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The Geostationary Environment Monitoring Spectrometer (GEMS) onboard the Geostationary Korea Multi-Purpose Satellite-2B (GEO-KOMPSAT-2B) satellite observes the hourly volcanic SO2 over Asia. In this study, the various physical characteristics of volcanic plumes have been investigated based on hourly volcanic SO2 measurements. The transport direction, path and speed, and altitude of volcanic SO2 plume emitted from Nishinoshima in Japan, Etna in Italy, and Dukono located in Halmahera, Indonesia were calculated. The SO2 plume from Nishinoshima, Japan, moved westward at a maximum speed of 57 km/h on August 4, 2020. The SO2 plume generated from Etna was observed to move over China using both GEMS and TROPOMI, and moved at an altitude of 11–14 km and a speed of 162–190 km/h. In the case of the SO2 plume from the Dukono volcano flowed into an average of 3.6 Mg of SO2 per hour to the cities of nearby islands. GEMS can be utilized for an improvement in the prediction accuracy of SO2 plume transport using a chemical transport model due to the availability of hourly volcanic SO2 height information. In addition, hourly observations of SO2 concentrations are expected to protect SO2 exposure through rapid forecasting for people in cities around the volcano.

Hexagonal boron nitride (h-BN), an insulating two-dimensional (2D) layered material, has recently attracted tremendous interest motivated by the extraordinary properties it shows across the fields of optoelectronics, quantum optics, and electronics, being exotic material platforms for various applications. At an early stage of h-BN research, it has been explored as an ideal substrate and insulating layers for other 2D materials due to its atomically flat surface free of dangling bonds and charged impurities, and high thermal conductivity. Recent discoveries of structural and optical properties of h-BN have expanded potential applications into emerging electronics and photonics fields. h-BN shows a very efficient deep-ultraviolet band-edge emission despite its indirect bandgap nature, as well as stable room temperature single-photon emission over a wide wavelength range, showing a great potential for next-generation photonics. In addition, h-BN is extensively being adopted as active media for low energy electronics, including nonvolatile resistive switching memory, radio-frequency devices, and low dielectric constant materials for next-generation electronics. This article is protected by copyright. All rights reserved.

We present a remarkable improvement in the efficiency of AlGaN deep-ultraviolet light-emitting diodes (LEDs) enabled by the coupling of localized surface plasmon resonance (LSPR) mediated by a high-density array of Al nanoparticles (NPs). The Al NPs with an average diameter of ∼40 nm were uniformly distributed near the Al

The Geostationary Environment Monitoring Spectrometer (GEMS) onboard the Geostationary Korea Multi-Purpose Satellite-2B (GEO-KOMPSAT-2B) satellite was launched in February 2020 and observes the hourly volcanic SO2 in geostationary orbit. We For the first time show the hourly changes in volcanic SO2 distributions emitted and transported from several volcanoes over Asia. The various physical characteristics of volcanic plumes have been investigated based on hourly volcanic SO2 measurements. We estimated transport direction, path and speed, and altitude of volcanic SO2 plume emitted from Nishinoshima in Japan, Etna in Italy, Taal volcano in the Philippines and Dukono located in Halmahera, Indonesia. Before the eruption, Taal volcanic SO2 plumes, which were found to present within PBL, were transported mostly less than 100 km in various azimuth directions. Gradual increase in SO2 column densities was observed for about two months before a volcanic eruption from Taal. It implies that it might be possible to warn a volcanic eruption in advance which is subject to further investigation. GEMS can be further utilized for an improvement in prediction accuracy of SO2 plume transport using chemical transport model due to the availability of hourly volcanic SO2 height information.

