal seeds. 13) The amount of oxygen consumption of the seeds (in 24 hours after 24 hours water soaking) was negatively correlated with the average germination periods of the seeds.

• Korean Journal of Poultry Science
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• v.39 no.2
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• pp.87-95
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• 2012

This experiment was conducted to investigate the effects of varying levels of metabolizable energy (ME) and crude protein (CP) on growth performance and carcass characteristics in layer-type growing male chicks. Nine hundred 1-d-old Hy-Line Brown male chicks were randomly allocated to 30 pens in a $2{\times}3$ factorial design. The experimental diets contained 2 levels of ME (2,800 kcal/kg and 2,950 kcal/kg) in combination with 3 levels of CP (17%, 18.5%, and, 20%). A significant interaction of ME and CP on feed intake was observed (p<0.05). No interaction was observed between ME and CP for 53 d BW gain or FCR, which improved linearly with dietary CP levels (p<0.05). A significant interaction or tendency was observed between ME and CP levels. The intake of ME for 1 g BW gain was linearly decreased with increasing CP levels (p<0.001). The intake of CP per bird was significantly increased in low ME (2,800 kcal/kg) treatment than that of the high ME treatment (2,950 kcal/kg) (p<0.05), and dietary CP level had more influence on CP intake for gram BW gain than level of ME. The relative weights of liver, spleen, breast meat and, leg were not influenced by the dietary treatments. Serum BUN, albumin, creatinine, and the activities of GOT and GPT were not influenced significantly by the diet treatment. In conclusion, the growth performance in layer-type male chicks was linearly increased when the level of dietary CP increased. The ME and CP did not affect the carcass characteristics and blood profiles. Therefore, the optimum levels of dietary ME and CP to improve the growth were 2,800 kcal/kg and above 18.5% in layer-type growing male chicks, respectively.

• Tuberculosis and Respiratory Diseases
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• v.51 no.6
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• pp.559-569
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• 2001

Background : Pleural effusion is one of the most common clinical manifestations associated with a variety of pulmonary diseases such as malignancy, tuberculosis, and pneumonia. However, there are no useful laboratory tests to determine the specific cause of pleural effusion. Therefore, an attempt was made to analyze the various types of pleural effusion and search for useful laboratory tests for pleural effusion in order to differentiate between the diseases, especially between a malignant pleural effusion and a non-malignant pleural effusion. Methods : 93 patients with a pleural effusion, who visited the Severance hospital from January 1998 to August 1999, were enrolled in this study. Ultrasound-guided thoracentesis was done and a confirmational diagnosis was made by a gram stain, bacterial culture, Ziehl-Neelsen stain, a mycobacterial culture, a pleural biopsy and cytology. Results : The male to female ratio was 56 : 37 and the average age was $47.1{\pm}21.8$ years. There were 16 cases with a malignant effusion, 12 cases with a para-malignant effusion, 36 cases with tuberculosis, 22 cases with a para-pneumonic effusion, and 7 cases with transudate. The LDH2 fraction was significantly higher in the para-malignant effusion group compared to the para-pneumonic effusion group [$30.6{\pm}6.4%$ and $20.2{\pm}7.5%$, respectively (p<0.05)] and both the LDH1 and LDH2 fraction was significantly in the para-malignant effusion group compared to those with tuberculosis [$16.4{\pm}7.2%$ vs. $7.6{\pm}4.7%$, and $30.6{\pm}6.4%$ vs.$17.6{\pm}6.3%$, respectively (p<0.05)]. The pleural effusion/serum LDH4 fraction ratio was significantly lower in the malignant effusion group compared to those with tuberculosis [$1.5{\pm}0.8$ vs. $2.1{\pm}0.6$, respectively (p<0.05)]. The LDH4 fraction and the pleural effusion/serum LDH4 fraction ratio was significantly lower in the para-malignant effusion group compared to those with tuberculosis [$17.0{\pm}5.8%$ vs. $23.5{\pm}4.6%$ and $1.3{\pm}0.4$ vs. $2.1{\pm}0.6$, respectively (p<0.05)]. Conclusion : These results suggest that the LDH isoenzyme was the only useful biochemical test for a differential diagnosis of the various diseases. In particular, the most useful test was the pleural effusion/serum LDH4 fraction ratio to distinguish between a para-malignant effusion and a tuberculous effusion.

