New combined model for the prediction of regioselectivity in cytochrome P450/3A4 mediated metabolism

Cytochrome P450 3A4 metabolizes nearly 50% of the drugs currently in clinical use with a broad range of substrate specificity. Early prediction of metabolites of xenobiotic compounds is crucial for cost efficient drug discovery and development. We developed a new combined model, MLite, for the prediction of regioselectivity in the cytochrome P450 3A4 mediated metabolism. In the model, the ensemble catalyticphore- based docking method was implemented for the accessibility prediction, and the activation energy estimation method of Korzekwa et al. was used for the reactivity prediction. Four major metabolic reactions, aliphatic hydroxylation, N-dealkylation, O-dealkylation, and aromatic hydroxylation reaction, were included and the reaction data, metabolite information, were collected for 72 well-known substrates. The 47 drug molecules were used as the training set, and the 25 well-known substrates were used as the test set for the ensemble catalyticphore-based docking method. MLite predicted correctly about 76% of the first two sites in the ranking list of the test set. This predictability is comparable with that of another combined model, MetaSite, and the recently published QSAR model proposed by Sheridan et al. MLite also offers information about binding configurations of the substrate-enzyme complex. This may be useful in drug modification by the structure-based drug design.     

Phase-transfer catalytic aza-Michael addition of tert-butyl benzyloxycarbamate to electron-deficient olefins

A highly efficient phase-transfer catalytic aza-Michael addition of tert-butyl benzyloxycarbamate to a wide range of electron-deficient olefins is presented (90-99%).     

Tailoring the porous texture of activated carbons by CO<Subscript>2</Subscript> reactivation to produce electrodes for organic electrolyte-based EDLCs

Highly microporous carbon obtained by KOH etching of carbohydrates exhibited enhanced specific capacitance due to the increased adsorption of electrolyte ions on its large surface, which renders it a promising electrode material. However, the KOH-activated carbon electrode did not achieve its optimum charge capacity in organic electrolytes due to the limited accessibility of the electrolyte ions to the micropores, which hindered the adsorption of ions. The electrode performance was enhanced by enlarging the micropores of KOH-activated carbon to mesopores via reactivation in a stream of CO₂, which allowed the mesopore/micropore ratio to be increased without compromising the originally high specific surface area. The extended amount of mesopores increased the charge capacity of the electrode by enabling the large organic electrolyte ions to access the porous surface, as compared to untreated KOH-activated carbon.     

Zero path-length difference interferometry using filter response of unbalanced interferometer to an amplified spontaneous emission beat noise spectrum

Zero path-length difference interferometry is demonstrated using the filter response of an unbalanced interferometer to the spontaneous/spontaneous beat noise spectrum of an amplified spontaneous emission source. The method is applicable to path-length differences ranging from a few centimeters to several kilometers.     

Carrier frequency offset compensation for uplink of OFDM-FDMAsystems

A frequency offset compensation method for OFDM-FDMA, that can correct offsets after the DFT via circular convolution, is proposed as an alternative to the direct method that corrects frequency offsets by multiplying the complex exponents of the offset estimates before the DFT. In contrast to the direct method whose complexity increases proportional to the number of users, the computational load of the proposed scheme decreases as the number of users increases. It is shown that the proposed method is simpler to implement than the direct method when the number of users is greater than two. Furthermore, the former can outperform the latter, because a frequency offset compensation for one user after the DFT does not affect the data of other users. Computer simulation results demonstrate the advantage of the proposed method     

Design of organic supercapacitors with high performances using pore size controlled active materials

In this study, we thoroughly investigate the required properties of active materials for organic supercapacitors with high performances. In this regard, we synthesize carbon xerogels with different physical properties, including specific surface area and pore size. The carbon xerogels are prepared via the sol-gel reaction of resorcinol and formaldehyde under different gelation temperature conditions. Through Fourier-transform infrared, nitrogen adsorption–desorption, and scanning electron microscopy analysis, we can confirm that carbon xerogels with different physical properties can be successfully synthesized. We apply the prepared carbon xerogels to organic supercapacitor electrodes. As a result of electrochemical experiments, carbon xerogels with high surface area exhibit high electrochemical performances at low-rate charge?discharge processes. However, as the charge–discharge rate increases, carbon xerogels with low surface area and high conductivity exhibit higher performances. Therefore, the surface area of active materials is a key factor for supercapacitors with high performances at low-rate charge–discharge processes. However, the effects of conductivity can be more crucial as compared with those of surface area as the charge–discharge rates increase. In addition, we suggest that the physical properties of active materials should be differently optimized as the charge–discharge rate is employed.     

