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.

Carbon nanotube Schottky diode and directionally dependent field-effect transistor using asymmetrical contacts

We demonstrate the fabrication and operation of a carbon nanotube (CNT) based Schottky diode by using a Pd contact (high-work-function metal) and an Al contact (low-work-function metal) at the two ends of a single-wall CNT. We show that it is possible to tune the rectification current-voltage (I-V) characteristics of the CNT through the use of a back gate. In contrast to standard back gate field-effect transistors (FET) using same-metal source drain contacts, the asymmetrically contacted CNT operates as a directionally dependent CNT FET when gated. While measuring at source-drain reverse bias, the device displays semiconducting characteristics whereas at forward bias, the device is nonsemiconducting. © 2005 American Institute of Physics.

Nucleated polymerization with secondary pathways. I. Time evolution of the principal moments.

Self-assembly processes resulting in linear structures are often observed in molecular biology, and include the formation of functional filaments such as actin and tubulin, as well as generally dysfunctional ones such as amyloid aggregates. Although the basic kinetic equations describing these phenomena are well-established, it has proved to be challenging, due to their non-linear nature, to derive solutions to these equations except for special cases. The availability of general analytical solutions provides a route for determining the rates of molecular level processes from the analysis of macroscopic experimental measurements of the growth kinetics, in addition to the phenomenological parameters, such as lag times and maximal growth rates that are already obtainable from standard fitting procedures. We describe here an analytical approach based on fixed-point analysis, which provides self-consistent solutions for the growth of filamentous structures that can, in addition to elongation, undergo internal fracturing and monomer-dependent nucleation as mechanisms for generating new free ends acting as growth sites. Our results generalise the analytical expression for sigmoidal growth kinetics from the Oosawa theory for nucleated polymerisation to the case of fragmenting filaments. We determine the corresponding growth laws in closed form and derive from first principles a number of relationships which have been empirically established for the kinetics of the self-assembly of amyloid fibrils.

Tunable hydrodynamic chromatography of microparticles localized in short microchannels.

This paper describes a new way to perform hydrodynamic chromatography (HDC) for the size separation of particles based on a unique recirculating flow pattern. Pressure-driven (PF) and electro-osmotic flows (EOF) are opposed in narrow glass microchannels that expand at both ends. The resulting bidirectional flow turns into recirculating flow because of nonuniform microchannel dimensions. This hydrodynamic effect, combined with the electrokinetic migration of the particles themselves, results in a trapping phenomenon, which we have termed flow-induced electrokinetic trapping (FIET). In this paper, we exploit recirculating flow and FIET to perform a size-based separation of samples of microparticles trapped in a short separation channel using a HDC approach. Because these particles have the same charge (same zeta potential), they exhibit the same electrophoretic mobility, but they can be separated according to size in the recirculating flow. While trapped, particles have a net drift velocity toward the low-pressure end of the channel. When, because of a change in the externally applied PF or electric field, the sign of the net drift velocity reverses, particles can escape the separation channel in the direction of EOF. Larger particles exhibit a larger net drift velocity opposing EOF, so that the smaller particles escape the separation channel first. In the example presented here, a sample plug containing 2.33 and 2.82 microm polymer particles was introduced from the inlet into a 3-mm-long separation channel and trapped. Through tuning of the electric field with respect to the applied PF, the particles could be separated, with the advantage that larger particles remained trapped. The separation of particles with less than 500 nm differences in diameter was performed with an analytical resolution comparable to that of baseline separation in chromatography. When the sample was not trapped in the separation channel but located further downstream, separations could be carried out continuously rather than in batch. Smaller particles could successfully pass through the separation channel, and particles were separated by size. One of the main advantages of exploiting FIET for HDC is that this method can be applied in quite short (a few millimeters) channel geometries. This is in great contrast to examples published to date for the separation of nanoparticles in much longer micro- and nanochannels.

Binding of the molecular chaperone αB-crystallin to Aβ amyloid fibrils inhibits fibril elongation.

