Metallo-drugs have been highly significant in the development of novel anticancer agents. Supramolecular drug agents allow the design and synthesis of a range of molecular architectures. The work in this thesis has built upon previous knowledge on this subject by undertaking novel biological studies on known metal supramolecular helicates as well as the design of a new helicate in order to improve upon existing drugs. In chapter three, the DNA three-way junction binding of a number of supramolecular cylinders is described. Three-way junction binding is a new mode of DNA recognition and relevant to the DNA replication fork, present in dividing cells. Chapter four outlines a number of novel in vitro studies on an iron supramolecular cylinder which indicate new, unsuspected and unprecedented biological actions. In chapter five biological studies of unsaturated ruthenium(II) helicates are discussed. These complexes combine a cisplatin like coordinative binding mode with a helical supramolecular design. Chapter six discusses the design of a synthetic route from an unsaturated ruthenium(II) complex to create a novel supramolecular compound with a tuneable ligand surface.

This thesis comprises two volumes, representing the research and clinical elements submitted to the University of Birmingham in partial fulfillment of the degree of Doctor of Clinical Psychology (DClinPsy). The first volume is the research component and contains three papers. The first paper is a review of the literature from 1980 to the present day, which has examined intellectual, behavioural and psychological characteristics in participants with Sotos syndrome. The second paper is an empirical study which examines the behavioural phenotype of participants with Sotos syndrome in comparison to 3 other genetic syndromes using standardised, well validated questionnaires. The third paper summarises these in language accessible to the general public. The second volume is the clinical component containing four Clinical Practice Reports and the abstract for an oral examination. These papers represent different aspects of work conducted during clinical placements. They include a paper which formulates from two different psychological perspectives, a service evaluation, a single case experimental design and a case study.

This thesis is concerned with computerised forensic 3-D facial reconstruction as a means of identification and involves the restoration of the face on the skull in an attempt to achieve a close likeness of the individual when alive. The reconstruction process begins with the biological identification of the skeletal remains, (age, sex, ancestry and build). Facial reconstruction is then carried out and essentially works by building the “face” up from the skull using soft tissue thicknesses at specific locations from existing data. However, it is used as a last resort on skeletonised, badly decomposed or mutilated corpses, when no other information is available; even then it is only accepted as corroborative evidence in court. It is performed in the hope that it may stimulate recognition, and consequently narrow the field of identification, allowing other tests to be carried out, such as radiographic and/or dental comparisons, DNA analysis or other means, to establish positive identification. The advantages of the computerised method over the manual clay reconstruction are speed, rapid editing capability, production of images that can be stored and reconstructions repeated at any time if required. Furthermore, in many cases, the original skull instead of a cast or model may be used for reconstruction because the 3-D computerised procedure is rapid and non invasive. However, the most significant advantage of this technique with regard to the aims and objectives of the thesis is that a number of alternative reconstructions may be produced sequentially for the same skull by using different facial templates from the database that meet the anthropological/biological criteria of the skull. The issues addressed by the study and therefore its main aims are: a) evaluation and b) improvement of the reliability of facial reconstruction using 3-D computer graphics. The methodology involved initially digitizing a skull using a low-power laser scanner and a video camera interfaced to a computer. From a database of previously scanned faces, ten facial templates were selected that matched the anthropological criteria of each of the skulls, i.e. age, sex, ancestry and build. Landmarks with their corresponding soft tissue thicknesses were then located and placed on the skull and the equivalent ones on the face. The 3-D computer graphics then reconstructed the face by morphing (warping) the facial template over the skull by matching the corresponding landmarks on the skull and face with the appropriate soft tissue thicknesses at those landmark locations. The soft tissue thicknesses used at their specific landmark locations also matched the anthropological criteria of the skulls, since soft tissue depths are dependent on age, sex, ancestry and build. One of the major problems with any reconstruction which affect its reliability for identification is the uncertainty of the shape of some of the individual characteristics of soft tissue structures such as shape of lips, ears and nose/nasal tip since there is not direct information on the skull regarding the shape of some of these features. In addition, with the laser scanning system, the faces within the database all have closed eyes, because of the potential laser hazard to the eyes. Thus it is necessary to add “opened” eyes, head and facial hair (where appropriate) to give a realistic appearance to the face. The software provides the facility to export a 2-D view in a TIFF or JPEG format from the 3-D reconstructed image. The file can then be imported into a police identi-kit system such as E-FIT™, which allows the addition of features. In this study five skulls of known individuals were used for reconstruction in the manner explained. Ten facial templates which fulfilled the anthropological criteria (age, sex, ancestry and build) for each skull were used for the rebuilding process, thus totalling fifty reconstructions. The study employed a psychological resemblance test (experiment 1) where 20 different assessors, were asked to select in each case study, the best three matches of the ten reconstructions with the ante-mortem photograph of the individual during life. The results from these tests were correlated with a mathematical shape analysis assessment using Procrustes Analysis in which, the skull was compared in turn with each of the ten facial templates of each case study (experiment 2).The ranking of the assessors’ reconstruction choice was correlated with the ranking of the Procrustes Analysis by using Spearman’s Rank Order Correlation. The results indicate that although not statistically significant, it would seem however, that in some of the case studies, the mathematical approach using Procrustes Analysis does seems to capture some perceptual similarity in human observers. Experiment 3, similar to experiment 1, was a further psychological resemblance test, which involved implementing E-Fit features on four of the ten reconstructed images per case study. Assessors were asked to select the closest E-Fit image match with the ante-mortem photograph. Again, results indicated that, although not statistically significant, adding E-Fit feature to the images appears to improve perceptual similarity in human observers, provided, the limitations of adding these characteristics are addressed. Furthermore, there also appears to be good agreement in most of the case studies between the two psychological resemblance tests using the two different sets of assessors in experiment 1 and 3 (reconstruction choice and E-Fit choice, respectively). Further work involving anthropometric comparisons and using two methods of assessment (landmark line matching between images and proportion indices) was also carried out (experiment 4). It was found that matching landmark lines between images appeared to be only of limited value due to the images not being aligned at exactly the same viewpoint and magnification. It should be appreciated that because the thesis was based on recognition and was not an anthropometric study, precise alignment of viewpoints was not a requirement. Hence using the same data from the study, although images were in the frontal view, they were not aligned to the accuracy acceptable for an anthropometric study as there was no requirement to so. It would appear that, although there was some correspondence between the discrepant distances and the first and second ranked reconstructions, no firm conclusions could be drawn from this technique and therefore does not assist in understanding the way observers made their choices. Further tests would need to be carried out (beyond the scope of the thesis) to reach any firm conclusions. Undoubtedly, given the complex nature of the recognition process, it would have been desirable to use reconstructions of persons known to the assessors rather than asking them to assess unfamiliar persons, since it is well established that familiar faces are easier to recognize than those that are unfamiliar to observers. It should be appreciated however, that, although the study was designed in this way for practical and ethical reasons, it nevertheless does not truly reflect the real operational forensic scenario. Furthermore, recognition/matching is a much more complex process and even a reconstructed face which may be generally morphologically similar to the person in life may not capture perceptual similarity in human observers, especially in an unfamiliar scenario. It is not certain that identification will always occur even when the facial reconstruction bears good resemblance to the target individual.

