The Critical Role of Passive Permeability in Designing Successful Drugs

Passive permeability is a key property in drug disposition and delivery. It is critical for gastrointestinal absorption, brain penetration, renal reabsorption, defining clearance mechanisms and drug-drug interactions. Passive diffusion rate is translatable across tissues and animal species, while the extent of absorption is dependent on drug properties, as well as in vivo physiology/pathophysiology. Design principles have been developed to guide medicinal chemistry to enhance absorption, which combine the balance of aqueous solubility, permeability and the sometimes unfavorable compound characteristic demanded by the target. Permeability assays have been implemented that enable rapid development of structure-permeability relationships for absorption improvement. Future advances in assay development to reduce nonspecific binding and improve mass balance will enable more accurately measurement of passive permeability. Design principles that integrate potency, selectivity, passive permeability and other ADMET properties facilitate rapid advancement of successful drug candidates to patients.     

Alloy optimisation of bainitic steel for large plastic mould

Based on the phase transformation theories, especially the T₀ concept of bainite transformation, alloy optimisation of bainitic steel with carbides has been carried out aiming at the produce of plastic mould with large cross-section. The effect of manganese and silicon on proeutectoid ferrite and bainite transformation is explored by dilatometric analysis, XRD and different microscopy techniques. The results show that after the alloy optimisation, the transformation of proeutectoid ferrite is suppressed and when the cooling rate is lower than 0·1°C?s^??1, the new lower bainite transformation appears by decreasing carbon capacity of austenite and promoting carbide precipitation. Industrial production proves that the optimised alloy SDP1 can meet the demand for the plastic mould with the thickness of 1050?mm.     

Popular biorthogonal wavelet filters via a lifting scheme and its application in image compression

A technique using a lifting scheme is presented for constructing compactly supported wavelets whose coefficients are composed of free variables locating in an interval. An efficient approach-based wavelet for image compression is developed by selecting the coefficients of the 9-7 wavelet filter and associated lifting scheme. Furthermore, the rationalised coefficients wavelet filter that can be implemented with simple integer arithmetic is achieved and its characteristic is close to the well known original irrational coefficients 9-7 wavelet filters developed by A. Cohen et al. (Commun. Pure Appl. Maths., vol.45, no.1, p.485-560, 1992). To reduce the computational cost of image coding applications further, an acceleration technique is proposed for the lifting steps. Software and hardware simulations show that the new method has very low complexity, and simultaneously preserves the high quality of the compressed image.     

Cover Picture: Arresting,Fixing, and Separating Dimers Composed of Uniform Silica Colloidal Spheres (Adv. Funct. Mater. 12/2006)

In colloidal suspensions of silica, particles undergo constant collisions. By controlling various parameters, the repulsive barrier can be reduced, thereby substantially increasing the number of collision‐induced dimerization events. Xia and co‐workers report on p. 1627 that the dimers could be arrested and then permanently fixed by introducing a small amount of fresh tetraethylorthosilicate into the colloidal suspension, with monodisperse dimer yields of up to 50 %. This yield could be increased to 80 % by centrifugation in a density gradient medium. When fresh tetraethylorthosilicate is introduced into a colloidal suspension of silica spheres, it hydrolyzes and condenses in situ to arrest and fix the dimers resulting from constant collisions between the spheres. By optimizing the experimental parameters (including the length of aging time) and the diameter of the silica spheres, as well as the concentrations of counterions, water, and ammonia, it is possible to routinely produce monodisperse dimers with a yield as high as 50 %. When combined with centrifugation using a density gradient medium, the yield of such dimers could be further increased to 80 %. It is believed that this method will provide a simple and versatile approach to the high‐volume production of dimers from spherical colloids composed of different materials. These dimers may find widespread use in a range of applications such as fabrication of photonic crystals and fundamental studies related to colloidal science.     

An MPEG‐4 Compliant Interactive Multimedia Streaming Platform Using Overlay Networks

This paper presents a multimedia streaming platform for efficiently transmitting MPEG‐4 content over IP networks. The platform includes an MPEG‐4 compliant streaming server and client, supporting object‐based representation of multimedia scenes, interactivity, and advanced encoding profiles defined by the ISO standard. For scalability purposes, we employ an application‐layer multicast scheme for media transmission using overlay networks. The overlay network, governed by the central entity of the network distribution manager, is dynamically deployed according to a set of pre‐defined criteria. The overlay network supports both broadcast delivery and video‐on‐demand content. The multimedia streaming platform is standards‐compliant and utilizes widespread multimedia protocols such as MPEG‐4, real‐time transport protocol, real‐time transport control protocol, and real‐time streaming protocol. The design of the overlay network was architected with the goal of transparency to both the streaming server and the client. As a result, many commercial implementations that use industry‐standard protocols can be plugged into the architecture relatively painlessly and can enjoy the benefits of the platform.     

