Novel hydrogels for keratoprosthesis

Hydrogels may be described as cross~linked hydrophilic polymers that swell but do not dissolve in water. They have been utilised in many biomedical applications, as there is the potential to manipulate the properties for a given application by changing the chemical structure of the constituent monomers. This project is focused on the development of novel hydrogels for keratoprosthesis (KPro). The most commonly used KPro model consists of a tansparent central stem witb a porous peripheral skirt. Clear poly (methyl methacrylate) (PMMA) core material used in the Strampelli KPros prosthesis has not been the cause of failure found in other core and skirt prostheses. However, epithelialization of this kind of solid, rigid optic material is clearly impossible. The approach to the development of a hydrogeJ for potential KPro use adopted in this work is to develop soft core material to mimic the properties of the natural cornea by incorporating some hydrophilic monomers such as N, N-dimethyacrylamide (NNSMA) N~vinyl pyrrolidone (NVP) and acryloylmorpholine (AMO) with methyl methactylate (MMA). Most of these materials have been used in other ophthalmic applications, such as contact lens. However, an unavoidable limitation of simple .MMA copolymers as conventional hydrogels is poor mechanical strength. The hydrogel for use in this application must be able to withstand the stresses involved during the surgical procedure involved with KPro surgery and the in situ stresses such as the deforming force of the eyelid during the blink cycle. Thus, semi-interpenetrating polymer networks (SIPNs) based on ester polyurethane, AMO, NVP and NNDMA were examined in this work and were found to have much improved mechanical properties at water contents between 40% and 70%. Polyethylene glycol monomethacrylate (PEG MA) was successfully incorporated in order to modulate protein deposition and cell adhesion. Porous peripheral skirts were fabricated using different types of porosigen. The water content mechanical properties, surface properties and cell response of these various materials have been investigated in this thesis. These studies demonstrated that simple hydrogel SIPNs which show isotropic mechanical behaviour, are not ideal KPro materials since they do not mimic the anisotropic behaviour of natural cornea. The final stage of the work has concentrated on the study of hydrogels reinforced with mesh materials. They offer a promising approach to making a hydrogel that is very flexible but strong under tension, thereby having mechanical properties closer to the natural cornea than has been previously possible.

A comparison of variational and Markov chain Monte Carlo methods for inference in partially observed stochastic dynamic systems

In recent work we have developed a novel variational inference method for partially observed systems governed by stochastic differential equations. In this paper we provide a comparison of the Variational Gaussian Process Smoother with an exact solution computed using a Hybrid Monte Carlo approach to path sampling, applied to a stochastic double well potential model. It is demonstrated that the variational smoother provides us a very accurate estimate of mean path while conditional variance is slightly underestimated. We conclude with some remarks as to the advantages and disadvantages of the variational smoother. © 2008 Springer Science + Business Media LLC.

Changing career models and capacity for innovation in professional services

A number of professional sectors have recently moved away from their longstanding career model of up-or-out promotion and embraced innovative alternatives. Professional labor is a critical resource in professional service firms. Therefore, changes to these internal labor markets are likely to trigger other innovations, for example in knowledge management, incentive schemes and team composition. In this chapter we look at how new career models affect the core organizing model of professional firms and, in turn, their capacity for and processes of innovation. We consider how professional firms link the development of human capital and the division of professional labor to distinctive demands for innovation and how novel career systems help them respond to these demands.

