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No description available.

No description available.

No description available.

No description available.

No description available.

Three nanoparticle systems were investigated for the nano-encapsulation and release of bioactive molecules. The first series of hydroxyethyl methacrylate-co-carboxyethyl acrylate random polymers were found, above their critical aggregation concentration (CAC), to self-assemble into spherical nanoparticles which dissociated when the external pH rose above 4. The second and third series were core:shell microgels, crosslinked with ethylene glycol dimethacrylate (EGDMA), made from a core composed of hydroxyethyl methacrylate (HEMA) and a carboxyethyl acrylate (CEA) shell which underwent volume transitions when the external solution was raised above pH 4. These nanoparticle systems were investigated using proton NMR, zeta-potential, dynamic light scattering (DLS), potentiometric titrations, gel permeation chromatography (GPC) and turbidity studies. The shape, morphology and core:shell architecture were imaged using transmission electron microscopy (TEM) staining with uranyl acetate and phosphotungstic acid (PTA), Cryo-TEM, scanning electron microscopy (SEM), cryo-SEM, confocal microscopy and optical microscopy. The micro gels were all shown to have good biocompatibility by slug mucosal tests. The uptake and release of three dyes; Rhodamine 6G, Coumarin 153, and 9-diethylamino-5-benzo[a]phenoxazinone (Nile red) were investigated. High uptake of the dye molecules was observed at pH 4 and high release at pH 7, with microgel particle separation from the aqueous solution being achieved by centrifugation. The micro gel systems were investigated for the uptake of the model pharmaceuticals paracetamol, caffeine, dopamine, ibuprofen, carbamazepine and riboflavin; all of which have been detected globally in drinking water supplies. The uptake of pharmaceuticals by the microgel systems was shown to be low at both pH 4 and pH 7. The low uptake was concluded to be caused by the carboxylic acids groups localised on the microgel surface creating a collapsed skin layer, so inhibiting the inward diffusion of additional drugs. The uptake and release experiments were performed using spectrofluorescence analysis and UV -visible spectrometry. All three nanoparticulate systems were filterable from aqueous media at low (15 psi) pressure using lab-cast polyethersulphone (PES) ultrafiltration membranes with a molecular weight cut off (MWCO) of 10kDa.

After years of research of the marine environments, its potential for drug discovery have been corroborated by the introduction of important therapeutic compounds such as Prialt, which is indicated for the management of severe chronic pain; and Yondelis for the treatment of advanced soft tissue sarcoma; as well as the promises of compounds such as salinosporamide A from the actinomycete Salinispora tropica.

In this study, "click chemistry" was used to assemble a collection of potential glycosidase inhibitors. Using different "click chemistry" conditions, 21 α-D- and β-D glucopyranosyl triazoles were synthesised and assayed as inhibitors of sweet almond β-glucosidase and yeast α-glucosidase. A set of moderately effective glycosidase inhibitors was identified. In the course of this work significant differences in the reactivity of the α- and β-glucopyranosyl azides under CuAAC conditions was noted. This matter was investigated by X-ray crystallography and, in keeping with the anomeric effect, pointed to a difference in partial charge distribution in the azide and sugar moieties. Starting from maltosyl and maltotriosyl azides another collection of 12 triazoles was synthesised and all of the libraries were assayed against starch degrading enzymes from barley. A moderate inhibitor of α-glucosidase was identified, as were several weak inhibitors of β-amylase.

One of the key problems in the new science of systems biology is inferring rate parameters for complex stochastic kinetic biochemical network models, using partial and discrete time- course measurements of the system state. Although exact inference for stochastic models is possible (Boys et al., 2008), it is computationally intensive for relatively small networks. We explore the Bayesian estimation of stochastic kinetic rate parameters using approximate methods, based on moment closure analysis of the underlying stochastic process. Moment closure has been widely studied and applied in many areas. In addition to using previous methodology, we introduce a technique to perform moment closure on models with rational rate laws, allowing applications to a larger class of models. By assuming a Gaussian distribution and using moment-closure estimates of the first two moments, we can greatly increase the speed of parameter inference. The parameter space can be efficiently explored by embedding this approximation into an MCMC procedure. Mixing problems often occur when estimating latent data values. We tackle this problem using a block updating approach conditioning on all adjacent data points. Sporulation in the bacteria Bacillus subtilis is a well studied mechanism of survival, yet in practice there are large costs associated with gene knockouts and laboratory experiments. We built a stochastic model of this process allowing for external factors that trigger sporulation, such as the response from the gene lexA to external factors endangering Bacillus subtilis. The calibration of the model is done with fluorescence microscopy data readings of levels of the GFP protein (Veening et al., 2009). Predictions were made from the model as to which gene knockouts would have large effects on the proportion of Bacillus subtilis that would sporulate.