The high spatial resolution TROPOspheric Monitoring Instrument (TROPOMI) launched in 2017 onboard the Sentinel-5 Precursor (S5P) platform provides important information on global volcanic and anthropogenic SO2 emissions, with an unprecedented level of details. More recently, the Geostationary Environmental Monitoring System (GEMS) was launched onboard the GEO-KOMPSAT-2B satellite in February 2020. GEMS has the unique capability of sensing SO2 over Asia at hourly resolution, offering great perspectives in monitoring and understanding emission process and pollution transport in the atmosphere. GEMS is the first satellite sensor of a geostationary constellation with the European (Sentinel-4) and US (TEMPO) counterparts.In a recent study (Theys et al., 2021), we proposed an approach called Covariance-Based Retrieval Algorithm (COBRA), different from the classical Differential Optical Absorption Spectroscopy (DOAS). Application of COBRA to TROPOMI SO2 column retrievals leads to a significant reduction of the retrieval noise and biases as compared to the TROPOMI operational (DOAS-based) SO2 product. COBRA even reveals new emission sources in long-term averaged SO2 maps.In this presentation, we apply COBRA for the retrieval of SO2 from GEMS spectra. The resulting SO2 vertical columns are presented and evaluated against different satellite data sets (GEMS L2 SO2 operational product, and TROPOMI SO2 COBRA and operational products) and ground-based measurements. While GEMS measures the same location several times per day, it is crucial to understand the retrieval bias and how it varies under varying observation geometry. This aspect and possible corrections will be discussed extensively.Theys, N., Fioletov, V., Li, C., De Smedt, I., Lerot, C., McLinden, C., Krotkov, N., Griffin, D., Clarisse, L., Hedelt, P., Loyola, D., Wagner, T., Kumar, V., Innes, A., Ribas, R., Hendrick, F., Vlietinck, J., Brenot, H., and Van Roozendael, M.: A Sulfur Dioxide Covariance-Based Retrieval Algorithm (COBRA): application to TROPOMI reveals new emission sources, Atmos. Chem. Phys., 21, 16727–16744, https://doi.org/10.5194/acp-21-16727-2021, 2021.

We presented a new functional GaInN-based light-emitting diode (LED) that is capable of protecting itself from unwanted thermal damage (a so-called self-protective LED). This functionality was achieved by incorporating VO2 nanowires on the LED chip. VO2 nanowires, as metal-insulator transition materials, show a phase transition from insulating to metallic at a characteristic transition temperature. By placing a VO2 nanowire between the n- and p-contacts of an LED, a parallel circuit was formed with the existing diode. As the VO2 nanowire became metal-like at its characteristic temperature, it induced a short-circuit state in the device, protecting the LED from heat damage at elevated temperatures. Details on the self-protective LED were elucidated, from a conceptual description to experimental proof.

We presented a new functional GaInN-based light-emitting diode (LED) that is capable of protecting itself from unwanted thermal damage (a so-called self-protective LED). This functionality was achieved by incorporating VO2 nanowires on the LED chip. VO2 nanowires, as metal-insulator transition materials, show a phase transition from insulating to metallic at a characteristic transition temperature. By placing a VO2 nanowire between the n- and p-contacts of an LED, a parallel circuit was formed with the existing diode. As the VO2 nanowire became metal-like at its characteristic temperature, it induced a short-circuit state in the device, protecting the LED from heat damage at elevated temperatures. Details on the self-protective LED were elucidated, from a conceptual description to experimental proof.

A new method was developed for classifying aerosol types involving a machine-learning approach to the use of satellite data. An Aerosol Robotic NETwork (AERONET)-based aerosol-type dataset was used as a target variable in a random forest (RF) model. The contributions of satellite input variables to the RF-based model were quantified to determine an optimal set of input variables. The new method, based on inputs of satellite variables, allows the classification of seven aerosol types: pure dust, dust-dominant mixed, pollution-dominant mixed aerosols, and pollution aerosols (strongly, moderately, weakly, and non-absorbing). The performance of the model was statistically evaluated using AERONET data excluded from the model training dataset. Model accuracy for classifying the seven aerosol types was 59%, improving to 72% for four types (pure dust, dust-dominant mixed, strongly absorbing, and non-absorbing). The performance of the model was evaluated against an earlier aerosol classification method based on the wavelength dependence of single-scattering albedo (SSA) and fine-mode-fraction values from AERONET. Typical wavelength dependences of SSA for individual aerosol types are consistent with those obtained for aerosol types by the new method. This study demonstrates that an RF-based model is capable of satellite aerosol classification with sensitivity to the contribution of non-spherical particles.

