Concise review:bone marrow for the treatment of spinal cord injury: mechanisms and clinical applications

Transplantation of bone marrow stem cells into spinal cord lesions enhances axonal regeneration and promotes functional recovery in animal studies. There are two types of adult bone marrow stem cell; hematopoietic stem cells (HSCs), and mesenchymal stem cells (MSCs). The mechanisms by which HSCs and MSCs might promote spinal cord repair following transplantation have been extensively investigated. The objective of this review is to discuss these mechanisms; we briefly consider the controversial topic of HSC and MSC transdifferentiation into central nervous system cells but focus on the neurotrophic, tissue sparing, and reparative action of MSC grafts in the context of the spinal cord injury (SCI) milieu. We then discuss some of the specific issues related to the translation of HSC and MSC therapies for patients with SCI and present a comprehensive critique of the current bone marrow cell clinical trials for the treatment of SCI to date.

Integrated analytic hierarchy process and its applications:a literature review

Due to its wide applicability and ease of use, the analytic hierarchy process (AHP) has been studied extensively for the last 20 years. Recently, it is observed that the focus has been confined to the applications of the integrated AHPs rather than the stand-alone AHP. The five tools that commonly combined with the AHP include mathematical programming, quality function deployment (QFD), meta-heuristics, SWOT analysis, and data envelopment analysis (DEA). This paper reviews the literature of the applications of the integrated AHPs. Related articles appearing in the international journals from 1997 to 2006 are gathered and analyzed so that the following three questions can be answered: (i) which type of the integrated AHPs was paid most attention to? (ii) which area the integrated AHPs were prevalently applied to? (iii) is there any inadequacy of the approaches? Based on the inadequacy, if any, some improvements and possible future work are recommended. This research not only provides evidence that the integrated AHPs are better than the stand-alone AHP, but also aids the researchers and decision makers in applying the integrated AHPs effectively.

Optimising transmission capacity: long distance and terrestrial applications

This paper identifies the important limiting processes in transmission capacity for amplified soliton systems. Some novel control techniques are described for optimizing this capacity. In particular, dispersion compensation and phase conjugation are identified as offering good control of jitter without the need for many new components in the system. An advanced average soliton model is described and demonstrated to permit large amplifier spacing. The potential for solitons in high-dispersion land-based systems is discussed and results are presented showing 10 Gbit s$^{-1}$ transmission over 1000 km with significant amplifier spacing.

Writing and characterisation methods for UV-photosensitivity based devices and their applications

The underlying work to this thesis focused on the exploitation and investigation of photosensitivity mechanisms in optical fibres and planar waveguides for the fabrication of advanced integrated optical devices for telecoms and sensing applications. One major scope is the improvement of grating fabrication specifications by introducing new writing techniques and the use of advanced characterisation methods for grating testing. For the first time the polarisation control method for advanced grating fabrication has successfully been converted to apodised planar waveguide fabrication and the development of a holographic method for the inscription of chirped gratings at arbitrary wavelength is presented. The latter resulted in the fabrication of gratings for pulse-width suppression and wavelength selection in diode lasers. In co-operation with research partners a number of samples were tested using optical frequency domain and optical low coherence reflectometry for a better insight into the limitations of grating writing techniques. Using a variety of different fabrication methods, custom apodised and chirped fibre Bragg gratings were written for the use as filter elements for multiplexer-demultiplexer devices, as well as for short pulse generation and wavelength selection in telecommunication transmission systems. Long period grating based devices in standard, speciality and tapered fibres are presented, showing great potential for multi-parameter sensing. One particular scope is the development of vectorial curvature and refractive index sensors with potential for medical, chemical and biological sensing. In addition the design of an optically tunable Mach-Zehnder based multiwavelength filter is introduced. The discovery of a Type IA grating type through overexposure of hydrogen loaded standard and Boron-Germanium co-doped fibres strengthened the assumption of UV-photosensitivity being a highly non-linear process. Gratings of this type show a significantly lower thermal sensitivity compared to standard gratings, which makes them useful for sensing applications. An Oxford Lasers copper-vapour laser operating at 255 nm in pulsed mode was used for their inscription, in contrast to previous work using CW-Argon-Ion lasers and contributing to differences in the processes of the photorefractive index change

