James A. Elliott

Positive and negative selection in transgenic mice expressing a T-cell receptor specific for influenza nucleoprotein and endogenous superantigen.

A transgenic mouse was generated expressing on most (>80%) of thymocytes and peripheral T cells a T-cell receptor isolated from a cytotoxic T-cell clone (F5). This clone is CD8+ and recognizes αα366-374 of the nucleoprotein (NP 366-374) of influenza virus (A/NT/60/68), in the context of Class ,MHC Db (Townsend et al., 1986). The receptor utilizes the Vβ11 and Vα4 gene segments for the β chain and α chain, respectively (Palmer et al., 1989). The usage of Vβ11 makes this TcR reactive to Class II IE molecules and an endogenous ligand recently identified as a product of the endogenous mammary tumour viruses (Mtv) 8, 9, and 11 (Dyson et al., 1991). Here we report the development of F5 transgenic T cells and their function in mice of the appropriate MHC (C57BL/10 H-2b, IE-) or in mice expressing Class II MHC IE (e.g., CBA/Ca H-2k and BALB/c H-2d) and the endogenous Mtv ligands. Positive selection of CD8+ T cells expressing the Vβ11 is seen in C57BL/10 transgenic mice (H-2b). Peripheral T cells from these mice are capable of killing target cells in an antigen-dependent manner after a period of in vitro culture with IL-2. In the presence of Class II MHC IE molecules and the endogenous Mtv ligand, most of the single-positive cells carrying the transgenic T-cell receptor are absent in the thymus. Unexpectedly, CD8+ peripheral T-cells in these (H-2k or H-2d) F5 mice are predominantly Vβ11 positive and also have the capacity to kill targets in an antigen-dependent manner. This is true even following backcrossing of the F5 TcR transgene to H-2d scid/scid mice, in which functional rearrangement of endogenous TcR alpha- and beta-chain genes is impaired.

Hydration of Nafion® studied by AFM and X-ray scattering

Nafion® is a commercially available perfluorosulphonate cation exchange membrane commonly used as a perm-selective separator in chlor-alkali electrolysers and as the electrolyte in solid polymer fuel cells. This usage arises because of its high mechanical, thermal and chemical stability coupled with its high conductivity and ionic selectivity, which depend strongly on the water content. The membrane was therefore studied in different states of hydration with two complementary techniques: atomic force microscopy (AFM) and small angle X-ray scattering (SAXS) combined with a maximum entropy (MaxEnt) reconstruction. Tapping mode phase imaging was successfully used to identify the hydrophobic and hydrophilic regions of Nafion. The images support the MaxEnt interpretation of a cluster model of ionic aggregation, with spacings between individual clusters ranging from 3 to 5 nm, aggregating to form cluster agglomerates with sizes from 5 to 30 nm. Both techniques indicate that the number density of ionic clusters changes as a function of water content, and this explains why the bulk volumetric swelling in water is observed to be significantly less than the swelling inferred from scattering measurements.

Optical microstructure and viscosity enhancement for an epoxy resin matrix containing multiwall carbon nanotubes

This paper describes rheological measurements and associated optical microstructural observations of multiwall carbon nanotubes (MWCNTs) suspended in an epoxy resin matrix. The base epoxy resin was found to be essentially Newtonian, and the progressive incorporation of nanotubes enhanced the low shear rate viscosity of the suspension by nearly two decades. At higher shear rates, the suspension viscosity asymptotically thinned to the viscosity of the matrix alone. The low shear rate viscosity enhancement was correlated with the optical observations of interconnected aggregates of carbon nanotubes, which themselves were induced by the low shear conditions. Intermediate shear rates resulted in a reduction in the size of the aggregates. High shear rates appeared to cause near-complete dispersal of the aggregates. From these results it is conjectured that for this suspension, shear thinning is connected with the breaking of the interconnected networks between nanotubes and or aggregates of nanotubes, and not b...

In-situ deformation of an open-cell flexible polyurethane foam characterised by 3D computed microtomography

The deformation behaviour of an open-cell flexible polyurethane foam was observed using X-ray microtomography on the ID19 beamline at the ESRF in Grenoble, France. Tomographs, consisting of 1024 voxels cubed, were collected with a voxel size of 6.6 μm from a small region near the centre of the foam at a range of compressive strains between 0 and 80%. The results show that the initial stages of compression are taken up by small amounts of elastic bending in struts that are inclined to the compression direction. At 23% strain, entirely collapsed bands were observed in the structure. By 63% strain, there was evidence of struts impinging on each other, corresponding to the densification regime. The compression of an irregular foam (i.e. one with strut length and cell size distributions) appears to involve a sudden change in modulus, accompanied by localised increases in density. Observations of this nature would have been extremely difficult to interpret unambiguously without the ability to carry out sequential microtomographic imaging under realistic in situ loading conditions. The process of finite element analysis (FEA) was begun by constructing node-strut models from the experimental data by a mathematical skeletonisation process. These were used to derive node coordination, strut-length and cell-size distributions. However, direct comparison of the elastic properties with FEA was hampered by the absence of periodicity in the experimentally determined foam structures.

