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.

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.

Creative Activism: a pedagogical and research tool

Environmental activism has a long history in protest, addressing issues of degradation and segregation that threaten existing ecologies, social and built fabrics. Environmental activism is traditionally understood as a reaction, chiefly by groups of people, against a perceived external threat. In the 60’s and 70’s, an activist stance began to emerge in the work of some artists and architects, who used creative methods such as performances, happenings, temporary spatial interventions etc to convey their political/aesthetic messages. Some of this work engaged directly with communities but predominantly it was the production of one individual working ‘outside’ society. However such actions demonstrated not only the power of the visual in conveying a political message but also the potential of conceptual creative approaches to reveal alternative values and hidden potentials. This marked a shift from activism as protestation towards an activism of reconceptualisation. Recently, activist groups have developed a more politically informed process. Whilst their ‘tools’ may resemble work from the 60’s and 70’s , their methodologies are non-traditional, ’rhizomatic’, pedagogical and fluid; working alongside, rather than against, the established power and funding structures. Such creative processes build new, often unexpected, stakeholder networks; offer neutral spaces in which contentious issues can be faced; and create better understanding of values and identities. They can also lead to permanent improvements and development in the physical fabric. This paper will discuss a pedagogical example of activism in architectural education. The event (www.fourdaysontheoutside.com) is in its fifth year of existence and as such has revealed a value and impulse beyond its learning and teaching value. The paper will discuss how the event contributes to the university’s outreach programme and how its structure acts as a seedbed for potential research projects and partnerships. UK Universities talk extensively about applied research but have few actual strategies by which to generate it. Fourdaysontheoutside offers some potential ways forward.

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.