Mixture density network training by computation in parameter space

Training Mixture Density Network (MDN) configurations within the NETLAB framework takes time due to the nature of the computation of the error function and the gradient of the error function. By optimising the computation of these functions, so that gradient information is computed in parameter space, training time is decreased by at least a factor of sixty for the example given. Decreased training time increases the spectrum of problems to which MDNs can be practically applied making the MDN framework an attractive method to the applied problem solver.

Inventory parameter management and focused continuous improvement for repetitive batch manufacturers

What this thesis proposes is a methodology to assist repetitive batch manufacturers in the adoption of certain aspects of the Lean Production principles. The methodology concentrates on the reduction of inventory through the setting of appropriate batch sizes, taking account of the effect of sequence dependent set-ups and the identification and elimination of bottlenecks. It uses a simple Pareto and modified EBQ based analysis technique to allocate items to period order day classes based on a combination of each item's annual usage value and set-up cost. The period order day classes the items are allocated to are determined by the constraints limits in the three measured dimensions, capacity, administration and finance. The methodology overcomes the limitations associated with MRP in the area of sequence dependent set-ups, and provides a simple way of setting planning parameters taking this effect into account by concentrating on the reduction of inventory through the systematic identification and elimination of bottlenecks through set-up reduction processes, so allowing batch sizes to reduce. It aims to help traditional repetitive batch manufacturers in a route to continual improvement by: Highlighting those areas where change would bring the greatest benefits. Modelling the effect of proposed changes. Quantifying the benefits that could be gained through implementing the proposed changes. Simplifying the effort required to perform the modelling process. It concentrates on increasing flexibility through managed inventory reduction through rationally decreasing batch sizes, taking account of sequence dependent set-ups and the identification and elimination of bottlenecks. This was achieved through the development of a software modelling tool, and validated through a case study approach.

The use of microviscometry to study polymer dissolution from solid dispersion drug delivery systems

Solid dispersions can be used to improve dissolution of poorly soluble drugs and PVP is a common polymeric carrier in such systems. The mechanisms controlling release of drug from solid dispersions are not fully understood and proposed theories are dependent on an understanding of the dissolution behaviour of both components of the dispersion. This study uses microviscometry to measure small changes in the viscosity of the dissolution medium as the polymer dissolves from ibuprofen-PVP solid dispersions. The microviscometer determines the dynamic and kinematic viscosity of liquids based on the rolling/falling ball principle. Using a standard USP dissolution apparatus, the dissolution of the polymer from the solid dispersion was easily measured alongside drug release. Drug release was found to closely follow polymer dissolution at the molecular weights and ratios used. The combination of sensitivity and ease of use make microviscometry a valuable technique for the elucidation of mechanisms governing drug release from polymeric delivery systems. © 2004 Elsevier B.V. All rights reserved.

Systems biology approach to study permeability of paracetamol and its solid dispersion

Physiological changes that take place at cellular level are usually reflective of their level of gene expression. Different formulation excipients have an impact on physiological behavior of the exposed cells and in turn affect transporter genes, enterocyte-mediated metabolism and toxicity biomarkers. The aim of this study was to prepare solid dispersion of paracetamol and evaluate genetic changes that occur in Caco-2 cell lines during the permeability of paracetamol alone and paracetamol solid dispersion formulations. Paracetamol-PEG 8000 solid dispersion was prepared by melt fusion method and the formulation was characterised using differential scanning calorimetry (DSC), scanning electron microscopy (SEM) and Fourier transform infrared spectroscopy (FTIR). Formulation of solid dispersion resulted in the conversion of crystalline drug into an amorphous form. Permeability studies showed that paracetamol absorption was higher from the solid dispersion formulation. DNA microarrays analysis was carried out in order to investigate the involvement of any efflux/uptake transporters in paracetamol or its solid dispersion permeability. Neither transporter carriers nor efflux proteins were found to be involved in the absorption of paracetamol or its PEG solid dispersion. Gene expression analysis established that paracetamol toxicity was potentially reduced upon formulation into solid dispersion when ATP binding cassette (ABC) and solute carrier transporter (SLC) genes were analyzed.

