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In silico discovery and evaluation of phytochemicals binding mechanism against human catechol-O-methyltransferase as a putative bioenhancer of L-DOPA therapy in Parkinson disease

  • Rath, Surya Narayan;Jena, Lingaraja;Bhuyan, Rajabrata;Mahanandia, Nimai Charan;Patri, Manorama
    • Genomics & Informatics
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    • v.19 no.1
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    • pp.7.1-7.13
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    • 2021
  • Levodopa (L-DOPA) therapy is normally practised to treat motor pattern associated with Parkinson disease (PD). Additionally, several inhibitory drugs such as Entacapone and Opicapone are also cosupplemented to protect peripheral inactivation of exogenous L-DOPA (~80%) that occurs due to metabolic activity of the enzyme catechol-O-methyltransferase (COMT). Although, both Entacapone and Opicapone have U.S. Food and Drug Administration approval but regular use of these drugs is associated with high risk of side effects. Thus, authors have focused on in silico discovery of phytochemicals and evaluation of their effectiveness against human soluble COMT using virtual screening, molecular docking, drug-like property prediction, generation of pharmacophoric property, and molecular dynamics simulation. Overall, study proposed, nine phytochemicals (withaphysalin D, withaphysalin N, withaferin A, withacnistin, withaphysalin C, withaphysalin O, withanolide B, withasomnine, and withaphysalin F) of plant Withania somnifera have strong binding efficiency against human COMT in comparison to both of the drugs i.e., Opicapone and Entacapone, thus may be used as putative bioenhancer in L-DOPA therapy. The present study needs further experimental validation to be used as an adjuvant in PD treatment.

Climatology of Equatorial Plasma Bubbles in Ionospheric Connection Explorer/Far-UltraViolet (ICON/FUV) Limb Images

  • Park, Jaeheung;Mende, Stephen B.;Eastes, Richard W.;Frey, Harald U.
    • Journal of Astronomy and Space Sciences
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    • v.39 no.3
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    • pp.87-98
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    • 2022
  • The Far-UltraViolet (FUV) imager onboard the Ionospheric Connection Explorer (ICON) spacecraft provides two-dimensional limb images of oxygen airglow in the nightside low-latitude ionosphere that are used to determine the oxygen ion density. As yet, no FUV limb imager has been used for climatological analyses of Equatorial Plasma Bubbles (EPBs). To examine the potential of ICON/FUV for this purpose, we statistically investigate small-scale (~180 km) fluctuations of oxygen ion density in its limb images. The seasonal-longitudinal variations of the fluctuation level reasonably conform to the EPB statistics in existing literature. To further validate the ICON/FUV data quality, we also inspect climatology of the ambient (unfiltered) nightside oxygen ion density. The ambient density exhibits (1) the well-known zonal wavenumber-4 signatures in the Equatorial Ionization Anomaly (EIA) and (2) off-equatorial enhancement above the Caribbean, both of which agree with previous studies. Merits of ICON/FUV observations over other conventional data sets are discussed in this paper. Furthermore, we suggest possible directions of future work, e.g., synergy between ICON/FUV and the Global-scale Observations of the Limb and Disk (GOLD) mission.

MESHLESS AND HOMOTOPY PERTURBATION METHODS FOR ONE DIMENSIONAL INVERSE HEAT CONDUCTION PROBLEM WITH NEUMANN AND ROBIN BOUNDARY CONDITIONS

  • GEDEFAW, HUSSEN;GIDAF, FASIL;SIRAW, HABTAMU;MERGIAW, TADESSE;TSEGAW, GETACHEW;WOLDESELASSIE, ASHENAFI;ABERA, MELAKU;KASSIM, MAHMUD;LISANU, WONDOSEN;MEBRATE, BENYAM
    • Journal of applied mathematics & informatics
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    • v.40 no.3_4
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    • pp.675-694
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    • 2022
  • In this article, we investigate the solution of the inverse problem for one dimensional heat equation with Neumann and Robin boundary conditions, that is, we determine the temperature and source term with given initial and boundary conditions. Three radial basis functions(RBFs) have been used for numerical solution, and Homotopy perturbation method for analytic solution. Numerical solutions which are obtained by considering each of the three RBFs are compared to the exact solution. For appropriate value of shape parameter c, numerical solutions best approximates exact solutions. Furthermore, we have shown the impact of noisy data on the numerical solution of u and f.

