A self-referenced optical intensity sensor network using POFBGs for biomedical applications

This work bridges the gap between the remote interrogation of multiple optical sensors and the advantages of using inherently biocompatible low-cost polymer optical fiber (POF)-based photonic sensing. A novel hybrid sensor network combining both silica fiber Bragg gratings (FBG) and polymer FBGs (POFBG) is analyzed. The topology is compatible with WDM networks so multiple remote sensors can be addressed providing high scalability. A central monitoring unit with virtual data processing is implemented, which could be remotely located up to units of km away. The feasibility of the proposed solution for potential medical environments and biomedical applications is shown.

The role of the innate immune system in the clearance of apoptotic cells

Rapid clearance of dying cells is a vital feature of apoptosis throughout development, tissue homeostasis and resolution of inflammation. The phagocytic removal of apoptotic cells is mediated by both professional and amateur phagocytes, armed with a series of pattern recognition receptors that participate in host defence and apoptotic cell clearance. CD14 is one such molecule. It is involved in apoptotic cell clearance (known to be immunosuppressive and anti-inflammatory) and binding of the pathogen-associated molecular pattern, lipopolysaccharides (a pro-inflammatory event). Thus CD14 is involved in the assembly of two distinct ligand-dependent macrophage responses. This project sought to characterise the involvement of the innate immune system, particularly CD14, in the removal of apoptotic cells. The role of non-myeloid CD14 was also considered and the data suggests that the expression of CD14 by phagocytes may define their professional status as phagocytes. To assess if differential CD14 ligation causes the ligand-dependent divergence in macrophage responses, a series of CD14 point mutants were used to map the binding of apoptotic cells and lipopolysaccharides. Monoclonal antibodies, 61D3 and MEM18, known to interfere with ligand-binding and responses, were also mapped. Data suggests that residue 11 of CD14, is key for the binding of 61D3 (but not MEM18), LPS and apoptotic cells, indicating lipopolysaccharides and apoptotic cells bind to similar residues. Furthermore using an NF-kB reporter, results show lipopolysaccharides but not apoptotic cells stimulate NF-kB. Taken together these data suggests ligand-dependent CD14 responses occur via a mechanism that occurs downstream of CD14 ligation but upstream of NF-?B activation. Alternatively apoptotic cell ligation of CD14 may not result in any signalling event, possibly by exclusion of TLR-4, suggesting that engulfment receptors, (e.g. TIM-4, BAI1 and Stablin-2) are required to mediate the uptake of apoptotic cells and the associated anti-inflammatory response.

The n-tuple classifier: too good to ignore

The n-tuple pattern recognition method has been tested using a selection of 11 large data sets from the European Community StatLog project, so that the results could be compared with those reported for the 23 other algorithms the project tested. The results indicate that this ultra-fast memory-based method is a viable competitor with the others, which include optimisation-based neural network algorithms, even though the theory of memory-based neural computing is less highly developed in terms of statistical theory.

Neural networks: A principled perspective

Introductory accounts of artificial neural networks often rely for motivation on analogies with models of information processing in biological networks. One limitation of such an approach is that it offers little guidance on how to find optimal algorithms, or how to verify the correct performance of neural network systems. A central goal of this paper is to draw attention to a quite different viewpoint in which neural networks are seen as algorithms for statistical pattern recognition based on a principled, i.e. theoretically well-founded, framework. We illustrate the concept of a principled viewpoint by considering a specific issue concerned with the interpretation of the outputs of a trained network. Finally, we discuss the relevance of such an approach to the issue of the validation and verification of neural network systems.

Developments of the generative topographic mapping

The generative topographic mapping (GTM) model was introduced by Bishop et al. (1998, Neural Comput. 10(1), 215-234) as a probabilistic re- formulation of the self-organizing map (SOM). It offers a number of advantages compared with the standard SOM, and has already been used in a variety of applications. In this paper we report on several extensions of the GTM, including an incremental version of the EM algorithm for estimating the model parameters, the use of local subspace models, extensions to mixed discrete and continuous data, semi-linear models which permit the use of high-dimensional manifolds whilst avoiding computational intractability, Bayesian inference applied to hyper-parameters, and an alternative framework for the GTM based on Gaussian processes. All of these developments directly exploit the probabilistic structure of the GTM, thereby allowing the underlying modelling assumptions to be made explicit. They also highlight the advantages of adopting a consistent probabilistic framework for the formulation of pattern recognition algorithms.