Advanced fibre gratings and their applications

This thesis describes a detailed study of advanced fibre grating devices using Bragg (FBG) and long-period (LPG) structures and their applications in optical communications and sensing. The major contributions presented in this thesis are summarised below. One of the most important contributions from the research work presented in this thesis is a systematic theoretical study of many distinguishing structures of fibre gratings. Starting from the Maxwell equations, the coupled-mode equations for both FBG and LPG were derived and the mode-overlap factor was analytically discussed. Computing simulation programmes utilising matrix transform method based on the models built upon the coupled-mode equations were developed, enabling simulations of spectral response in terms of reflectivity, bandwidth, sidelobes and dispersion of gratings of different structures including uniform and chirped, phase-shifted, Moiré, sampled Bragg gratings, phase-shifted and cascaded long-period gratings. Although the majority of these structures were modelled numerically, analytical expressions for some complex structures were developed with a clear physical picture. Several apodisation functions were proposed to improve sidelobe suppression, which guided effective production of practical devices for demanding applications. Fibre grating fabrication is the other major part involved in the Ph.D. programme. Both the holographic and scan-phase-mask methods were employed to fabricate Bragg and long-period gratings of standard and novel structures. Significant improvements were particularly made in the scan-phase-mask method to enable the arbitrarily tailoring of the spectral response of grating devices. Two specific techniques - slow-shifting and fast-dithering the phase-mask implemented by a computer controlled piezo - were developed to write high quality phase-shifted, sampled and apodised gratings. A large number of LabVIEW programmes were constructed to implement standard and novel fabrication techniques. In addition, some fundamental studies of grating growth in relating to the UV exposure and hydrogenation induced index were carried out. In particular, Type IIa gratings in non-hydrogenated B/Ge co-doped fibres and a re-generated grating in hydrogenated B/Ge fibre were investigated, showing a significant observation of thermal coefficient reduction. Optical sensing applications utilising fibre grating devices form the third major part of the research work presented in this thesis. Several experiments of novel sensing and sensing-demodulating were implemented. For the first time, an intensity and wavelength dual-coding interrogation technique was demonstrated showing significantly enhanced capacity of grating sensor multiplexing. Based on the mode-splitting measurement, instead of using conventional wavelength-shifting detection technique, successful demonstrations were also made for optical load and bend sensing of ultra-high sensitivity employing LPG structures. In addition, edge-filters and low-loss high-rejection bandpass filters of 50nm stop-band were fabricated for application in optical sensing and high-speed telecommunication systems

Transglutaminase 2 cross-linking of matrix proteins: biological significance and medical applications

This review summarises the functions of the enzyme tissue transglutaminase (TG2) in the extracellular matrix (ECM) both as a matrix stabiliser through its protein cross-linking activity and as an important cell adhesion protein involved in cell survival. The contribution of extracellular TG2 to the pathology of important diseases such as cancer and fibrosis are discussed with a view to the potential importance of TG2 as a therapeutic target. The medical applications of TG2 are further expanded by detailing the use of transglutaminase cross-linking in the development of novel biocompatible biomaterials for use in soft and hard tissue repair.