Gene expression studies have revealed that there is more than one cellular pathway governing growth inhibition and apoptosis. Mutations in the ras oncogene that(activate ras) are known to lead to the inactivation of genes that are directly involved in these pathways of growth inhibition and apoptosis. Oncogenic activated ras inhibits TGF-P signalling through the down-regulation of RII expression and abrogates apoptotic pathways through down-modulation of PAR-4 gene expression. A majority of pancreatic turnours harbour K-ras point mutations and these mutations dysregulate, the growth inhibition and apoptosis processes. This leads us to hypothesize that K-ras mutant phenotype status in pancreatic turnours will alter the expression of the RII and PAR-4 genes, and would further dysregulate growth inhibitory and apoptotic processes. In this study, the majority of pancreatic turnours showed down-regulation of RII and PAR-4 gene expression. A strong correlation of down-regulation of RII and PAR-4 with K-ras mutational status was observed. In particular, down regulation of PAR-4 correlated with poor survival in patients with pancreatic adenocarcinomas. Blocking the function of oncogenic ras by using a famesyltransferase inhibitor (Frl) restored RII expression and TGF-P signalling, and this caused enhanced sensitivity of cell lines to radiation. The restoration of RH function by FrI was linked to down-modulation of DNA methyltransferase enzyme that is often implicated in hypermethylation of promoters. Over-expression of RII in pancreatic tumour cells led to the restoration of TGF-P signalling and enhancement of radiation sensitivity. Induction of the pro-apoptotic effector gene, bav (bcI-2 family member) by radiation in RII over-expressed pancreatic cancer cells, was found to be a key mechanism involved in radiation sensitivity. Overexpression of PAR-4 sensitized the cells to radiation and this sensitization was linked to down-modulation of radiation induced Bcl-2 protein. Together, these findings strongly suggest that the restoration of function of the key growth inhibitory and cell death genes RII and PAR-4, which are affected by oncogenic ras mutations in pancreatic turnours will restore and enhance cellular responses to radiation induced clonogenic inhibition and apoptosis.