Neural networks: A principled perspective

Introductory accounts of artificial neural networks often rely for motivation on analogies with models of information processing in biological networks. One limitation of such an approach is that it offers little guidance on how to find optimal algorithms, or how to verify the correct performance of neural network systems. A central goal of this paper is to draw attention to a quite different viewpoint in which neural networks are seen as algorithms for statistical pattern recognition based on a principled, i.e. theoretically well-founded, framework. We illustrate the concept of a principled viewpoint by considering a specific issue concerned with the interpretation of the outputs of a trained network. Finally, we discuss the relevance of such an approach to the issue of the validation and verification of neural network systems.

Are poor mathematics skills associated with visual deficits in temporal processing?

Developmental learning disabilities such as dyslexia and dyscalculia have a high rate of co-occurrence in pediatric populations, suggesting that they share underlying cognitive and neurophysiological mechanisms. Dyslexia and other developmental disorders with a strong heritable component have been associated with reduced sensitivity to coherent motion stimuli, an index of visual temporal processing on a millisecond time-scale. Here we examined whether deficits in sensitivity to visual motion are evident in children who have poor mathematics skills relative to other children of the same age. We obtained psychophysical thresholds for visual coherent motion and a control task from two groups of children who differed in their performance on a test of mathematics achievement. Children with math skills in the lowest 10% in their cohort were less sensitive than age-matched controls to coherent motion, but they had statistically equivalent thresholds to controls on a coherent form control measure. Children with mathematics difficulties therefore tend to present a similar pattern of visual processing deficit to those that have been reported previously in other developmental disorders. We speculate that reduced sensitivity to temporally defined stimuli such as coherent motion represents a common processing deficit apparent across a range of commonly co-occurring developmental disorders.

The use of loop mirrors and chirped fibre Bragg gratings in actively-modelocked fibre lasers

The development of an all-optical communications infrastructure requires appropriate optical switching devices and supporting hardware. This thesis presents several novel fibre lasers which are useful pulse sources for high speed optical data processing and communications. They share several attributes in common: flexibility, stability and low-jitter output. They all produce short (picosecond) and are suitable as sources for soliton systems. The lasers are all-fibre systems using erbium-doped fibre for gain, and are actively-modelocked using a dual-wavelength nonlinear optical loop mirror (NOLM) as a modulator. Control over the operating wavelength and intra-cavity dispersion is obtained using a chirped in-fibre Bragg grating.Systems operating both at 76MHz and gigahertz frequencies are presented, the latter using a semiconductor laser amplifier to enhance nonlinear action in the loop mirror. A novel dual-wavelength system in which two linear cavities share a common modulator is presented with results which show that the jitter between the two wavelengths is low enough for use in switching experiments with data rates of up to 130Gbit/s.

Dark solitons in optical communication systems

This thesis presents experimental and theoretical work on the use of dark optical solitons as data carriers in communications systems. The background chapters provide an introduction to nonlinear optics, and to dark solitons, described as intensity dips in a bright background, with an asymmetrical phase profile. The motivation for the work is explained, considering both the superior stability of dark solitons and the need for a soliton solution suitable for the normal, rather than the anomalous (bright soliton) dispersion regime. The first chapters present two generation techniques, producing packets of dark solitons via bright pulse interaction, and generating continuous trains of dark pulses using a fibre laser. The latter were not dark solitons, but were suitable for imposition of the required phase shift by virtue of their extreme stability. The later chapters focus on the propagation and control of dark solitons. Their response to periodic loss and gain is shown to result in the exponential growth of spectral sidebands. This may be suppressed by reducing the periodicity of the loss/gain cycle or using periodic filtering. A general study of the response of dark solitons to spectral filtering is undertaken, showing dramatic differences in the behaviour of black and 99.9% grey solitons. The importance of this result is highlighted by simulations of propagation in noisy systems, where the timing jitter resulting from random noise is actually enhanced by filtering. The results of using sinusoidal phase modulation to control pulse position are presented, showing that the control is at the expense of serious modulation of the bright background. It is concluded that in almost every case, dark and bright solitons have very different properties, and to continue to make comparisons would not be so productive as to develop a deeper understanding of the interactions between the dark soliton and its bright background.

