Measuring the kinetics of amyloid fibril elongation using quartz crystal microbalances.

Kinetic measurements of amyloid growth provide insight into the free energy landscape of this supramolecular process and are crucial in the search for potent inhibitors of the main disorders with which it is associated, including Alzheimer's and Parkinson's diseases and Type II diabetes. In recent years, a new class of surface-bound biosensor assays, e.g., those based on surface plasmon resonance (SPR) and the quartz crystal microbalance (QCM) have been established as extremely valuable tools for kinetic measurements of amyloid formation. Here we describe detailed protocols of how QCM techniques can be used to monitor the elongation of amyloid fibrils in real time and to study the influence of external factors on the kinetics of amyloid growth with unprecedented accuracy.

Uncertainty increases pain: evidence for a novel mechanism of pain modulation involving the periaqueductal gray.

Predictions about sensory input exert a dominant effect on what we perceive, and this is particularly true for the experience of pain. However, it remains unclear what component of prediction, from an information-theoretic perspective, controls this effect. We used a vicarious pain observation paradigm to study how the underlying statistics of predictive information modulate experience. Subjects observed judgments that a group of people made to a painful thermal stimulus, before receiving the same stimulus themselves. We show that the mean observed rating exerted a strong assimilative effect on subjective pain. In addition, we show that observed uncertainty had a specific and potent hyperalgesic effect. Using computational functional magnetic resonance imaging, we found that this effect correlated with activity in the periaqueductal gray. Our results provide evidence for a novel form of cognitive hyperalgesia relating to perceptual uncertainty, induced here by vicarious observation, with control mediated by the brainstem pain modulatory system.

An analysis of competing toughening mechanisms in layered and particulate solids

The relative potency of common toughening mechanisms is explored for layered solids and particulate solids, with an emphasis on crack multiplication and plasticity. First, the enhancement in toughness due to a parallel array of cracks in an elastic solid is explored, and the stability of co-operative cracking is quantified. Second, the degree of synergistic toughening is determined for combined crack penetration and crack kinking at the tip of a macroscopic, mode I crack; specifically, the asymptotic problem of self-similar crack advance (penetration mode) versus 90 ° symmetric kinking is considered for an isotropic, homogeneous solid with weak interfaces. Each interface is treated as a cohesive zone of finite strength and toughness. Third, the degree of toughening associated with crack multiplication is assessed for a particulate solid comprising isotropic elastic grains of hexagonal shape, bonded by cohesive zones of finite strength and toughness. The study concludes with the prediction of R-curves for a mode I crack in a multi-layer stack of elastic and elastic-plastic solids. A detailed comparison of the potency of the above mechanisms and their practical application are given. In broad terms, crack tip kinking can be highly potent, whereas multiple cracking is difficult to activate under quasi-static conditions. Plastic dissipation can give a significant toughening in multi-layers especially at the nanoscale. © 2013 Springer Science+Business Media Dordrecht.