EFFECT OF ULTRASONIC VIBRATION ON ENAMEL AND DENTIN BOND STRENGTH AND RESIN INFILTRATION IN ALL-IN-ONE ADHESIVE SYSTEMS (All-in-one 접착제에서 초음파진동이 법랑질과 상아질의 결합강도와 레진침투에 미치는 영향)

  • Lee, Bum-Eui;Jang, Ki-Taeg;Lee, Sang-Hoon;Kim, Chong-Chul;Hahn, Se-Hyun
    • Journal of the korean academy of Pediatric Dentistry
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    • v.31 no.1
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    • pp.66-78
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    • 2004
  • The objective of this study was to apply the vibration technique to reduce the viscosity of bonding adhesives and thereby compare the bond strength and resin penetration in enamel and dentin achieved with those gained using the conventional technique and vibration technique. For enamel specimens, thirty teeth were sectioned mesio-distally. Sectioned two parts were assigned to same adhesive system but different treatment(vibration vs. non-vibration). Each specimen was embedded in 1-inch inner diameter PVC pipe with a acrylic resin. The buccal and lingual surfaces were placed so that the tooth and the embedding medium were at the same level. The samples were subsequently polished silicon carbide abrasive papers. Each adhesive system was applied according to its manufacture's instruction. Vibration groups were additionally vibrated for 15 seconds before curing. For dentin specimen, except removing the coronal part and placing occlusal surface at the mold level, the remaining procedures were same as enamel specimen. Resin composite(Z250. 3M. U.S.A.) was condensed on to the prepared surface in two increments using a mold kit(Ultradent Inc., U.S.A.). Each increments was light cured for 40 seconds. After 24 hours in tap water at room temperature, the specimens were thermocycled for 1000cycles. Shear bond strengths were measured with a universal testing machine(Instron 4465, England). To investigate infiltration patterns of adhesive materials, the surface of specimens was examined with scanning electron microscope. The results were as follows: 1. In enamel the mean values of shear bond strengths in vibration groups(group 2, 4, 6) were greater than those of non-vibration group(group 1, 3, 5). The differences were statistically significant except AQ bond group. 2. In dentin, the mean values of shear bond strengths in vibration groups(group 2, 4, 6) were greater than those of non-vibration groups(group 1, 3, 5). But the differences were not statistically significant except One-Up Bond F group. 3. The vibration group showed more mineral loss in enamel and longer resin tag and greater number of lateral branches in dentin under SEM examination.

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Biological activity in hot water extract from fermented Coix lacryma-jobi L. var. mayuen Stapf. by Hericium erinaceum (Bull. : Fr.) (노루궁뎅이균사발효 율무 열수추출물의 유용성분 및 생리활성)

  • Yun, Kyeong-Won;Kim, Kyung-Je;Jin, Seong-Woo;Koh, Young-Woo;Im, Seung-Bin;Ha, Neul-I;Jeong, Hee-Gyeong;Jeong, Sang-Wook;Seo, Kyoung-Sun
    • Journal of Mushroom
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    • v.18 no.1
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    • pp.20-28
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    • 2020
  • This study was conducted to determine the antioxidant, nitrite scavenging, melanin tyrosinase inhibitory, and melanogenesis inhibitory activities of fermented Coix lacryma-jobi L. var. mayuen Stapf. by Hericium erinaceum (Bull.: Fr.) mycelial hot water extract (FCLHE). Additionally, we analyzed β-glucan and ergosterol contents in FCLHE and C. lacryma-jobi hot water extract (CLHE). The ergosterol and β-glucan contents in FCLHE were 740.2 mg% and 245.3 mg%, respectively, whereas these components were not detected in CLHE. FCLHE showed higher cell viability than CLHE. When B16F10 cells were treated with 500 ㎍/mL each of CLHE and FCLHE, the FCLHE treated cells produced 8.9 uM nitric oxide (NO), which was lower than that produced by CLHE treated cells (10.6 uM). The FCLHE treated cells showed significantly greater tyrosinase inhibition and melanin production at all tested concentrations than when compared to the CLHE treated group. Antioxidant parameters such as DPPH and ABTS radical scavenging activities were higher in FCLHE than in CLHE. These results suggest that FCLHE can be used as a raw material for functional foods, for food additives, and in the cosmetic industry.