Switching and generation of ultrashort pulses using all-fibre devices

Serial and parallel interconnection of photonic devices is integral to the construction of any all-optical data processing system. This thesis presents results from a series of experiments centering on the use of the nonlinear-optical loop mirror (NOLM) switch in architectures for the manipulation and generation of ultrashort pulses. Detailed analysis of soliton switching in a single NOLM and cascade of two NOLM's is performed, centering on primary limitations to device operation, effect of cascading on amplitude response, and impact of switching on the characteristics of incident pulses. By using relatively long input pulses, device failure due to stimulated Raman generation is postponed to demonstrate multiple-peaked switching for the first time. It is found that while cascading leads to a sharpening of the overall switching characteristic, pulse spectral and temporal integrity is not significantly degraded, and emerging pulses retain their essential soliton character. In addition, by including an asymmetrically placed in-fibre Bragg reflector as a wavelength selective loss element in the basic NOLM configuration, both soliton self-switching and dual-wavelength control-pulse switching are spectrally quantised. Results are presented from a novel dual-wavelength laser configuration generating pulse trains with an ultra-low rms inter-pulse-stream timing jitter level of 630fs enabling application in ultrafast switching environments at data rates as high as 130GBits/s. In addition, the fibre NOLM is included in architectures for all-optical memory, demonstrating storage and logical inversion of a 0.5kByte random data sequence; and ultrafast phase-locking of a gain-switched distributed feedback laser at 1.062GHz, the fourteenth harmonic of the system baseband frequency. The stringent requirements for environmental robustness of these architectures highlight the primary weaknesses of the NOLM in its fibre form and recommendations to overcome its inherent drawbacks are presented.

The innate immune system and the clearance of apoptotic cells

Apoptosis, programmed cell death, is used by multicellular organisms to remove cells that are in excess, damaged or diseased. Activation of the apoptosis programme generates "eat me" signals on the surface of the apoptotic cell that mediate recognition and clearance by the innate immune system. CD14, a pattern recognition receptor expressed on macrophages, is widely known for its ability to recognise the pathogen-associated molecular pattern lipopolysaccharide (LPS) and promote inflammation. However, CD14 has also been shown to mediate binding and removal of apoptotic cells in a process that is anti-inflammatory suggesting CD14 is capable of producing two distinct, ligand-dependent macrophage responses. Whilst the molecular basis for this dichotomy has yet to be defined it is clear that CD14 defines a point of interest on the macrophage surface where we may study ligand-specific responses of macrophages. Our work seeks to define the molecular mechanisms underlying the involvement of CD14 in the non-inflammatory clearance of apoptotic cells. Here we used three different differentiation strategies to generate macrophages from the monocytic cell line THP-1. The resultant macrophage models were characterised to assess the expression and function of CD14 within each model system. Whilst each macrophage model shows increased levels of surface CD14 expression, our results demonstrate significant differences in the various models’ abilities to respond to LPS and clear apoptotic cells in a CD14-dependent manner. TLR4 levels correlated positively with LPS responsiveness but not CD14-dependent apoptotic cell clearance or anti-inflammatory responses to apoptotic cells. These observations suggest CD14-dependent apoptotic cell clearance is not dependent on TLR4. Taken together our data support the notion that the CD14 ligand-dependent responses to LPS and apoptotic cells derive from changes at the macrophage surface. The nature and composition of the CD14-co-receptor complex for LPS and apoptotic cell binding and responses is the subject of further study.

CD14 and innate immune clearance of apoptotic cells

Rapid elimination of cells undergoing programmed cell death (apoptosis) is vital to maintain tissue homeostasis. The phagocytic removal of apoptotic cells (AC) is mediated by innate immune molecules, professional phagocytes and amateur phagocytes that recognise "eat me" signals on the surface of the AC. CD14, a pattern recognition receptor expressed on macrophages, is widely known for its ability to recognise the pathogen-associated molecular pattern lipopolysaccharide (LPS) and promote inflammation. CD14 also mediates the binding and removal of AC, a process that is considered to be anti-inflammatory therefore suggesting CD14 is capable of producing two distinct ligand-dependent responses. Our work seeks to define the molecular mechanisms underlying the involvement of CD14 in the non-inflammatory clearance of AC. Here we describe three different differentiation strategies used to generate macrophages from the monocytic cell line THP-1. Whilst CD14 expression was increased in each macrophage model we demonstrate significant differences in the various macrophage models' abilities to respond to LPS and clear AC. We show that CD14 expression correlates with CD14-dependent AC clearance and anti-inflammatory responses to AC. However LPS responsiveness correlates, as expected, with TLR4 but not CD14 expression. These observations suggest CD14-dependent AC clearance is not dependent on TLR4. Taken together our data support the notion that CD14 ligand-dependent responses to LPS and AC are derived from changes at the macrophage surface. The nature and composition of the CD14-co-receptor complex for LPS and AC binding and consequent responses is the subject of further study.

