New insights in the activation of human cholesterol esterase to design potent anti-cholesterol drugs

Primary hypercholesterolemia is the root cause for major health issues like coronary heart disease and atherosclerosis. Regulating plasma cholesterol level, which is the product of biosynthesis as well as dietary intake, has become one of the major therapeutic strategies to effectively control these diseases. Human cholesterol esterase (hCEase) is an interesting target involved in the regulation of plasma cholesterol level and thus inhibition of this enzyme is highly effective in the treatment of hypercholesterolemia. This study was designed to understand the activation mechanism that enables the enzyme to accommodate long chain fatty acids and to identify the structural elements for the successful catalysis. Primarily the activation efficiencies of three different bile salts were studied and compared using molecular dynamics simulations. Based on the conformations of major surface loops, hydrogen bond interactions, and distance analyses, taurocholate was concluded as the preferred activator of the enzyme. Furthermore, the importance of two bile salt binding sites (proximal and remote) and the crucial role of $7\upalpha $ -OH group of the bile salts in the activation of hCEase was examined and evidenced. The results of our study explain the structural insights of the activation mechanism and show the key features of the bile salts responsible for the enzyme activation which are very useful in hypolipidemic drug designing strategies.     

White phosphorescent organic light-emitting diodes using double emissive layer with three dopants for color stability

We fabricate white phosphorescent organic light-emitting diodes （PHOLEDs） with three dopants and double emissive layer （EML） to achieve color stability. The white PHOLEDs use FIrpic dopant for blue EML （B- EML）, and Ir（ppy）3：Ir（piq）3 dopants for green：red EML （GR-EML） with N,N＇-dicarbazolyl-3, 5-benzene （mCP） as host material. Thicknesses of B-EML and GR-EML are adjusted to form a narrow recombination zone at two EML＇s interface and charge trapping happens in EML according to wide highest occupied molecular orbital and/or lowest unoccupied molecular orbital energy band gap of mCP and smaller energy band gap of dopants. The total thickness of both EMLs is fixed at 30 nm in the device structure of ITO （150 nm）/MoO3 （2 nm）/N,N＇-diphenyl-N,N＇-bis（1-naphthyl-phenyl）-（1,1″-biphenyl）-4, 4＇-diamine （70 nm）/ meP：Firpic-8.0% （12 nm）/mCP：Ir（ppy）3-3.0%：Ir（piq）3-1.5% （18 nm）/2″,2＇,2＂＇-（1,3,5-benzinetriyl）-tris（1- phenyl-l-H-benzimidazole） （30 nm）/8-hydroxyquinolinolato-lithium （2 nm）/A1 （120 nm）. White PHOLED shows 18.25 cd/A of luminous efficiency and white color coordinates of （0.358 and 0.378） at 5000 cd/m2 and color stability with slight CIExy change of （0.028 and 0.002） as increasing luminance from 1000 to 5000 cd/m^2.     

Bochner–Riesz Means with Respect to a Generalized Cylinder

We study the L ^p boundedness of the generalized Bochner–Riesz means S ^λ which are defined as $$S^{\lambda}f(x) = \mathcal{F}^{-1} \left[\left(1 - \rho \right)_{+}^{\lambda} \widehat{f} \right](x)$$ where ${\rho(\xi) = {\rm max}\{|\xi_{1}|, \ldots, |\xi_{\ell}|\}}$ for ${\xi = (\xi_{1},\ldots, \xi_{\ell}) \in \mathbb{R}^{{d}_{1}} \times \cdots \times \mathbb{R}^{{d}_{\ell}}}$ and ${\mathcal{F}^{-1}}$ is the inverse Fourier transform.     

Development and validation of a multiresidue method for determination of 82 pesticides in water using GC

Several methods used for the multiresidue analysis of pesticides from the environment and drinking water have been reported. However, most of these reports dealt with a small number of targeted pesticides or some special groups. A method that is simple, faster, and more cost‐effective than the environmental protection agency (EPA) method has been developed for the analysis of 82 frequently used pesticides in water samples obtained from Yeongsan and Sumjin rivers, as well as rice fields located in various locations around the two rivers. The samples were extracted by dichloromethane, and the pesticides were analyzed using a GC‐electron capture detector (ECD), followed by confirmation with GC‐MS. Recoveries were found to be between 82 and 120.1% for most of the tested pesticides, which were in agreement with the standard values dictated by the EPA. The method was potentially applied to 66 water samples for human consumption and 90 water samples from the rice fields and irrigation ditches that were collected from June to September 2007. Oxadiazon, butachlor, and alachlor were detected in some of the river water samples collected in June, iprobenfos (IBP) was detected in samples collected in August, and no pesticide was detected in September. On the other hand, chlorpyrifos‐methyl, IBP, hexaconazole, diazinon, oxadiazon, butachlor, and isoprothiolane were detected at relatively high concentrations in 48 rice paddy field water samples collected between June and September 2007. Alachlor in one sample and procymidone in some of the rice paddy field water samples were also detected in trace amounts. The results were consistent with the temporal pattern of pesticide application in Korean rice fields.     