Lithologic and Structural Controls and Geochemistry of Uranium Deposition in the Ogcheon Black-Slate Formation (옥천대(沃川帶) 우라늄광층(鑛層)의 구조규제(構造規制) 및 지구화학적(地球化學的) 특성연구(特性硏究))

  • Lee, Dai Sung;Yun, Suckew;Lee, Jong Hyeog;Kim, Jeong Taeg
    • Economic and Environmental Geology
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    • v.19 no.spc
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    • pp.19-41
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    • 1986
  • Structural, radioactive, petrological, petrochemical, mineralogical and stable isotopic study as well as the review of previous studies of the uranium-bearing slates in the Ogcheon sequence were carried out to examine the lithological and structural controls, and geochemical environment in the uranium deposition in the sequence. And the study was extended to the coal-bearing formation (Jangseong Series-Permian) to compare the geochemical and sedimentologic aspects of uranium chemistry between Ogcheon and Hambaegsan areas. The results obtained are as follows: 1. The uranium mineralization occurs in the carbonaceous black slates of the middle to lower Guryongsan formation and its equivalents in the Ogcheon sequence. In general, two or three uranium-bearing carbonaceous beds are found with about 1 to 1.5km stratigraphic interval and they extend from Chungju to Jinsan for 90km in distance, with intermittent igneous intrusions and structural Jisturbances. Average thickness of the beds ranges from 20 to 1,500m. 2. These carbonaceous slate beds were folded by a strong $F_1$-fold and were refolded by subsequent $F_1$-fold, nearly co-axial with the $F_1$, resulting in a repeated occurrence of similar slate. The carbonaceous beds were swelled in hing zones and were shrinked or thined out in limb by the these foldings. Minor faulting and brecciation of the carbonaceous beds were followed causing metamorphism of these beds and secondary migration and alteration of uranium minerals and their close associations. 3. Uranium-rich zones with high radioactive anomalies are found in Chungju, Deogpyong-Yongyuri, MiwonBoun, Daejeon-Geumsan areas in the range of 500~3,700 cps (corresponds to 0.017~0.087%U). These zones continue along strike of the beds for several tens to a few hundred meters but also discontinue with swelling and pinches at places that should be analogously developed toward underground in their vertical extentions. The drilling surveyings in those area, more than 120 holes, indicate that the depth-frequency to uranium rich bed ranging 40~160 meter is greater. 4. The features that higher radioactive anomalies occur particularly from the carbonaceous beds among the argillaceous lithologic units, are well demonstrated on the cross sections of the lithology and radioactive values of the major uranium deposits in the Ogcheon zone. However, one anomalous radioactive zone is found in a l:ornfels bed in Samgoe, near Daejeon city. This is interpreted as a thermal metamorphic effect by which original uranium contents in the underlying black slate were migrated into the hornfels bed. 5. Principal minerals of the uranium-bearing black slates are quartz, sericite, biotite and chlorite, and as to chemical composition of the black slates, $Al_2O_3$ contents appear to be much lower than the average values by its clarke suggesting that the Changri basin has rather proximal to its source area. 6. The uranium-bearing carbonaceous beds contain minor amounts of phosphorite minerals, pyrite, pyrrhotite and other sulfides but not contain iron oxides. Vanadium. Molybdenum, Barium, Nickel, Zirconium, Lead, Cromium and fixed Carbon, and some other heavy metals appear to be positive by correlative with uranium in their concentrations, suggesting a possibility of their genetic relationships. The estimated pH and Eh of the slate suggests an euxenic marine to organic-rich saline water environment during uranium was deposited in the middle part of Ogcheon zone. 7. The Carboniferous shale of Jangseong Series(Sadong Series) of Permian in Hambaegsan area having low radioactivity and in fluvial to beach deposits is entirely different in geochemical property and depositional environment from the middle part of Ogcheon zone, so-called "Pibanryong-Type Ogcheon Zone". 8. Synthesizing various data obtained by several aspects of research on uranium mineralization in the studied sequence, it is concluded that the processes of uranium deposition were incorporated with rich organic precipitation by which soluble uranyl ions, $U{_2}^{+{+}}$ were organochemically complexed and carried down to the pre-Ogcheon sea bottoms formed in transitional environment, from Red Sea type basin to Black Sea type basin. Decomposition of the organic matter under reducing conditions to hydrogen sulfide, which reduced the $UO{_2}^{+2}$ ions to the insoluble uranium dioxide($UO_2$), on the other side the heavy metals are precipitated as sulfides. 9. The EPMA study on the identification of uraninite and others and the genetic interpretation of uranium bearing slates by isotopic values of this work are given separately by Yun, S. in 1984.