The junction temperature, one of the major parameters that strongly affect the performance of light-emitting diodes (LEDs), increases during operation because of the power dissipated as heat within an LED device. Therefore, LED devices with poor characteristics are expected to have higher junction temperatures for the same driving conditions. In this study, an observation contrary to this expectation is presented: a deep-ultraviolet LED device with superior electrical characteristics shows a higher junction temperature at the same input electrical power than a device with poor characteristics. A simple equivalent circuit comprising a diode, a series resistor, and shunt components is employed to elucidate this counter-intuitive observation by considering the possible heat sources inside the LED device. It is found that the junction temperature is mainly dominated by the power dissipated at the diode instead of the other possible heat sources including the Joule heating effect of the resistive components.

A sensitive and simple detection method coupling ultra-performance liquid chromatography with tandem mass spectrometry was developed and validated to analyze sumatriptan levels in human plasma. The plasma sample preparations for the analysis were based on liquid–liquid extraction with ethyl acetate, evaporation, and reconstitution. MS/MS detection was performed on a triple-quadrupole tandem mass spectrometer by monitoring the protonated parent → daughter ion pairs at m/z 296 → 58 and m/z 388 → 71 for sumatriptan and terazosin (internal standard), respectively. The method was validated with respect to its specificity, linearity, sensitivity, accuracy, precision, recovery, and stability. The calibration curve was linear from 0.5 to 50 ng/mL (r > 0.999). The mean extraction recovery for sumatriptan was higher than 62.3%. The method accuracy was within 97.4%, and the relative standard deviation of the intra- and inter-day precision values was within 11.7% at all quality control levels. Plasma samples that contained sumatriptan were stable under three freeze–thaw cycles, short- and long-term storage, and autosampler conditions. This method was successfully applied to a pharmacokinetic study conducted with 10 healthy volunteers. After oral administration of 50-mg sumatriptan and serial blood sampling over 12 h, the mean area under the plasma concentration–time curve from time 0 to 12 h and the maximum plasma concentration were 116.2 ng h/mL and 33.2 ng/mL, respectively.

The aim of this study was to investigate the pharmacokinetics and dose proportionality of a single, intravenous dose of pazufloxacin mesilate, an injectable fluoroquinolone antibiotic, in healthy Korean male volunteers.In this open-label, four-dose, parallel study, subjects were randomized to receive a single dose of pazufloxacin mesilate 300, 500, 600, and 1,000 mg (n = 6, 20, 6, and 8, respectively) administered as a 1-h intravenous infusion. Blood and urine samples were collected serially from 0 to 24 h after drug administration and analyzed using a validated HPLC method. Tolerability was assessed by monitoring clinical laboratory parameters and adverse events.After single-dose intravenous administration of pazufloxacin mesilate, the mean C(max) for groups treated with 300, 500, 600, and 1,000 mg doses ranged from 5.11 to 18.06 μg/mL; the mean AUC(0-t) ranged from 13.70 to 58.60 μg × h/mL. Pazufloxacin exhibits Lack of dose proportionality was concluded over the dose range of 300 - 1,000 mg, based on linear regression model and power model . At all four dosages studied, pazufloxacin mesilate was well tolerated.Our data suggest that all regimens of pazufloxacin administration were well tolerated. Pazufloxacin exhibits lack of dose proportionality over the dose range of 300 - 1,000 mg.

Levofloxacin and cyclosporine show different pharmacokinetic properties, but are known to be dose proportional within the therapeutic range. The authors evaluated the pharmacokinetic proportionality of levofloxacin and cyclosporine over a 100-fold dose range in healthy human volunteers, by liquid chromatography-tandem mass spectrometry (LC-MS/MS).Two independent, randomized, crossover studies were performed. For levofloxacin, eight volunteers were randomly assigned in a 1:1 ratio to receive a low dose (7.5 mg) orally or intravenously, followed by a 1-week washout period and administration via the alternate route. After another 1-week washout period, a therapeutic dose (750 mg) was administered to all eight subjects. For cyclosporine, another eight volunteers received a low dose (2 mg) or a therapeutic dose (200 mg) orally with a 1-week washout period. Drug concentrations were determined by LC-MS/MS.For levofloxacin, the mean values for dose-normalized C(max) and AUC(last) with the two doses were as follows: therapeutic dose, 15.2 ± 4.6 ng/ml/mg and 103.6 ± 15.5 ng·h/ml/mg, respectively; low dose, 17.1 ± 6.5 ng/ml/mg and 72.6 ± 8.7 ng·h/ml/mg, respectively. For cyclosporine, the mean values for dose-normalized C(max) and AUC(last) were as follows: therapeutic dose, 4.9 ± 1.5 ng/ml/mg and 15.4 ± 4.9 ng·h/ml/mg, respectively; low dose, 1.6 ± 0.6 ng/ml/mg and 9.3 ± 7.3 ng·h/ml/mg, respectively.In this study levofloxacin, which is completely absorbed and primarily eliminated renally without modification, showed better pharmacokinetic proportionality than cyclosporine, which is poorly absorbed and extensively metabolized.