Modelling of morphology and proton transport in PFSA membranes

Computational modelling studies of the structure of perfluorosulfonic acid (PFSA) ionomer membranes consistently exhibit a nanoscopic phase-separated morphology in which the ionic side chains and aqueous counterions segregate from the fluorocarbon backbone to form clusters or channels. Although these investigations do not unambiguously predict the size or shape of the clusters, and whether or not the channels percolate the matrix or if the connections between them are more transient, the sequence of co-monomers along the main chain appears strongly to influence the domain size of the ionic regions, with more blocky sequences giving rise to larger domain sizes. The fundamental insight that substantial rearrangement of the sulfonic acid terminated side chains and fluorocarbon backbone takes place during swelling or shrinkage is borne out by both molecular and mesoscale simulations of model PFSA polymers, along with ab initio electronic structure calculations of minimally hydrated oligomeric fragments. Molecular-level modelling of proton transport in PFSA membranes attests to the complexity of the underlying mechanisms and the need to examine the chemical and physical processes at several distinct time and length scales. These investigations have revealed that the conformation of the fluorocarbon backbone, flexibility of the sidechains, and degree of aggregation and association of the sulfonic acid groups under minimally hydrated conditions collectively control the dissociation of the protons and the formation of Zundel and Eigen cations. The former appear to be the dominant charge carriers when the limiting water content allows only for the formation of a contact ion pair with the tethered sulfonate anion. As the water content increases, solvent-separated Eigen ions begin to appear, indicating that the dominant mechanism for diffusion of protons occurs over a region approximately 4 A away from the sulfonate groups. Finally, both the vehicular and Grotthuss shuttling mechanisms contribute to the mobility of the protons but, surprisingly, they are not always correlated, resulting in a lower overall diffusion coefficient. In summary, as the preceding observations indicate, the state of computational modelling of PFSA membranes has progressed sufficiently over the last decade to enable its use as a powerful predictive tool with which to guide the process of designing novel membrane materials for fuel cell applications.

A Model for the Strength of Yarn-like Carbon Nanotube Fibers

A model for the strength of pure carbon nanotube (CNT) fibers is derived and parametrized using experimental data and computational simulations. The model points to the parameters of the subunits that must be optimized in order to produce improvements in the strength of the macroscopic CNT fiber, primarily nanotube length and shear strength between CNTs. Fractography analysis of the CNT fibers reveals a fibrous fracture surface and indicates that fiber strength originates from resistance to nanotube pull-out and is thus proportional to the nanotube-nanotube interface contact area and shear strength. The contact area between adjacent nanotubes is determined by their degree of polygonization or collapse, which in turn depends on their diameter and number of layers. We show that larger diameter tubes with fewer walls have a greater degree of contact, as determined by continuum elasticity theory, molecular mechanics, and image analysis of transmission electron micrographs. According to our model, the axial stress in the CNTs is built up by stress transfer between adjacent CNTs through shear and is thus proportional to CNT length, as supported by data in the literature for CNT fibers produced by different methods and research groups. Our CNT fibers have a yarn-like structure in that rather than being solid, they are made of a network of filament subunits. Indeed, the model is consistent with those developed for conventional yarn-like fibers.

Interaction of Ethanol and Water with the {101̅4} Surface of Calcite

Molecular dynamics simulations have been used to model the interaction between ethanol, water, and the {1014} surface of calcite. Our results demonstrate that a single ethanol molecule is able to form two interactions with the mineral surface (both Ca-O and O-H), resulting in a highly ordered, stable adsorption layer. In contrast, a single water molecule can only form one or other of these interactions and is thus less well bound, resulting in a more unstable adsorption layer. Consequently, when competitive adsorption is considered, ethanol dominates the adsorption layer that forms even when the starting configuration consists of a complete monolayer of water at the surface. The computational results are in good agreement with the results from atomic force microscopy experiments where it is observed that a layer of ethanol remains attached to the calcite surface, decreasing its ability to interact with water and for growth at the {1014} surface to occur. This observation, and its corresponding molecular explanation, may give some insight into the ability to control crystal form using mixtures of different organic solvents.