The University of Salford has developed a program in order to improve the control of lower limb orthotics thus improving the ability of paraplegics to walk. Although the system is greatly needed for rehabilitation it is hoped that the final system would enable paraplegics to walk in the community. The present project, which is based on previous designs such as the R. G. O (Reciprocating Gait Orthbsis), strives to add external power at the hips of the R. G. O. The constructed prototype is made of a mechanical skeleton with each leg driven by a brushless motor and a lead screw. The main purpose of this project is to design a control system to control the motion of the legs. The first step in achieving this task was to model the various components of the system separately and then derive a model using system identification that will describe the behaviour of the whole system. The starting point was a mechanical device with two motors mounted one at either hip. A full mathematical analysis of the system is carried out. Once a mathematical model is derived for the RG. O with the two motors it can be used to carry out real time simulations using MATLAB. Once the model is derived it must be validated to make sure it is actually a mathematical representation of the system. The identified model is usually very accurate as it is based on the actual system performance. Then real time simulations of the theoretical and the identified model are compared. If the theoretical model behaves in the same way as the identified model then it is validated and may be used for further work. The models derived using system identification were validated and gave a good comparison when compared to real data. A pole placement controller was designed and tested based on these models. The controller performance was tested with the orthosis unloaded, loaded with artificial loads (a plaster leg weighing 10 Kg). The controller managed to follow the pre-set trajectory reasonably well. The orthosis was then tested with a volunteer in it. Again the performance was very encouraging. The fmal Project will be P. C driven System with the possibility of using NiCAD Batteries as the power source. The main tools, which will be used in order to carry out simulations and comparisons of theoretical and practical results, are MATLAB. The software used was C.

This thesis describes research conducted into the measure- ment of pedestrian movement. It starts with an examination of current pedestrian detection and tracking systems, looking at several different technologies including image-processing systems. It highlights, as other authors have, that there is still a substantial gap between the abilities of existing pedestrian measurement and tracking systems and the requirements of users of such systems. After the review it provides an introduction to human gait and its use as a biometric. It then examines the IRISYS people counter, a low resolution infrared detector, used for this research. The detector's advantages and disadvantages are discussed, a detailed description of the data produced is provided. The thesis then describes in detail a study establishing that human gait information can be measured by the IRISYS people counter. It examines the use of the detectors in stereo to measure the height of the people; however the results are not impressive. During this investigation the presence of oscillations likely to relate to this walking gait is noted in the data. A second study is carried out confirming that the noted oscillation originates from human gait and further data is gathered to enable the development of measurement algorithms. The magnitude of the walking oscillation noted is examined in detail. It is found to be both individualistic and highly correlated to gender. A gender distribution algorithm is presented and evaluated on data captured in two different locations. These show very promising results. Several different methods are described for processing the infor-mation to extract a measure of cadence. The cadence is found to be individualistic and shows interesting correlations to height and leg length. This thesis advances the field of pedestrian measurement by conducting pedestrian motion studies and developing algorithms for measuring human gait.

Ears are a new biometric with major advantage in that they appear to maintain their structure with increasing age. Current approaches have exploited 2D and 3D images of the ear in human identification. Contending that the ear is mainly a planar shape we use 2D images, which are consistent with deployment in surveillance and other planar-image scenarios. So far ear biometric approaches have mostly used general properties and overall appearance of ear images in recognition, while the structure of the ear has not been discussed. In this thesis, we propose a new model-based approach to ear biometrics. Our model is a part-wise description of the ear structure. By embryological evidence of ear development, we shall show that the ear is indeed a composite structure of individual components. Our model parts are derived by a stochastic clustering method on a set of scale invariant features on a training set. We shall review different accounts of ear formation and consider some research into congenital ear anomalies which discuss apportioning various components to the ear's complex structure. We demonstrate that our model description is in accordance with these accounts. We extend our model description, by proposing a new wavelet-based analysis with a specific aim of capturing information in the ear's outer structures. We shall show that this section of the ear is not sufficiently explored by the model, while given that it exhibits large variations in shape, intuitively, it is significant to the recognition process. In this new analysis, log-Gabor filters exploit the frequency content of the ear's outer structures. In recognition, ears are automatically enrolled via our new enrolment algorithm, which is based on the elliptical shape of ears in head profile images. These samples are then recognized via the parts selected by the model. The incorporation of the wavelet-based analysis of the outer ear structures forms an extended or hybrid method. The performance is evaluated on test sets selected from the XM2VTS database. By results, bothin modelling and recognition, our new model-based approach does indeed appear to be a promising new approach to ear biometrics. In this, the recognition performance has improved notably by the incorporation of our new wavelet-based analysis. The main obstacle hindering the deployment of ear biometrics is the potential occlusion by hair. A model-based approach has a further attraction, since it has an advantage in handling noise and occlusion. Also, by localization, a wavelet can offer performance advantages when handling occluded data. A robust matching technique is also added to restrict the influence of corrupted wavelet projections. Furthermore, our automatic enrolment is tolerant of occlusion in ear samples. We shall present a thorough evaluation of performance in occlusion, using PCA and a robust PCA for comparison purposes. Our hybrid method obtains promising results recognizing occluded ears. Our results have confirmed the validity of this approach both in modelling and recognition. Our new hybrid method does indeed appear to be a promising new approach to ear biometrics, by guiding a model-based analysis via anatomical knowledge.

