Antiangiogenic Activity and in Silico Cereblon Binding Analysis of Novel Thalidomide Analogs

Due to its antiangiogenic and anti-immunomodulatory activity, thalidomide continues to be of clinical interest despite its teratogenic actions, and efforts to synthesize safer, clinically active thalidomide analogs are continually underway. In this study, a cohort of 27 chemically diverse thalidomide analogs was evaluated for antiangiogenic activity in an ex vivo rat aorta ring assay. The protein cereblon has been identified as the target for thalidomide, and in silico pharmacophore analysis and molecular docking with a crystal structure of human cereblon were used to investigate the cereblon binding abilities of the thalidomide analogs. The results suggest that not all antiangiogenic thalidomide analogs can bind cereblon, and multiple targets and mechanisms of action may be involved.     

A simple model for a two-stage chemical reaction with diffusion

We analyse the evolution of a two-stage chemical reaction betweentwo neighbouring plumes of reactants. Under the assumption thatthe plumes are approximately Gaussian we derive a system ofordinary differential equations for the total amount, the centroidand the variance of each reactant. We compare the solution ofthese equations with full numerical simulation of the reaction.Excellent agreement is obtained, with solution of the near-Gaussianmodel requiring considerably less computational effort thanthe full simulations. Of key importance is the yield of thereaction, and we discuss this feature in particular.     

Measurement of the K S mean lifetime from π+π− and π0π0 decays using K L decays to determine the acceptance

A precision measurement of the K _S mean lifetime has been performed by comparing, in the same experimental setup, the distributions of two-pion decays of neutral kaons produced by high energy proton-beryllium interactions in two targets at a relative distance variable between 112 and 160 m. The value obtained combining the results from π⁺π^? and π⁰π⁰ decays is τ_s = (0.8971 ± 0.0021) 10^?10 s.     

Imaging cytoplasmic cAMP in mouse brainstem neurons

Background  

cAMP is an ubiquitous second messenger mediating various neuronal functions, often as a consequence of increased intracellular Ca²⁺ levels. While imaging of calcium is commonly used in neuroscience applications, probing for cAMP levels has not yet been performed in living vertebrate neuronal tissue before.     

Some addition reactions of pentafluorothiophenol and pentafluorobenzenesulfenyl chloride

The addition reactions of pentafluorothiophenol, C₆F₅SH, and pentafluorobenzenesulfenyl choloride, C₆F₅SCl, with various unsaturated systems, including alkenes, alkynes, oxiranes, thiiranes, diazo compounds, aldehydes, ketones, and nitriles have been examined. The physical properties of the new compounds are reported together with some spectroscopic data.     

Approximate quantum cloning with nuclear magnetic resonance

Here we describe a nuclear magnetic resonance (NMR) experiment that uses a three qubit NMR device to implement the one-to-two approximate quantum cloning network of Buzek et al. [Phys. Rev. A 56, 3446 (1997)]. As expected the experimental results indicate that the network clones all input states with similar fidelities, but as a result of decoherence and incoherent evolution arising from B(1) inhomogeneity the total fidelity achieved does not exceed the measurement bound.     

Reactions of some nitrofluoroaromatics with the methanethiolate anion

Previous studies on the reactions of simple fluoroaromatics, C₆F_xH_6?x′ with sodium methanethiolate in an ethylene glycol/pyridine solvent mixture have shown that at least two fluorine atoms remained C₆F₅H + SMe^? → C₆F₂H(SMe)₂ on the aromatic ring. When the reactions of simple nitrofluoroaromatics, C₆F_xH_yNO₂ were studied under the same conditions stepwise replacement of all the aromatic fluorines was observed. This clearly demonstrates the activating effect of the nitro group in these reactions, and is in marked contrast to the deactivating effect of the amino group observed previously in analogous reactions of the fluoroaniline. Details of these reactions will be discussed. In one case the expected substitution was not observed and an azoxybenzene was formed.

The methylthio group can readily be oxidized, but

simple reduction of the nitrogroup to an amino group was not feasible.All the new compounds isolated have been characterized by chemical analysis and mass spectroscopy. The structures have been determined by NMR spectroscopy usually proton and/or fluorine, but in cases of ambiguity the carbon-13 spectra have also been examined.     

Hadron accelerators for radiotherapy

Over the last twenty years the treatment of cancer with protons and light nuclei such as carbon ions has moved from being the preserve of research laboratories into widespread clinical use. A number of choices now exist for the creation and delivery of these particles, key amongst these being the adoption of pencil beam scanning using a rotating gantry; attention is now being given to what technologies will enable cheaper and more effective treatment in the future. In this article the physics and engineering used in these hadron therapy facilities is presented, and the research areas likely to lead to substantive improvements. The wider use of superconducting magnets is an emerging trend, whilst further ahead novel high-gradient acceleration techniques may enable much smaller treatment systems. Imaging techniques to improve the accuracy of treatment plans must also be developed hand-in-hand with future sources of particles, a notable example of which is proton computed tomography.     

Exchange and correlation in density functional theory and quantum chemistry

The nature of exchange, dynamic correlation (DC) and left–right correlation (LRC) is considered in density functional theory and wavefunction‐based quantum chemistry. The presence of LRC in approximate exchange density functionals is highlighted and the separation of LRC and DC is considered. For H₂, the Heitler–London approach is shown to include the essential elements of exchange and LRC. The arguments are illustrated by a comparison of Gaussian orbital s‐optimised Heitler–London and OPTX potential energy curves. They agree well near equilibrium, but differ at large distances due to the inability of the OPTX form to describe the dissociation process. LRC and DC values determined using the two approaches are compared. The influence of higher angular momentum functions in the Heitler–London approach is then investigated (commonly called self‐consistent valence bond); the agreement with OPTX degrades, leading to a larger value of LRC and a smaller value of DC at H₂ equilibrium. © 2009 Wiley Periodicals, Inc. Int J Quantum Chem, 2011