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CYP1A2 is one of the main Cytochrome P450 enzymes in the human liver associated with the metabolism of several xenobiotics. CYP1A2 is especially involved in the metabolic activation of different procarcinogens. Therefore, the development of cancer may be inhibited by inhibiting CYP1A2 activity. Here, the inhibitory effect of HYIpro-3-1 and its derivatives on CYP1A2 activity in human liver microsomes (HLM) was studied through LC-MS/MS using a cocktail assay. Among the four compounds, HYIpro-3-1 showed the most selective and strongest inhibitory effect on CYP1A2 at IC50 values of 0.1 µM in HLMs and inhibition was confirmed using purified human CYP1A2. It was determined that inhibition is reversible because the inhibitory effect of HYIpro-3-1 is not dependent on preincubation time. HYIpro-3-1 showed a typical pattern of competitive inhibition for CYP1A2-catalyzed phenacetin O-deethylation, based on the Lineweaver-Burk plot, with a Ki value of 0.05 μM in HLMs; the secondary plot also showed a linear pattern. In our study, HYIpro-3-1 was proposed as a novel inhibitor with the capacity to selectively inhibit CYP1A activity in HLMs. This article is protected by copyright. All rights reserved.

After the 2016 Gyeongju Earthquake (MW 5.5) in SE Korea, the NNE‒SSW-striking Yangsan Fault (YF) seismicity has emerged as a significant scientific issue and hazard. Despite previous stu...

A CaO-B2O3-SiO2 (CBS) glass/40 wt% Al2O3 composite sintered at 900°C exhibited a dense microstructure with a low porosity of 0.21%. This composite contained Al2O3 and anorthite phases, but pure glass sintered at 900°C has small quantities of wollastonite and diopside phases. This composite was measured to have a high bending strength of 323 MPa and thermal conductivity of 3.75 W/(mK). The thermal conductivity increased when the composite was annealed at 850°C after sintering at 900°C, because of the increase in the amount of the anorthite phase. 0.25 wt% graphene oxide and 0.75 wt% multi-wall carbon nanotubes were added to the CBS/40 wt% Al2O3 composite to further enhance the thermal conductivity and bending strength. The specimen sintered at 900°C and subsequently annealed at 850°C exhibited a large bending strength of 420 MPa and thermal conductivity of 5.51 W/(mK), indicating that it would be a highly effective substrate for a chip-type supercapacitor.

Rhombohedral 0.69Pb(Zr0.47Ti0.53)-0.31Pb(Zn0.6Ni0.4)NbO3 (PZT-PZNN) ceramics were textured using 10.0 vol. % BaTiO3 (BT) platelets along the direction at 950°C with a high Lotgering factor of 95.3%. BT platelets did not react with the PZT-PZNN ceramics, and the textured PZT-PZNN ceramic had a tetragonal structure. The PZT-PZNN ceramics exhibited a strain of 0.174% with a piezoelectric strain constant (d*33) of 580 pC/N at 3.0 kV/mm. The textured PZT-PZNN ceramic showed an increased strain of 0.276% and d*33 of 920 pC/N at 3.0 kV/mm, which can be explained by the domain rotation. However, the d33 values of the textured specimens are smaller than those of the untextured specimens because of the small remanent polarization and relative dielectric constant of BT platelets. The textured PZT-PZNN ceramic synthesized in this work can be used for piezoelectric multilayer actuators because of its large strain and low sintering temperature.

We study the magnetoconductance and dephasing in a strongly localized regime in black phosphorus (BP) devices. The phase coherence length, lφ obtained from the magnetoconductance follows a temperature dependence of T–1/3 in the strongly localized regime with kFle < 1 (ξ < lφ) based on the Ioffe–Regel criterion. Here kF, le and ξ are the Fermi wave vector, mean free path and localization length, respectively. The conductance behavior as a function of temperature confirms that the transport regime of our BP is in a variable-range-hopping regime, which results in the strongly localized regime.