Biophysical evaluation of two red-shifted hypocrellin B derivatives as novel PDT agents

Two novel cyclohexane-1,2-diamino and N,N dimethyl amino-propyl substituted hypocrellin B derivatives, abbreviated as CHA2HB and DMAHB, respectively were synthesized. These derivatives exhibited enhanced absorption in phototherapeutic window. Photodynamic action of these derivatives, investigated using optical and electron spin resonance methods, depended on both Type I and Type II mechanisms. Gel electrophoresis indicated 1O2/O2(.-) mediated DNA damage. CHA2HB displayed 20 fold increase in light dependent cytotoxicity on colon cancer cell line (HCT 116) than the well-known hypocrellin B (HB). The light induced, LD(50) values for CHA2HB and DMAHB were found to be 0.1 microM and 1.5 microM, respectively. The singlet oxygen generating efficiency followed the order HB>CHA(2)HB>DMAHB. But, the enhanced red absorption as well as the hydrophilicity renders the CHA2HB a better photodynamic therapeutic agent.     

Interface modification of polymer stabilized cholesteric liquid crystal

Films were made by incorporating various quantities of fluoroalkyl acrylate (FA) into the chain termini of polyurethane acrylate oligomer of polymer stabilized cholesteric liquid crystals (PSCLCs). The effects of switching voltage, scanning electron and polarized optical microscope morphologies, texture transition and reversibility, and contact angle of the films were then studied. It was found that the switching voltage of the film decreased with the addition of FA up to 0.8 wt%, beyond which it increased. The decrease and increase were respectively explained in terms of decreased interface energy as noted from the contact angle of the LC on polymer surface, and too small droplet size as noted from the SEM. Copyright © 2008 John Wiley & Sons, Ltd.     

Pt-polyaniline nanocomposite on boron-doped diamond electrode for amperometic biosensor with low detection limit

Boron-doped diamond electrodes covered with a nanostructured Pt nanoparticle-polyaniline composite have been fabricated and employed as sensitive amperometric sensors with low detection limit. A highly conductive boron-doped diamond thin film (BDD) was prepared by chemical vapor deposition, and its morphology was characterized by scanning electron microscopy and transmission electron microscopy. The nanostructured composite layer was grown on the BDD electrode by electrochemical deposition of polyaniline and Pt nanoparticles. Glucose oxidase (GOx) was then adsorptively immobilized on the modified BDD electrode. The biosensor displays a large surface area, high catalytic activity of the Pt nanoparticles, efficient electron mediation through the conducting polymer, and low background current of the electrode. The biosensor exhibits an excellent response to glucose, with a broad linear range from 5.9 μM to 0.51 mM, a sensitivity of 5.5 μA·mM^?1, a correlation coefficient (R) of 0.9947, and a detection limit of 0.10 μM. The apparent Michaelis-Menten constant (K _M ^app ) and the maximum current density of the electrode are 4.1 mM and 0.021 mA, respectively. This suggests that the immobilized GOx possesses a higher affinity for glucose at the lower K _M ^app , and that the enzymatic reaction rate constitutes the rate-limiting step of the response.     

Asymmetric polymer electrolyte membranes for water management of fuel cells

Water management is one of the critical issues of polymer electrolyte membrane fuel cells because dehydration of a membrane increases membrane-resistance whereas excessive water flooding at the cathode impedes the gaseous diffusion of oxygen to reaction sites at the wetted catalyst surface. In this study, we have developed an asymmetric polymer electrolyte membrane that facilitates water management. The structural modification of the membrane strongly affected water management, due primarily to the fact that water must move through the membrane during fuel cell operation. The asymmetric membrane improved transport of water from the cathode to the anode when the hydrophilic side of the membrane located to the cathode, thereby enhancing overall fuel cell performance under both fully humidified and non-humidified conditions.     

Parathyroid hormone accelerates decompensation following left ventricular hypertrophy

Parathyroid hormone (PTH) treatment was previously shown to improve cardiac function after myocardial infarction by enhancing neovascularization and cell survival. In this study, pressure overload-induced left ventricular hypertrophy (LVH) was induced in mice by transverse aortic banding (TAB) for 2 weeks. We subsequently evaluated the effects of a 2-week treatment with PTH or saline on compensated LVH. After another 4 weeks, the hearts of the mice were analyzed by echocardiography, histology, and molecular biology. Echocardiography showed that hearts of the PTH-treated mice have more severe failing phenotypes than the saline-treated mice following TAB with a greater reduction in fractional shortening and left ventricular posterior wall thickness and with a greater increase in left ventricular internal dimension. Increases in the heart weight to body weight ratio and lung weight to body weight ratio following TAB were significantly exacerbated in PTH-treated mice compared to saline-treated mice. Molecular markers for heart failure, fibrosis, and angiogenesis were also altered in accordance with more severe heart failure in the PTH-treated mice compared to the saline-treated mice following TAB. In addition, the PTH-treated hearts were manifested with increased fibrosis accompanied by an enhanced SMAD2 phosphorylation. These data suggest that the PTH treatment may accelerate the process of decompensation of LV, leading to heart failure.