A novel and economical method for preparing CaO-based high-temperature CO2 absorbents for sorption-enhanced hydrogen production is introduced. CaO–MgO absorbents prepared by the co-precipitation method show excellent cyclic stability but poor absorption capacity (∼8–14 g CO2/100 g absorbent). An additional hydration process provided spacious CO2 pathways resulting in a significant increase of the absorption capacity (∼17.4–47.8 g CO2/100 g absorbent) with excellent cyclic stability. As the MgO content increased, the absorption ratio of the absorbent and the degree of CaO conversion also increased. In addition, XRD analysis revealed that the hydration process followed by calcination at 900 °C led to the formation of a partial solid solution in the CaO–MgO absorbent containing 25 wt% MgO.

An enteric-coated formulation of triflusal (triflusal EC), an antiplatelet agent, was developed to reduce the high incidence of gastrointestinal adverse events (AEs). The aim of this study is to compare the pharmacokinetics, pharmacodynamics and safety of triflusal EC with triflusal in healthy Korean male subjects to determine bioequivalence and non-inferiority for the purposes of marketing approval.A randomized, open-label, two-period, crossover study was conducted in 38 subjects. Either triflusal EC or triflusal was administered orally as a single 900 mg loading dose (day 1) followed by eight 600 mg/day maintenance doses on days 2 - 9, with a 13-day washout period. The plasma concentrations of 2-hydroxy-4-trifluoromethyl benzoic acid (HTB), the predominant active metabolite of triflusal, were assessed after administration of the loading dose, using HPLC/MS/MS. The platelet aggregation response to arachidonic acid was determined using turbidimetric aggregometry.The 90% CIs, for the geometric mean ratios of the log-transformed AUC(τ) and C(max) of HTB were seen to be within the predetermined range of 0.8 - 1.25. Triflusal EC was also shown to be non-inferior in its anti-aggregatory effect. No serious AEs were reported during this study.The pharmacokinetic and pharmacodynamic profiles of the two triflusal formulations met the requirements for bioequivalence and non-inferiority, respectively. Both formulations were well tolerated.

The aim of this study was to compare the pharmacokinetics (PK) and safety of fimasartan (BR-A-657), an angiotensin II receptor antagonist, between healthy young (19 - 45 years) and older (≥ 65 years) male subjects.To assess the effect of age on PK and safety, fimasartan was administered as a single 240 mg tablet to 12 young and 10 older male subjects, followed by serial blood sampling over 48 h. Plasma concentrations of fimasartan were analyzed using validated HPLC-MS/MS. Clinical and laboratory adverse events were assessed.After oral administration of 240 mg fimasartan, the mean area under the plasma concentration-time curve from time zero to infinity (AUC(0→∞)) was 2899.0 ng/ml/h in the older, which was significantly greater than in young subjects (1767.4 ng/ml/h; p = 0.03). The geometric mean AUC(0→∞) was 69.4% higher in older than in young subjects. The maximum plasma concentration (C(max)), time to reach C(max) and elimination half-life for fimasartan did not differ significantly between the older and young groups. Importantly, fimasartan was well tolerated during this study.While some PK parameters were statistically different between the two groups, the effect of age on the PK was modest (e.g., AUC increasetwofold in older subjects).

An improved method for determining levels of levosulpiride in human plasma using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was developed and validated. The protein precipitation method was used for plasma sample preparation. Levosulpiride and an internal standard (IS) were isocratically separated on a UPLC BEH C(18) column with a mobile phase of ammonium formate buffer (1mM, adjusted to pH 3 with formic acid) and acetonitrile (60:40, v/v). MS/MS detection was performed by monitoring the parent-->daughter pair of levosulpiride and the IS at m/z 342-->112 and 329-->256, respectively. The method was linear from 2.5 to 200ng/mL and exhibited acceptable precision and percent recovery. The method was successfully demonstrated in pharmacokinetic and bioequivalence studies of two levosulpiride oral formulations administered to healthy volunteers. When compared to the previous LC-MS methods, the proposed method is faster, well-validated, and uses lesser plasma volume and a similar sensitivity. The use of UPLC allowed rapid and sensitive quantification of levosulpiride, making this method suitable for high-throughput clinical applications.

