Relationship between prion propensity and the rates of individual molecular steps of fibril assembly.

Peptides and proteins possess an inherent propensity to self-assemble into generic fibrillar nanostructures known as amyloid fibrils, some of which are involved in medical conditions such as Alzheimer disease. In certain cases, such structures can self-propagate in living systems as prions and transmit characteristic traits to the host organism. The mechanisms that allow certain amyloid species but not others to function as prions are not fully understood. Much progress in understanding the prion phenomenon has been achieved through the study of prions in yeast as this system has proved to be experimentally highly tractable; but quantitative understanding of the biophysics and kinetics of the assembly process has remained challenging. Here, we explore the assembly of two closely related homologues of the Ure2p protein from Saccharomyces cerevisiae and Saccharomyces paradoxus, and by using a combination of kinetic theory with solution and biosensor assays, we are able to compare the rates of the individual microscopic steps of prion fibril assembly. We find that for these proteins the fragmentation rate is encoded in the structure of the seed fibrils, whereas the elongation rate is principally determined by the nature of the soluble precursor protein. Our results further reveal that fibrils that elongate faster but fracture less frequently can lose their ability to propagate as prions. These findings illuminate the connections between the in vitro aggregation of proteins and the in vivo proliferation of prions, and provide a framework for the quantitative understanding of the parameters governing the behavior of amyloid fibrils in normal and aberrant biological pathways.

Fabrication of an organic field effect transistor using nano imprinting of Ag inks and semiconducting polymers

A simple and cheap procedure for flexible electronics fabrication was demonstrated by imprinting metallic nanoparticles (NPs) on flexible substrates. Silver NPs with an average diameter of 10 nm were prepared via an improved chemical approach and Ag Np ink was produced in α-terpineol with a concentration up to 15%. Silver micro/nanostructures with a dimension varying from nanometres to microns were produced on a flexible substrate (polyimide) by imprinting the as-prepared silver ink. The fine fluidic properties of an Ag NP/α-terpineol solution and low melting temperatures of silver nanoparticles render a low pressure and low temperature procedure, which is well suited for flexible electronics fabrication. The effects of sintering and mechanical bending on the conductivity of imprinted silver contacts were also investigated. Large area organic field effect transistors (OFET) on flexible substrates were fabricated using an imprinted silver electrode and semiconducting polymer. The OFET with silver electrodes imprinted from our prepared oleic acid stabilized Ag nanoparticle ink show an ideal ohmic contact; therefore, the OFET exhibit high performance (Ion/Ioff ratio: 1 × 103; mobility: 0.071 cm2 V-1 s-1). © 2010 IOP Publishing Ltd.

Multispacecraft refueling optimization considering the J2 perturbation and window constraints

The optimization of a near-circular low-Earth-orbit multispacecraft refueling problem is studied. The refueling sequence, service time, and orbital transfer time are used as design variables, whereas the mean mission completion time and mean propellant consumed by orbital maneuvers are used as design objectives. The J2 term of the Earth's nonspherical gravity perturbation and the constraints of rendezvous time windows are taken into account. A hybridencoding genetic algorithm, which uses normal fitness assignment to find the minimum mean propellant-cost solution and fitness assignment based on the concept of Pareto-optimality to find multi-objective optimal solutions, is presented. The proposed approach is demonstrated for a typical multispacecraft refueling problem. The results show that the proposed approach is effective, and that the J2 perturbation and the time-window constraints have considerable influences on the optimization results. For the problems in which the J2 perturbation is not accounted for, the optimal refueling order can be simply determined as a sequential order or as the order only based on orbitalplane differences. In contrast, for the problems that do consider the J2 perturbation, the optimal solutions obtained have a variety of refueling orders and use the drift of nodes effectively to reduce the propellant cost for eliminating orbital-plane differences. © 2013 by the American Institute of Aeronautics and Astronautics, Inc. All rights reserved.

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.

Widening engineering horizons: Addressing the complexity of sustainable development

The complex, fragmented and diverse aspects of a sustainable development perspective are translated into an eight-point framework that defines a problem boundary larger than that traditionally adopted by civil engineers. This leads to practical questions intended to inform engineers who ask 'am I being sustainable?' during project implementation. The value of the questions is tested against a case history of a wastewater treatment project. This demonstrates the relevance of the questions to successive project delivery phases of defining the problem, choosing a solution and implementing that solution through design, construction and operation. The case history highlights that answers to several of the additional questions raised by considering this wider problem space are currently buried within government and clients' policies, regulations and standard practice; these answers may not be accessible to the professional engineer.