Hypercoiling and hydrophobically associating polymers : interfacial synthesis, surface properties and pharmaceutical applications

The objective of the work described was to identify and synthesize a range of biodegradable hypercoiling or hydrophobically associating polymers to mimic natural apoproteins, such as those found in lung surfactant or plasma apolipoproteins. Stirred interfacial polymerization was used to synthesize potentially biodegradable aromatic polyamides (Mw of 12,000-26,000) based on L-Iysine, L-Iysine ethyl ester, L-ornithine and DL-diaminopropionic acid, by reaction with isophthaloyl chloride. A similar technique was used to synthesize aliphatic polyamides based on L-Iysine ethyl ester and either adipoyl chloride or glutaryl chloride resulting in the synthesis of poly(lysine ethyl ester adipamide) [PLETESA] or poly(lysine ethyl ester glutaramide) (Mw of 126,000 and 26,000, respectively). PLETESA was found to be soluble in both polar and non-polar solvents and the hydrophobic/hydrophilic balance could be modified by partial saponification (66-75%) of the ethyl ester side chains. Surface or interfacial tension/pH profiles were used to assess the conformation of both the poly(isophthalamides) and partially saponified PLETESA in aqueous solution. The results demonstrated that a loss of charge from the polymer was accompanied by an initial fall in surface activity, followed by a rise in activity, and ultimately, by polymer precipitation. These observations were explained by a collapse of the polymer chains into non-surface active intramolecular coils, followed by a transition to an amphipathic conformation, and finally to a collapsed hydrophobe. 2-Dimensional NMR analysis of polymer conformation in polar and non-polar solvents revealed intramolecular associations between the hydrophobic groups within partially saponified PLETESA. Unsaponified PLETESA appeared to form a coiled structure in polar solvents where the ethyl ester side chains were contained within the polymer coil. The implications of the secondary structure of PLETESA and potential biomedical applications are 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.

Optical fibre sensors and their applications in the industrial weighing and aerospace industries

This thesis presents the design, fabrication and testing of novel grating based Optical Fibre Sensor (OFS) systems being interrogated using “off the shelf” interrogation systems, with the eventual development of marketable commercial systems at the forefront of the research. Both in the industrial weighing and aerospace industries, there has been a drive to investigate the feasibility of using optical fibre sensors being deployed where traditionally their electrical or mechanical counterparts would traditionally have been. Already, in the industrial weighing industry, commercial operators are deploying OFS-based Weigh-In-Motion (WIM) systems. Likewise, in the aerospace industry, OFS have been deployed to monitor such parameters as load history, impact detection, structural damage, overload detection, centre of gravity and the determination of blade shape. Based on the intrinsic properties of fibre Bragg gratings (FBGs) and Long Period Fibre Gratings (LPFGs), a number of novel OFS-based systems have been realised. Experimental work has shown that in the case of static industrial weighing, FBGs can be integrated with current commercial products and used to detect applied loads. The work has also shown that embedding FBGs in e-glass, to form a sensing patch, can result in said patches being bonded to rail track, forming the basis of an FBG-based WIM system. The results obtained have been sufficiently encouraging to the industrial partner that this work will be progressed beyond the scope of the work presented in this thesis. Likewise, and to the best of the author’s knowledge, a novel Bragg grating based systems for aircraft fuel parameter sensing has been presented. FBG-based pressure sensors have been shown to demonstrate good sensitivity, linearity and repeatability, whilst LPFG-based systems have demonstrated a far greater sensitivity when compared to FBGs, as well the advantage of being potentially able to detect causes of fuel adulteration based on their sensitivity to refractive index (RI). In the case of the LPFG-based system, considerable work remains to be done on the mechanical strengthening to improve its survivability in a live aircraft fuel tank environment. The FBG system has already been developed to an aerospace compliant prototype and is due to be tested at the fuel testing facility based at Airbus, Filton, UK. It is envisaged by the author that in both application areas, continued research in this area will lead to the eventual development of marketable commercial products.