Protein interactions studied by SAXS:effect of ionic strength and protein concentration for BSA in aqueous solutions

We have studied a series of samples of bovine serum albumin (BSA) solutions with protein concentration, c, ranging from 2 to 500 mg/mL and ionic strength, I, from 0 to 2 M by small-angle X-ray scattering (SAXS). The scattering intensity distribution was compared to simulations using an oblate ellipsoid form factor with radii of 17 x 42 x 42 A, combined with either a screened Coulomb, repulsive structure factor, S-SC(q), or an attractive square-well structure factor, S-SW(q). At pH = 7, BSA is negatively charged. At low ionic strength, I <0.3 M, the total interaction exhibits a decrease of the repulsive interaction when compared to the salt-free solution, as the net surface charge is screened, and the data can be fitted by assuming an ellipsoid form factor and screened Coulomb interaction. At moderate ionic strength (0.3-0.5 M), the interaction is rather weak, and a hard-sphere structure factor has been used to simulate the data with a higher volume fraction. Upon further increase of the ionic strength (I >= 1.0 M), the overall interaction potential was dominated by an additional attractive potential, and the data could be successfully fitted by an ellipsoid form factor and a square-well potential model. The fit parameters, well depth and well width, indicate that the attractive potential caused by a high salt concentration is weak and long-ranged. Although the long-range, attractive potential dominated the protein interaction, no gelation or precipitation was observed in any of the samples. This is explained by the increase of a short-range, repulsive interaction between protein molecules by forming a hydration layer with increasing salt concentration. The competition between long-range, attractive and short-range, repulsive interactions accounted for the stability of concentrated BSA solution at high ionic strength.

Glucosamine-induced insulin resistance in L6 muscle cells

Background: Glucosamine increases flux through the hexosamine pathway, causing insulin resistance and disturbances similar to diabetic glucose toxicity. Aim: This study examines the effect of glucosamine on glucose uptake by cultured L6 muscle cells as a model of insulin resistance. Methods: Glucose uptake by L6 myotubes was measured using the non-metabolized glucose analogue 2-deoxy-D-glucose after incubation with glucosamine for 4 and 24 h, with and without insulin and several other agents (metformin, peroxovanadium and D-pinitol) that improve glucose uptake in diabetic states. Results: After 4 h, high concentrations of glucosamine (5 × 10-3 and 10-2 M) reduced basal and insulin-stimulated glucose uptake by up to 50%. After 24 h, the effect of insulin was completely abolished by 10-2 M glucosamine and reduced over 50% by 5 × 10-3 M glucosamine. Lower concentrations of glucosamine did not significantly alter glucose uptake. The effect of glucosamine could not be attributed to cytotoxicity assessed by the Trypan Blue test. Metformin, peroxovanadium and D-pinitol, each of which increased glucose uptake by L6 cells, did not prevent the decrease in glucose uptake with glucosamine. Conclusion: Glucosamine decreased insulin-stimulated glucose uptake by L6 muscle cells, providing a potential model of insulin resistance with similarities to glucose toxicity. Insulin resistance induced by glucosamine was not reversed by three agents (metformin, peroxovanadium and D-pinitol) known to enhance or partially mimic the effects of insulin. © 2004 Blackwell Publishing Ltd.

An X-ray micro-fluorescence study to investigate the distribution of Al, Si, P and Ca ions in the surrounding soft tissue after implantation of a calcium phosphate-mullite ceramic composite in a rabbit animal model

Synthetic calcium phosphates, despite their bioactivity, are brittle. Calcium phosphate-mullite composites have been suggested as potential dental and bone replacement materials which exhibit increased toughness. Aluminium, present in mullite, has however been linked to bone demineralisation and neurotoxicity: it is therefore important to characterise the materials fully in order to understand their in vivo behaviour. The present work reports the compositional mapping of the interfacial region of a calcium phosphate-20 wt% mullite biocomposite/soft tissue interface, obtained from the samples implanted into the long bones of healthy rabbits according to standard protocols (ISO-10993) for up to 12 weeks. X-ray micro-fluorescence was used to map simultaneously the distribution of Al, P, Si and Ca across the ceramic-soft tissue interface. A well defined and sharp interface region was present between the ceramic and the surrounding soft tissue for each time period examined. The concentration of Al in the surrounding tissue was found to fall by two orders of magnitude, to the background level, within similar to 35 mu m of the implanted ceramic.