K(Nb1−xMnx)O3 (KN1−xMx) ceramics with 0.005 ≤ x ≤ 0.015 were sintered at 1020°C through a normal sintering process without the formation of a liquid phase. They exhibited double polarization versus electric field (P–E) hysteresis and sprout-shaped strain versus electric field (S–E) curves owing to the presence of a defect dipole (PD), which was formed between the acceptor Mn3+ ion and the oxygen vacancy. Moreover, the aging process was not required to develop the PD. The KN1−xMx ceramics exhibited a large strain of ~0.2% at 6.0 kV/mm. For the KN0.985M0.015 ceramic, this large strain was maintained after 104 cycles of an electric field of 6.0 kV/mm. This ceramic also maintained a double hysteresis curve at 200°C. Therefore, the KN0.985M0.015 ceramic has a large electric field-induced strain, along with good thermal and fatigue properties for multilayer piezoelectric actuators.

Four new D—A type copolymers with 2D-conjugated side-chain identified PfToBT, PbToBT, PfTDPP and PbTDPP, containing two acceptors 4,7-dithien-2-yl-benzo[c][1,2,5]thiadiazole (DTBT), and diketopyrrolopyrrole (DPP) linked by thiophene donors, are obtained using Pd-catalyzed Stille-coupling reaction. These polymers show a broad visible-near-infrared absorption band (Eg = 1.79–1.66 eV) and possess a relatively low-lying HOMO level at −5.34 to −5.12 eV. All the polymer:PC70BM blend films showed edge-on structure and have similar dπ-spacing values. According to the structure of conjugated side-chain, the vertical distributions of polymer chains and PC70BM within the BHJ (bulk heterojunction) were different. When DPP used as an acceptor, conjugated side chains of the polymer coexisted with PC70BM in same position. The BHJ film prepared from PfToBT, PbToBT had a discontinuous network between polymer and PC70BM, whereas films from PfTDPP and PbTDPP formed continuous and evenly distributed network between them. This optimized vertical morphology promotes hole transport along respective pathways of polymers and fullerenes in the vertical direction, leading to high JSC. PbTDPP shows PCE up to 2.9% (Jsc of 9.4 mA/cm2, Voc of 0.68 V, and FF of 0.44). © 2016 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2016, 54, 2746–2759

GSK5182 (4-[(Z)-1-[4-(2-dimethylaminoethyloxy)phenyl]-hydroxy-2-phenylpent-1-enyl]phenol) is a specific inverse agonist for estrogen-related receptor γ, a member of the orphan nuclear receptor family that has important functions in development and homeostasis. This study was performed to elucidate the metabolites of GSK5182 and to characterize the enzymes involved in its metabolism. Incubation of human liver microsomes with GSK5182 in the presence of NADPH resulted in the formation of three metabolites, M1, M2 and M3. M1 and M3 were identified as N-desmethyl-GSK5182 and GSK5182 N-oxide, respectively, on the basis of liquid chromatography-tandem mass spectrometric (LC-MS/MS) analysis. M2 was suggested to be hydroxy-GSK5182 through interpretation of its MS/MS fragmentation pattern. In addition, the specific cytochrome P450 (P450) and flavin-containing monooxygenase (FMO) isoforms responsible for GSK5182 oxidation to the three metabolites were identified using a combination of correlation analysis, chemical inhibition in human liver microsomes and metabolism by expressed recombinant P450 and FMO isoforms. GSK5182 N-demethylation and hydroxylation is mainly mediated by CYP3A4, whereas FMO1 and FMO3 contribute to the formation of GSK5182 N-oxide from GSK5182. The present data will be useful for understanding the pharmacokinetics and drug interactions of GSK5182 in vivo. Copyright © 2014 John Wiley & Sons, Ltd.