Mode control in multimode optical fibre and its applications

This thesis describes an investigation into methods for controlling the mode distribution in multimode optical fibres. The major contributions presented in this thesis are summarised below. Emerging standards for Gigabit Ethernet transmission over multimode optical fibre have led to a resurgence of interest in the precise control, and specification, of modal launch conditions. In particular, commercial LED and OTDR test equipment does not, in general, comply with these standards. There is therefore a need for mode control devices, which can ensure compliance with the standards. A novel device consisting of a point-load mode-scrambler in tandem with a mode-filter is described in this thesis. The device, which has been patented, may be tuned to achieve a wide range of mode distributions and has been implemented in a ruggedised package for field use. Various other techniques for mode control have been described in this work, including the use of Long Period Gratings and air-gap mode-filters. Some of the methods have been applied to other applications, such as speckle suppression and in sensor technology. A novel, self-referencing, sensor comprising two modal groups in the Mode Power Distribution has been designed and tested. The feasibility of a two-channel Mode Group Diversity Multiplexed system has been demonstrated over 985m. A test apparatus for measuring mode distribution has been designed and constructed. The apparatus consists of a purpose-built video microscope, and comprehensive control and analysis software written in Visual Basic. The system may be fitted with a Silicon camera or an InGaAs camera, for measurement in the 850nm and 130nm transmission windows respectively. A limitation of the measurement method, when applied to well-filled fibres, has been identified and an improvement to the method has been proposed, based on modelled Laguerre Gauss field solutions.

Ionic and neutral hydrogels for dermal and ophthalmic applications

This thesis is concerned with the use of ionic and neutral hydrogels in dermal and ocular applications with particular reference to controlled release applications. The work consists of three interconnected themes.The first area of study is the use of skin adhesive bioelectrode hydrogels as ground plate electrodes for ophthalmic iontophoresis applications. The work provides a basis of understanding the relative contributions made by ionic monomers (such as sodium s-(acrylamide)-2-methyl propane sulphonate and acrylic acid-bis-(3-sulfopropyl-ester, potassium salt) and neutral monomers (such as acryloymorpholine, N,N-dimethylacrylamide and N-vinyl pyrrolidone) to adhesion, rheology and impedance of bioelectrode gels. The general advantage of neutral monomers, which have been used to successfully replace ionic monomers, is that they enable more effective control of independent anion and cation species (for example potassium chloride and sodium chloride) unlike ionic monomers where polymerisation produces an immobile polyanion thus limiting cation mobility. Secondly, release from a completely neutral hydrogel under the influence of mechanical shaking was studied for the case of crosslinked polyvinyl alcohol (PVA) containing low concentration of linear soluble PVA in a contact lens application. The soluble PVA was observed to be eluting by reptation from the lens matrix due to the mechanical action of the eyelid. This process was studied in an in vitro model, which in this research was used as a basis for developing a lens made with enhanced release polymer. The third area of work is related to the factors that control drug release (in particular non-steroidal anti-inflammatory drugs) from a hydrogel matrix. This links both electrotherapy applications, such as transcutaneous electrical nerve stimulation, in which the passive diffusion from the gel could be used in conjunction with enhanced transmission across the dermal surface with passive diffusion from a contact lens matrix and the development of therapeutic contact lenses.

Proteoglycan analogues for ophthalmic and orthopaedic applications

The successful development of biomaterials is increasingly influenced by biomimesis essentially the use of biological structures as design templates. This approach has been used here in the design of injectable systems for the nucleus of the intervertebral disc, corneal inlays and intraocular lenses (IOLs). The strategy is based on the use of C-linked sulphonates to mimic the O-linked sulphate groups that are the hydration drivers in proteoglycans. The elastic modulus of the materials can be tailored for specific applications.

Retinal vessel tortuosity measures and their applications

Structural retinal vascular characteristics, such as vessel calibers, tortuosity and bifurcation angles are increasingly quantified in an objective manner, slowly replacing subjective qualitative disease classification schemes. This paper provides an overview of the current methodologies and calculations used to compute retinal vessel tortuosity. We set out the different parameter calculations and provide an insight into the clinical applications, while critically reviewing its pitfalls and shortcomings.