Emulation of random output simulators

Computer models, or simulators, are widely used in a range of scientific fields to aid understanding of the processes involved and make predictions. Such simulators are often computationally demanding and are thus not amenable to statistical analysis. Emulators provide a statistical approximation, or surrogate, for the simulators accounting for the additional approximation uncertainty. This thesis develops a novel sequential screening method to reduce the set of simulator variables considered during emulation. This screening method is shown to require fewer simulator evaluations than existing approaches. Utilising the lower dimensional active variable set simplifies subsequent emulation analysis. For random output, or stochastic, simulators the output dispersion, and thus variance, is typically a function of the inputs. This work extends the emulator framework to account for such heteroscedasticity by constructing two new heteroscedastic Gaussian process representations and proposes an experimental design technique to optimally learn the model parameters. The design criterion is an extension of Fisher information to heteroscedastic variance models. Replicated observations are efficiently handled in both the design and model inference stages. Through a series of simulation experiments on both synthetic and real world simulators, the emulators inferred on optimal designs with replicated observations are shown to outperform equivalent models inferred on space-filling replicate-free designs in terms of both model parameter uncertainty and predictive variance.

Polarisation mode dispersion induced transmission penalties for long-haul high speed optical communication systems

Results of full numerical simulations of a guiding-centre soliton system with randomly birefringent SMF fibre are shown and analysed. It emerges that the soliton system becomes unstable even for small amounts of PMD.

Simulation of guiding-centre soliton transmission system stability in the presence of polarisation mode dispersion

Results of full numerical simulations of a guiding-centre soliton system with randomly birefringent SMF fibre are shown and analysed. It emerges that the soliton system becomes unstable even for small amounts of PMD.

Polarisation mode dispersion correlations with the coarse-step method

Having a fixed differential-group delay (DGD) term b′ in the coarse-step method results in a repetitive pattern in the autocorrelation function (ACF). We solve this problem by inserting a varying DGD term at each integration step. Furthermore we compute the range of values needed for b′ and simulate the phenomenon of polarisation mode dispersion for different statistical distributions of b′. We examine systematically the modified coarse-step method compared to the analytical model, through our simulation results. © 2006 Elsevier B.V. All rights reserved.

Numerical Q parameter estimates for scalar and vector models in optical communication system simulations

The Q parameter scales differently with the noise power for the signal-noise and the noise-noise beating terms in scalar and vector models. Some procedures for including noise in the scalar model largely under-estimate the Q parameter. We propose a simple method for including noise within a scalar model which will allow both the noise-noise dominated limit and the signal-noise dominated limit to be treated consistently. © 2005 Elsevier B.V. All rights reserved.

Tunable compensation of second and third order dispersion by non-uniformly strained chirped fibre Bragg grating

A novel fibre grating device is demonstrated with tuneable chromatic dispersion slope. The tuning range is 70 to 190 ps/nm and 0 to 25 ps/nm2 for the second and third order dispersion, respectively.

Q parameter scaling in scalar and vector models with dominant signal-noise and noise-noise beating terms

The Q parameter scales differently with the noise power for the signal-noise and the noise-noise beating terms in scalar and vector models. Some procedures for including noise in the scalar model largely under-estimate the Q parameter.

Experimental observation of autosoliton propagation in a dispersion-managed system guided by nonlinear optical loop mirrors

Observation of autosoliton propagation in a dispersion-managed optical transmission system controlled by in-line nonlinear fiber loop switches is reported for what is believed to be the first time. The system is based on a strong dispersion map with large amplifier spacing. Operation at transmission rates of 10 and 40 Gbits/s is demonstrated. ©2004 Optical Society of America.

Stable propagation of solitons with increased energy through the combined action of dispersion management and periodic saturable absorption

It is shown, through numerical simulations, that by using a combination of dispersion management and periodic saturable absorption it is possible to transmit solitonlike pulses with greatly increased energy near to the zero net dispersion wavelength. This system is shown to support the stable propagation of solitons over transoceanic distances for a wide range of input powers.