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.