Rozprawy doktorskie na temat „241D”

Les alcaloïdes sont des substances que l'on retrouve à la fois dans le règne animal et végétal. Ce travail a pour objet le développement de la cyanation anodique comme nouvelle méthode destinée à synthétiser des pipéridines substituées. Notre approche est basée sur l'utilisation d'α-aminonitriles. Par application de cette méthode, nous avons réalisé la synthèse de la coniine, l'alcaloïde de la grande ciguë, en 5 étapes avec un rendement global de 31%. Cette stratégie de synthèse a permis la préparation de pipéridines 2,6-disubstituées de configuration relative trans comme la solenopsine A. Une synthèse diastéréosélective de l'alcaloïde 241D a été développée par utilisation d'un groupement stéréodirecteur. Par application de notre méthode de synthèse, nous avons proposé une nouvelle voie de synthèse de la pumiliotoxine C. Un choix approprié des conditions opératoires a permis l'incorporation des chaînes en position α et α' de l'atome d'azote de la pipéridine.

CARACTERIZACIÓN DE CEPAS TOXIGÉNICAS DEL GÉNERO Fusarium MEDIANTE TÉCNICAS DE BIOLOGÍA MOLECULAR. Las micotoxinas son metabolitos producidos por un amplio grupo de hongos, entre los que se encuentran los pertenecientes al género Fusarium. Se han detectado como contaminantes naturales en mayor o en menor grado en un gran número de productos agrícolas y manufacturados y, si llegan a ser consumidas, pueden causar una gran variedad de efectos tóxicos en humanos y animales. Dentro de los cereales, el maíz es uno de los más vulnerables a la colonización por especies del género Fusarium y, por consiguiente, a la contaminación por las micotoxinas que produce dicho género. Es por ello que en este trabajo se aislaron estos hongos a partir de granos de maíz destinados al consumo humano y animal. Estos análisis, además de aportarnos los aislados necesarios para la identificación y detección de la producción de micotoxinas, sirvieron para el estudio comparativo entre los medios de cultivo Patata Dextrosa Agar (PDA) y Agar Verde Malaquita, destacándose este último por su selectividad para el aislamiento de hongos del género Fusarium frente otros géneros. Una vez obtenidos los aislados, nos centramos en la identificación por PCR de especies del género Fusarium procedentes de grano de maíz y la detección de especies productoras de tricotecenos (deoxinivalenol (DON) y nivalenol (NIV)). Como controles se utilizaron cepas de referencia: suministradas por la Colección Española de Cultivos Tipo. De los hongos obtenidos en la primera parte de este trabajo se seleccionaron 377 pertenecientes al género Fusarium. Estos aislados fueron analizados mediante PCR utilizando diferentes iniciadores específicos. Con este método se obtuvo la identificación de las especies F. graminearum, F. proliferatum, F. oxysporum y F. verticillioides. La técnica PCR también permitió la detección de cepas productoras de tricotecenos, así como la de aislados productores de DON. Para comprobar la especificidad
Gómez López, ED. (2008). Caracterización de cepas toxigénicas del género fusarium mediante técnicas de biología molecular [Tesis doctoral no publicada]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/3346
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La tristeza de los cítricos es una de las enfermedades de mayor importancia en el cultivo de los cítricos. Dada la imposibilidad práctica de contener su dispersión y evitar su evolución hacia formas más virulentas, el control de los daños mediante protección cruzada o mediante resistencia mediada por genes del patógeno utilizando plantas transgénicas requiere un conocimiento detallado de las interacciones CTV-cítricos. Para este estudio se inocularon cuatro aislados con distintas características patogénicas en lima Mexicana (LM), Citrus macrophylla (CM), naranjo dulce (ND) y naranjo amargo (NA). La estimación de la carga viral mediante ELISA y RT-PCR cuantitativa a tiempo real en la primera brotación y al cabo de 9 meses, mostró que NA ofrece una resistencia inicial a la invasión por CTV. Asimismo, sugirió que la intensidad de los síntomas inducidos por CTV no era una consecuencia directa de la acumulación viral. El análisis de la actividad replicativa de las distintas combinaciones aislado/huésped reveló una cinética de acumulación viral paralela a la actividad replicativa. Por otro lado, mientras en los huéspedes susceptibles se detectaron siRNAs de CTV en la primera brotación, la activación del silenciamiento en NA fue mucho más tardía indicando que la resistencia inicial a la acumulación viral en este huésped no era consecuencia del silenciamiento. Posteriormente, se analizó en más detalle el tipo de limitaciones que ofrecía NA a la invasión sistémica de CTV observándose que éste presentaba una limitación al movimiento viral. El virus se detectó inicialmente en la raíz y el nivel de acumulación del mismo afectaba la posterior carga viral en la copa, de forma variable según los aislados, así para el aislado T385 la raíz actuaría como reservorio viral. Finalmente, el empleo de la tecnología de las micromatrices de cDNA permitió analizar a nivel transcriptómico la respuesta del NA al inicio de la infección por CTV y confirmar las hipótesis formuladas anteriormente.