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Changes in Physicochemical Composition of Sea Urchin Roe by Steaming Treatment (열처리 조건에 따른 성게 알의 이화학적 성분 변화)

  • Lee, Sung-Uk;Lee, Hye-Young;Kim, Seong-Ho;Kim, Duk-Jin
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.41 no.4
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    • pp.550-560
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    • 2012
  • This study was performed to investigate the physicochemical properties of sea urchin ($Anthocidaris$ $crassispina$, $Pseudocentrotus$ $depressus$, $Hernicentrotus$ $pulcherrimus$) roe as a processed or canned food by steaming treatment. Proximate compositions of $A.$ $crassispina$ roe and $P.$ $depressus$ roe were similar, but water, crude ash, and carbohydrate contents of $H.$ $pulcherrimus$ roe showed little differences. Proximate compositions of sea urchin roe showed slight differences with steaming time, raw samples showed no differences. Glycine content of the three raw sea urchin roe samples showed the highest concentration among free amino acids, followed by arginine, alanine, and lysine, in order. Total free amino acid contents of raw sea urchin roe were 754.70 mg% ($A.$ $crassispina$), 567.75 mg% ($P.$ $depressus$), and 449.44 mg% ($H.$ $pulcherrimus$). Total free amino acid content of 5 min steaming sample was highest among steaming and canning conditions. ATP, ADP, and AMP contents of raw $P.$ $depressus$ roe sample was higher than those of $A.$ $crassispina$and $H.$ $pulcherrimus$ roe. Major fatty acids of the three raw sea urchin roe samples were myristic acid, palmitic acid, and EPA. S.F.A. content of raw samples of $A.$ $crassispina$and $H.$ $pulcherrimus$ roe was higher than U.F.A content, whereas U.F.A. content of $P.$ $depressus$ roe was highest among the three raw samples. For minerals K, P, Fe, and Zn contents were highest in $A.$ $crassispina$roe while Ca, Mg, Na, and Cu contents were highest in $H.$ $pulcherrimus$ roe. For heavy metals, Cd, Pb and As were detected in all samples in trace amounts under the criteria of the Korea food codex.

Estrogeicity of Genistein and Bisphenol A (콩류식품의 주성분인 Genistein과 식품포장재 및 용기에 사용되는 Bisphenol A의 에스트로젠 효과에 관한 연구)

  • 강경선;이영순;신광순
    • Journal of Food Hygiene and Safety
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    • v.13 no.2
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    • pp.106-111
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    • 1998
  • This study has been focused on both estrogenic and proliferating activity of genistein (GEN) and bisphenol A (BPA). GEN and BPA enhance the proliferation of estrogen-dependent MCF-7 human breast cancer cells at concentrations as low as 100 nM of GEN and 8 ng/ml of BP A achieving similar effect to that of estradiol at 1 nM. Expression of the estrogen responsive gene, pS2 was also induced in MCF-7 cells by treatment with genistein at dose as low as 1 nM and BPA at dose as low as 4 ng/ml. Using 21 day-old ovariectomized nude mice, we examined end-bud formation and mammary gland development after treatment with bisphenol A or genistein. Compared with untreated control, mammary gland development and end-bud formation were significantly increased in mice fed genistein or bisphenol A (p<0.05). Taken together, it is concluded that GEN and BP A can act as an estrogen agonist resulting in cell proliferation and induction of the estrogen responsive pS2 gene in MCF-7 cells in vitro and in athymic mice in vivo, respectively. Therefore, it is suggested that GEN and BP A might modulate human endocrine system and these compounds might be considered as a endocrine modulator at the low levels of doses.

