Dislocation dynamics modelling of the creep behaviour of particle-strengthened materials.

Plastic deformation in crystalline materials occurs through dislocation slip and strengthening is achieved with obstacles that hinder the motion of dislocations. At relatively low temperatures, dislocations bypass the particles by Orowan looping, particle shearing, cross-slip or a combination of these mechanisms. At elevated temperatures, atomic diffusivity becomes appreciable, so that dislocations can bypass the particles by climb processes. Climb plays a crucial role in the long-term durability or creep resistance of many structural materials, particularly under extreme conditions of load, temperature and radiation. Here we systematically examine dislocation-particle interaction mechanisms. The analysis is based on three-dimensional discrete dislocation dynamics simulations incorporating impenetrable particles, elastic interactions, dislocation self-climb, cross-slip and glide. The core diffusion dominated dislocation self-climb process is modelled based on a variational principle for the evolution of microstructures, and is coupled with dislocation glide and cross-slip by an adaptive time-stepping scheme to bridge the time scale separation. The stress field caused by particles is implemented based on the particle-matrix mismatch. This model is helpful for understanding the fundamental particle bypass mechanisms and clarifying the effects of dislocation glide, climb and cross-slip on creep deformation.

Fluorescence labelling of extracellular vesicles using a novel thiol-based strategy for quantitative analysis of cellular delivery and intracellular traffic.

Extracellular vesicles, including exosomes, are naturally derived nanovesicles generated in and released by numerous cell types. As extracellular entities they have the capacity to interact with neighbouring cells and distant tissues and affect physiological processes as well as being implicated in numerous diseases including tumorigenesis and neurodegeneration. They are also under intense investigation as delivery vectors for biotherapeutics. The ways in which EVs interact with recipient cells to influence cell physiology and deliver a macromolecular payload are at the early stages of exploration. A significant challenge within these studies is the ability to label EVs directly or indirectly with fluorescent probes to allow visualization without compromising functionality. Here, we present a thiol-based fluorescence labelling method allowing comprehensive analysis of the cellular uptake of prostate cancer derived EVs in live cells using confocal microscopy. Labelling of the EVs in this way did not influence their size and had no effect on their ability to induce differentiation of lung fibroblasts to myofibroblasts. For endocytosis analyses, depletion of key endocytic proteins and the use of chemical inhibitors (Dynasore, EIPA, Rottlerin and IPA-3) indicated that fluid-phase endocytosis and/or macropinocytosis was involved in EV internalisation. Over a period of six hours EVs were observed to increasingly co-localise with lysosomes, indicating a possible termination point following internalisation. Overall this method provides new opportunities for analysing the cellular dynamics of EVs as biological entities affecting cell and whole body physiology as well as investigating their potential as drug delivery vectors.

Initiation and growth kinetics of solidification cracking during welding of steel.

Solidification cracking is a key phenomenon associated with defect formation during welding. To elucidate the failure mechanisms, solidification cracking during arc welding of steel are investigated in situ with high-speed, high-energy synchrotron X-ray radiography. Damage initiates at relatively low true strain of about 3.1% in the form of micro-cavities at the weld subsurface where peak volumetric strain and triaxiality are localised. The initial micro-cavities, with sizes from 10 × 10-6 m to 27 × 10-6 m, are mostly formed in isolation as revealed by synchrotron X-ray micro-tomography. The growth of micro-cavities is driven by increasing strain induced to the solidifying steel. Cavities grow through coalescence of micro-cavities to form micro-cracks first and then through the propagation of micro-cracks. Cracks propagate from the core of the weld towards the free surface along the solidifying grain boundaries at a speed of 2-3 × 10-3 m s-1.

The effect of suction during die fill on a rotary tablet press.