Dielectric and electro-optical properties of some cyanobiphenyl liquid-crystals

A variety of methods have been reviewed for obtaining parallel or perpendicular alignment in liquid-crystal cells. Some of these methods have been selected and developed and were used in polarised spectroscopy, dielectric and electro-optic studies. Also, novel dielectric and electro-optic cells were constructed for use over a range of temperature. Dielectric response of thin layers of E7 and E8 (eutectic mixture liquid-crystals) have been measured in the frequency range (12 Hz-100 kHz) and over a range of temperature (183-337K). Dielectric spectra were also obtained for supercooled E7 and E8 in the Hz and kHz range. When the measuring electric field was parallel to the nematic director, one loss peak (low-frequency relaxation process) was observed for E7 and for E8, that exhibits a Debye-type behaviour in the supercooled systems. When the measuring electric field was perpendicular to the nematic director, two resolved dielectric processes have been observed. The phase transitions, effective molecular polarisabilities, anisotropy of polarisabilities and order parameters of three liquid crystal homologs (5CB, 6CB, and 7CB), 60CB and three eutectic nematic mixtures E7, E8, and E607 were calculated using optical and density data measured at several temperatures. The order parameters calculated using the different methods of Vuks, Neugebauer, Saupe-Maier, and Palffy-Muhoray are nearly the same for the liquid crystals considered in the present study. Also, the interrelationship between density and refractive index and the molecular structure of these liquid crystals were established. Accurate dielectric and dipole results of a range of liquid-crystal forming molecules at several temperatures have reported. The role of the cyano-end group, biphenyl core, and flexible tail in molecular association, were investigated using the dielectric method for some molecules which have a structural relationship to the nematogens. Analysis of the dielectric data for solution of the liquid-crystals indicated a high molecular association, comparable to that observed in the nematic or isotropic phases. Electro-optic Kerr effect were investigated for some alkyl cyanobiphenyls, their nematic mixtures and the eutectic mixture liquid-crystals E7 and E8 in the isotropic phase and solution. The Kerr constant of these liquid crystals found to be very high at the nematic-isotropic transition temperatures as the molecules are expected to be highly ordered close to phase transition temperatures. Dynamic Kerr effect behaviour and transient molecular reorientation were also observed in thin layers of some alkyl cyanobiphenyls. Dichroic ratio R and order parameters of solutions containing some azo and anthraquinone dyes in the nematic solvent (E7 and E8), were investigated by the measurement of the intensity of the absorption bands in the visible region of parallel aligned samples. The effective factors on the dichroic ratio of the dyes dissolved in the nematic solvents were determined and discussed.

A study of cluster analysis techniques and their applications

This thesis seeks to describe the development of an inexpensive and efficient clustering technique for multivariate data analysis. The technique starts from a multivariate data matrix and ends with graphical representation of the data and pattern recognition discriminant function. The technique also results in distances frequency distribution that might be useful in detecting clustering in the data or for the estimation of parameters useful in the discrimination between the different populations in the data. The technique can also be used in feature selection. The technique is essentially for the discovery of data structure by revealing the component parts of the data. lhe thesis offers three distinct contributions for cluster analysis and pattern recognition techniques. The first contribution is the introduction of transformation function in the technique of nonlinear mapping. The second contribution is the us~ of distances frequency distribution instead of distances time-sequence in nonlinear mapping, The third contribution is the formulation of a new generalised and normalised error function together with its optimal step size formula for gradient method minimisation. The thesis consists of five chapters. The first chapter is the introduction. The second chapter describes multidimensional scaling as an origin of nonlinear mapping technique. The third chapter describes the first developing step in the technique of nonlinear mapping that is the introduction of "transformation function". The fourth chapter describes the second developing step of the nonlinear mapping technique. This is the use of distances frequency distribution instead of distances time-sequence. The chapter also includes the new generalised and normalised error function formulation. Finally, the fifth chapter, the conclusion, evaluates all developments and proposes a new program. for cluster analysis and pattern recognition by integrating all the new features.

Exploratory database visualisation: the application and assessment of data and dimensionality reduction

This thesis describes the development of a complete data visualisation system for large tabular databases, such as those commonly found in a business environment. A state-of-the-art 'cyberspace cell' data visualisation technique was investigated and a powerful visualisation system using it was implemented. Although allowing databases to be explored and conclusions drawn, it had several drawbacks, the majority of which were due to the three-dimensional nature of the visualisation. A novel two-dimensional generic visualisation system, known as MADEN, was then developed and implemented, based upon a 2-D matrix of 'density plots'. MADEN allows an entire high-dimensional database to be visualised in one window, while permitting close analysis in 'enlargement' windows. Selections of records can be made and examined, and dependencies between fields can be investigated in detail. MADEN was used as a tool for investigating and assessing many data processing algorithms, firstly data-reducing (clustering) methods, then dimensionality-reducing techniques. These included a new 'directed' form of principal components analysis, several novel applications of artificial neural networks, and discriminant analysis techniques which illustrated how groups within a database can be separated. To illustrate the power of the system, MADEN was used to explore customer databases from two financial institutions, resulting in a number of discoveries which would be of interest to a marketing manager. Finally, the database of results from the 1992 UK Research Assessment Exercise was analysed. Using MADEN allowed both universities and disciplines to be graphically compared, and supplied some startling revelations, including empirical evidence of the 'Oxbridge factor'.