Dynamics of pattern writing and erasure in photorefractive lithium niobate for data storage applications

The present rate of technological advance continues to place significant demands on data storage devices. The sheer amount of digital data being generated each year along with consumer expectations, fuels these demands. At present, most digital data is stored magnetically, in the form of hard disk drives or on magnetic tape. The increase in areal density (AD) of magnetic hard disk drives over the past 50 years has been of the order of 100 million times, and current devices are storing data at ADs of the order of hundreds of gigabits per square inch. However, it has been known for some time that the progress in this form of data storage is approaching fundamental limits. The main limitation relates to the lower size limit that an individual bit can have for stable storage. Various techniques for overcoming these fundamental limits are currently the focus of considerable research effort. Most attempt to improve current data storage methods, or modify these slightly for higher density storage. Alternatively, three dimensional optical data storage is a promising field for the information storage needs of the future, offering very high density, high speed memory. There are two ways in which data may be recorded in a three dimensional optical medium; either bit-by-bit (similar in principle to an optical disc medium such as CD or DVD) or by using pages of bit data. Bit-by-bit techniques for three dimensional storage offer high density but are inherently slow due to the serial nature of data access. Page-based techniques, where a two-dimensional page of data bits is written in one write operation, can offer significantly higher data rates, due to their parallel nature. Holographic Data Storage (HDS) is one such page-oriented optical memory technique. This field of research has been active for several decades, but with few commercial products presently available. Another page-oriented optical memory technique involves recording pages of data as phase masks in a photorefractive medium. A photorefractive material is one by which the refractive index can be modified by light of the appropriate wavelength and intensity, and this property can be used to store information in these materials. In phase mask storage, two dimensional pages of data are recorded into a photorefractive crystal, as refractive index changes in the medium. A low-intensity readout beam propagating through the medium will have its intensity profile modified by these refractive index changes and a CCD camera can be used to monitor the readout beam, and thus read the stored data. The main aim of this research was to investigate data storage using phase masks in the photorefractive crystal, lithium niobate (LiNbO3). Firstly the experimental methods for storing the two dimensional pages of data (a set of vertical stripes of varying lengths) in the medium are presented. The laser beam used for writing, whose intensity profile is modified by an amplitudemask which contains a pattern of the information to be stored, illuminates the lithium niobate crystal and the photorefractive effect causes the patterns to be stored as refractive index changes in the medium. These patterns are read out non-destructively using a low intensity probe beam and a CCD camera. A common complication of information storage in photorefractive crystals is the issue of destructive readout. This is a problem particularly for holographic data storage, where the readout beam should be at the same wavelength as the beam used for writing. Since the charge carriers in the medium are still sensitive to the read light field, the readout beam erases the stored information. A method to avoid this is by using thermal fixing. Here the photorefractive medium is heated to temperatures above 150�C; this process forms an ionic grating in the medium. This ionic grating is insensitive to the readout beam and therefore the information is not erased during readout. A non-contact method for determining temperature change in a lithium niobate crystal is presented in this thesis. The temperature-dependent birefringent properties of the medium cause intensity oscillations to be observed for a beam propagating through the medium during a change in temperature. It is shown that each oscillation corresponds to a particular temperature change, and by counting the number of oscillations observed, the temperature change of the medium can be deduced. The presented technique for measuring temperature change could easily be applied to a situation where thermal fixing of data in a photorefractive medium is required. Furthermore, by using an expanded beam and monitoring the intensity oscillations over a wide region, it is shown that the temperature in various locations of the crystal can be monitored simultaneously. This technique could be used to deduce temperature gradients in the medium. It is shown that the three dimensional nature of the recording medium causes interesting degradation effects to occur when the patterns are written for a longer-than-optimal time. This degradation results in the splitting of the vertical stripes in the data pattern, and for long writing exposure times this process can result in the complete deterioration of the information in the medium. It is shown in that simply by using incoherent illumination, the original pattern can be recovered from the degraded state. The reason for the recovery is that the refractive index changes causing the degradation are of a smaller magnitude since they are induced by the write field components scattered from the written structures. During incoherent erasure, the lower magnitude refractive index changes are neutralised first, allowing the original pattern to be recovered. The degradation process is shown to be reversed during the recovery process, and a simple relationship is found relating the time at which particular features appear during degradation and recovery. A further outcome of this work is that the minimum stripe width of 30 ìm is required for accurate storage and recovery of the information in the medium, any size smaller than this results in incomplete recovery. The degradation and recovery process could be applied to an application in image scrambling or cryptography for optical information storage. A two dimensional numerical model based on the finite-difference beam propagation method (FD-BPM) is presented and used to gain insight into the pattern storage process. The model shows that the degradation of the patterns is due to the complicated path taken by the write beam as it propagates through the crystal, and in particular the scattering of this beam from the induced refractive index structures in the medium. The model indicates that the highest quality pattern storage would be achieved with a thin 0.5 mm medium; however this type of medium would also remove the degradation property of the patterns and the subsequent recovery process. To overcome the simplistic treatment of the refractive index change in the FD-BPM model, a fully three dimensional photorefractive model developed by Devaux is presented. This model shows significant insight into the pattern storage, particularly for the degradation and recovery process, and confirms the theory that the recovery of the degraded patterns is possible since the refractive index changes responsible for the degradation are of a smaller magnitude. Finally, detailed analysis of the pattern formation and degradation dynamics for periodic patterns of various periodicities is presented. It is shown that stripe widths in the write beam of greater than 150 ìm result in the formation of different types of refractive index changes, compared with the stripes of smaller widths. As a result, it is shown that the pattern storage method discussed in this thesis has an upper feature size limit of 150 ìm, for accurate and reliable pattern storage.

