A study of the micro-mechanics of granular media

The development of more realistic constitutive models for granular media, such as sand, requires ingredients which take into account the internal micro-mechanical response to deformation. Unfortunately, at present, very little is known about these mechanisms and therefore it is instructive to find out more about the internal nature of granular samples by conducting suitable tests. In contrast to physical testing the method of investigation used in this study employs the Distinct Element Method. This is a computer based, iterative, time-dependent technique that allows the deformation of granular assemblies to be numerically simulated. By making assumptions regarding contact stiffnesses each individual contact force can be measured and by resolution particle centroid forces can be calculated. Then by dividing particle forces by their respective mass, particle centroid velocities and displacements are obtained by numerical integration. The Distinct Element Method is incorporated into a computer program 'Ball'. This program is effectively a numerical apparatus which forms a logical housing for this method and allows data input and output, and also provides testing control. By using this numerical apparatus tests have been carried out on disc assemblies and many new interesting observations regarding the micromechanical behaviour are revealed. In order to relate the observed microscopic mechanisms of deformation to the flow of the granular system two separate approaches have been used. Firstly a constitutive model has been developed which describes the yield function, flow rule and translation rule for regular assemblies of spheres and discs when subjected to coaxial deformation. Secondly statistical analyses have been carried out using data which was extracted from the simulation tests. These analyses define and quantify granular structure and then show how the force and velocity distributions use the structure to produce the corresponding stress and strain-rate tensors.

Developing a scalable model of recombinant protein yield from Pichia pastoris:the influence of culture conditions, biomass and induction regime

Background The optimisation and scale-up of process conditions leading to high yields of recombinant proteins is an enduring bottleneck in the post-genomic sciences. Typical experiments rely on varying selected parameters through repeated rounds of trial-and-error optimisation. To rationalise this, several groups have recently adopted the 'design of experiments' (DoE) approach frequently used in industry. Studies have focused on parameters such as medium composition, nutrient feed rates and induction of expression in shake flasks or bioreactors, as well as oxygen transfer rates in micro-well plates. In this study we wanted to generate a predictive model that described small-scale screens and to test its scalability to bioreactors. Results Here we demonstrate how the use of a DoE approach in a multi-well mini-bioreactor permitted the rapid establishment of high yielding production phase conditions that could be transferred to a 7 L bioreactor. Using green fluorescent protein secreted from Pichia pastoris, we derived a predictive model of protein yield as a function of the three most commonly-varied process parameters: temperature, pH and the percentage of dissolved oxygen in the culture medium. Importantly, when yield was normalised to culture volume and density, the model was scalable from mL to L working volumes. By increasing pre-induction biomass accumulation, model-predicted yields were further improved. Yield improvement was most significant, however, on varying the fed-batch induction regime to minimise methanol accumulation so that the productivity of the culture increased throughout the whole induction period. These findings suggest the importance of matching the rate of protein production with the host metabolism. Conclusion We demonstrate how a rational, stepwise approach to recombinant protein production screens can reduce process development time.

A generalized Drucker–Prager viscoplastic yield surface model for asphalt concrete

A generalized Drucker–Prager (GD–P) viscoplastic yield surface model was developed and validated for asphalt concrete. The GD–P model was formulated based on fabric tensor modified stresses to consider the material inherent anisotropy. A smooth and convex octahedral yield surface function was developed in the GD–P model to characterize the full range of the internal friction angles from 0° to 90°. In contrast, the existing Extended Drucker–Prager (ED–P) was demonstrated to be applicable only for a material that has an internal friction angle less than 22°. Laboratory tests were performed to evaluate the anisotropic effect and to validate the GD–P model. Results indicated that (1) the yield stresses of an isotropic yield surface model are greater in compression and less in extension than that of an anisotropic model, which can result in an under-prediction of the viscoplastic deformation; and (2) the yield stresses predicted by the GD–P model matched well with the experimental results of the octahedral shear strength tests at different normal and confining stresses. By contrast, the ED–P model over-predicted the octahedral yield stresses, which can lead to an under-prediction of the permanent deformation. In summary, the rutting depth of an asphalt pavement would be underestimated without considering anisotropy and convexity of the yield surface for asphalt concrete. The proposed GD–P model was demonstrated to be capable of overcoming these limitations of the existing yield surface models for the asphalt concrete.