• 한국균학회소식:학술대회논문집
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• 2016.05a
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• pp.19-20
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• 2016

Sesquiterpenoids are defined as $C_{15}$ compounds derived from farnesyl pyrophosphate (FPP), and their complex structures are found in the tissue of many diverse plants (Degenhardt et al. 2009). FPP's long chain length and additional double bond enables its conversion to a huge range of mono-, di-, and tri-cyclic structures. A number of cyclic sesquiterpenes with alcohol, aldehyde, and ketone derivatives have key biological and medicinal properties (Fraga 1999). Fungi, such as the wood-rotting Polyporus brumalis, are excellent sources of pharmaceutically interesting natural products such as sesquiterpenoids. In this study, we investigated the biosynthesis of P. brumalis sesquiterpenoids on modified medium. Fungal suspensions of 11 white rot species were inoculated in modified medium containing $C_6H_{12}O_6$, $C_4H_{12}N_2O_6$, $KH_2PO_4$, $MgSO_4$, and $CaCl_2$ for 20 days. Cultivation was stopped by solvent extraction via separation of the mycelium. The metabolites were identified as follows: propionic acid (1), mevalonic acid lactone (2), ${\beta}$-eudesmane (3), and ${\beta}$-eudesmol (4), respectively (Figure 1). The main peaks of ${\beta}$-eudesmane and ${\beta}$-eudesmol, which were indicative of sesquiterpene structures, were consistently detected for 5, 7, 12, and 15 days These results demonstrated the existence of terpene metabolism in the mycelium of P. brumalis. Polyporus spp. are known to generate flavor components such as methyl 2,4-dihydroxy-3,6-dimethyl benzoate; 2-hydroxy-4-methoxy-6-methyl benzoic acid; 3-hydroxy-5-methyl phenol; and 3-methoxy-2,5-dimethyl phenol in submerged cultures (Hoffmann and Esser 1978). Drimanes of sesquiterpenes were reported as metabolites from P. arcularius and shown to exhibit antimicrobial activity against Gram-positive bacteria such as Staphylococcus aureus (Fleck et al. 1996). The main metabolites of P. brumalis, ${\beta}$-Eudesmol and ${\beta}$-eudesmane, were categorized as eudesmane-type sesquiterpene structures. The eudesmane skeleton could be biosynthesized from FPP-derived IPP, and approximately 1,000 structures have been identified in plants as essential oils. The biosynthesis of eudesmol from P. brumalis may thus be an important tool for the production of useful natural compounds as presumed from its identified potent bioactivity in plants. Essential oils comprising eudesmane-type sesquiterpenoids have been previously and extensively researched (Wu et al. 2006). ${\beta}$-Eudesmol is a well-known and important eudesmane alcohol with an anticholinergic effect in the vascular endothelium (Tsuneki et al. 2005). Additionally, recent studies demonstrated that ${\beta}$-eudesmol acts as a channel blocker for nicotinic acetylcholine receptors at the neuromuscular junction, and it can inhibit angiogenesis in vitro and in vivo by blocking the mitogen-activated protein kinase (MAPK) signaling pathway (Seo et al. 2011). Variation of nutrients was conducted to determine an optimum condition for the biosynthesis of sesquiterpenes by P. brumalis. Genes encoding terpene synthases, which are crucial to the terpene synthesis pathway, generally respond to environmental factors such as pH, temperature, and available nutrients (Hoffmeister and Keller 2007, Yu and Keller 2005). Calvo et al. described the effect of major nutrients, carbon and nitrogen, on the synthesis of secondary metabolites (Calvo et al. 2002). P. brumalis did not prefer to synthesize sesquiterpenes under all growth conditions. Results of differences in metabolites observed in P. brumalis grown in PDB and modified medium highlighted the potential effect inorganic sources such as $C_4H_{12}N_2O_6$, $KH_2PO_4$, $MgSO_4$, and $CaCl_2$ on sesquiterpene synthesis. ${\beta}$-eudesmol was apparent during cultivation except for when P. brumalis was grown on $MgSO_4$-free medium. These results demonstrated that $MgSO_4$ can specifically control the biosynthesis of ${\beta}$-eudesmol. Magnesium has been reported as a cofactor that binds to sesquiterpene synthase (Agger et al. 2008). Specifically, the $Mg^{2+}$ ions bind to two conserved metal-binding motifs. These metal ions complex to the substrate pyrophosphate, thereby promoting the ionization of the leaving groups of FPP and resulting in the generation of a highly reactive allylic cation. Effect of magnesium source on the sesquiterpene biosynthesis was also identified via analysis of the concentration of total carbohydrates. Our current study offered further insight that fungal sesquiterpene biosynthesis can be controlled by nutrients. To profile the metabolites of P. brumalis, the cultures were extracted based on the growth curve. Despite metabolites produced during mycelia growth, there was difficulty in detecting significant changes in metabolite production, especially those at low concentrations. These compounds may be of interest in understanding their synthetic mechanisms in P. brumalis. The synthesis of terpene compounds began during the growth phase at day 9. Sesquiterpene synthesis occurred after growth was complete. At day 9, drimenol, farnesol, and mevalonic lactone (or mevalonic acid lactone) were identified. Mevalonic acid lactone is the precursor of the mevalonic pathway, and particularly, it is a precursor for a number of biologically important lipids, including cholesterol hormones (Buckley et al. 2002). Farnesol is the precursor of sesquiterpenoids. Drimenol compounds, bi-cyclic-sesquiterpene alcohols, can be synthesized from trans-trans farnesol via cyclization and rearrangement (Polovinka et al. 1994). They have also been identified in the basidiomycota Lentinus lepideus as secondary metabolites. After 12 days in the growth phase, ${\beta}$-elemene caryophyllene, ${\delta}$-cadiene, and eudesmane were detected with ${\beta}$-eudesmol. The data showed the synthesis of sesquiterpene hydrocarbons with bi-cyclic structures. These compounds can be synthesized from FPP by cyclization. Cyclic terpenoids are synthesized through the formation of a carbon skeleton from linear precursors by terpene cyclase, which is followed by chemical modification by oxidation, reduction, methylation, etc. Sesquiterpene cyclase is a key branch-point enzyme that catalyzes the complex intermolecular cyclization of the linear prenyl diphosphate into cyclic hydrocarbons (Toyomasu et al. 2007). After 20 days in stationary phase, the oxygenated structures eudesmol, elemol, and caryophyllene oxide were detected. Thus, after growth, sesquiterpenes were identified. Per these results, we showed that terpene metabolism in wood-rotting fungi occurs in the stationary phase. We also showed that such metabolism can be controlled by magnesium supplementation in the growth medium. In conclusion, we identified P. brumalis as a wood-rotting fungus that can produce sesquiterpenes. To mechanistically understand eudesmane-type sesquiterpene biosynthesis in P. brumalis, further research into the genes regulating the dynamics of such biosynthesis is warranted.