Remediation strategies of shaft and common mode voltages in adjustable speed drive systems

AC motors are largely used in a wide range of modern systems, from household appliances to automated industry applications such as: ventilations systems, fans, pumps, conveyors and machine tool drives. Inverters are widely used in industrial and commercial applications due to the growing need for speed control in ASD systems. Fast switching transients and the common mode voltage, in interaction with parasitic capacitive couplings, may cause many unwanted problems in the ASD applications. These include shaft voltage and leakage currents. One of the inherent characteristics of Pulse Width Modulation (PWM) techniques is the generation of the common mode voltage, which is defined as the voltage between the electrical neutral of the inverter output and the ground. Shaft voltage can cause bearing currents when it exceeds the amount of breakdown voltage level of the thin lubricant film between the inner and outer rings of the bearing. This phenomenon is the main reason for early bearing failures. A rapid development in power switches technology has lead to a drastic decrement of switching rise and fall times. Because there is considerable capacitance between the stator windings and the frame, there can be a significant capacitive current (ground current escaping to earth through stray capacitors inside a motor) if the common mode voltage has high frequency components. This current leads to noises and Electromagnetic Interferences (EMI) issues in motor drive systems. These problems have been dealt with using a variety of methods which have been reported in the literature. However, cost and maintenance issues have prevented these methods from being widely accepted. Extra cost or rating of the inverter switches is usually the price to pay for such approaches. Thus, the determination of cost-effective techniques for shaft and common mode voltage reduction in ASD systems, with the focus on the first step of the design process, is the targeted scope of this thesis. An introduction to this research – including a description of the research problem, the literature review and an account of the research progress linking the research papers – is presented in Chapter 1. Electrical power generation from renewable energy sources, such as wind energy systems, has become a crucial issue because of environmental problems and a predicted future shortage of traditional energy sources. Thus, Chapter 2 focuses on the shaft voltage analysis of stator-fed induction generators (IG) and Doubly Fed Induction Generators DFIGs in wind turbine applications. This shaft voltage analysis includes: topologies, high frequency modelling, calculation and mitigation techniques. A back-to-back AC-DC-AC converter is investigated in terms of shaft voltage generation in a DFIG. Different topologies of LC filter placement are analysed in an effort to eliminate the shaft voltage. Different capacitive couplings exist in the motor/generator structure and any change in design parameters affects the capacitive couplings. Thus, an appropriate design for AC motors should lead to the smallest possible shaft voltage. Calculation of the shaft voltage based on different capacitive couplings, and an investigation of the effects of different design parameters are discussed in Chapter 3. This is achieved through 2-D and 3-D finite element simulation and experimental analysis. End-winding parameters of the motor are also effective factors in the calculation of the shaft voltage and have not been taken into account in previous reported studies. Calculation of the end-winding capacitances is rather complex because of the diversity of end winding shapes and the complexity of their geometry. A comprehensive analysis of these capacitances has been carried out with 3-D finite element simulations and experimental studies to determine their effective design parameters. These are documented in Chapter 4. Results of this analysis show that, by choosing appropriate design parameters, it is possible to decrease the shaft voltage and resultant bearing current in the primary stage of generator/motor design without using any additional active and passive filter-based techniques. The common mode voltage is defined by a switching pattern and, by using the appropriate pattern; the common mode voltage level can be controlled. Therefore, any PWM pattern which eliminates or minimizes the common mode voltage will be an effective shaft voltage reduction technique. Thus, common mode voltage reduction of a three-phase AC motor supplied with a single-phase diode rectifier is the focus of Chapter 5. The proposed strategy is mainly based on proper utilization of the zero vectors. Multilevel inverters are also used in ASD systems which have more voltage levels and switching states, and can provide more possibilities to reduce common mode voltage. A description of common mode voltage of multilevel inverters is investigated in Chapter 6. Chapter 7 investigates the elimination techniques of the shaft voltage in a DFIG based on the methods presented in the literature by the use of simulation results. However, it could be shown that every solution to reduce the shaft voltage in DFIG systems has its own characteristics, and these have to be taken into account in determining the most effective strategy. Calculation of the capacitive coupling and electric fields between the outer and inner races and the balls at different motor speeds in symmetrical and asymmetrical shaft and balls positions is discussed in Chapter 8. The analysis is carried out using finite element simulations to determine the conditions which will increase the probability of high rates of bearing failure due to current discharges through the balls and races.