Comellas Serra, M. (2009). Estudio de la interacción entre naranjo amargo y el virus de la tristeza de los cítricos [Tesis doctoral no publicada]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/7323
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Interés del estudio: el desarrollo vascular de las plantas, y más concretamente del xilema es un proceso determinante en el correcto desarrollo de las plantas, y vital para la formación de los recursos madereros de los mismos. Objetivos: los dos objetivos principales de esta tesis son: a) establecer los mecanismos moleculares por los cuales la termoespermina controla la correcta formación del xilema. b) encontrar las diferencias estructurales entre las diversas aminopropil transferasas, que les confieren a cada una de ellas su actividad específica. Elementos de la metodología a destacar: Para esta tesis se han empleado técnicas generales de biología molecular como PCR, digestiones, transformación de bacterias, expresión y purificación de proteínas; y otras técnicas más específicas de la biología molecular de plantas como son la generación de plantas transgénicas y el cartografiado de plantas mutantes generadas por tratamiento químico. Además se han empleado técnicas de cromatografía para el manejo de HPLC y GC-MS. Resultados logrados: las dos principales conclusiones de esta tesis son: a) el papel de ACL5 y/o de la termoespermina es impedir la muerte prematura durante la diferenciación del xilema. El mecanismo más probable es la promoción de la traducción de los genes AJAX, que codifican factores de transcripción bHLH. b) la discriminación de sustratos por parte de las aminopropil transferasas y putrescina-N-metil transferasas no se explica únicamente por diferencias en los centros activos.
Vera Sirera, FJ. (2011). Bases moleculares de la síntesis de termoespermina y sus implicaciones en el desarrollo vascular de Arabidopsis thaliana [Tesis doctoral no publicada]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/10689
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I risultati degli ultimi decenni hanno mostrato che tutti gli Ammassi Globulari (GCs) ospitano Popolazioni Multiple (MPs) caratterizzate da significative differenze nelle abbondanze di He ed elementi leggeri. Tuttavia, manca ancora un modello teorico/scenario interpretativo in grado di spiegare in maniera convincente la loro origine. Tutti i modelli prevedono che le stelle di seconda generazione (2G, ovvero stelle arricchite in Na e N) formino un sotto-sistema centralmente più segregato di quello di prima generazione (1G). In sistemi collisionali (come i GCs) ci si aspetta che qualunque differenza iniziale tra le varie popolazioni sia progressivamente cancellata dall'evoluzione dinamica dell'ammasso. Tuttavia, sistemi dinamicamente giovani potrebbero ancora conservare memoria della loro configurazione primordiale e permettere quindi di ottenere vincoli fondamentali per i modelli. Il lavoro di Tesi si inserisce esattamente in questo contesto, essendo dedicato allo studio delle MPs in NGC 2419, l’ammasso globulare dinamicamente più giovane della Via Lattea. L'analisi fotometrica di dati HST in bande ottiche e ultraviolette ha permesso di distinguere ben 4 popolazioni di stelle in questo ammasso e lo studio delle loro proprietà strutturali ha portato a un risultato sorprendente: le stelle appartenenti alle tre popolazioni di 2G hanno essenzialmente la stessa distribuzione radiale di quelle di 1G. Data la giovane età dinamica di NGC 2419, questo implica che le stelle di 2G si siano formate con la stessa concentrazione delle precedenti, in disaccordo con l'assunzione comune a tutti i modelli teorici. Questo risultato ha importanti implicazioni anche sul problema della massa iniziale dei GCs e sul loro contributo alla massa dell'alone della Via Lattea.