RATIONALE Uridine 5'-diphosphoglucuronosyltransferase (UGT) enzymes are essential for the clearance of many drugs; however, altered UGT activity is a potential cause of adverse drug-drug interactions (DDI). The early detection of potential DDI is an important aspect of drug discovery that has led to the development of new screening methods for drug interactions. We developed a screening method for the simultaneous evaluation of six human liver UGT enzyme activites using in vitro cocktail incubation and tandem mass spectrometry. METHODS The two in vitro cocktail doses were developed to minimize drug interactions among substrates. The method is based on liquid chromatography/tandem mass spectrometry (LC/MS/MS). Electrospray ionization (ESI) in both positive and negative modes was used to quantify the metabolites and the diagnostic loss of the glucuronosyl moiety to form the aglycone product was estimated using the selected reaction monitoring (SRM) mode. RESULTS The method was validated by comparing inhibition data obtained from the incubation of each individual probe substrate alone with data from the cocktail method. The intra- and inter-day accuracy and precision data for the six UGT metabolites ranged from 92.2 to 100.3% and less than 15.2%, respectively. The IC50 values showed no significant differences between individual and cocktail incubations. CONCLUSIONS As a screening technique for inhibitory interactions of these six human liver UGT enzymes, this method will be useful for advancing mechanistic understanding of drug interactions. Copyright © 2014 John Wiley & Sons, Ltd.

Nematic liquid crystals (NLCs) are introduced to P3HT:PCBM-based bulk heterojunction polymer solar cells (PSCs) as processing additives for low processing temperatures. To investigate why the addition of NLCs improves the efficiency of PSCs, the photon absorbance properties are observed using UV–vis spectroscopy and photoluminescence. Then, the degree of crystallinity of P3HT is examined through X-ray diffraction analysis. In addition, changes in the nanostructure and surface morphology of the P3HT:PCBM blend film are observed through atomic force microscopy and transmission electron microscopy.

Obovatol, a major constituent of the leaves of Magnolia obovata Thunb, is known to inhibit nuclear factor-κB activity and arachidonic acid-induced platelet aggregation. This study was performed to identify the metabolites of obovatol in human liver microsomes. Human liver microsomes incubated with obovatol in the presence of NADPH and/or UDPGA resulted in the formation of six metabolites, M1-M6. M1 and M2 were identified as hydroxyobovatol, on the basis of liquid chromatography/tandem mass spectrometric (LC-MS/MS) analysis. M1, M2 and obovatol were further metabolized to their glucuronide conjugates, obovatol-glucuronide (M3), obovatol-diglucuronide (M4) and hydroxyobovatol-glucuronide (M5 and M6). The inhibitory potency of obovatol on eight major human P450s was also investigated in human liver microsomes. In these experiments, obovatol strongly inhibited CYP2C19-mediated S-mephenytoin hydroxylase activity with an IC(50) value of 0.8 µM, which could have implications for drug-drug interactions.

Phanerozoic granitoids in South Korea are classified into four primary spatiotemporal groups showing geochemical and isotopic diversity. This study presents the first in situ Hf isotope data for zircons extracted from representative outcrops of each granitoid group. The core-to-rim variation in eHf values observed in some zircon grains provides evidence for open-system processes influenced by the input of more primitive melts or interactions with pre-existing crustal materials. A general core-to-rim decrease in Lu/Hf and Th/U ratios indicates a progressive compositional change in the melts during magmatic differentiation. Contrasting evolutionary paths demonstrated by zircon eHf values suggest that the Neoproterozoic to Palaeozoic crust including the Permian granitoids was recycled during the Cretaceous to Palaeogene magmatism in south-eastern Korea, whereas the Palaeoarchaean to Palaeoproterozoic crust provided major source material for the Triassic to Jurassic granitoids in central Korea.

Background and Aim: DA-9701, a novel prokinetic agent formulated with Pharbitis Semen and Corydalis Tuber, has strong prokinetic effects, and enhances gastric compliance in conscious dogs. In this study, the effects of DA-9701 on gastric accommodation were studied in conscious dogs. Methods: Beagle dogs with an implanted gastric cannula in the stomach were used in this study. After an overnight fast, the dogs received DA-9701 orally, or served as a positive control that received sumatriptan or a negative control before ingestion of a meal. The basal and postprandial gastric volumes were monitored at a constant operating pressure using an electronic barostat. To investigate the long-lasting effects on increased postprandial gastric volume, the area under the volume versus time curve (AUC) was calculated. Results: DA-9701 significantly increased the basal gastric volume compared to the negative controls (P

