Molecular and absolute crystal structure of pindolol-1-(1H-indol-4-yloxy)-3-[(1-methylethyl)amino]-2-propanol: A specific beta-adrenoreceptor antagonist with partial agonist activity

The crystal and molecular structure of pindolol, 1-(1H indol-4-yloxy)-3-[(1-methylethyl)amino]-2-propanol, has been determined by direct methods. Crystals are tetragonal, ,a=b=15.809(4),c=11.246(2) Å,Z=8,D _c=1.174 mg m^–3. The finalR-factor for 2271 reflections withI>2(I) is 0.038. Refinement by full-matrix least-squares on F² also enabled the absolute configuration of the structure to be established. The molecule is essentially planar, including much of the side-chain which is stabilized by the existence of two intramolecular H-bonds, between the ethyl oxygen and OH group, and between the OH and side-chain amide groups, respectively. The crystal structure is formed by three intermolecular hydrogen bonds including two side-chain-side-chain interactions, between ethyl oxygen to amide and OH to amide, and an interaction between the side-chain OH to indole NH.     

Euphorbiasteroid Abrogates EGFR and Wnt/β-Catenin Signaling in Non-Small-Cell Lung Cancer Cells to Impart Anticancer Activity

EGFR and Wnt/β-catenin signaling pathways play a prominent role in tumor progression in various human cancers including non-small-cell lung carcinoma (NSCLC). Transactivation and crosstalk between the EGFR and Wnt/β-catenin pathways may contribute to the aggressiveness of cancers. Targeting these oncogenic pathways with small molecules is an attractive approach to counteract various types of cancers. In this study, we demonstrate the effect of euphorbiasteroid (EPBS) on the EGFR and Wnt/β-catenin pathways in NSCLC cells. EPBS induced preferential cytotoxicity toward A549 (wildtype EGFR-expressing) cells over PC-9 (mutant EGFR-expressing) cells. EPBS suppressed the expression of EGFR, Wnt3a, β-catenin, and FZD-1, and the reduction in β-catenin levels was found to be mediated through the activation of GSK-3β. EPBS reduced the phosphorylation of GSK-3β^S9 with a parallel increase in β-TrCP and phosphorylation of GSK-3β^Y216. Lithium chloride treatment increased the phosphorylation of GSK-3β^S9 and nuclear localization of β-catenin, whereas EPBS reverted these effects. Forced expression or depletion of EGFR in NSCLC cells increased or decreased the levels of Wnt3a, β-catenin, and FZD-1, respectively. Overall, EPBS abrogates EGFR and Wnt/β-catenin pathways to impart its anticancer activity in NSCLC cells.     

Recent Advances in Randomness Extraction

The area of randomness extraction has seen interesting advances in recent years, with rapid progress on many longstanding open problems, along with the introduction of many new notions that played a key role in this development. We survey this progress and highlight new definitions and notions that have been the subject of intense study in recent work.     

A validated HPLC‐PDA method for identification and quantification of two bioactive alkaloids,ephedrine and cryptolepine,in different Sida species

A simple, rapid, accurate and reproducible reverse‐phase HPLC method has been developed for the identification and quantification of two alkaloids ephedrine and cryptolepine in different extracts of Sida species using photodiode array detection. Baseline separation of the two alkaloids was achieved on a Waters RP‐18 X‐terra column (250 × 4.6 mm, 5 µm) using a solvent system consisting of a mixture of water containing 0.1% Trifluoroacetic acid (TFA) and acetonitrile in a gradient elution mode with detection at 210 and 280 nm for ephedrine and cryptolepine, respectively. The calibration curves were linear in a concentration range of 10–250 µg/mL for both the alkaloids with correlation coefficient values >0.99. The limits of detection and quantification for ephedrine and cryptolepine were 5 and 10 µg/mL and 2.5 and 5 µg/mL, respectively. Relative standard deviation values for intra‐day and inter‐day precision were 1.22 and 1.04% for ephedrine and 1.71 and 2.06% for cryptolepine, respectively. Analytical recovery ranged from 92.46 to 103.95%. The developed HPLC method was applied to identify and quantify ephedrine and cryptolepine in different extracts of Sida species. Copyright © 2013 John Wiley & Sons, Ltd.     