A rapid, specific, and sensitive method utilizing reversed-phase ultra-performance liquid chromatography tandem mass spectrometry (UPLC–MS/MS) was developed and validated to determine finasteride levels in human plasma. The plasma samples were prepared by liquid–liquid extraction with ethyl acetate, evaporation, and reconstitution. MS/MS analyses were performed on a triple–quadrupole tandem mass spectrometer by monitoring protonated parent → daughter ion pairs at m/z 373 → 305 for finasteride and m/z 237 → 194 for carbamazepine (internal standard, IS). The method was validated with respect to linearity, recovery, specificity, accuracy, precision, and stability. The method exhibited a linear response from 0.1 to 30 ng/mL ( r 2 > 0.998). The limit of quantitation for finasteride in plasma was 0.1 ng/mL. The relative standard deviation (RSD) of intra- and inter-day measurements was less than 15% and the method was accurate within −6.0% to 2.31% at all quality-control levels. The mean extraction recovery was higher than 83% for finasteride and 84% for the IS. Plasma samples containing finasteride were stable under the three sets of conditions tested and the processed samples were stable up to 29 h in an autosampler at 5 °C. Detection and quantitation of both analytes within 3 min make this method suitable for high-throughput analyses. The method was successfully applied to a pharmacokinetic study of finasteride in healthy volunteers following oral administration.

In this work, we introduce an approach to detect vehicles for driver assistance, or warning system. For driver assistance system, it must detect both lanes (left and right side lane), and discover vehicles ahead of the test vehicle. Therefore, in this study, we use a camera, it is installed on the windscreen of the test vehicle. Images from the camera are used to detect three lanes, and detect multiple vehicles. In lane detection, line detection and vanishing point estimation are used. For the vehicle detection, we combine the horizontal and vertical edge detection, the horizontal edge is used to detect the vehicle candidates, and then the vertical edge detection is used to verify the vehicle candidates. The proposed algorithm works with of 480 × 640 image frame resolution. The system was tested on the highway in Korea.

A liquid chromatographic method for analysis of pazufloxacin mesilate in human plasma and urine has been developed and validated for selectivity, sensitivity, accuracy, precision, and stability in pharmacokinetic analysis. The sensitivity of the method was 0.02 μg mL−1 in plasma and 0.5 μg mL−1 in urine, with overall intra-day and inter-day precision (RSD

Generally, LCD(liquid crystal display) driver IC(integrated circuit) requires high voltage of more than 10V and adopts MTI(middle trench isolation) scheme which is deeply trenched to get isolation characteristics on the high voltage according to chip shrinkage. The Vth(Threshold Voltage) shift of HV devices after HTOL(high temperature operating life time) becomes much more serious hazard for product reliability. HV p-channel MOSFET(PMOS) with trench isolation scheme are especially sensitive to these Vth shift issues caused by HEIP. It was found that electron trapping at interface between sidewall oxide and nitride liner in middle trench isolation(MTI) induces channel shorting due to punch through by lowering Vth at the corner of transistor, thereby resulting in the leakage current. This leakage current increment caused by Vth shift makes logic function fail. In this paper, we propose the optimized sidewall thickness and the effectiveness of additional ion implant process which have strong resistance against hot electron induced punch through regarding that offset leakage current is increased after HTOL(high temperature operating lifetime) stressing test for devices prepared with MTI processing scheme.

The c-Myc oncoprotein functions as a transcription factor that can transform normal cells into tumor cells, as well as playing a direct role in normal cell proliferation. The c-Myc protein transactivates cellular promoters by recruiting nuclear cofactors to chromosomal sites through an N-terminal transactivation domain. We have previously reported the identification and functional characterization of four different c-Myc cofactors: TRRAP, hGCN5, TIP49, and TIP48. Here we present the identification and characterization of the actin-related protein BAF53 as a c-Myc-interacting nuclear cofactor that forms distinct nuclear complexes. In addition to the human SWI/SNF-related BAF complex, BAF53 forms a complex with TIP49 and TIP48 and a separate biochemically distinct complex containing TRRAP and a histone acetyltransferase which does not contain TIP60. Using deletion mutants of BAF53, we show that BAF53 is critical for c-Myc oncogenic activity. Our results indicate that BAF53 plays a functional role in c-Myc-interacting nuclear complexes.

