Surface attachment of protein fibrils via covalent modification strategies.

Chemical control of surface functionality and topography is an essential requirement for many technological purposes. In particular, the covalent attachment of monomeric proteins to surfaces has been the object of intense studies in recent years, for applications as varied as electrochemistry, immuno-sensing, and the production of biocompatible coatings. Little is known, however, about the characteristics and requirements underlying surface attachment of supramolecular protein nanostructures. Amyloid fibrils formed by the self-assembly of peptide and protein molecules represent one important class of such structures. These highly organized beta-sheet-rich assemblies are a hallmark of a range of neurodegenerative disorders, including Alzheimer's disease and type II diabetes, but recent findings suggest that they have much broader significance, potentially representing the global free energy minima of the energy landscapes of proteins and having potential applications in material science. In this paper, we describe strategies for attaching amyloid fibrils formed from different proteins to gold surfaces under different solution conditions. Our methods involve the reaction of sulfur containing small molecules (cystamine and 2-iminothiolane) with the amyloid fibrils, enabling their covalent linkage to gold surfaces. We demonstrate that irreversible attachment using these approaches makes possible quantitative analysis of experiments using biosensor techniques, such as quartz crystal microbalance (QCM) assays that are revolutionizing our understanding of the mechanisms of amyloid growth and the factors that determine its kinetic behavior. Moreover, our results shed light on the nature and relative importance of covalent versus noncovalent forces acting on protein superstructures at metal surfaces.

Post-earthquake behaviour of footings employing densification to mitigate liquefaction

In situ densification is a popular technique to protect shallow foundations from the effects of earthquake-induced liquefaction, current design being based on semiempirical rules. Poor understanding of the mechanisms governing the performance of soil-structure systems during and after earthquakes inhibits the use of narrow densified zones, which could contribute to optimise the use of densification if the increase in post-earthquake settlement is restrained. Therefore this paper investigates the long-term behaviour of a footing built on densified ground and surrounded by liquefiable ground, centrifuge experiments being used to identify the mechanisms occurring in the ground during and after a seismic simulation. The differential excess pore pressure generated in the ground during the shaking and the processes of vertical stress concentration and subsequent redistribution observed under the footing dominate the system behaviour. The results enlighten the complex mechanisms determining the post-earthquake settlement when densification is carried out to mitigate liquefaction effects. The improvement in performance resulting from widening the zone of densification is rationally explained which encourages the development of new design concepts that may enhance the future use of densification as a liquefaction resistance measure. © 2007 Thomas Telford Ltd.

Asymptotic behaviour of approximate Bayesian estimators

Although approximate Bayesian computation (ABC) has become a popular technique for performing parameter estimation when the likelihood functions are analytically intractable there has not as yet been a complete investigation of the theoretical properties of the resulting estimators. In this paper we give a theoretical analysis of the asymptotic properties of ABC based parameter estimators for hidden Markov models and show that ABC based estimators satisfy asymptotically biased versions of the standard results in the statistical literature.