Para que los microorganismos probióticos ejerzan su efecto beneficioso sobre el huésped, han de encontrarse en proporciones elevadas en el producto y ser capaces de sobrevivir en suficiente cantidad al tránsito gastrointestinal. Se ha producido una cierta discrepancia entre diferentes líneas de investigación a la hora de afirmar los efectos beneficiosos del yogur tradicional. Algunas de ellas aseguran que sus bacterias no son capaces de sobrevivir al tracto gastrointestinal mientras que otras afirman lo contrario. En este trabajo se planteó desarrollar métodos rápidos alternativos a los tradicionales de cultivo para estudiar las propiedades probióticas de las bacterias contenidas en yogures naturales. Se procedió al aislamiento, identificación y caracterización molecular de las bacterias lácticas presentes en yogures naturales. Se realizó la puesta a punto de las técnicas de PCR y FISH para la detección de ambos microorganismos. Se desarrolló la técnica DVC-FISH para la detección de células viables de Lactobacillus delbrueckii subsp bulgaricus y Streptococcus thermophilus que permitió determinar su resistencia in vitro a los jugos gastrointestinales. Finalmente, se hizo un estudio in vivo de la supervivencia al tracto gastrointestinal de estas cepas y se estudió la evolución de la microbiota intestinal a lo largo del ensayo. Este ensayo permitió demostrar la presencia de Streptococcus thermophilus viables en las heces humanas tras la ingesta de producto. La técnica DVC-FISH se mostró como el método más rápido y eficaz para la determinación de la viabilidad de LAB en matrices complejas. Se observó que el consumo de yogur durante un periodo determinado produce un aumento de la microbiota endógena de lactobacilos así como una disminución de la población de enterobacterias.
García Hernández, J. (2010). Técnicas moleculares aplicadas a la caracterización y estudio de la supervivencia de bacterias lácticas del yogur [Tesis doctoral no publicada]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/14010
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Recent years have seen a growth in the manufacturing of nanoparticles for their uses in various fields of science and technology. However, this explosion in the production and use of nanoparticles has in turn resulted in growing concerns regarding their impact on public health and the environment (Hoet, 2004). One major route of entry into the human body is through the air-blood barrier in the lungs. The air-blood barrier at the alveolar region in most mammals is normally about 500-600 nm in thickness (Bartels, 1979) and is mainly responsible for the selective transport of gases and certain vital solutes across the membrane (Theodore, 1975). This selective transport across these barriers is regulated by tight junction protein complexes that bind two adjacent cells in the tissue. This particular selective transport mechanism is highly attractive for the drugs industry due to which the lung epithelial barriers could provide a novel mode for delivery to patients (such a system already exist for patients suffering from asthama, where they use an inhaler to deliver their dosage). However, to develop such drug delivery systems it is necessary to study the effects either through in vivo and/or in vitro research methods. For the purpose of this thesis an in vitro system using the Calu-3 cell line (cultured on two types of membrane systems) was used in the attempt at mimicing certain barrier properties (mainly transport of solutes across the membrane and integrity/tightness of the cell monolayers) present in the in vivo state. Calu-3 cells were maintained on two different sets of porous membrane types, one was the commercially available Transwell® membranes (Costar/Fisher) and the other was the self-fabricated (at CSEM, Switzerland) silicon nitride membranes. The silicon nitride membranes