2,4,6-Trinitro-N-[4-(phenyldiazenyl)phenyl)phenyl]aniline

The title compound, C18H12N6O6 was prepared from the reaction of 4-(phenyldiazenyl)aniline (aniline yellow) with picrylsulfonic acid. The dihedral angle formed by the two benzene rings of the diphenyldiazenyl ring system 6.55(13)deg. and that formed by the rings of the picrate-aniline ring system is 48.76(12)deg. The molecule contains an intramolecular aniline-nitro N-H...O hydrogen bond.

Non-invasive assessment of tear film surface quality

The tear film plays an important role preserving the health of the ocular surface and maintaining the optimal refractive power of the cornea. Moreover dry eye syndrome is one of the most commonly reported eye health problems. This syndrome is caused by abnormalities in the properties of the tear film. Current clinical tools to assess the tear film properties have shown certain limitations. The traditional invasive methods for the assessment of tear film quality, which are used by most clinicians, have been criticized for the lack of reliability and/or repeatability. A range of non-invasive methods of tear assessment have been investigated, but also present limitations. Hence no “gold standard” test is currently available to assess the tear film integrity. Therefore, improving techniques for the assessment of the tear film quality is of clinical significance and the main motivation for the work described in this thesis. In this study the tear film surface quality (TFSQ) changes were investigated by means of high-speed videokeratoscopy (HSV). In this technique, a set of concentric rings formed in an illuminated cone or a bowl is projected on the anterior cornea and their reflection from the ocular surface imaged on a charge-coupled device (CCD). The reflection of the light is produced in the outer most layer of the cornea, the tear film. Hence, when the tear film is smooth the reflected image presents a well structure pattern. In contrast, when the tear film surface presents irregularities, the pattern also becomes irregular due to the light scatter and deviation of the reflected light. The videokeratoscope provides an estimate of the corneal topography associated with each Placido disk image. Topographical estimates, which have been used in the past to quantify tear film changes, may not always be suitable for the evaluation of all the dynamic phases of the tear film. However the Placido disk image itself, which contains the reflected pattern, may be more appropriate to assess the tear film dynamics. A set of novel routines have been purposely developed to quantify the changes of the reflected pattern and to extract a time series estimate of the TFSQ from the video recording. The routine extracts from each frame of the video recording a maximized area of analysis. In this area a metric of the TFSQ is calculated. Initially two metrics based on the Gabor filter and Gaussian gradient-based techniques, were used to quantify the consistency of the pattern’s local orientation as a metric of TFSQ. These metrics have helped to demonstrate the applicability of HSV to assess the tear film, and the influence of contact lens wear on TFSQ. The results suggest that the dynamic-area analysis method of HSV was able to distinguish and quantify the subtle, but systematic degradation of tear film surface quality in the inter-blink interval in contact lens wear. It was also able to clearly show a difference between bare eye and contact lens wearing conditions. Thus, the HSV method appears to be a useful technique for quantitatively investigating the effects of contact lens wear on the TFSQ. Subsequently a larger clinical study was conducted to perform a comparison between HSV and two other non-invasive techniques, lateral shearing interferometry (LSI) and dynamic wavefront sensing (DWS). Of these non-invasive techniques, the HSV appeared to be the most precise method for measuring TFSQ, by virtue of its lower coefficient of variation. While the LSI appears to be the most sensitive method for analyzing the tear build-up time (TBUT). The capability of each of the non-invasive methods to discriminate dry eye from normal subjects was also investigated. The receiver operating characteristic (ROC) curves were calculated to assess the ability of each method to predict dry eye syndrome. The LSI technique gave the best results under both natural blinking conditions and in suppressed blinking