The molecular chaperone αB-crystallin is a small heat-shock protein that is upregulated in response to a multitude of stress stimuli, and is found colocalized with Aβ amyloid fibrils in the extracellular plaques that are characteristic of Alzheimer's disease. We investigated whether this archetypical small heat-shock protein has the ability to interact with Aβ fibrils in vitro. We find that αB-crystallin binds to wild-type Aβ(42) fibrils with micromolar affinity, and also binds to fibrils formed from the E22G Arctic mutation of Aβ(42). Immunoelectron microscopy confirms that binding occurs along the entire length and ends of the fibrils. Investigations into the effect of αB-crystallin on the seeded growth of Aβ fibrils, both in solution and on the surface of a quartz crystal microbalance biosensor, reveal that the binding of αB-crystallin to seed fibrils strongly inhibits their elongation. Because the lag phase in sigmoidal fibril assembly kinetics is dominated by elongation and fragmentation rates, the chaperone mechanism identified here represents a highly effective means to inhibit fibril proliferation. Together with previous observations of αB-crystallin interaction with α-synuclein and insulin fibrils, the results suggest that this mechanism is a generic means of providing molecular chaperone protection against amyloid fibril formation.

Tapered bow-tie lasers for high energy Q-switched pulse generation

A new kind of Q switched laser, the bow tie laser is introduced. This type of laser permits large area facets at both ends so that generation of high optical powers involve low optical intensities to prevent optical damage. The incorporation of doubled tapered waveguide structure to the Q switched multicontact laser has increased the optical pulse energies and peak powers of the laser.

Improving design quality and value in the built environment through knowledge of intangibles

Raising design quality and value in the built environment requires continuous improvement, drawing on feedback from clients or occupiers and other industry players. The challenging task for architectural and engineering designers has always been to use their intellectual knowledge to deliver both forms of benefits, tangibles and intangibles, in the built environment. Increasingly as clients demand best value for money, there is a greater need to understand the potential from intangibles, to see projects not as ends in themselves but as means to improved quality of life and wealth creation. As we begin to understand more about how - through the design of the built environment - to deliver these improvements in outcomes, clients will be better placed to expect their successful delivery from designers, and designers themselves will be better placed to provide them. This paper discusses cross-disciplinary issues about intangibles and is aimed at designers, clients, investors and entrepreneurs within the built environment. It presents some findings from a minuscule study that investigated intangible benefits in a new primary school. © 2004 IEEE.

Fluid-structure interaction with mean flow: Over-scattering and unstable resonance growth

It is known theoretically [1-3] that infinitely long fluid loaded plates in mean flow exhibit a range of unusual phenomena in the 'long time' limit. These include convective instability, absolute instability and negative energy waves which are destabilized by dissipation. However, structures are necessarily of finite length and may have discontinuities. Moreover, linear instability waves can only grow over a limited number of cycles before non-linear effects become dominant. We have undertaken an analytical and computational study to investigate the response of finite, discontinuous plates to ascertain if these unusual effects might be realized in practice. Analytically, we take a "wave scattering" [2,4] - as opposed to a "modal superposition" [5] - view of the fluttering plate problem. First, we solve for the scattering coefficients of localized plate discontinuities and identify a range of parameter space, well outside the convective instability regime, where over-scattering or amplified reflection/transmission occurs. These are scattering processes that draw energy from the mean flow into the plate. Next, we use the Wiener-Hopf technique to solve for the scattering coefficients from the leading and trailing edges of a baffled plate. Finally, we construct the response of a finite, baffled plate by a superposition of infinite plate propagating waves continuously scattering off the plate ends and solve for the unstable resonance frequencies and temporal growth rates for long plates. We present a comparison between our computational results and the infinite plate theory. In particular, the resonance response of a moderately sized plate is shown to be in excellent agreement with our long plate analytical predictions. Copyright © 2010 by ASME.