Superconducting properties of Gd-Ba-Cu-O single grains processed from a new, Ba-rich precursor compound

Gd-Ba-Cu-O (GdBCO) single grains have been previously melt-processed successfully in air using a generic Mg-Nd-Ba-Cu-O (Mg-NdBCO) seed crystal. Previous research has revealed that the addition of a small amount of BaO 2 to the precursor powders prior to melt processing can suppress the formation of Gd/Ba solid solution, and lead to a significant improvement in superconducting properties of the single grains. Research into the effects of a higher Ba content on single grain growth, however, has been limited by the relatively small grain size in the earlier studies. This has been addressed by developing Ba-rich precursor compounds Gd-163 and Gd-143, fabricated specifically to enable the presence of greater concentrations of Ba during the melt process. In this study, we propose a new processing route for the fabrication of high performance GdBCO single grain bulk superconductors in air by enriching the precursor powder with these new Ba rich compounds. The influence of the addition of the new compounds on the microstructures and superconducting properties of GdBCO single grains is reported. © 2008 IOP Publishing Ltd.

Bypass transition to sustained thermoacoustic oscillations in a linearly stable rijke tube

In this paper we examine triggering in a simple linearly-stable thermoacoustic system using techniques from flow instability and optimal control. Firstly, for a noiseless system, we find the initial states that have highest energy growth over given times and from given energies. Secondly, by varying the initial energy, we find the lowest energy that just triggers to a stable periodic solution. We show that the corresponding initial state grows first towards an unstable periodic solution and, from there, to the stable periodic solution. This exploits linear transient growth, which arises due to nonnormality in the governing equations and is directly analogous to bypass transition to turbulence. Thirdly, we introduce noise that has similar spectral characteristics to this initial state. We show that, when triggering from low noise levels, the system grows to high amplitude self-sustained oscillations by first growing towards the unstable periodic solution of the noiseless system. This helps to explain the experimental observation that linearly-stable systems can trigger to self-sustained oscillations even with low background noise. © 2010 by University of Cambridge. Published by the American Institute of Aeronautics and Astronautics, Inc.

Modelling the evolution of uncertainty levels during design

Design work involves uncertainty that arises from, and influences, the progressive development of solutions. This paper analyses the influences of evolving uncertainty levels on the design process. We focus on uncertainties associated with choosing the values of design parameters, and do not consider in detail the issues that arise when parameters must first be identified. Aspects of uncertainty and its evolution are discussed, and a new task-based model is introduced to describe process behaviour in terms of changing uncertainty levels. The model is applied to study two process configuration problems based on aircraft wing design: one using an analytical solution and one using Monte-Carlo simulation. The applications show that modelling uncertainty levels during design can help assess management policies, such as how many concepts should be considered during design and to what level of accuracy. © 2011 Springer-Verlag.

The deposition of small particles from a turbulent air flow in a curved duct

The paper describes an experimental and theoretical study of the deposition of small spherical particles from a turbulent air flow in a curved duct. The objective was to investigate the interaction between the streamline curvature of the primary flow and the turbulent deposition mechanisms of diffusion and turbophoresis. The experiments were conducted with particles of uranine (used as a fluorescent tracer) produced by an aerosol generator. The particles were entrained in an air flow which passed vertically downwards through a long straight channel of rectangular cross-section leading to a 90° bend. The inside surfaces of the channel and bend were covered with tape to collect the deposited particles. Following a test run the tape was removed in sections, the uranine was dissolved in sodium hydroxide solution and the deposition rates established by measuring the uranine concentration with a luminescence spectrometer. The experimental results were compared with calculations of particle deposition in a curved duct using a computer program that solved the ensemble-averaged particle mass and momentum conservation equations. A particle density-weighted averaging procedure was used and the equations were expressed in terms of the particle convective, rather than total, velocity. This approach provided a simpler formulation of the particle turbulence correlations generated by the averaging process. The computer program was used to investigate the distance required to achieve a fully-developed particle flow in the straight entry channel as well as the variation of the deposition rate around the bend. The simulations showed good agreement with the experimental results. © 2012 Elsevier Ltd.

Near-ultraviolet zinc oxide nanowire sensor using low temperature hydrothermal growth.

Two near-ultraviolet (UV) sensors based on solution-grown zinc oxide (ZnO) nanowires (NWs) which are only sensitive to photo-excitation at or below 400 nm wavelength have been fabricated and characterized. Both devices keep all processing steps, including nanowire growth, under 100 °C for compatibility with a wide variety of substrates. The first device type uses a single optical lithography step process to allow simultaneous in situ horizontal NW growth from solution and creation of symmetric ohmic contacts to the nanowires. The second device type uses a two-mask optical lithography process to create asymmetric ohmic and Schottky contacts. For the symmetric ohmic contacts, at a voltage bias of 1 V across the device, we observed a 29-fold increase in current in comparison to dark current when the NWs were photo-excited by a 400 nm light-emitting diode (LED) at 0.15 mW cm(-2) with a relaxation time constant (τ) ranging from 50 to 555 s. For the asymmetric ohmic and Schottky contacts under 400 nm excitation, τ is measured between 0.5 and 1.4 s over varying time internals, which is ~2 orders of magnitude faster than the devices using symmetric ohmic contacts.