conditions, which was closely followed by HSV. The DWS did not perform as well as LSI or HSV. The main limitation of the HSV technique, which was identified during the former clinical study, was the lack of the sensitivity to quantify the build-up/formation phase of the tear film cycle. For that reason an extra metric based on image transformation and block processing was proposed. In this metric, the area of analysis was transformed from Cartesian to Polar coordinates, converting the concentric circles pattern into a quasi-straight lines image in which a block statistics value was extracted. This metric has shown better sensitivity under low pattern disturbance as well as has improved the performance of the ROC curves. Additionally a theoretical study, based on ray-tracing techniques and topographical models of the tear film, was proposed to fully comprehend the HSV measurement and the instrument’s potential limitations. Of special interested was the assessment of the instrument’s sensitivity under subtle topographic changes. The theoretical simulations have helped to provide some understanding on the tear film dynamics, for instance the model extracted for the build-up phase has helped to provide some insight into the dynamics during this initial phase. Finally some aspects of the mathematical modeling of TFSQ time series have been reported in this thesis. Over the years, different functions have been used to model the time series as well as to extract the key clinical parameters (i.e., timing). Unfortunately those techniques to model the tear film time series do not simultaneously consider the underlying physiological mechanism and the parameter extraction methods. A set of guidelines are proposed to meet both criteria. Special attention was given to a commonly used fit, the polynomial function, and considerations to select the appropriate model order to ensure the true derivative of the signal is accurately represented. The work described in this thesis has shown the potential of using high-speed videokeratoscopy to assess tear film surface quality. A set of novel image and signal processing techniques have been proposed to quantify different aspects of the tear film assessment, analysis and modeling. The dynamic-area HSV has shown good performance in a broad range of conditions (i.e., contact lens, normal and dry eye subjects). As a result, this technique could be a useful clinical tool to assess tear film surface quality in the future.

Diagnosing dry eye with dynamic-area high-speed videokeratoscopy

Dry eye syndrome is one of the most commonly reported eye health conditions. Dynamic-area highspeed videokeratoscopy (DA-HSV) represents a promising alternative to the most invasive clinical methods for the assessment of the tear film surface quality (TFSQ), particularly as Placido-disk videokeratoscopy is both relatively inexpensive and widely used for corneal topography assessment. Hence, improving this technique to diagnose dry eye is of clinical significance and the aim of this work. First, a novel ray-tracing model is proposed that simulates the formation of a Placido image. This model shows the relationship between tear film topography changes and the obtained Placido image and serves as a benchmark for the assessment of indicators of the ring’s regularity. Further, a novel block-feature TFSQ indicator is proposed for detecting dry eye from a series of DA-HSV measurements. The results of the new indicator evaluated on data from a retrospective clinical study, which contains 22 normal and 12 dry eyes, have shown a substantial improvement of the proposed technique to discriminate dry eye from normal tear film subjects. The best discrimination was obtained under suppressed blinking conditions. In conclusion,this work highlights the potential of the DA-HSV as a clinical tool to diagnose dry eye syndrome.

rac-2-Aminopyridinium cis-2-carboxycyclohexane-1-carboxylate

In the structure of the title compound, C5H7N2+ C8H11O4-, the cis-anions associate through head-to-tail carboxylic acid carboxyl O-H...O hydrogen-bonds [graph set C(7)], forming chains which extend along c and are inter-linked through the carboxyl groups forming cyclic R2/2(8) associations with the pyridinium and an amine H donor of the cation. Further amine...carboxyl N-H...O interactions form enlarged centrosymmetric rings [graph set R4/4(18)] and extensions down b to give a three-dimensional structure.