On the Feasibility of Growing Pb[(Zn1/3Nb2/3)0.91Ti0.09]O3 Single Crystals

Pb[(Zn_1/3Nb_2/3)_0.91Ti_0.09]O₃ (PZNT91/9) single crystals were grown by two methods: from solution using PbO as a self‐fluxing agent (SC method) and directly from the melt without fluxing (MC method). In both growth methods, an allomeric Pb[(Mg_1/3‐Nb_2/3)_0.69Ti_0.31]O₃ (PMNT69/31) single crystal was used as a seed. X‐ray diffraction patterns of ground crystals showed that phase‐pure perovskite PZNT91/9 single crystals were successfully fabricated by the above two methods. The composition of the crystals obtained by both the SC and MC methods was analyzed using X‐ray fluorescence, which confirmed that the crystal composition is close to the nominal value, although volatilization of PbO and segregation during crystal growth are inevitable. The MC PZNT91/9 crystals exhibit excellent piezoelectric properties, with the piezoelectric constant, d₃₃, in the range of 1800–2200 pC N^–1. This value is comparable to that of the SC crystals. However, the MC crystals show an abnormal dielectric behavior. In contrast with the SC crystals, in the MC crystals a much broader dielectric peak appears in the dielectric response curves, accompanied by a much lower peak temperature of around 105 °C. Furthermore, frequency dispersion is apparent over a much wider temperature range (even more apparent than in pure relaxors), where a large, i.e., about 70 °C, full width at half maximum (FWHM) for the dielectric peaks is observed in the dielectric response. It is speculated that such an unusual phenomenon correlates with defects, microinhomogeneities, and polar regions in the as‐grown MC crystals. The origins of this abnormality have not been interpreted in detail until now. However, optical observation of the domain structure confirms that both the SC and MC crystals possess complex structural states.     

Formation and inhibition of free radicals in electrically stressed and aged insulating polymers

Previous work has shown that prebreakdown, electrical aging, and breakdown phenomena are directly associated with charge carriers injected from electrical contacts and their subsequent dissociative trapping and recombination. In addition, the energy released from each trapping or recombination event is dissipated in the breaking of the bonds of macromolecules, thus forming free radicals and new traps in the electrically stressed insulating polymers, as predicted by Kao's model. It is this gradual degradation process that leads to electrical aging and destructive breakdown. New experimental results are presented to confirm previous findings and a new approach to inhibit the degradation process by the incorporation of suitable dopants into the polymer. The concentration of free radicals in the polymer increases with an increasing electric field at a fixed stress time of 250 h and with increasing stress time at a fixed electric field of 833 kV cm^?1. The concentration of free radicals is directly related to the concentration of new traps created by stress. However, when suitable dopants are incorporated, the initiation voltage for the occurrence of electrical treeing and the breakdown strength are both increased. The dopants tend to create shallow traps and have little effect on the deep trap concentration. This implies that the dopants act as free‐radical scavengers that tend to satisfy the unpaired electrons of the broken bonds, which create new acceptor‐like electron traps and new shallow traps. By doing so, the shallow traps screen the deep traps, thereby reducing the energy released during trapping and recombination and the probability of breaking the macromolecular bonds and causing structural degradation. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 89: 3416–3425, 2003     

Pack cementation process for the formation of refractory metal modified aluminide coatings on nickel-base superalloys

The vapour phase compositions of a series of pack powder mixtures containing elemental Al and Hf or W powders as depositing sources and CrCl₃·6H₂O or AlF₃or CrF₃as activators were analysed in an attempt to further develop the pack cementation process to codeposit Al and Hf or W to form diffusion coatings on nickel base superalloys. The results suggested that Al could be codeposited with Hf, but not with W, from the vapour phase. Compared with both AlF₃and CrF₃, CrCl₃·6H₂O has been shown to be a more suitable activator for codepositing Al with Hf. The optimum coating temperature was identified to be in the range of 1050°C to 1150°C. Based on the thermochemical analysis, a series of coating deposition studies were undertaken, which confirmed that codeposition of Al and Hf could be achieved at a deposition temperature of 1100°C in the CrCl₃·6H₂O activated packs containing elemental Al and Hf powders. The coating obtained had a multilayer structure consisting of a Ni₇Hf₆Al₁₆top layer and a NiAl layer underneath, followed by a diffusion zone, which revealed that the coating was formed by the outward Ni diffusion. It is suggested that the compositions suitable for codeposition of Al and Hf could be effectively identified by comparing the vapour pressures of HfCl₄and HfCl₃with that of AlCl in the packs activated by chloride salts. It has also been experimentally demonstrated that, although W could not be deposited from the vapour phase, a high volume of fine W particles can be entrapped into the outer NiAl coating layer formed by the outward Ni diffusion using a modified pack configuration. This leads to the formation of a composite coating layer with W particles evenly distributed in a matrix of NiAl. It is suggested that this modified pack process could be similarly applied to develop nickel aluminide coatings containing other refractory metals that may not be codeposited with Al from the vapour phase.