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Diagnostic Accuracy of PET and MR for Detecting Liver Metastasis from Colorectal Cancer (대장-직장암의 간전이에서 FDG PET과 MR의 진단 성능)

  • Park, Eun-Kyung;Kang, Won-Jun;Eo, Jae-Seon;Lee, Dong-Soo;Chung, June-Key;Lee, Myung-Chul
    • Nuclear Medicine and Molecular Imaging
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    • v.40 no.5
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    • pp.249-256
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    • 2006
  • Purpose: Although computed tomography (CT) is widely used for diagnosing liver metastasis from colorectal cancer, diagnostic accuracy of CT is not satisfactory. Magnetic resonance (MR) imaging and F-18 FDG PET has been reported to be superior to CT. However, studies on direct comparison of PET and MR are scarce. We compared the diagnostic accuracy of FDG PET and MR in detecting liver metastasis from colorectal cancer. Materials and Methods: Among 363 colorectal cancer patients who underwent F-18 FDG PET (ECAT, Siemens-CTI, Knoxville; Gemini, Philips, Milpitas, U.S.), 26 patients (M:F=17:9, age=$62{\pm}11$) underwent MR to evaluate suspicious metastatic liver lesions. Finally, 35 liver lesions detected by CT from 26 patients were enrolled for analysis. PET and MR results were compared with pathologic reports, clinical findings or follow-up results. Results: Of the 35 lesions, 18 lesions (51.4%) were diagnosed as liver metastases, while remaining 17 (48.6%) as benign. The sensitivity and the specificity of PET were 94.4% and 94.1%, respectively, compared to 100% and 82.4% for MR. MR and PET was concordant in 30 lesions (85.7%: 17 metastatic (94.4%) and 13 benign (76.5%) lesions. ROC curve analysis revealed maximal SUV of 3.1 as the optimum standard in differentiating metastatic from benign liver lesions (AUC=0.897, p<0.001, sensitivity 83.3%, specificity 94.1%). For small lesions less than 1 cm ln diameter (n=20), diagnostic accuracy of PET was comparable to that of MR. Conclusion: F-18 FDG PET showed good diagnostic performance in detecting liver metastasis from colorectal cancer, which was comparable to MR.

Enhancement of Excretory Production of an Exoglucanase from Escherichia coli with Phage Shock Protein A (PspA) Overexpression

  • Wang, Y.Y.;Fu, Z.B.;Ng, K.L.;Lam, C.C.;Chan, A.K.N.;Sze, K.F.;Wong, W.K.R.
    • Journal of Microbiology and Biotechnology
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    • v.21 no.6
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    • pp.637-645
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    • 2011
  • Production of recombinant proteins by excretory expression has many advantages over intracellular expression in Escherichia coli. Hyperexpression of a secretory exoglucanase, Exg, of Cellulomonas fimi was previously shown to saturate the SecYEG pathway and result in dramatic cell death of E. coli. In this study, we demonstrated that overexpression of the PspA in the JM101(pM1VegGcexL-pspA) strain enhanced excretion of Exg to 1.65 U/ml using shake-flask cultivation, which was 80% higher than the highest yield previously obtained from the optimized JM101(pM1VegGcexL) strain. A much higher excreted Exg activity of 4.5 U/ml was further achieved with high cell density cultivation using rich media. Furthermore, we showed that the PspA overexpression strain enjoyed an elevated critical value (CV), which was defined as the largest quotient between the intracellular unprocessed precursor and its secreted mature counterpart that was still tolerable by the host cells prior to the onset of cell death, improving from the previously determined CV of 20/80 to the currently achieved CV of 45/55 for Exg. The results suggested that the PspA overexpression strain might tolerate a higher level of precursor Exg making use of the SecYEG pathway for secretion. The reduced lethal effect might be attributable to the overexpressed PspA, which was postulated to be able to reduce membrane depolarization and damage. Our findings introduce a novel strategy of the combined application of metabolic engineering and construct optimization to the attainment of the best possible E. coli producers for secretory/excretory production of recombinant proteins, using Exg as the model protein.