were particularly unique, in the sense that their thickness was only 500nm (compared to the polymer Transwell® membranes) and also presented the possibility of miniaturising the Calu-3 in vitro system. Miniaturisation helps reduce the use of test solutions and allow the development of high throughput screening devices for biological applications (Beebe, 2002). When the possibility of miniaturisation occurs along side a biological application it is often the case that microflows would be necessary for maintaining cell culture within small areas inside the devices. Therefore, microfluidics was vital in providing the opportunity for miniaturised cell based systems. In this study PDMS (Polydimethyl siloxane) based microfluidic devices were used for developing the cell culture and concentration gradient devices. The final purpose of this poject was to create a scaleable modular integrated device allowing the analysis of the induced effects on Calu-3 cells against nanoparticle/solute translocation and assessing cell monolayer integrity using a real time TEER measurement system. This miniaturised in vitro multilayered microfluidic setup consisted of three main components, a top layer micro channel (fabricated in PDMS), the middle silicon wafer bearing the silicon nitride membrane (also bearing the electrodes for measuring TEER of the cultured cell monolayer) and the bottom layer micro channel. This modular device would help assess Calu-3 cell monolayers resposes to toxic solutions and hopefully assist towards developing a novel analysis system device to study the effects of such toxic solutions in real time.

Wireless Visual Sensor Networks (WVSNs) have gained significant importance in the last few years and have emerged in several distinctive applications. The main aim of this research is to investigate the use of adaptive Compressive Sensing (CS) for efficient target detection and tracking in WVSN-based surveillance applications. CS is expected to overcome the WVSN resource constraints such as memory limitation, communication bandwidth and battery constraints. In addition, adaptive CS dynamically chooses variable compression rates according to different data sets to represent captured images in an efficient way hence saving energy and memory space. In this work, a literature review on compressive sensing, target detection and tracking for WVSN is carried out to investigate existing techniques. Only single view target tracking is considered to keep minimum number of visual sensor nodes in a wake-up state to optimize the use of nodes and save battery life which is limited in WVSNs. To reduce the size of captured images an adaptive block CS technique is proposed and implemented to compress the high volume data images before being transmitted through the wireless channel. The proposed technique divides the image to blocks and adaptively chooses the compression rate for relative blocks containing the target according to the sparsity nature of images. At the receiver side, the compressed image is then reconstructed and target detection and tracking are performed to investigate the effect of CS on the tracking performance. Least mean square adaptive filter is used to predicts target's next location, an iterative quantized clipped LMS technique is proposed and compared with other variants of LMS and results have shown that it achieved lower error rates than other variants of lMS. The tracking is performed in both in- door and outdoor environments for single/multi targets. Results have shown that with adaptive block compressive sensing (CS) up to 31% measurements of data are required to be transmitted for less sparse images and 15% for more sparse, while preserving the 33dB image quality and the required detection and tracking perfor- mance. Adaptive CS resulted in 82% energy saving as compared to transmitting the required image with no CS.