Instabilities in free-surface electroosmotic flows

Instability of a thin electrolyte film undergoing a direct current electroosmotic flow has been investigated. The film with a compliant electrolyte–air interface is flowing over a rigid charged substrate. Unlike previous studies, inclusion of the Maxwell stresses in the formulation shows the presence of a new finite wavenumber shear-flow mode of instability, alongside the more frequently observed long-wave interfacial mode. The shear mode is found to be the dominant mode of instability when the electrolyte–solid and electrolyte–air interfaces are of opposite charge or of same charge but have very large zeta-potential at the electrolyte–air interface. The conditions for mode-switch (interfacial to shear) and the direction of the travelling waves are discussed through stability diagrams. Interestingly, the analysis shows that when the interfaces are of nearly same zeta potential, the ‘free’ electrolyte–air interface behaves more like a ‘stationary’ wall because of the ion transport in the reverse direction of the flow.     

Two-dimensional electronic transport in In0.53Ga0.47As quantum Wells

Transport properties of the electrons itinerant two dimensionality in a square quantum well of In_0.53Ga_0.47As are studied in the framework of Fermi-Dirac statistics including the relevant scattering mechanisms. An iterative solution of the Boltzmann equation shows that the ohmic mobility is controlled by LO phonon scattering at room temperature, but below 130 K alloy scattering is predominant. The calculated mobilities with a suitable value of the alloy scattering potential agree with the experimental results over a range of lattice temperature. For lattice temperatures below 25 K where the carrier energy loss is governed by the deformation potential acoustic scattering, the warm electron coefficient is found to be negative. Its magnitude decreases with increasing lattice temperature and is greater for larger channel widths. Values of the small-signal AC mobility of hot electrons at a lattice temperature of 4.2 K are obtained for different sheet carrier densities and channel widths. Cut-off frequencies around 100 GHz are indicated.Dedicated to H.-J. Queisser on the occasion of his 60th birthday     

Krichever-Novikov global operator formalism: NSR superstring in curved background

The Neveu-Schwarz-Ramond type II closed superstring is considered to evolve in a curved space-time manifold. The Krichever-Novikov global operator formalism is used to construct the generators of a super-conformal algebra on a Riemann surface . The computation for the quantum algebra of these generators is explicitly presented. It is shown that the theory is free from super-conformal anomalies if the target manifold is ten dimensional and satisfies the Ricci flatness condition.     

Surface Coating Rescues Proteins from Magnetite Nanoparticle Induced Damage

The presence of magnetic nanoparticles (NPs) in physiological systems induces toxicity through its effects on mitochondrial function and reactive oxygen species (ROS) imbalance. Magnetic NP induced cytotoxicity has been elaborately evaluated for impending threats, however, a detailed investigation is lacking. It is shown that the interaction of Fe₃O₄ NPs with cytochrome c can lead to different events based on the NPs to protein ratio, the solution conditions, and the type of surface protection. At low NPs concentration, rapid binding and subsequent electron transfer are the preferred events while at higher concentration slow oxidative modification of the protein is initiated. The slow event of protein modification yields conformational disorientation, loss of stability, and formation of amyloid‐like structures with cytochrome c. The possibility that the NP induced oxidative stress and age can work in concert to compromise different aspects of cellular quality control processes is discussed. Suitable surface modifications of the NPs inhibit their direct binding to the protein molecules and minimize NP induced toxicity.     

Measurement and analysis of excitation functions for alpha-induced reactions in copper

Excitation functions for the production of⁶⁸Ga,⁶⁷Ga,⁶⁶Ga,⁶⁵Ga +⁶⁵Zn and⁶¹Cu fromα-induced reactions in natural copper have been measured in the energy range ≈ 10–40 MeV using the stacked foil technique. A stack of nine copper foils was irradiated by a 40 MeVα-beam. Theγ-rays emitted from the irradiated samples were recorded. Excitation functions have also been calculated theoretically using a statistical model with and without the inclusion of pre-equilibrium emission of particles. Pre-equilibrium component simulated by exciton model shows that the inclusion of pre-equilibrium emission gives better agreement between experimental and theoretical excitation functions. Pre-equilibrium fraction depends on the incident energy and the target mass number.