Discovery of novel cathepsin S inhibitors by pharmacophore-based virtual high-throughput screening

The cysteine protease cathepsin S (CatS) is involved in the pathogenesis of autoimmune disorders, atherosclerosis, and obesity. Therefore, it represents a promising pharmacological target for drug development. We generated ligand-based and structure-based pharmacophore models for noncovalent and covalent CatS inhibitors to perform virtual high-throughput screening of chemical databases in order to discover novel scaffolds for CatS inhibitors. An in vitro evaluation of the resulting 15 structures revealed seven CatS inhibitors with kinetic constants in the low micromolar range. These compounds can be subjected to further chemical modifications to obtain drugs for the treatment of autoimmune disorders and atherosclerosis.

Injection of metallic elements into an electron-beam ion trap using a Knudsen cell

A method of injecting metallic elements into an electron-beam ion trap (EBIT) is described. The method is advantageous over the conventional coaxial and pulsed injection methods in two ways: (a) complicated switching of injection and extraction beams can be avoided when extracting beams of highly charged ions from the EBIT and (b) a beam of stable intensity can be achieved. This method may be applicable to any metallic elements or metallic compounds that have vapor pressures of similar to 0.1 Pa at a temperature lower than 1900 degrees C. We have employed this method for the extraction of highly charged ions of Bi, Er, Fe, and Ho. (c) 2006 American Institute of Physics.

A Virtual Inspection Technique for Assessing the Dimensional Accuracy of Forged Compressor Blades Using FE Modeling and CMM Inspection

This paper presents research for developing a virtual inspection system that evaluates the dimensional tolerance of forged aerofoil blades formed using the finite element (FE) method. Conventional algorithms adopted by modern coordinate measurement processes have been incorporated with the latest free-form surface evaluation techniques to provide a robust framework for the dimensional inspection of FE aerofoil models. The accuracy of the approach had been verified with a strong correlation obtained between the virtual inspection data and coordinate measurement data from corresponding aerofoil components.

The nonformative elements of religious life: questioning the ‘sociology of spirituality’ paradigm

Sociological assertions of religious vitality in Euro-American societies have developed a paradigm of spirituality in which, following earlier studies of the New Age, a distinction is drawn between external authority and self-authority. Methodologically and theoretically problematic, this paradigm diverts attention from people’s social practices and interactions, especially in relation to multiple religious authorities. Drawing upon ethnographic fieldwork with an English religious network, and building upon the work of Pierre Bourdieu, this paper considers situations in which multiple authorities tend to relativize each other. Conceptualizing this in terms of nonformativeness - the lack of authorities’ abilities formatively to shape religious identity, habitus, and competition over religious capital - a new understanding of individual secularization emerges that questions assertions of vitality.

Using Virtual Reality to Analyze Sports Performance

Improving performance in sports requires a better understanding of the perception-action loop employed by athletes. Because of its inherent limitations, video playback doesn't permit this type of in-depth analysis. Interactive, immersive virtual reality can overcome these limitations and foster a better understanding of sports performance.

Does the level of graphical detail of a virtual handball thrower influence a goal-keeper's motor response?

The authors investigated how different levels of detail (LODs) of a virtual throwing action can influence a handball goalkeeper's motor response. Goalkeepers attempted to stop a virtual ball emanating from five different graphical LODs of the same virtual throwing action. The five levels of detail were: a textured reference level (L0), a non-textured level (L1), a wire-frame level (L2), a point-light-display (PLD) representation (L3) and a PLD level with reduced ball size (L4). For each motor response made by the goalkeeper we measured and analyzed the time to respond (TTR), the percentage of successful motor responses, the distance between the ball and the closest limb (when the stopping motion was incorrect) and the kinematics of the motion. Results showed that TTR, percentage of successful motor responses and distance with the closest limb were not significantly different for any of the five different graphical LODs. However the kinematics of the motion revealed that the trajectory of the stopping limb was significantly different when comparing the L1 and L3 levels, and when comparing the L1 and L4 levels. These differences in the control of the goalkeeper's actions suggests that the different level of information available in the PLD representations ( L3 and L4) are causing the goalkeeper to adopt different motor strategies to control the approach of their limb to stop the ball.