Effects of constraint curvature on structural instability: tensile buckling and multiple bifurcations

Bifurcation of an elastic structure crucially depends on the curvature of the constraints against which the ends of the structure are prescribed to move, an effect which deserves more attention than it has received so far. In fact, we show theoretically and we provide definitive experimental verification that an appropriate curvature of the constraint over which the end of a structure has to slide strongly affects buckling loads and can induce: (i.) tensile buckling; (ii.) decreasing- (softening), increasing- (hardening), or constant-load (null stiffness) postcritical behaviour; (iii.) multiple bifurcations, determining for instance two bifurcation loads (one tensile and one compressive) in a single-degree-of-freedom elastic system. We show how to design a constraint profile to obtain a desired postcritical behaviour and we provide the solution for the elastica constrained to slide along a circle on one end, representing the first example of an inflexional elastica developed from a buckling in tension. These results have important practical implications in the design of compliant mechanisms and may find applications in devices operating in quasi-static or dynamic conditions.

SynGAP isoforms exert opposing effects on synaptic strength.

Alternative promoter usage and alternative splicing enable diversification of the transcriptome. Here we demonstrate that the function of Synaptic GTPase-Activating Protein (SynGAP), a key synaptic protein, is determined by the combination of its amino-terminal sequence with its carboxy-terminal sequence. 5' rapid amplification of cDNA ends and primer extension show that different N-terminal protein sequences arise through alternative promoter usage that are regulated by synaptic activity and postnatal age. Heterogeneity in C-terminal protein sequence arises through alternative splicing. Overexpression of SynGAP α1 versus α2 C-termini-containing proteins in hippocampal neurons has opposing effects on synaptic strength, decreasing and increasing miniature excitatory synaptic currents amplitude/frequency, respectively. The magnitude of this C-terminal-dependent effect is modulated by the N-terminal peptide sequence. This is the first demonstration that activity-dependent alternative promoter usage can change the function of a synaptic protein at excitatory synapses. Furthermore, the direction and degree of synaptic modulation exerted by different protein isoforms from a single gene locus is dependent on the combination of differential promoter usage and alternative splicing.

Blade Loading and Its Application in the Mean-Line Design of Low Pressure Turbines

In order to minimize the number of iterations to a turbine design, reasonable choices of the key parameters must be made at the preliminary design stage. The choice of blade loading is of particular concern in the low pressure (LP) turbine of civil aero engines, where the use of high-lift blades is widespread. This paper considers how blade loading should be measured, compares the performance of various loss correlations, and explores the impact of blade lift on performance and lapse rates. To these ends, an analytical design study is presented for a repeating-stage, axial-flow LP turbine. It is demonstrated that the long-established Zweifel lift coefficient (Zweifel, 1945, "The Spacing of Turbomachine Blading, Especially with Large Angular Deflection" Brown Boveri Rev., 32(1), pp. 436-444) is flawed because it does not account for the blade camber. As a result the Zweifel coefficient is only meaningful for a fixed set of flow angles and cannot be used as an absolute measure of blade loading. A lift coefficient based on circulation is instead proposed that accounts for the blade curvature and is independent of the flow angles. Various existing profile and secondary loss correlations are examined for their suitability to preliminary design. A largely qualitative comparison demonstrates that the loss correlations based on Ainley and Mathieson (Ainley and Mathieson, 1957, "A Method of Performance Estimation for Axial-Flow Turbines," ARC Reports and Memoranda No. 2974; Dunham and Came, 1970, "Improvements to the Ainley-Mathieson Method of Turbine Performance Prediction," Trans. ASME: J. Eng. Gas Turbines Power, July, pp. 252-256; Kacker and Okapuu, 1982, "A Mean Line Performance Method for Axial Flow Turbine Efficiency," J. Eng. Power, 104, pp. 111-119). are not realistic, while the profile loss model of Coull and Hodson (Coull and Hodson, 2011, "Predicting the Profile Loss of High-Lift Low Pressure Turbines," J. Turbomach., 134(2), pp. 021002) and the secondary loss model of (Traupel, W, 1977, Thermische Turbomaschinen, Springer-Verlag, Berlin) are arguably the most reasonable. A quantitative comparison with multistage rig data indicates that, together, these methods over-predict lapse rates by around 30%, highlighting the need for improved loss models and a better understanding of the multistage environment. By examining the influence of blade lift across the Smith efficiency chart, the analysis demonstrates that designs with higher flow turning will tend to be less sensitive to increases in blade loading. © 2013 American Society of Mechanical Engineers.

Structurally programmed capillary folding of carbon nanotube assemblies.