Generation of profluorescent isoindoline nitroxides using click chemistry

Novel profluorescent nitroxides bearing a triazole linker between the coumarin fluorophore and an isoindoline nitroxide were prepared in good yields using the coppercatalyzed azide�alkyne 1,3-dipolar cycloaddition reaction (CuAAC). Nitroxides containing 7-hydroxy and 7-diethylamino substitution on their coumarin rings displayed significant fluorescence suppression, and upon reaction with methyl radicals, normal fluorescence emission was returned. The fluorescence emission for the 7-hydroxycoumarin nitroxide and its diamagnetic analogue was found to be strongly influenced by pH with maximal fluorescence emission achieved in basic solution. Solvent polarity was also shown to affect fluorescence emission. The significant difference in fluorescence output between the nitroxides and their corresponding diamagnetic analogues makes these compounds ideal tools for monitoring processes involving free-radical species.

2,3-Dimethoxy-10-oxostrychnidinium 2-(2,4,6-trinitroanilino)benzoate monohydrate : a 1:1 proton-transfer salt of brucine with o-picraminobenzoic acid

In the structure of the 1:1 proton-transfer compound of brucine with 2-(2,4,6-trinitroanilino)benzoic acid C23H27N2O4+ . C13H7N4O8- . H~2~O, the brucinium cations form the classic undulating ribbon substructures through overlapping head-to-tail interactions while the anions and the three related partial water molecules of solvation (having occupancies of 0.73, 0.17 and 0.10) occupy the interstitial regions of the structure. The cations are linked to the anions directly through N-H...O(carboxyl) hydrogen bonds and indirectly by the three water molecules which form similar conjoint cyclic bridging units [graph set R2/4(8)] through O-H...O(carbonyl) and O(carboxyl) hydrogen bonds, giving a two-dimensional layered structure. Within the anion, intramolecular N-H...O(carboxyl) and N H...O(nitro) hydrogen bonds result in the benzoate and picrate rings being rotated slightly out of coplanarity inter-ring dihedral angle 32.50(14)\%]. This work provides another example of the molecular selectivity of brucine in forming stable crystal structures and also represents the first reported structure of any form of the guest compound 2-(2,4,6-trinitroanilino)benzoic acid.

A new control-volume finite-element scheme for heterogeneous porous media : application to the drying of softwood

An improved mesoscopic model is presented for simulating the drying of porous media. The aim of this model is to account for two scales simultaneously: the scale of the whole product and the scale of the heterogeneities of the porous medium. The innovation of this method is the utilization of a new mass-conservative scheme based on the Control-Volume Finite-Element (CV-FE) method that partitions the moisture content field over the individual sub-control volumes surrounding each node within the mesh. Although the new formulation has potential for application across a wide range of transport processes in heterogeneous porous media, the focus here is on applying the model to the drying of small sections of softwood consisting of several growth rings. The results conclude that, when compared to a previously published scheme, only the new mass-conservative formulation correctly captures the true moisture content evolution in the earlywood and latewood components of the growth rings during drying.

