Requirement of the NPXY motif in the integrin beta 3 subunit cytoplasmic tail for melanoma cell migration in vitro and in vivo.

The NPXY sequence is highly conserved among integrin beta subunit cytoplasmic tails, suggesting that it plays a fundamental role in regulating integrin-mediated function. Evidence is provided that the NPXY structural motif within the beta 3 subunit, comprising residues 744-747, is essential for cell morphological and migratory responses mediated by integrin alpha v beta 3 in vitro and in vivo. Transfection of CS-1 melanoma cells with a cDNA encoding the wild-type integrin beta 3 subunit, results in de novo alpha v beta 3 expression and cell attachment, spreading, and migration on vitronectin. CS-1 cells expressing alpha v beta 3 with mutations that disrupt the NPXY sequence interact with soluble vitronectin or an RGD peptide, yet fail to attach, spread, or migrate on immobilized ligand. The biological consequences of these observations are underscored by the finding that CS-1 cells expressing wild-type alpha v beta 3 acquire the capacity to form spontaneous pulmonary metastases in the chick embryo when grown on the chorioallantoic membrane. However, migration-deficient CS-1 cells expressing alpha v beta 3 with mutations in the NPXY sequence lose this ability to metastasize. These findings demonstrate that the NPXY motif within the integrin beta 3 cytoplasmic tail is essential for alpha v beta 3-dependent post-ligand binding events involved in cell migration and the metastatic phenotype of melanoma cells

Performance of a carbon/carbon composite clutch during Formula One race start conditions

A single clutch-plate interface dynamometer (SCID) was designed and commissioned to facilitate friction and thermal performance testing of single clutch-plate pairs. Narrow (~2mm) high-temperature (1300-1650°C) hot bands were observed during SCID tests at high rotational speeds and clamp loads typical of race starts. Migration of the hot bands occurred between successive engagements but not during single engagements. Scanning electron microscope (SEM) images showed that the thickness of the friction film formed on the friction surfaces appeared to become thicker as the amount of friction work increased. A thermomechanically coupled finite element analysis (TCFEA) was then developed by coupling Matlab and Abaqus to simulate the thermo-mechanical response of a single clutch-plate pair during SCID testing. With allowance for wear, the model predicts high degrees of contact localisation resulting in a single distinct hot band of comparable temperature and width to those recorded during SCID testing

Optimisation of alumina coated lightweight brake rotor

Aluminium alloys have been used extensively in the automotive industry to reduce the weight of a vehicle and improve fuel consumption which in turn leads to a reduction in engine emissions. The main aim of the current study is to replace the conventional cast iron rotor material with a lightweight alternative such as coated aluminium alloy. The main challenge has been to meet both the cost and functional demands of modern mass-produced automotive braking systems. A sensitivity analysis based on the Taguchi approach was carried out to investigate the effect of various parameters on the thermal performance of a typical candidate disc brake. Wrought aluminium disc brake rotors coated with alumina on the rubbing surfaces were determined to have the best potential for replacing the conventional cast iron rotor at reasonable cost. Optimisation of the structure was subsequently carried out using a genetic algorithm on the selected coated aluminium disc brake rotor. This determines the optimum thickness of the coating and the composition of the substrate based on selected criteria. Prototype aluminium disc brake rotors were coated with alumina using the Plasma Electrolytic Oxidation (PEO) technique and the thermal performance of these lightweight rotors was investigated experimentally using a brake dynamometer. A high speed thermal imaging system was used to evaluate and measure the rubbing surface temperature of the coated brake rotors. The experimental results showed generally good agreement with the numerical predictions. The coated wrought aluminium disc brake rotor was demonstrated to give good thermal and friction performance up to relatively high rubbing surface temperatures of the order of 500°C

Airflow Simulation and Measurement of Brake Wear Particle Emissions with a Novel Test Rig

Particle emissions generated by the braking systems of road vehicles represents a significant non-exhaust contributor. Fine particles such as these are transported through airborne routes. They are known to adversely affect human health and currently there are no policies in place to regulate them. Before this issue can be addressed, it is important to characterise brake wear debris which is the purpose of this study. A newly-developed test rig consisting of a closed but ventilated enclosure surrounds a brake dynamometer equipped with a cast iron rotor. A sampling probe was made in accordance with the isokinetic principles in order to withdraw a representative aerosol sample from the outlet duct. Measurements of real-time particulate numbers and mass distributions are recorded using a Dekati ELPI®+ unit and the brake materials were tested under drag-braking conditions. Prior to measurements, Computational Fluid Dynamics (CFD) simulations were performed to investigate the most suitable sampling points used in the experiments. Preliminary experimental results show that there is a noticeable increase in particle numbers, compared to background levels, with a corresponding change in the mass distribution; coarser particles become more prominent during these braking events. These results provide confidence in the performance of the test rig and its ability to measure airborne brake wear debris in order to compare emissions from various friction pairs

Turing mechanism for homeostatic control of synaptic density during C. elegans growth

We propose a mechanism for the homeostatic control of synapses along the ventral cord of Caenorhabditis elegans during development, based on a form of Turing pattern formation on a growing domain. C. elegans is an important animal model for understanding cellular mechanisms underlying learning and memory. Our mathematical model consists of two interacting chemical species, where one is passively diffusing and the other is actively trafficked by molecular motors, which switch between forward and backward moving states (bidirectional transport). This differs significantly from the standard mechanism for Turing pattern formation based on the interaction between fast and slow diffusing species. We derive evolution equations for the chemical concentrations on a slowly growing one-dimensional domain, and use numerical simulations to demonstrate the insertion of new concentration peaks as the length increases. Taking the passive component to be the protein kinase CaMKII and the active component to be the glutamate receptor GLR-1, we interpret the concentration peaks as sites of new synapses along the length of C. elegans, and thus show how the density of synaptic sites can be maintained

