Successful screening of large encoded combinatorial libraries leading to the discovery of novel p38 MAP kinase inhibitors

Screening of more than 2 million compounds comprising 41 distinct encoded combinatorial libraries revealed a novel structural class of p38 mitogen-activated protein (MAP) kinase inhibitors. The methodology used for screening large encoded combinatorial libraries combined with the statistical interpretation of screening results is described. A strong preference for a particular triaminotriazine aniline amide was discovered based on biological activity observed in the screening campaign. Additional screening of a focused follow-up combinatorial library yielded data expanding the unique combinatorial SAR and emphasizing an extraordinary preference for this particular building block and structural class. The preference is further highlighted when the p38 inhibitor data set is compared to data obtained for a panel of other kinases.     

Deviations from linearity in statistical evaluation of linearity in assay validation

Linearity and linear range are the key evaluations of the accuracy in assay validation. The average deviation from linearity (ADL) and the sum of squares of deviations from linearity (SSDL) have been proposed for assessment of the linearity. However, both ADL and SSDL do no consider the variability of the assay for evaluation of linearity. Therefore, we proposed the coefficient of variation of deviations from linearity (CVDL) as an alternative measure for the linearity assessment. For the inference of evaluation of linearity, we proposed testing procedures based on generalized pivotal quantities (GPQ) of ADL and CVDL for evaluation of linearity. The simulation studies were conducted to empirically investigate the size and power between the three methods. The simulation results show that all three methods adequately control size. However, the ADL method is uniformly more powerful than the other two methods. A numeric example illustrates the proposed methods. Copyright © 2009 John Wiley & Sons, Ltd.     

Free energy in vertically aligned liquid crystal mode

Vertical alignment (VA) is a widely applied operation mode for liquid crystal displays. To achieve optimum brightness, the electrode of VA is often patterned with fish-bone fine slits to generate fringe field, so the negative liquid crystal aligns along the fine slits when the electric field is applied. VA is usually simply modelled by the bend geometry along the cell gap. However, defects, domain boundaries and periodical splay induced by the fine slits also exist in real pixels and disturb the liquid crystal alignment. Polymer-stabilised VA test cells with various fine slit pitches which lead to various strength of fringe field were fabricated to observe the deformation of liquid crystal. Then the models of liquid crystal deformation nearby the defects and in the fine slit area were proposed to calculate the electromagnetic (f_EM) and elastic free energy (f_elastic). The results show that the key factor to regulate f_EM and f_elastic is the pitch of the fine slits, and the optimum liquid crystal alignment is obtained when f_EM and f_elastic are equal. The models are useful for further investigation on the dynamics of liquid crystal alignment and applications in industrial products.     

Morphology and crystallization behavior of poly(l‐lactide)/poly(butylene oxalate) blends

The isothermal crystallization of poly(l ‐lactide) (PLLA) in blends with poly(butylene oxalate) (PBOX) is investigated by time‐resolved small‐angle X‐ray scattering, differential scanning calorimetry, and optical microscopy. We focus on the temperatures at which only PLLA crystallizes while PBOX is amorphous. It is obtained that the addition of PBOX causes a reduction of the melting temperature of PLLA. The lamellar thickness of PLLA crystals decreases whereas the amorphous layer thickness increases with blend composition, suggesting the occurrence of the interlamellar incorporation upon the addition of PBOX. The crystal growth rate and morphology of PLLA/PBOX blends are analyzed by polarized optical microscopy. The spherulite growth rate of PLLA is found to increase with the addition of PBOX. Analysis of the isothermal crystallization in terms of the Lauritzen and Hoffman equation give the reduction of the fold surface free energy upon the addition of PBOX in PLLA, indicating that the mobility of the PLLA chains is significantly improved due to the presence of PBOX. © 2014 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2015 , 53, 192–202     

Organic–Inorganic Hybrid Zinc Phosphate with 28‐Ring Channels

An organic–inorganic hybrid zinc phosphate with 28‐ring channels was synthesized by use of an organic ligand instead of organic amine template under a hydro(solvo)thermal condition. This crystalline zinc phosphate contains large channels constructed from 28 zinc and phosphate tetrahedral units. The walls of the channels consist of two types of zincophosphate chains, in which the Zn atoms are coordinated by 2,4,5‐tri(4‐pyridyl)‐imidazole ligands as pendent groups. This compound exhibits yellow emission and interesting properties of removing cobalt, cadmium, and mercury cations from aqueous solution. A new two‐dimensional organic–inorganic hybrid zincophosphate was also obtained by changing the solvent mixture ratios in the synthesis.     

Gold and Silver Nanomaterial‐Based Optical Sensing Systems

Gold and silver nanomaterials (NMs) such as nanoparticles (NPs) and nanoclusters (NCs) possessing interesting optical properties have become popular sensing materials. With strong surface plasmon resonance (SPR) absorption, extraordinary stability, ease in preparation, conjugation, and biocompatibility, Au NPs are employed to develop sensitive and selective sensing systems for a variety of analytes. However, small sizes of Au and Ag NCs with interesting photoluminescence (PL) properties are used in many PL‐based sensing systems for the detection of important analytes. In addition, many bimetallic AuM NMs possessing strong catalytic activity are used to develop highly sensitive fluorescent sensors. This review article is categorized in four sections based on the NMs used in the sensing systems, including Au NPs, bimetallic AuM NMs, Au NCs, and DNA–Ag NCs. In each section, synthetic strategies and optical properties of the NMs are provided briefly, followed by emphasis on their analytical applications in the detection of small molecules, metal ions, DNA, proteins, and cells. Current challenges and future prospects of these NMs‐based sensing systems will be addressed.     

Maxima in hypercubes

We derive a Berry‐Esseen bound, essentially of the order of the square of the standard deviation, for the number of maxima in random samples from (0,1)^d. The bound is, although not optimal, the first of its kind for the number of maxima in dimensions higher than two. The proof uses Poisson processes and Stein's method. We also propose a new method for computing the variance and derive an asymptotic expansion. The methods of proof we propose are of some generality and applicable to other regions such as d‐dimensional simplex. © 2005 Wiley Periodicals, Inc. Random Struct. Alg., 2005