Esprit Futur : Le Corbusier and José Oubrerie at Saint-Pierre De Firminy, Firminy-Vert, France, 1968–2006

What is the secret mesmerism that death possesses and under the operation of which a modern architect – strident, confident, resolute – becomes rueful, pessimistic, or melancholic?1 Five years before Le Corbusier’s death at sea in 1965, the architect reluctantly agreed to adopt the project for L’Église Saint-Pierre de Firminy in Firminy-Vert (1960–2006), following the death of its original architect, André Sive, from leukemia in 1958.2 Le Corbusier had already developed, in 1956, the plan for an enclave in the new “green” Firminy town, which included his youth and culture center and a stadium and swimming pool; the church and a “boîte à miracles” near the youth center were inserted into the plan in the ’60s. (Le Corbusier was also invited, in 1962, to produce another plan for three Unités d’Habitation outside Firminy-Vert.) The Saint-Pierre church should have been the zenith of the quartet (the largest urban concentration of works by Le Corbusier in Europe, and what the architect Henri Ciriani termed Le Corbusier’s “acropolis”3) but in the early course of the project, Le Corbusier would suffer the diocese’s serial objections to his vision for the church – not unlike the difficulties he experienced with Notre Dame du Haut at Ronchamp (1950–1954) and the resistance to his proposed monastery of Sainte-Marie de la Tourette (1957–1960). In 1964, the bishop of Saint-Étienne requested that Le Corbusier relocate the church to a new site, but Le Corbusier refused and the diocese subsequently withdrew from the project. (With neither the approval, funds, nor the participation of the bishop, by then the cardinal archbishop of Lyon, the first stone of the church was finally laid on the site in 1970.) Le Corbusier’s ambivalence toward the project, even prior to his quarrels with the bishop, reveals...

A communitarian theory of the education rights of students with disabilities

There is a lack of writing on the issue of the education rights of people with disabilities by authors of any theoretical persuasion. While the deficiency of theory may be explained by a variety of historical, philosophical and practical considerations, it is a deficiency which must be addressed. Otherwise, any statement of rights rings out as hollow rhetoric unsupported by sound reason and moral rectitude. This paper attempts to address this deficiency in education rights theory by postulating a communitarian theory of the education rights of people with disabilities. The theory is developed from communitarian writings on the role of education in democratic society. The communitarian school, like the community within which it nests, is inclusive. Schools both reflect and model the shape of communitarian society and have primary responsibility for teaching the knowledge and virtues which will allow citizens to belong to and function within society. Communitarians emphasise responsibilities, however, as the corollary of rights and require the individual good to yield to community good when the hard cases arise. The article not only explains the basis of the right to an inclusive education, therefore, but also engages with the difficult issue of when such a right may not be enforceable.

Estimation and control for an open-source quadcopter

This paper describes modelling, estimation and control of the horizontal translational motion of an open-source and cost effective quadcopter — the MikroKopter. We determine the dynamics of its roll and pitch attitude controller, system latencies, and the units associated with the values exchanged with the vehicle over its serial port. Using this we create a horizontal-plane velocity estimator that uses data from the built-in inertial sensors and an onboard laser scanner, and implement translational control using a nested control loop architecture. We present experimental results for the model and estimator, as well as closed-loop positioning.

A longitudinal assessment of chronic wound fluid to detect biochemical indicators of healing