Microlight-emitting diodes (µLEDs) are emerging solutions for both high-quality displays and lighting technologies. However, the overall light output power density of these devices is low, as the emission area is shielded by the p-electrodes required for current injection. In this study, instead of the more conventionally used indium tin oxide (ITO), an AlN thin film with nanoscale conducing filaments (CFs) is used, referred to as CF-AlN, as a transparent conducting electrode (TCE), to enhance the output power density from the same emission area. As a result of this modification, the electroluminescence intensity is enhanced by 10% at an injection current of 10 mA, and the current density is improved by 13% at a forward voltage of 4.9 V, in comparison to the parameters observed with ITO-based µLEDs. This improvement is attributed to the higher transmittance of CF-AlN TCEs, together with efficient hole injection from the p-electrode into the light-emitting layer, through the CFs formed in the AlN layer. In addition, using transmission electron microscopy analyses, the origin of the CFs is directly identified as the diffusion of In and Sn ions, which provides critical insight into the conduction mechanism of AlN-based TCEs.

Glass, silicon, poly(dimethylsil-oxane) (PDMS), and poly(methylmethacrylate) (PMMA)have been used for the fabrication of miniaturized devices.Fabrication with glass or silicon substrates requires relativelycomplex processes, and the fabrication costs are high.Relatively cheap polymers such as PDMS or PMMA arenot suitable for application in organic chemical processesowing to their low chemical stability and easy swelling.

We report the preparation of aminopropyl-functionalized magnesium phyllosilicate (Mg-organoclay) conjugated to fluorescein isothiocyanate (FITC) functionality (FITC-organoclay) by one-pot sol-gel synthesis. The physical characteristics of the Mg- and FITC-organoclays were examined by scanning electron microscopy (SEM), X-ray diffraction (XRD), FT-IR and UV-Vis spectrophotometry. X-ray fluorescence and elemental analysis were conducted to confirm the composition of the Mg-organoclay. The FITC-organoclay particles were polydispersed with an average particle size of approximately 50 nm, as determined from SEM images. The XRD patterns of FITC-organoclay exhibited broad peaks and reduced basal d(001) indicating a less condensed and more disordered structure than was observed for Mg-organoclay. The conjugation between FITC- and Mg-organoclay was characterized by FT-IR spectroscopy. Fluorescence excitation and emission spectral data demonstrated the successful conjugation of FITC dye molecules to the Mg-organoclay. The time-resolved fluorescence measurements revealed that FITC had a lifetime of 4.58 ns, whereas the lifetime of FITC-organoclay required a double exponential fit (tau(1,2) = 0.72 and 2.68 ns). As a result, the lifetime of the FITC-organoclay was shorter than that of FITC in ethanol and indicated moderate photostability in the solution state. The cellular uptake of FITC-organoclay in human lung alveolar carcinoma epithelial cells (A549) was quantified and characterized.

Minimal change nephrotic syndrome (MCNS) is the most common cause of the nephrotic syndrome in children, accounting for 90% of cases under the age of 10 years and more than 50% in older children. It has been proposed that MCNS reflects a disorder of T-lymphocytes. These T cells are thought to release a cytokine - so-called permeability factor - that injures the glomerular epithelial cells. The identity of this permeability factor is still uncertain. Epithelial cell damage may lead to albuminuria in MCNS by altering the metabolism of polyanions, such as heparan sulphates, that constitute most of the normal charge barrier to the glomerular filtration of macromolecules such as albumin. In contrast, in focal segmental glomerulosclerosis (FSGS) the proteinuria is primarily due to an increased number of large pores in the glomerular basement membrane, leading to an impairment in size selectivity. It has been documented by repeated renal biopsies that some patients with apparent MCNS at the initial biopsy progress to FSGS. Morphological signs which have been proposed to identify the high-risk subset of MCNS include widespread IgM deposits (IgM nephropathy) and diffuse mesangial hypercellularity. It has been also documented that the initial biopsy of paediatric patients who subsequently showed FSGS had larger glomeruli from children with MCNS and healthy controls. Therefore, the presence of glomerular hypertrophy in biopsies of apparent MCNS appeared to be a high specific indicator of increased risk for progression to FSGS. In comparison with MCNS, a higher proportion of patients with mild mesangial hypercellularity are initial non-responder. More severe degree of mesangial hypercellularity, as seen in patients with diffuse mesangial hypercellularity, was associated with an even poorer initial response to steroid. Accordingly, it appears that mesangial proliferative glomerulonephritis is a more severe form of MCNS in which the initial injury is greater, leading to mesangial dysfunction and a slower rate of recovery, and this disorder is a part of the MCNS-FSGS spectrum. In this viewpoint, it can also be said that FSGS is the most severe form of MCNS in which the initial injury is the greatest, so the majority of patients with FSGS are non-responders to steroid and progress to chronic renal failure. In summary, documents define the risk for progressive renal disease based on the presence of mesangial hypercellularity and glomerular hypertrophy in renal biopsies of patients with MCNS, thus directing vigilant follow up and more aggressive treatment of high-risk patients.