Cyclosporine is an immunosuppressant drug used in organ transplants or for the treatment of autoimmune diseases. We developed and validated a simple, sensitive, and specific method using UPLC-MS/MS to determine cyclosporine levels in human whole blood. MS/MS detection was performed in the positive electrospray ionization mode with multiple reaction monitoring. Cyclosporine was extracted from whole-blood samples using ascomycin as an internal standard. The mass transitions m/z 1203.49 → 1185.53 and m/z 814.71 → 796.67 were used to assay the analyte and IS. This method was validated with respect to linearity, specificity, accuracy, precision, recovery, and stability. The method exhibited a linear response from 10 to 1000 ng mL(-1) with correlation coefficient values >0.99. The precision and the accuracy values were within 15%, except at the lower limit of quatification (LLOQ). Cyclosporine was stable in whole blood with no evidence of degradation. This method was successfully applied to a pharmacokinetic study of cyclosporine in healthy volunteers following oral administration.

The ATM-related TRRAP protein is a component of several different histone acetyltransferase (HAT) complexes but lacks the kinase activity characteristic of other ATM family members. We identified a novel function for this evolutionarily conserved domain in its requirement for the assembly of a functional HAT complex. Ectopic expression of TRRAP protein with a mutation in the ATM-related domain inhibits Myc-mediated oncogenic transformation. The Myc-binding region of TRRAP maps to a separable domain, and ectopic expression of this domain inhibits cell growth. These findings demonstrate that the ATM-related domain of TRRAP forms a structural core for the assembly and recruitment of HAT complexes by transcriptional activators.

Drug-induced torsades de pointes (TdP), a life-threatening arrhythmia associated with prolongation of the QT interval, has been a significant reason for withdrawal of several medicines from the market. Prolongation of the QT interval is considered as the best biomarker for predicting the torsadogenic risk of a new chemical entity. Because of the difficulty assessing the risk for TdP during drug development, we evaluated the metabolic phenotype for predicting QT prolongation induced by sparfloxacin, and elucidated the metabolic pathway related to the QT prolongation. We performed electrocardiography analysis and liquid chromatography-mass spectroscopy-based metabolic profiling of plasma samples obtained from 15 guinea pigs after administration of sparfloxacin at doses of 33.3, 100, and 300 mg/kg. Principal component analysis and partial least squares modelling were conducted to select the metabolites that substantially contributed to the prediction of QT prolongation. QTc increased significantly with increasing dose (r = 0.93). From the PLS analysis, the key metabolites that showed the highest variable importance in the projection values (>1.5) were selected, identified, and used to determine the metabolic network. In particular, cytidine-5'-diphosphate (CDP), deoxycorticosterone, L-aspartic acid and stearic acid were found to be final metabolomic phenotypes for the prediction of QT prolongation. Metabolomic phenotypes for predicting drug-induced QT prolongation of sparfloxacin were developed and can be applied to cardiac toxicity screening of other drugs. In addition, this integrative pharmacometabolomic approach would serve as a good tool for predicting pharmacodynamic or toxicological effects caused by changes in dose.

Bo-yang-hwan-o-tang (BHT) is an oriental herbal medicine for treating brain disorders such as cerebral ischemia. The objective of this study was to develop an economically feasible and time-saving high-throughput screening method to monitor the potential inhibitory effects of BHT on human cytochrome P450 (CYP) enzymes in vitro. Two cocktail sets were used for incubation of human liver microsomes: Cocktail A: 6 probe substrates for CYP1A2, CYP2A6, CYP2C8, CYP2C19, CYP2D6, CYP3A4; Cocktail B: 3 for CYP2B6, CYP2C9, CYP2E1. The concentrations of the substrate metabolites were simultaneously analyzed using UPLC/MS/MS. The BHT extract had almost negligible inhibitory effects on the nine human CYP isoforms tested, with the half-maximal inhibitory concentration value ranged from 3624.99 to 45412.44 μg/ml. The results suggest that BHT extract has no inhibitory effects on CYP isoforms within the clinically recommended dosage range. We conclude that BHT might be free of drug-herb interactions when co-administered with other medicines. However, more in vivo human studies are needed to confirm these results. The high-throughput screening method can be a useful tool for drug discovery and for understanding drug interactions.