Design and synthesis of small molecules with difluoroquinoxaline units for OSCs

Abstract

We designed and synthesized three novel small molecule donors (SM1, SM2 and SM3) that consist of thiophene as the electron-donating end group and 6,?7-?difluoroquinoxaline moiety as a novel electron-withdrawing core group. The organic low band gap molecules with 6,?7-?difluoroquinoxaline and thiophene units were synthesized using Stille coupling to generate SM1, SM2 and SM3. The absorption of SM2 and SM3 in solution was red shifted due to increased conjugation length of added thiophene units. In case of SM2 and SM3, introduction of hexyl chain in terminal thiophene units improve solubility in organic solvent. The maximum absorption peaks of SM1, SM2 and SM3 in solid thin films were at 482, 505 and 518?nm, respectively. SM3 was red shifted as compare to SM2 due to increased π-π stacking of electron donor materials.     

Characteristics of Exposure to Chloromethylisothiazolinone (CMIT) and Methylisothiazolinone (MIT) among Humidifier Disinfectant-Associated Lung Injury (HDLI) Patients in South Korea

This study aimed to quantify both chloromethylisothiazolinone (CMIT) and methylisothiazolinone (MIT) dissolved in different product brands and to characterize the exposure to these chemicals among humidifier disinfectant-associated lung injury (HDLI) patients. Both CMIT and MIT dissolved in different humidifier disinfectant (HD) products were quantified using gas chromatography–mass spectrometry. The inhalation level of CMIT and MIT was estimated based on HD-associated factors as reported by HDLI patients. A total of eleven HD products marketed until the end of 2011 were found to contain CMIT and/or MIT. The level of combined CMIT and/or MIT dissolved in these HD products ranged from 12 to 353 ppm. The level varied among HD products and the year of manufacture. The average inhalation levels were estimated to be 7.5, 4.1, and 3.2 μg/m³ for the definite, probable, and possible groups, respectively. If probable and possible groups were collapsed together, the inhalation level of the collapsed group was significantly different from that of the definite group (p < 0.001). All HDLI patients responded as having used HD not only while sleeping, but also as having a humidifier treated with HD within close proximity every day in insufficiently ventilated spaces. These HD use characteristics of patients may be directly/indirectly linked to the HDLI development.     

Experimental study on fluid selection for a stable Taylor cone formation via micro-PIV measurement

In this study, the visualization of the flow inside a Taylor cone formed during an electrohydrodynamic (EHD) spraying is conducted to analyze its stability among five liquid candidates. A micro-PIV with a micro-nozzle is used for the visualization, and the physical properties as well as measured values are utilized in the analysis. First, in forming the Taylor cone, the electrohydrodynamic force is required to be sufficiently large in order to overcome the surface tension of the liquid. Thus, among the five liquids tested here, three, in this case IPA, EtOH, and MeOH, form a Taylor cone due to the relatively low surface tension levels as compared to the others. Once electrohydrodynamic jetting occurs, the average and maximum velocities become monotonically proportional to the average current. As the velocities are the smallest in using IPA, the circulation flow becomes superior to the extrusive flow, which yields the stable formation of a Taylor cone. Also, low fluctuation of the instantaneous currents supports the stable formation of IPA. Consequently, IPA shows the most stable formation of the Taylor cone in our condition due to the lowest average current and low-level surface tension. Eventually, micro-PIV would be a good tool in choosing an optimal fluid for stable EHD spraying.     

Conjugated Polyelectrolyte and Aptamer Based Potassium Assay via Single‐ and Two‐Step Fluorescence Energy Transfer with a Tunable Dynamic Detection Range

A new potassium ion detection assay was developed using a dye‐labeled aptamer and conjugated polyelectrolyte (CPE) as a signaling platform via 1‐step and 2‐step fluorescence resonance energy transfer. Guanine‐rich K⁺‐specific aptamers were designed as K⁺ ion recognition species with 6‐carboxyfluorescein (6‐FAM) and 6‐carboxytetramethylrhodamine (6‐TAMRA) at both termini. In the presence of K⁺ ions, the aptamers undergo a conformational change from an unfolded to folded form by forming a G‐quadruplex with K⁺, bringing two dyes in proximity. FRET‐induced 6‐TAMRA emission was proportional to [K⁺] in a range of 22.5 μm –100 mm in water without interference by the presence of excess Na⁺ ions (100 mm ). Upon the addition of CPE, a two‐step FRET process from CPE to 6‐TAMRA via 6‐FAM was enabled, showing an intensified 6‐TAMRA signal with K⁺ ions. The dynamic detection range and limit of detection (LOD) was fine‐tuned from ～millimolar to ～nanomolar concentrations of K⁺ by modulating the signal amplification effect of CPE. The LOD was determined to be ≈3.0 nm . This detection assay also showed high selectivity against other metal ions. This sensing scheme can be extended to the detection of a wide range of target materials by simply modifying the recognition aptamer sequence.