An example of the use of neural computing techniques in materials science - The modelling of fatigue thresholds in Ni-base superalloys

Two adaptive numerical modelling techniques have been applied to prediction of fatigue thresholds in Ni-base superalloys. A Bayesian neural network and a neurofuzzy network have been compared, both of which have the ability to automatically adjust the network's complexity to the current dataset. In both cases, despite inevitable data restrictions, threshold values have been modelled with some degree of success. However, it is argued in this paper that the neurofuzzy modelling approach offers real benefits over the use of a classical neural network as the mathematical complexity of the relationships can be restricted to allow for the paucity of data, and the linguistic fuzzy rules produced allow assessment of the model without extensive interrogation and examination using a hypothetical dataset. The additive neurofuzzy network structure means that redundant inputs can be excluded from the model and simple sub-networks produced which represent global output trends. Both of these aspects are important for final verification and validation of the information extracted from the numerical data. In some situations neurofuzzy networks may require less data to produce a stable solution, and may be easier to verify in the light of existing physical understanding because of the production of transparent linguistic rules. © 1999 Elsevier Science S.A.

Antiwindup design for induction motor control in the field weakening domain

Operation of induction machines in the high-speed and/or high-torque range requires field-weakening to comply with voltage and current physical limitations. This paper presents an anti-windup approach to this problem: rather than developing an ad-hoc field weakening strategy in the high-speed region, we equip an unconstrained vector-control design with an anti-windup module that automatically adjusts the current and flux set-points so that voltage and current constraints are satisfied at every operating point. The anti-windup module includes a feedforward modification of the set point aimed at maximizing the available torque in steady-state and a feedback modification of the controller based on an internal model-based antiwindup scheme. This paper includes a complete stability analysis of the proposed solution and presents encouraging experimental results on an industrial drive. © 2012 IEEE.

Generalized power method for sparse principal component analysis

In this paper we develop a new approach to sparse principal component analysis (sparse PCA). We propose two single-unit and two block optimization formulations of the sparse PCA problem, aimed at extracting a single sparse dominant principal component of a data matrix, or more components at once, respectively. While the initial formulations involve nonconvex functions, and are therefore computationally intractable, we rewrite them into the form of an optimization program involving maximization of a convex function on a compact set. The dimension of the search space is decreased enormously if the data matrix has many more columns (variables) than rows. We then propose and analyze a simple gradient method suited for the task. It appears that our algorithm has best convergence properties in the case when either the objective function or the feasible set are strongly convex, which is the case with our single-unit formulations and can be enforced in the block case. Finally, we demonstrate numerically on a set of random and gene expression test problems that our approach outperforms existing algorithms both in quality of the obtained solution and in computational speed. © 2010 Michel Journée, Yurii Nesterov, Peter Richtárik and Rodolphe Sepulchre.

Computational engineering design for micro-scale combustion devices: A thermally improved configuration

A multi-objective design optimisation study has been carried out with the objectives to improve the overall efficiency of the device and to reduce the fuel consumption for the proposed micro-scale combustor design configuration. In a previous study we identified the topology of the combustion chamber that produced improved behaviour of the device in terms of the above design criteria. We now extend our design approach, and we propose a new configuration by the addition of a micro-cooling channel that will improve the thermal behaviour of the design as previously suggested in literature. Our initial numerical results revealed an improvement of 2.6% in the combustion efficiency when we applied the micro-cooling channel to an optimum design configuration we identified from our earlier multi-objective optimisation study, and under the same operating conditions. The computational modelling of the combustion process is implemented in the commercial computational fluid dynamics package ANSYS-CFX using Finite Rate Chemistry and a single step hydrogen-air reaction. With this model we try to balance good accuracy of the combustion solution and at the same time practicality within the context of an optimisation process. The whole design system comprises also the ANSYS-ICEM CFD package for the automatic geometry and mesh generation and the Multi-Objective Tabu Search algorithm for the design space exploration. We model the design problem with 5 geometrical parameters and 3 operational parameters subject to 5 design constraints that secure practicality and feasibility of the new optimum design configurations. The final results demonstrate the reliability and efficiency of the developed computational design system and most importantly we assess the practicality and manufacturability of the revealed optimum design configurations of micro-combustor devices. Copyright © 2013 by ASME.

Nanoengineering coaxial carbon nanotube-dual-polymer heterostructures.

We describe studies of new nanostructured materials consisting of carbon nanotubes wrapped in sequential coatings of two different semiconducting polymers, namely, poly(3-hexylthiophene) (P3HT) and poly(9,9'-dioctylfluorene-co-benzothiadiazole) (F8BT). Using absorption spectroscopy and steady-state and ultrafast photoluminescence measurements, we demonstrate the role of the different layer structures in controlling energy levels and charge transfer in both solution and film samples. By varying the simple solution processing steps, we can control the ordering and proportions of the wrapping polymers in the solid state. The resulting novel coaxial structures open up a variety of new applications for nanotube blends and are particularly promising for implementation into organic photovoltaic devices. The carbon nanotube template can also be used to optimize both the electronic properties and morphology of polymer composites in a much more controlled fashion than achieved previously, offering a route to producing a new generation of polymer nanostructures.