The molecular structures of methacryl-grafted polysiloxane resins from 3-(trimethoxysilyl)propyl methacrylate (MPTS) and diphenylsilanediol (DPSD) were determined by theoretical computation and experimental measurement. The molecular structures obtained from theoretical computation coincided well with those from experimental measurement, and we found that the structural changes in the resins could be controlled by precursor compositions. While molecular weights and polysiloxane chain lengths of the resins increase with DPSD contents, their molecular sizes do not vary significantly. In the present study, molecular sizes and shapes of the resins with various compositions are hypothesized theoretically and proven experimentally. © 2005 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 43: 827–836, 2005

Inorganic–organic hybrid polymers have been developed and tested for evaluation in optical and electrical applications. Although hybrid inorganic–organic polymers can be synthesized by sol–gel chemistry at first, the physical properties of hybrid inorganic–organic polymers are changed during thin film-making processes, that is, photocuring and thermal curing. To investigate the effect of photoinitiator on the material properties during processing, a model system containing methacrylic groups as organically polymerizable units was selected. The conversion of CC double bond of methacrylic groups depending on some kinds of photoinitiator quantities was characterized by Fourier transform infrared spectroscopy. It was confirmed to correlate the degree of CC double bond conversion with the refractive indices. Thermodynamically, the enthalpy of the photopolymerization of hybrid polymer was investigated by UV–DSC. UV–DSC spectra showed the exothermic nature of photopolymerization of ORMOCER® to be in dependence of photoinitiator quantities. © 2004 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 42: 1979–1986, 2004

In this paper, it will be shown that we can reduce the driving voltage and improve the luminance and luminous efficacy of Plasma Display Panel(PDP) significantly by blocking the diffusion of impurities into the cathode layer which occurs during the high temperature process like panel assembly. The TOF-SIMS(Time-of-Flight Secondary Ion Mass Spectrometry) results show that the diffusion of impurities like Al, Na and K into the cathode layer can be effectively prevented by the adoption of a blocking layer made of SiO2. Another beneficial effect is the significant reduction of the aging time. It has been confirmed through the panel experiment that the impurity diffusion barrier is effective in reducing the voltage, aging time and increasing the luminous efficacy for both of the PDPs with a single MgO and a SrO-MgO double cathode layer with more spectacular improvements in the latter case.