A mechanism for Turing pattern formation with active and passive transport

We propose a novel mechanism for Turing pattern formation that provides a possible explanation for the regular spacing of synaptic puncta along the ventral cord of C. elegans during development. The model consists of two interacting chemical species, where one is passively diffusing and the other is actively trafficked by molecular motors. We identify the former as the kinase CaMKII and the latter as the glutamate receptor GLR-1. We focus on a one-dimensional model in which the motor-driven chemical switches between forward and backward moving states with identical speeds. We use linear stability analysis to derive conditions on the associated nonlinear interaction functions for which a Turing instability can occur. We find that the dimensionless quantity γ = αd/v2 has to be sufficiently small for patterns to emerge, where α is the switching rate between motor states, v is the motor speed, and d is the passive diffusion coefficient. One consequence is that patterns emerge outside the parameter regime of fast switching where the model effectively reduces to a twocomponent reaction-diffusion system. Numerical simulations of the model using experimentally based parameter values generates patterns with a wavelength consistent with the synaptic spacing found in C. elegans. Finally, in the case of biased transport, we show that the system supports spatially periodic patterns in the presence of boundary forcing, analogous to flow distributed structures in reaction-diffusion-advection systems. Such forcing could represent the insertion of new motor-bound GLR-1 from the soma of ventral cord neurons

An Instrumented Walking-Aid to Assess and Retrain Gait

An instrumented walking-aid, the iWA system, has been developed to measure kinematic and kinetic properties of walking aid (WA) use and deliver feedback to improve gait. The clinical requirements, technical specification and design of the system are developed through clinical collaboration. The development of the system is described, including hardware components and data analysis used to process the measured data for assessment. The system measurements are validated under controlled laboratory conditions. The iWA system is evaluated in a typical UK clinical environment by a participant in a rehabilitation session. The resultant data successfully capture the quality of the participant’s walking aid use and agree with clinical opinion, supporting the efficacy of this approach

Bifurcation analysis of pattern formation in a two-dimensional hybrid reaction–transport model

Following up on our work on Turing pattern formation in a one-dimensional reaction-transport model, we explore the emergence of patterns in a two dimensional model described by a system of PDEs for passively transported diffusing particles (PT) and actively transported motor-driven particles (AT). We first propose a model where the actively transported particles are taken to be functions of spatial locations x ∈ R and velocity v. We then consider two special simplifying cases where particles are transported at (i) constant speeds v so that the concentration of AT particles is taken to be a function of spatial location and velocity angle θ ∈ S 1 and (ii) discrete velocities (still with constant speed) in directions along a lattice tiling the plane. In the former case the system is equivariant with respect to the so called shift-twist action of the Euclidean group E(2) acting on functions on R 2 × S 1 , while in the latter case it is equivariant with respect to the group DN n R2 where DN (N = 4 for square and N = 6 for hexagonal) is the holohedry group of the lattice. In both cases, we use symmetric bifurcation theory to analyze the planforms emerging from a Turing bifurcation, should it occur. In the discrete velocity square lattice case, we are able to prove that a Turing bifurcation does indeed occur as the dimensionless parameter γ = αD/v2 crosses some critical value. Here, D is the diffusion coefficient for the passively diffusing particles and α is the switching rate between motor states

Thermal performance of peo coated lightweight brake rotors compared with grey cast iron

Brake rotors play a significant role in converting the vehicle kinetic energy into heat energy that is dissipated through conduction and convection. The automotive industry has been looking for many years to develop lightweight brake rotors to reduce vehicle weight and subsequently improve fuel efficiency and vehicle emissions targets. Uncoated wrought aluminium alloys and metal matrix composite (Al-MMC) rotors have been reported to have insufficient safety margin for most passenger car applications. In this study, the thermal performance of coated and uncoated lightweight aluminium disc brake rotors was investigated numerically and experimentally, using both small scale and full size brake dynamometers. Five small scale solid brake rotors were investigated: grey cast iron, forged aluminium alloy (6082), the same 6082 alloy but with an alumina surface layer applied by plasma electrolytic oxidation (PEO), cast aluminium MMC (AMC640XA), and the same MMC again with PEO alumina surface layer. The disc and pad temperatures, brake pressure, coefficient of friction and brake torque were monitored during the tests for each disc brake material. In addition, a two dimensional axisymmetric finite element model was developed using Abaqus software in order to investigate the temperature distribution through the disc. The 2D FE model demonstrated good overall agreement with the experimental results and showed the same general trends. It was found that the PEO coated aluminium alloy has the best overall performance of the lightweight rotors tested in terms of friction and structural integrity at elevated temperature

Testing stock market convergence: a non-linear factor approach

This paper applies the Phillips and Sul (Econometrica 75(6):1771–1855, 2007) method to test for convergence in stock returns to an extensive dataset including monthly stock price indices for five EU countries (Germany, France, the Netherlands, Ireland and the UK) as well as the US between 1973 and 2008. We carry out the analysis on both sectors and individual industries within sectors. As a first step, we use the Stock and Watson (J Am Stat Assoc 93(441):349–358, 1998) procedure to filter the data in order to extract the long-run component of the series; then, following Phillips and Sul (Econometrica 75(6):1771–1855, 2007), we estimate the relative transition parameters. In the case of sectoral indices we find convergence in the middle of the sample period, followed by divergence, and detect four (two large and two small) clusters. The analysis at a disaggregate, industry level again points to convergence in the middle of the sample, and subsequent divergence, but a much larger number of clusters is now found. Splitting the cross-section into two subgroups including euro area countries, the UK and the US respectively, provides evidence of a global convergence/divergence process not obviously influenced by EU policies