Medial compartment loading is a significant factor in the progression of medial compartment osteoarthritis and medial unicompartmental replacement arthroplasty is a popular surgical treatment for medial unicompartmental knee osteoarthritis. However, there is no consensus on importance of alignment in medial unicompartmental knee replacement in orthopaedic literature. Static alignment measures like Hip Knee Ankle (HKA) angle and location of mechanical axis (MA) on the tibial plateau are known to affect loading of the knee. In addition, Peak knee adduction moment (PKAM) and angular adduction impulse (Add Imp) measured on instrumented gait analysis are recognised proxies for medial compartment loading especially in the coronal plane. A review of ninety four unicompartmental knee replacements revealed that survivorship at 10 years was 94% and at 15 years was 87%. Significantly better (p<0.01) function scores as measured by the 50 point Bristol Knee score was demonstrated in knees with good alignment where the mechanical axis passed through zones 0 or 1. An investigation into 18 medial unicompartmental knee replacements resulted in a statistically significant improvement in all domains of WOMAC score and the modified knee society score. Medial unicompartmental replacement arthroplasty resulted in a statistically significant improvement in gait velocity (p<0.01) and double limb support time (p <0.001). Further investigations into the kinetic and kinematic parameters showed excellent reliability. The coronal plane kinetics, peak knee adduction moments (ICC = 0.99), sagittal plane kinematics, flexion (ICC =0.98), sagittal plane plane kinetics, flexion extension moment (ICC =0.87), transverse plane kinematics, rotation (ICC=0.87) and transverse plane kinetics, rotation moment (ICC =0.76) showed excellent reliability as per Fleiss’s classification for intra class coefficients. Only coronal plane kinematics, varus valgus (ICC= 0.66) did not fall into the excellent category, but was still considered good. The coronal plane loading parameters improved significantly following medial unicompartmental replacement (p<0.05). The reduction in loading was related to the correction in alignment. The only sagittal plane kinetic parameter that improved significantly following medial unicompartmental replacement was the early stance extension moment (p = 0.05). The transverse plane kinetics, sagittal, coronal and transverse plane kinematics did not show statistically significant differences between the preoperative and postoperative groups. On single regression analysis, the mean adduction angle (MAA, p = 0.007) was a better predictor of coronal plane loading in the preoperative group, while the Hip Knee Ankle angle (HKA, p=0.01) was the better predictor in the postoperative group. As the adduction moments between individual knees was variable between knees even though normalised for height and weight, the percentage improvement in PKAM (%ΔPKAM) and Add Imp (%ΔAdd. Imp) was used for further analysis. On multiple regression, the effect of change of HKA (ΔHKA) was more significant (p = 3.5E-09) on %ΔAdd. Imp, than ΔMAA (p = 0.01). The correction in HKA was a significant predictor of improvement in the Add Imp (r2 = 0.90) and PKAM (r2 = 0.50). For every one degree correction of static alignment (HKA) a 7% improvement can be achieved in coronal plane loading (Add Imp). On comparison of coronal and transverse plane loading data between the asymptomatic non arthritic knees and replaced knees in this group of participants, the adduction moment curve, parameters like PKAM, Add Imp and rotation moments were nearly identical, implying that articular surfaces, does not seem to have a significant effect on the regulation of its own loading. The improvement of loading with correction of alignment is likely to have an impact on wear and subsequent survivorship of the prosthesis.

While stars are relatively well understood, the timescales on which they form are still debated. The young cluster NGC 2264 is an ideal region in which to test hypotheses about the timescale of star and cluster formation. Co-eval stars at any given e�ective temperature are expected to have similar luminosities and radii, but previous research on clusters, including NGC 2264, has found that this may not be the case. In this thesis, �bre spectroscopy from the FLAMES spectrograph is used to �nd radial and projected equatorial velocities for many low-mass pre-main sequence stars in NGC 2264. Projected radii are estimated by combining these data with published rotation periods. The projected radius distribution is compared with models incorporating radius and age dispersions. These methods circumvent many uncertainties that arise when using luminosities to infer ages from the Hertzsprung-Russell diagram (HRD). Comparisons of models and data favour a spread of radii that is inconsistent with a coeval population but consistent with the spread of ages seen in the HRD. Modeldependent, but distance-independent, ages of 1 - 2.6 Myrs are found, and agreement with ages determined from the HRD is found for a cluster distance of 770� 46 pc. The cluster velocity dispersion is well resolved, and a connection between spatial and kinematic substructure is established. The substructure is unlikely to be responsible for the observed age dispersion. A catalogue of 547 spectroscopic observations of stars in NGC 2264 is presented, with measurements of radial and projected equatorial velocities.

