Quantitative approaches for characterising fibrillar protein nanostructures

Polypeptide sequences have an inherent tendency to self-assemble into filamentous nanostructures commonly known as amyloid fibrils. Such self-assembly is used in nature to generate a variety of functional materials ranging from protective coatings in bacteria to catalytic scaffolds in mammals. The aberrant self-assembly of misfolded peptides and proteins is also, however, implicated in a range of disease states including neurodegenerative conditions such as Alzheimer's and Parkinson's diseases. It is increasingly evident that the intrinsic material properties of these structures are crucial for understanding the thermodynamics and kinetics of the pathological deposition of proteins, particularly as the mechanical fragmentation of aggregates enhances the rate of protein deposition by exposing new fibril ends which can promote further growth. We discuss here recent advances in physical techniques that are able to characterise the hierarchical self-assembly of misfolded protein molecnles and define their properties. © 2010 Materials Research Society.

Wear of hardfacing white cast irons by solid particle erosion

The response of three commercial weld-hardfacing alloys to erosive wear has been studied. These were high chromium white cast irons, deposited by an open-arc welding process, widely used in the mineral processing and steelmaking industries for wear protection. Erosion tests were carried out with quartz sand, silicon carbide grit and blast furnace sinter of two different sizes, at a velocity of 40 m s-1 and at impact angles in the range 20° to 90°. A monolithic white cast iron and mild steel were also tested for comparison. Little differences were found in the wear rates when silica sand or silicon carbide grit was used as the erodent. Significant differences were found, however, in the rankings of the materials. Susceptibility to fracture of the carbide particles in the white cast irons played an important role in the behaviour of the white cast irons. Sinter particles were unable to cause gross fracture of the carbides and so those materials with a high volume fraction of carbides showed the greatest resistance to erosive wear. Silica and silicon carbide were capable of causing fracture of the primary carbides. Concentration of plastic strain in the matrix then led to a high wear rate for the matrix. At normal impact with silica or silicon carbide erodents mild steel showed a greater resistance to erosive wear than these alloys. © 1995.

High efficiency liquid crystal lasers giving "white light" emission from arrays and flexible substrates

The self-organization of the helical structure of chiral nematic liquid crystals combined with their sensitivity to electric fields makes them particularly interesting for low-threshold, wavelength tunable laser devices. We have studied these organic lasers in detail, ranging from the influence specific macroscopic properties, such as birefringence and order parameter, have on the output characteristics, to practical systems in the form of two-dimensional arrays, double-pass geometries and paintable lasers. Furthermore, even though chiral nematics are responsive to electric fields there is no facile means by which the helix periodicity can be adjusted, thereby allowing laser wavelength tuning, without adversely affecting the optical quality of the resonator. Therefore, in addition to studying the liquid crystal lasers, we have focused on finding a novel method with which to alter the periodicity of a chiral nematic using electric fields without inducing defects and degrading the optical quality factor of the resonator. This paper presents an overview of our research, describing (i) the correlation between laser output and material properties,(ii) the importance of the gain medium,(iii) multicolor laser arrays, and (iv) high slope efficiency (>60%) silicon back-plane devices. Overall we conclude that these materials have great potential for use in versatile organic laser systems.

The Effect of Motivation on Movement: A Study of Bradykinesia in Parkinson's Disease

Background: Bradykinesia is a cardinal feature of Parkinson's disease (PD). Despite its disabling impact, the precise cause of this symptom remains elusive. Recent thinking suggests that bradykinesia may be more than simply a manifestation of motor slowness, and may in part reflect a specific deficit in the operation of motivational vigour in the striatum. In this paper we test the hypothesis that movement time in PD can be modulated by the specific nature of the motivational salience of possible action-outcomes. Methodology/Principal Findings: We developed a novel movement time paradigm involving winnable rewards and avoidable painful electrical stimuli. The faster the subjects performed an action the more likely they were to win money (in appetitive blocks) or to avoid a painful shock (in aversive blocks). We compared PD patients when OFF dopaminergic medication with controls. Our key finding is that PD patients OFF dopaminergic medication move faster to avoid aversive outcomes (painful electric shocks) than to reap rewarding outcomes (winning money) and, unlike controls, do not speed up in the current trial having failed to win money in the previous one. We also demonstrate that sensitivity to distracting stimuli is valence specific. Conclusions/Significance: We suggest this pattern of results can be explained in terms of low dopamine levels in the Parkinsonian state leading to an insensitivity to appetitive outcomes, and thus an inability to modulate movement speed in the face of rewards. By comparison, sensitivity to aversive stimuli is relatively spared. Our findings point to a rarely described property of bradykinesia in PD, namely its selective regulation by everyday outcomes. © 2012 Shiner et al.

Dopamine and performance in a reinforcement learning task: evidence from Parkinson's disease.

The role dopamine plays in decision-making has important theoretical, empirical and clinical implications. Here, we examined its precise contribution by exploiting the lesion deficit model afforded by Parkinson's disease. We studied patients in a two-stage reinforcement learning task, while they were ON and OFF dopamine replacement medication. Contrary to expectation, we found that dopaminergic drug state (ON or OFF) did not impact learning. Instead, the critical factor was drug state during the performance phase, with patients ON medication choosing correctly significantly more frequently than those OFF medication. This effect was independent of drug state during initial learning and appears to reflect a facilitation of generalization for learnt information. This inference is bolstered by our observation that neural activity in nucleus accumbens and ventromedial prefrontal cortex, measured during simultaneously acquired functional magnetic resonance imaging, represented learnt stimulus values during performance. This effect was expressed solely during the ON state with activity in these regions correlating with better performance. Our data indicate that dopamine modulation of nucleus accumbens and ventromedial prefrontal cortex exerts a specific effect on choice behaviour distinct from pure learning. The findings are in keeping with the substantial other evidence that certain aspects of learning are unaffected by dopamine lesions or depletion, and that dopamine plays a key role in performance that may be distinct from its role in learning.

Dopamine and performance in a reinforcement learning task: Evidence from Parkinson's disease

The role dopamine plays in decision-making has important theoretical, empirical and clinical implications. Here, we examined its precise contribution by exploiting the lesion deficit model afforded by Parkinson's disease. We studied patients in a two-stage reinforcement learning task, while they were ON and OFF dopamine replacement medication. Contrary to expectation, we found that dopaminergic drug state (ON or OFF) did not impact learning. Instead, the critical factor was drug state during the performance phase, with patients ON medication choosing correctly significantly more frequently than those OFF medication. This effect was independent of drug state during initial learning and appears to reflect a facilitation of generalization for learnt information. This inference is bolstered by our observation that neural activity in nucleus accumbens and ventromedial prefrontal cortex, measured during simultaneously acquired functional magnetic resonance imaging, represented learnt stimulus values during performance. This effect was expressed solely during the ON state with activity in these regions correlating with better performance. Our data indicate that dopamine modulation of nucleus accumbens and ventromedial prefrontal cortex exerts a specific effect on choice behaviour distinct from pure learning. The findings are in keeping with the substantial other evidence that certain aspects of learning are unaffected by dopamine lesions or depletion, and that dopamine plays a key role in performance that may be distinct from its role in learning. © 2012 The Author.

An in computo investigation of the Landau-Kleffner syndrome

We describe a computational model of the thalamus and the cortex able to reproduce some essential epileptiform features commonly observed in the Landau-Kleffner syndrome. Investigation with this realistic model leads us to the formulation of a cellular mechanism that could be responsible for the epileptic discharges occuring with this severe syndrome. Understanding this mechanism is of prime importance for developing new therapeutical strategies. © 2007 IEEE.