• Journal of Intelligence and Information Systems
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• v.28 no.1
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• pp.155-174
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• 2022

From January 2020 to October 2021, more than 500,000 academic studies related to COVID-19 (Coronavirus-2, a fatal respiratory syndrome) have been published. The rapid increase in the number of papers related to COVID-19 is putting time and technical constraints on healthcare professionals and policy makers to quickly find important research. Therefore, in this study, we propose a method of extracting useful information from text data of extensive literature using LDA and Word2vec algorithm. Papers related to keywords to be searched were extracted from papers related to COVID-19, and detailed topics were identified. The data used the CORD-19 data set on Kaggle, a free academic resource prepared by major research groups and the White House to respond to the COVID-19 pandemic, updated weekly. The research methods are divided into two main categories. First, 41,062 articles were collected through data filtering and pre-processing of the abstracts of 47,110 academic papers including full text. For this purpose, the number of publications related to COVID-19 by year was analyzed through exploratory data analysis using a Python program, and the top 10 journals under active research were identified. LDA and Word2vec algorithm were used to derive research topics related to COVID-19, and after analyzing related words, similarity was measured. Second, papers containing 'vaccine' and 'treatment' were extracted from among the topics derived from all papers, and a total of 4,555 papers related to 'vaccine' and 5,971 papers related to 'treatment' were extracted. did For each collected paper, detailed topics were analyzed using LDA and Word2vec algorithms, and a clustering method through PCA dimension reduction was applied to visualize groups of papers with similar themes using the t-SNE algorithm. A noteworthy point from the results of this study is that the topics that were not derived from the topics derived for all papers being researched in relation to COVID-19 (