Background: Moderate to severe chronic pain affects one in five of adults. The prevalence and impact of pain increase with age. Pain may increase the risk of mortality but the relationship is not clear. Aims: To test the hypothesis that pain increases the risk of mortality, to test if the relationship was dependent on pain classification and identify mediators and moderators of the relationship. Methods: A systematic review and meta-analysis evaluated existing evidence. Survival analyses (Cox’s proportional hazard modelling and a novel technique to assess mediation within survival models) were conducted on two large population studies of adults aged ≥50 years; the English Longitudinal Study of Ageing (ELSA) (n=6324) and the North Staffordshire Osteoarthritis Project (NorStOP) (n=10985). Lifestyle, health, social and psychological factors were tested as potential mediators. Sex and comorbidity were tested as moderators. Results: In the systematic review pooled analysis from 7 studies revealed a modest but non-significant risk of mortality for people with chronic pain (Mortality Rate Ratio 1.14, 95%CI (0.95, 1.37)). In survival analyses the relationship with mortality was influenced by pain classification: pain that was troubling (1.29 (1.12, 1.49)) or that interfered with daily activities (1.88 (1.54, 2.29)) was associated with an increased risk of mortality while reporting any pain was not (1.06 (0.95, 1.19)). The strongest mediators in ELSA that were replicated in NorStOP were functional limitation (Hazard Ratio 1.31; 95%CI (1.20, 1.39)), physical inactivity (1.14 (1.10, 1.20)) and poor self-rated health (1.32 (1.23, 1.41)). Sex and comorbidity moderated the extent of some mediating pathways (e.g. depression) but the findings were inconsistent between datasets. Conclusion: Specific opportunities to reduce mortality risk for people with pain were identified. At a population level, mortality risk for people with pain could be reduced by the effective management of pain and its impact.

Despite much enthusiasm for the practice of peer mentoring by ex-offenders it has received very little empirical scrutiny. This thesis examines the micro dynamics and intimate interactions within these relationships. In doing so it highlights how mentors are often much more than functional additions to existing criminal justice systems. They are also presented as teachers, co-operators and critical agents. The narratives in this study highlight how dominant forms of knowledge often minimise or miss the lived experiences of crime and change. In contrast, peer mentors place lived experiences at the centre of their approach and in doing so they critically question exclusionary practices and re-humanise themselves and their peers. The work of peer mentors also highlights and at times challenges the hidden power dynamics that are subsumed when ‘regular’ interventions take place. But, mentoring cannot avoid or operate outside of these power relationships. It can and does generate other power dynamics. Whilst many of these complex relations remain hidden in current evaluations of the practice they are rendered visible here. Data were obtained from qualitative interviews with eighteen peer mentors, twenty peer mentees, four service coordinators and two Probation officers, who were drawn from a range of voluntary sector providers in the North of England. Observations of practice were also carried out, including: volunteer recruitment processes; training courses; and formal supervision sessions. Where possible mentors were also observed facilitating group work with their peers. The analysis of the data drew upon techniques of thematic analysis and critical discourse analysis focusing upon how mentoring was described, performed and justified by participants. As a result of this analysis five overarching themes emerged. These are: identity, agency, values, change and power.

Massive screens of chemical libraries for antimalarial activity have identified thousands of compounds that exhibit sub-micromolar potency against the blood stage of the malaria parasite Plasmodium falciparum. Triaging these compounds to establish priorities to take forward for development requires additional information regarding their activity. Key amongst their pharmacodynamics (PD) properties is the rate of kill– with a rapid cytocidal effect specifically identified as a key requirement for a Single Exposure Radical Cure and Prophylaxis (SERCaP) product. Compounds that exert an immediate cytocidal effect rapidly reduce parasite burden to ameliorate the morbidity and mortality of disease. With the overall aim to accelerate drug screening by validating a rapid rate of kill, the validation of a novel, quick (6hr) and potentially scalable bioluminescence rate of kill (BroK) assay is described here that demonstrates a good correlation with in vitro recrudescence-based rate of kill data and available in vivo clinical findings. The BRoK assay was used to screen the Medicine for Malaria Venture Malaria Box to identify compounds with rapid cytocidal activity. Seventeen compounds have an initial rate of kill greater than artemisinins, with a further 39 compounds exhibiting a rate of kill between chloroquine and artemisinins. These compounds represent potential Target Candidate Profile, compounds for a SERCaP product. This work highlights the opportunity for the BRoK assay as a hit discovery tool. In addition, the potential for this assay in lead validation through structure activity relationship studies are highlighted.

