1‐Arylsulfonyl‐5‐(N‐hydroxyacrylamide)indolines Histone Deacetylase Inhibitors Are Potent Cytokine Release Suppressors

A series of 1‐arylsulfonyl‐5‐(N‐hydroxyacrylamide)indolines ( 7 – 15 ) has been developed; the compounds exhibited potent histone deacetylase (HDAC) inhibitory activities. Notably, almost all of this series exhibited better HDAC‐inhibitory and antiproliferative activities than 3‐(1‐benzenesulfonyl‐1H‐indol‐5‐yl)‐N‐hydroxyacrylamide ( 6 ), as reported in a previous study. Among these compounds, 3‐[1‐(4‐methoxybenzenesulfonyl)‐2,3‐dihydro‐1H‐indol‐5‐yl]‐N‐hydroxyacrylamide ( 9 ) showed a two‐ to tenfold increase in activity compared to SAHA ( 1 ) in the suppression of lipopolysaccharide‐induced cytokine production. Compound 9 also caused a marked reduction in carrageenan‐induced acute inflammation in a rat model. Taken together, these data indicated that 1‐arylsulfonyl‐5‐(N‐hydroxyacrylamide)indolines HDAC inhibitors exhibit potent anti‐inflammatory activity.     

TrkB Receptor Signalling: Implications in Neurodegenerative,Psychiatric and Proliferative Disorders

The Trk family of receptors play a wide variety of roles in physiological and disease processes in both neuronal and non-neuronal tissues. Amongst these the TrkB receptor in particular has attracted major attention due to its critical role in signalling for brain derived neurotrophic factor (BDNF), neurotrophin-3 (NT3) and neurotrophin-4 (NT4). TrkB signalling is indispensable for the survival, development and synaptic plasticity of several subtypes of neurons in the nervous system. Substantial evidence has emerged over the last decade about the involvement of aberrant TrkB signalling and its compromise in various neuropsychiatric and degenerative conditions. Unusual changes in TrkB signalling pathway have also been observed and implicated in a range of cancers. Variations in TrkB pathway have been observed in obesity and hyperphagia related disorders as well. Both BDNF and TrkB have been shown to play critical roles in the survival of retinal ganglion cells in the retina. The ability to specifically modulate TrkB signalling can be critical in various pathological scenarios associated with this pathway. In this review, we discuss the mechanisms underlying TrkB signalling, disease implications and explore plausible ameliorative or preventive approaches.     

Structure and thermodynamic properties of zircon-coffinite solid solutions according to the semiempirical atomistic simulation data

Structure and thermodynamic properties of zircon, coffinite, and zircon-coffinite solid solutions were subject to semiempirical atomistic simulation on the assumption of compositional disordering of mixed crystals: (Zr_{1 ? x} , U _x )SiO₄, where x = 0.02, 0.05, 0.08, 0.11, 0.14, 0.28, 0.50, 0.72, and 0.86. The solid solutions significantly depart from the Vegard and Retgers laws. The (Zr_{1 ? x} , U _x )SiO₄ mixed crystal structure is characterized by anisotropic expansion (largely in the a and b directions) under growth in x related to anisotropy of structural relaxation degree of the cation-oxygen interatomic spacing in the (Zr, U)O₈ polyhedron. Increase in x parameters is accompanied by increase in average size of cation-oxygen polyhedrons and silica-oxygen tetrahedrons and by growth of interatomic spacing dispersion; maximum dispersion values are observed at x = 0.5–0.6. The distortions in local structures of ZrO₈ and UO₈ dodecahedrons and silica-oxygen tetrahedrons in the solid solution were analyzed on the basis of calculated functions of interatomic distance distribution. The obtained results demonstrate the possibility to assess numerically the structural (geometrical) disordering degree of the compositionally disordered solid solution depending on its composition. The calculated thermodynamic characteristics of solid solutions forecast the following solubility range limits: 2 mol % USiO₄ in zircon and 5 mol % ZrSiO₄ in coffinite under ～1750 K.     

Particle Motion in Simple Shear Flow with Gravity

The motion of aerosol particles in simple shear flow, subject to gravity, is analyzed. The combination of gravity and shear-induced lift is shown to give rise to particle drift. It is shown that in shear flow near a wall, when gravity points in the direction of flow, particles drift towards the wall, while for gravity pointing against the flow the drift is away from the wall. These results are also demonstrated experimentally, with fair qualitative agreement between analysis and experiments.     

Dielectric Drying

ABSTRACT

Dielectric heating is a term which covers both radio frequency (RF) and microwave systems. It has been used for industrial drying for many years because it has a number of advantages over other drying processes. These advantages include the volumetric dissipation of energy throughout a product, and the ability to automatically level any moisture variation within it. It is generally true to say that these techniques can only be justified in processes involving material of “high” value being processed in modest quantities but when combination with other fuel fired techniques there may be opportunities to broaden the range of applications. In addition to a desciption of current industrial applications, the theory of dielectric heating, the similarities and differences between RF and microwave are discussed together the effects of the dielectric roperties of a product on the design of the equipment