Computational Techniques at the Organic−Inorganic Interface in Biomineralization

Just over ninety years ago, the first edition of D’Arcy Thompson’s book On Growth and Form appeared. Much of it is long out of date, but D’Arcy Thompson makes a point of fundamental importance in his discussion of the morphology of inorganic crystals in biological systems. He points out that the deposition of minerals in the living body, the complex shapes and symmetries often seen, cannot be explained by simple ideas of crystal packing. He speculates (and in 1919 it could be no more than speculation) on the importance of “directing forces”, using the analogy of ordering in liquid crystals discussed in the work of Lehman. In some cases, it was already clear that a pre-existing template controlled the growth of the inorganic material and D’Arcy Thompson shows how the complex forms of the silicate skeletons of sponges and radiolarians can be explained using simple models based on froths and bubbles that somehow constrain the growth of the inorganic material in their interstices. This presence of some controlling growth mechanism distinguishes two kinds of biomineralization process. Biologically induced mineralization occurs when minerals form as a byproduct of the activity of cells or their interaction with the surrounding environment. The morphologies and phases observed are usually similar to those seen in nonbiological systems. Biologically controlled mineralization is regulated by the organism, and the resulting structures have a physiological function (or sometimes functions). In this review, we are concerned only with the second case, biologically controlled mineralization. * Address for corresponding author: Department of Engineering Materials, Sir Robert Hadfield Building, University of Sheffield, Mappin St., Sheffield S1 3JD, U.K. Telephone: +44 114 222 5957. Fax: +44 114 222 5943. E-mail: j.harding@sheffield.ac.uk. Chem. Rev. 2008, 108, 4823–4854 4823

Novel approaches to multiscale modelling in materials science

Abstract Computational modelling techniques are now widely employed in materials science, due to recent advances in computing power and simulation methodologies, since they can enable rapid testing of theoretical predictions or understanding of complex experimental data at relatively low cost. However, many problems at the leading edge of materials science involve collective phenomena that occur over a range of time and length scales which are intrinsically difficult to capture in a single simulation. This review summarises some of the latest developments in multiscale modelling techniques over the past decade, as applied to selected problems in materials science and engineering, thereby motivating the reader to explore how such techniques might be applied in their own area of specialty. Methods for accelerating molecular dynamics by enhancement of kinetic barrier crossing, such as hyperdynamics and metadynamics, are discussed alongside mesoscale simulation techniques, such as dissipative particle dynamics or adaptive coarse graining, for enabling larger and longer simulations. The applications are mainly focused on simulations of microstructure and mechanical properties, and examples of surface diffusion in metals, radiation damage in ceramics, strengthening of nanocrystalline metals and alloys, crack propagation in brittle solids, polymer chain relaxation in nanocomposites and the control of nucleation in biomimetic materials are discussed.

A comparative study of the hydrated morphologies of perfluorosulfonic acid fuel cell membranes with mesoscopic simulations

The hydrated morphology of Nafion, the short-side-chain (SSC), and 3M perfluorosulfonic acid (PFSA) fuel cell membranes have been investigated through dissipative particle dynamics (DPD) simulations as a function of ionomer equivalent weight (EW) and degree of hydration. Coarse-grained mesoscale models were constructed by dividing each hydrated ionomer into components consisting of: a common polytetrafluoroethylene backbone bead, ionomer specific backbone beads, a terminal side chain bead, and a bead consisting of a cluster of six water molecules. Flory–Huggins χ-parameters describing the interactions between the various DPD particles were calculated. Equilibrated morphologies were determined for the SSC and 3M PFSA membranes both at EWs of 678 and 978, and Nafion with an EW of 1244. The hydration level was varied in each system with water contents corresponding to 5, 7, 9, 11, and 16 H2O/SO3H. The high EW ionomers exhibit significantly greater dispersion of the water regions than the low EW membranes. Water contour plots reveal that as the hydration level is increased, the isolated water clusters present at the lower water contents increase in size eventually forming continuous regions resembling channels or pores particularly at a hydration of 16 H2O/SO3H. The DPD simulations reveal differences in the hydrated morphology when only the side chain length was altered and indicate that the 3MPFSA ionomer exhibits much larger clusters of water when compared to the SSC ionomer at the same EW and water content above 9 H2O/SO3H. The average size of the clusters were estimated from the water–water particles’ RDFs and vary from about 2 nm to nearly 13 nm for hydration levels from λ = 5 to λ = 16. Finally, computed Bragg spacing in each of the hydrated membranes indicate separation of the domains containing the water from 2 to 6 nm, exhibiting an approximately linear relationship with hydration.