We demonstrate the fabrication of horizontally aligned carbon nanotube (HA-CNT) networks by spatially programmable folding, which is induced by self-directed liquid infiltration of vertical CNTs. Folding is caused by a capillary buckling instability and is predicted by the elastocapillary buckling height, which scales with the wall thickness as t(3/2). The folding direction is controlled by incorporating folding initiators at the ends of the CNT walls, and the initiators cause a tilt during densification which precedes buckling. By patterning these initiators and specifying the wall geometry, we control the dimensions of HA-CNT patches over 2 orders of magnitude and realize multilayered and multidirectional assemblies. Multidirectional HA-CNT patterns are building blocks for custom design of nanotextured surfaces and flexible circuits.

The soft impact response of composite laminate beams

The quasi-static and dynamic responses of laminated beams of equal areal mass, made from monolithic CFRP and Ultra high molecular weight Polyethylene (UHMWPE), have been measured. The end-clamped beams were impacted at mid-span by metal foam projectiles to simulate localised blast loading. The effect of clamping geometry on the response was investigated by comparing the response of beams bolted into the supports with the response of beams whose ends were wrapped around the supports. The effect of laminate shear strength upon the static and dynamic responses was investigated by testing two grades of each of the CFRP and UHMWPE beams: (i) CFRP beams with a cured matrix and uncured matrix, and (ii) UHMWPE laminates with matrices of two different shear strengths. Quasi-static stretch-bend tests indicated that the load carrying capacity of the UHWMPE beams exceeds that of the CFRP beams, increases with diminishing shear strength of matrix, and increases when the ends are wrapped rather than through-bolted. The dynamic deformation mode of the beams is qualitatively different from that observed in the quasi-static stretch-bend tests. In the dynamic case, travelling hinges emanate from the impact location and propagate towards the supports; the beams finally fail by tensile fibre fracture at the supports. The UHMWPE beams outperform the CFRP beams in terms of a lower mid-span deflection for a given impulse, and a higher failure impulse. Also, the maximum attainable impulse increases with decreasing shear strength for both the UHMWPE and CFRP beams. The ranking of the beams for load carrying capacity in the quasi-static stretch-bend tests is identical to that for failure impulse in the impact tests. Thus, the static tests can be used to gauge the relative dynamic performances of the beams. © 2013 Elsevier Ltd. All rights reserved.

Simulations of thermal upgrading methods for oil shale reservoirs

This paper analyzes reaction and thermal front development in porous reservoirs with reacting flows, such as those encountered in shale oil extraction. A set of dimensionless parameters and a 3D code are developed in order to investigate the important physical and chemical variables of such reservoirs when heated by in situ methods. This contribution builds on a 1D model developed for the precursor study to this work. Theory necessary for this study is presented, namely shale decomposition chemical mechanisms, governing equations for multiphase flow in porous media and necessary closure models. Plotting the ratio of the thermal wave speed to the fluid speed allows one to infer that the reaction wave front ends where this ratio is at a minimum. The reaction front follows the thermal front closely, thus allowing assumptions to be made about the extent of decomposition solely by looking at thermal wave progression. Furthermore, this sensitivity analysis showed that a certain minimum permeability is required in order to ensure the formation of a traveling thermal wave. It was found that by studying the non-dimensional governing parameters of the system one can ascribe characteristic values for these parameters for given initial and boundary conditions. This allows one to roughly predict the performance of a particular method on a particular reservoir given approximate values for initial and boundary conditions. Channelling and flow blockage due to carbon residue buildup impeded each method's performance. Blockage was found to be a result of imbalanced heating. Copyright 2012, Society of Petroleum Engineers.

Europium-directed self-assembly of a luminescent supramolecular gel from a tripodal terpyridine-based ligand.

Eu(III), the last piece in the puzzle: Europium-induced self-assembly of ligands having a C(3)-symmetrical benzene-1,3,5-tricarboxamide core results in the formation of luminescent gels. Supramolecular polymers are formed through hydrogen bonding between the ligands. The polymers are then brought together into the gel assembly through the coordination of terpyridine ends by Eu(III) ions (blue dashed arrow: distance between two ligands in the strand direction).