Die fill on a rotary tablet press involves complex powder flow phenomena. Conventional techniques for measuring flowability do not normally provide information that is directly relevant to the design of powder feed systems or to the selection of press parameters for the die filling process. Sinka et al. [I.C. Sinka, L.C.R. Schneider, A.C.F. Cocks, Measurement of the flow properties of powders with special reference to die fill, in: International Journal of Pharmaceutics 280 (1-2) (2004) 27-38] used an experimental shoe-die system to characterise the flow behaviour of pharmaceutical powders. A rigorous data analysis procedure was developed by Schneider et al. [L.C.R. Schneider, I.C. Sinka, A.C.F. Cocks, Characterisation of the flow behaviour of pharmaceutical powders using a model die-shoe filling system, in: Powder Technology (in press)] to evaluate the experimental results, however, when scaling the results to a rotary tablet press, the die fill efficiency was underpredicted by a factor of approximately 2, because the experimental system did not capture major features of the rotary press flow process. The suction effect, whereby the lower punch is moved downwards while the top of the die is exposed to powder in the feed system, is a key element of the process. In this note we describe the development of a model shoe-die system that allows the effect of suction to be investigated. The results demonstrate the improvement offered by suction and illustrate how a fundamental understanding of die fill phenomena could assist the selection of process parameters to maximise the operational speed of a rotary press.

Measurement of the flow properties of powders with special reference to die fill.

The flow behaviour of four pharmaceutical powders was investigated using a model shoe-die-filling system. The variation of mass delivered to the die as a function of shoe velocity provides a measure of flowability. The paper discusses the concept of critical velocity, above which incomplete filling is observed, in the context of pharmaceutical powders. The filling process was recorded using a high-speed video system, which allowed the different flow patterns to be observed, and how this influences the critical velocity to be evaluated. The influence of humidity, which was investigated in detail for one of the powders, was found to be small. The initial conditioning of the material, the die opening and if die filling takes place in air or in vacuum, however, were found to change the flow behaviour significantly.

Crystalloids, colloids and kids: a review of paediatric burns in intensive care.

This is a retrospective review of all burns patients admitted to a paediatric intensive care unit (PICU) over a 7 year period. Resuscitation fluid therapy and clinical course are presented. Ninety-eight new burns victims were admitted with a mortality rate of 10.2%, all in burns of greater than 25% body surface area (BSA). The incidence of ARDS was 20%, with an 18% mortality rate. Of 85 patients with burns greater than 5% BSA, 33 received the hospital-recommended colloid-based resuscitation formula, 46 received a combination of crystalloids and colloids and in 6 patients the resuscitation regimen was not able to be determined. The aetiology, age distribution, sex ratio, severity of burns and length of stay in hospital did not alter significantly over the study period. The number of burns admissions to PICU increased, as did their duration of intubation and ICU stay. The hospital-recommended resuscitation formula consistently underestimated the fluid volume required for adequate resuscitation. No statistically significant difference in adverse effects was found between the resuscitation groups. This study is unable to recommend a definitive approach to the fluid resuscitation of burns shock in paediatrics and the best approach is one of meticulous fluid resuscitation titrated on clinical effect.

Modeling studies of the concurrent growth and neutralization of sulfuric acid aerosols under conditions in the human airways.

A kinetic model of coupled droplet growth, gas uptake, and chemical reaction has been used to examine the possible changes to sulfuric acid aerosols as a result of exposure to respiratory ammonia under the conditions in the human airways. Results for a wide range of initial droplet sizes and concentrations spanning the extremes of likely atmospheric conditions are presented. It is predicted that gas phase reactions of SO2 will not significantly affect the neutralizing capability of airways ammonia. The effects of physical and chemical parameters on aerosol neutralization and growth are discussed and in particular, predictions of neutralization in typical inhalation times for aerosols characteristic of severe persistent London fogs and modern urban conditions are compared. The analysis supports the suggestion that the London fog episodes were unique in the relationship of the acid droplets formed to the neutralizing capability of ammonia in the human airways and that simple extrapolation of mortality and morbidity data from such episodes to modern conditions is unlikely to be valid.