The search for the most effective method for the geometric parameterization of many internal fluid flow applications is ongoing. This thesis focuses on providing a general purpose automated parameterization strategy for use in design optimization. Commercial Computer-Aided Design (CAD) software, Computational Fluid Dynamics (CFD) software and optimizer tools are brought together to offer a generic and practical solution. A multi-stage parameterization technique for three-dimensional surface manipulation is proposed. The first stage in the process defines the geometry in a global sense, allowing large scale freedom to produce a wide variety of shapes using only a small set of design variables. Invariably, optimization using a simplified global parameterization does not provide small scale detail required for an optimal solution of a complex geometry. Therefore, a second stage is used subsequently to fine-tune the geometry with respect to the objective function being optimized. By using Kriging response surface methodology to support the optimization studies, two diverse applications, a Formula One airbox and a human carotid artery bifurcation, can be concisely represented through a global parameterization followed by a local parameterization.

Using biological traits, such as fingerprints, iris patterns and voice print, in identification and authentication has gained increasing attention due to the demand for a more secure environment. The potential of human walking as a biometric has only attracted interest in the computer vision community since the last decade. Nevertheless, the potential of human running gait as a biometric remains largely unexplored. Here, we propose an approach for an automated non-invasive/markerless person identification system by not only the walking, but also the running gait to explore the potential of these two biomechanically distinct gaits. Two motion models both invariant to walking and running, have been developed based on the concept of harmonic motion. The first is a bilateral symmetric model made up of an upper and a lower pendulum, representing the thigh and the lower leg, joined at the knee. The upper pendulum is simple harmonic motion whilst the lower pendulum uses an empirical model requiring parameter selection for the different gait mode and lacks analytical attributes. The second model has a forced coupled oscillator to describe the knee rotation as legs are considered to be imperfect pendula with energy loss. The rhythm and pattern of gaits are automatically extracted by a temporal evidence gathering technique with the motion models as the underlying temporal templates. The spatio-temporal characteristics of the gait patterns are described by a Fourier representation, which are in turn used to create unique gait signatures for the purpose of identification. Performance analysis demonstrates the potential of gait as a biometric, with running being more potent. This technique not only performs well in discriminating individuals, but also appears capable of distinguishing the gender and gait mode. Moreover, analysis shows that the knee rotation contributes significantly to discrimination capability. Based on the hypothesis that human walking and running gaits are intimately related by the musculo-skeletal structure and that the walking pattern is the phase-modulated version of running (or vice versa), a unique mapping/transform between individuals’ walking and running gait is developed, making the signature invariant to gait mode. Furthermore, this mapping can be used alone as a compressed signature or to buttress the original signature to further improve the recognition capability. Then, a generic relationship between walking and running has been investigated via a neural network. Due to the current size of the experimental dataset, the structure of the two signature spaces could not be drawn, at least not by this approach. However, results do suggest its possible existence. The effect of different camera views is an important application issue. The gait pattern perceived by machine vision at different viewpoints has been investigated. The frequency description of the gait pattern is linearly dependent on the camera sagittal view angle. The changes of both the magnitude and the phase component are symmetric about the fronto-parallel view. This linearity offers a convenient way to map the angular motion obtained from various camera sagittal views to the true motion, for the convenience of gait analysis. More importantly, this linearity can be exploited to develop view invariant gait signatures. The new and interesting findings of this work not only benefit biometrics research, but may also draw attention from other communities such as biomechanics and graphics applications.

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