Chronic venous leg ulcers are a detrimental health issue plaguing our society, resulting in long term pain, immobility and decreased quality of life for a large proportion of sufferers. The frequency of these chronic wounds has led current research to focus on the wound environment to provide important information regarding the prolonged, fluctuated or static healing patterns of these wounds. Disruption to the normal wound healing process results in release of multiple factors in the wound environment that could correlate to wound chronicity. These biochemical factors can often be detected through non-invasively sampling chronic wound fluid (CWF) from the site of injury. Of note, whilst there are numerous studies comparing acute and chronic wound fluids, there have not been any reports in the literature employing a longitudinal study in order to track biochemical changes in wound fluid as patients transition from a non-healing to healed state. Initially the objective of this study was to identify biochemical changes in CWF associated with wound healing using a proteomic approach. The proteomic approach incorporated a multi-dimensional liquid chromatography fractionation technique coupled with mass spectrometry (MS) to enable identification of proteins present in lower concentrations in CWF. Not surprisingly, many of the proteins identified in wound fluid were acute phase proteins normally expressed during the inflammatory phase of healing. However, the number of proteins positively identified by MS was quite low. This was attributed to the diverse range in concentration of protein species in CWF making it challenging to detect the diagnostically relevant low molecular weight proteins. In view of this, SELDI-TOF MS was also explored as a means to target low molecular weight proteins in sequential patient CWF samples during the course of healing. Unfortunately, the results generated did not yield any peaks of interest that were altered as wounds transitioned to a healed state. During the course of proteomic assessment of CWF, it became evident that a fraction of non-proteinaceous compounds strongly absorbed at 280 nm. Subsequent analyses confirmed that most of these compounds were in fact part of the purine catabolic pathway, possessing distinctive aromatic rings and which results in high absorbance at 254 nm. The accumulation of these purinogenic compounds in CWF suggests that the wound bed is poorly oxygenated resulting in a switch to anaerobic metabolism and consequently ATP breakdown. In addition, the presence of the terminal purine catabolite, uric acid (UA), indicates that the enzyme xanthine oxidoreductase (XOR) catalyses the reaction of hypoxanthine to xanthine and finally to UA. More importantly, the studies provide evidence for the first time of the exogenous presence of XOR in CWF. XOR is the only enzyme in humans capable of catalysing the production of UA in conjunction with a burst of the highly reactive superoxide radical and other oxidants like H2O2. Excessive release of these free radicals in the wound environment can cause cellular damage disrupting the normal wound healing process. In view of this, a sensitive and specific assay was established for monitoring low concentrations of these catabolites in CWF. This procedure involved combining high performance liquid chromatography (HPLC) with tandem mass spectrometry and multiple reaction monitoring (MRM). This application was selective, using specific MRM transitions and HPLC separations for each analyte, making it ideal for the detection and quantitation of purine catabolites in CWF. The results demonstrated that elevated levels of UA were detected in wound fluid obtained from patients with clinically worse ulcers. This suggests that XOR is active in the wound site generating significant amounts of reactive oxygen species (ROS). In addition, analysis of the amount of purine precursors in wound fluid revealed elevated levels of purine precursors in wound fluid from patients with less severe ulcers. Taken together, the results generated in this thesis suggest that monitoring changes of purine catabolites in CWF is likely to provide valuable information regarding the healing patterns of chronic venous leg ulcers. XOR catalysis of purine precursors not only provides a method for monitoring the onset, prognosis and progress of chronic venous leg ulcers, but also provides a potential therapeutic target by inhibiting XOR, thus blocking UA and ROS production. Targeting a combination of these purinogenic compounds and XOR could lead to the development of novel point of care diagnostic tests. Therefore, further investigation of these processes during wound healing will be worthwhile and may assist in elucidating the pathogenesis of this disease state, which in turn may lead to the development of new diagnostics and therapies that target these processes.

4-(4-Aminophenylsulfonyl)aniline-1,3-5-trinitrobenzene (1/2)

The asymmetric unit of the title co-crystalline 1:2 adduct C12H12N2O2 . 2(C6H3N3O6) contains two independent molecules of bis(4-aminophenyl)sulfone (the drug Dapsone) and four molecules of 1,3,5-trinitrobenzene and is extended into a two-dimensional hydrogen-bonded network structure through amino N-H...O hydrogen-bonding associations with nitro O- atom acceptors. In the two independent Dapsone molecules the inter-ring dihedral angles are 69.0(2) and 63.59(11)deg. Aromatic pi-pi interactions are also found between one of the Dapsone aromatic rings and a trinitrobenzene ring [minimum ring centroid separation 3.576(5)Ang.]. A 4-aminophenyl ring moiety of one of the Dapsone molecules and two nitro groups of a trinitrobenzene are disordered in a 50:50 ratio.

4-(4-Aminophenylsulfonyl)aniline-3,5-dinitrobenzoic acid (1/1)

In the title co-crystalline adduct of the drug Dapsone with 3,5-dinitrobenzoic acid, C~12~H~12~N~2~O~2~S . C~7~H~4~N~4~O~6~, the dihedral angle between the two aromatic rings of the Dapsone molecule is 75.4(2)deg. and those between these rings and that of the 3,5-dinitrobenzoic acid are 64.5(2) and 68.4(2)deg. A strong inter-species carboxylic acid O-H---N(amine) hydrogen-bond is found, which together with intermolecular amine N-H...O hydrogen-bonding associations with carboxyl, nitro and sulfone O-atom acceptors as well as weak pi-pi interactions between one of the Dapsone phenyl rings and the 3,5-dinitrobenzoic acid ring [minimum ring centroid separation 3.774(2)Ang.], give a two-dimensional network structure.