Injection of Escherichia coli into larvae of the coleopteran Tenebrio molitor resulted in the appearance of a dopamine-like substance on the electrochemical detector. To characterize this dopamine-like substance, we purified it to homogeneity from the immunized hemolymph and determined its molecular structure to be N-beta-alanyldopamine using the liquid chromatographic/tandem mass spectrometric method. Chemically synthesized N-beta-alanyldopamine showed the same retention time on HPLC as the purified N-beta-alanyldopamine from immunized larvae. To elucidate the molecular mechanism of N-beta-alanyldopamine synthesis in vivo, we examined the enzyme activity of Dopa decarboxylase against E. coli-injected hemolymph of T. molitor larvae. The enzyme activity of Dopa decarboxylase increased dramatically approximately 8 h after injection; Dopa decarboxylase activity of injected larvae being 10-times higher than naive larvae after 24 h. To evaluate the extent of quantitative changes of Dopa decarboxylase in response to bacterial challenge, Tenebrio Dopa decarboxylase was purified to homogeneity from the whole larvae and a cDNA clone for Tenebrio Dopa decarboxylase was isolated. RNA blot hybridization revealed that expression of the Dopa decarboxylase gene was activated transiently 3-8 h after E. coli challenge. Immunoprecipitation experiments showed that Tenebrio Dopa decarboxylase was detected from 8 to 24 h in E. coli-injected larval extract. Thus, bacterial injection into T. molitor larvae might induce transcriptional activation of a Dopa decarboxylase gene, and then synthesis of N-beta-alanyldopamine. The synthesized N-beta-alanyldopamine might be used as a substrate by phenoloxidase during melanin synthesis in the humoral defense response or the melanotic encapsulation reaction of the cellular defense response.

In batch cultures for L-ornithine production in which dissolved oxygen concentration and pH were closely controlled, time changes of redox potential were observed in connection with the profiles of cell, glucose, and ornithine concentrations. It was found that the redox potential profile had four different phases reflecting the physiological state of the culture and that it was closely related to cell concentration change. Effects of glucose and ornithine on the redox potential were identified in a separate series of experiments. On the basis of the experimental results, a correlation of redox potential to glucose, cell, and ornithine concentrations has been proposed. The proposed correlation can be used for on-line estimation of ornithine concentration from on-line data of redox potential, glucose concentration, and cell concentration.

The characteristics and performance of an autotuning proportional integral derivative (PID) controller developed by us have been investigated. The parameters for this controller, proportional gain, K, the integral time constant, τ i , and the derivative time constant, τ d , are on-line-tuned by using heuristic rules, requiring no a priori tuning. The controller showed a stable and robust performance, even when only K was online-tuned. However, the dynamic (or time delay) of the membrane-type dissolved oxygen (DO) probe caused oscillations in the DO concentration unless it was properly compensated. This required a prediction method. When all three controller parameters were on-line-adjusted, the DO probe dynamic could be effectively overcome with no separate prediction step

This review covers the utility of carbon disulfide and a solid support as starting materials for the synthesis of diverse, drug-like, five-membered ring heterocycles and their fused counterparts. For examples, the preparations of such five-membered ring heterocycles as thiophenes, thiazoles, fused-thiazoles, thiazolines, 2-thioxothiazolidin-4-ones (rhodamines), 2-thioxoimidazolidin-4-ones (thiohydantoins), benzoxazoles, benzimidazoles, imidazoloquinazolines, pyrazoles, fused-pyrazoles, 1,3,4-triazoles, oxadiazoles, and thiadiazoles are presented.

School of Chemistry and Molecular Engineering, Seoul National University, Seoul 151-742, KoreaReceived February 13, 2001 A stereoselective synthesis of 1 β-aminocarbapenems ( 11a-c) starting from 4-acetoxy-2-azetidinone derivative4 is described. 4-Acetoxy-2-azetidinone derivative (4) was reacted with the lithium enolate of benzophenoneimine of glycine phenyl ester ( 5f) to give alkylated product (R)-6f in good yield with high diastereoselectivity.The alkylated product (R)-6f was transformed to thioesters ( 7a-c) by transesterification with thiols, Thioesters(7a-c) were converted to their oxalimides (8a-c), followed by the phosphite-mediated reductive cyclization togive carbapenems (9a-c). Removal of all protecting groups of carbapenems (9a-c) afforded 1β-aminocarbap-enems (11a-c).Keywords : Carbapenems, Phosphite-mediated reductive cyclization, Benzophenone imines of glycine esters. IntroductionSince the discovery of thienamycin (1)

[reaction: see text] A stereocontrolled approach to the preparation of the Weinreb intermediate 3 has been developed. The important features of this approach are the creation of stereogenic centers through a cyclic amino acid ester-enolate Claisen rearrangement and the use of ring-closing metathesis for the construction of the azaspirocyclic skeleton.