In metabolomic research, it is important to reduce systematic error in experimental conditions. To ensure that metabolomic data from different studies are comparable, it is necessary to remove unwanted systematic factors by data normalization. Several normalization methods are used for metabolomic data, but the best method has not yet been identified. In this study, to reduce variation from non-biological systematic errors, we applied 1-norm, 2-norm, and quantile normalization methods to liquid chromatography-mass spectrometry (LC-MS)-based metabolomic data from human urine samples after oral administration of cyclosporine (high- and low-dose) in healthy volunteers and compared the effectiveness of the three methods. The principal component analysis (PCA) score plot showed more obvious groupings according to the cyclosporine dose after quantile normalization than after the other two methods and prior to normalization. Quantile normalization is a simple and effective method to reduce non-biological systematic variation from human LC-MS-based metabolomic data, revealing the biological variance.

HMC05, a formulation containing eight different herbal extracts, has been used widely for several thousand years in China, Japan, and Korea as a remedy for hypertension and headache. Although its anti-inflammatory effects in mouse monocytic cell lines and anti-atherosclerotic effects in apoE-knockout mice have been reported, the pharmacodynamic effects of HMC05 in human subjects have not yet been investigated. We evaluated the efficacy and tolerability of this drug in 14 healthy male Korean subjects with normal or high-normal blood pressure (BP) in a randomized, single-blind, crossover study with a 2-week washout period. Four 500-mg tablets of HMC05 or placebo were orally administered three times daily to nine subjects with normal BP and five subjects with high-normal BP for 4 weeks. To assess the pharmacodynamic effects of HMC05, levels of high-sensitivity C-reactive protein and homocysteine, BP, and flow-mediated vasodilation were measured before and after the 4-week medication period with evaluation of tolerability. All 14 subjects completed the study, and HMC05 was well tolerated with no significant adverse events. HMC05 did not exhibit a significant BP-lowering effect in either BP group, and there were no significant differences in other pharmacodynamic values after HMC05 or placebo administration in the two groups. Further study is needed to evaluate the efficacy and tolerability of HMC05 in an adequate number of patients with hypertension.

We demonstrate that transformation-transactivation domain-associated protein (TRRAP) binding and the recruitment of histone H3 and H4 acetyltransferase activities are required for the transactivation of a silent telomerase reverse transcriptase (TERT) gene in exponentially growing human fibroblasts by c-Myc or N-Myc protein. However, recruitment of TRRAP by c- or N-Myc is dispensable for the partial induction of several basally expressed genes in exponentially growing primary and immortalized fibroblasts. Furthermore, recruitment of TRRAP is required for c-Myc- or N-Myc-mediated oncogenic transformation but not for the partial restoration of the growth defect in myc-null fibroblasts. A segment of the adenovirus E1A protein fused to a transformation-defective N-Myc protein carrying a small deletion in the transactivation domain specifically restores interaction with TRRAP, activates the silent TERT gene, induces acetylation of histones H3 and H4 at the TERT promoter, and transforms primary cells. Accordingly, wild-type L-Myc is much less efficient in TRRAP binding, activation of the silent TERT gene, and transformation of primary fibroblasts. Nevertheless, L-Myc is a potent activator of several basally expressed genes and can fully restore the growth defect of myc-null cells. These results suggest a differential requirement for TRRAP for several Myc-mediated activities.

Ho-Seob Lihm 1† , Jaemin Cha 2,3† , Jeong Ju Seo 2,3 , Jeonghyeon Park 2,3 , Joomi Lee 2,3 , Hae Won Lee, Kyun Seop Bae, Woomi Kim, Young-Ran Yoon Department of Family Medicine, Kosin University College of Medicine, Busan, Department of Biomedical Science, Kyungpook National University Graduate School, Daegu, 3 Clinical Trial Center, Kyungpook National University Hospital, Daegu, Department of Clinical Pharmacology & Therapeutics, Asan Medical Center, Seoul, Department of Pharmacology, Kosin University College of Medicine, Busan