Background Constraint induced movement therapy (CIMT), an intervention to increase upper limb (UL) function post-stroke, is not used routinely by therapists in the United Kingdom; reasons for this are unknown. Using the Promoting Action on Research Implementation in Health Services (PARIHS) framework to analyse CIMT research and context, a series of related studies explored implementation of CIMT into practice. Methods and Findings Systematic review: nineteen CIMT randomised controlled trials found evidence of effectiveness in sub-acute stroke, but could not determine the most effective evidence-based protocols. Further review of qualitative data found paucity of evidence relating to acceptability and feasibility of CIMT. Focus group: perceptions of the feasibility, including facilitators and barriers, of implementing CIMT into practice were explored in a group of eight therapists. Thematic analysis identified five themes: personal characteristics; setting and support; ethical considerations; education and training; and practicalities, which need to be addressed prior to implementation of CIMT. Mixed-methods, pilot study (three single cases): pre- and post-CIMT (participant preferred protocol) interviews explored perceptions and experiences of CIMT, with pre- and post-CIMT measurement of participation and UL function. Findings indicated: (i) provision of evidence-based CIMT protocols was feasible, although barriers persisted; (ii) piloted data collection and analysis methods facilitated exploration of stroke survivors’ perceptions and experiences, and recorded participation and UL function. Conclusions Findings traversed PARIHS elements (evidence, context, facilitation), and should be considered prior to further CIMT implementation. Future studies of CIMT should explore: effects of CIMT protocol variations; characteristics of stroke survivors most likely to benefit from CIMT; interactions between CIMT and participation.

The reconstruction of critical-size bone defects following tumour resection or bone loss due to trauma is topical today and relates to the complexity of the treatment involved and poor healing outcomes. In bone bioengineering, the current trends are to explore novel methods of repairing these defects by using various bone substitutes. Various graft materials have been used for the restoration of these defects. A graft ideally needs to promote osteogenesis, osteoinduction and osteoconduction. The aim of this investigation was to assess the histological, radiographic and mechanical properties of the tissue regenerate following the application of tricalcium phosphate (TCP) scaffolding and recombinant human bone morphogenetic protein 7 (rhBMP-7) for the reconstruction of a critical-size osteoperiosteal mandibular continuity defect in the rabbit model. Highly purified and freeze dried recombinant human BMP-7 was used. It was produced by Chinese hamster ovary cells in culture and purified from the culture media. All the TCP samples had a porosity of 80% and average pore size of 100 – 500µm. For the rhBMP-7 loaded scaffolds; rhBMP-7 was reconstituted according to a recommended specification and 400ng were loaded by adsorption into the TCP scaffolds. Nine adult New Zealand white rabbits (3.0-4.0kg) were used for the planned study. In each case a unilateral osteoperiosteal mandibular body critical-size defect was created. In six cases the critical-size defect was filled with the rhBMP-7 on the TCP scaffolding, and in three cases the TCP was used alone. Assessments were made with plain radiographs at 0, 4, 8, and 12 weeks follow-up. Three months post-operatively the animals were sacrificed, the mandibles removed and the surgical sites were assessed with cone beam CT radiography, tested mechanically and analysed histologically. More bone regeneration was seen radiographically and histologically within the mandibles that received rhBMP-7 in the TCP, with evidence of both woven and lamellar bone formation. Union was obtained at the surgical site with no cartilage formation. The regenerated bone was confined to the area that had received the scaffold, with no calcification of the surrounding soft tissues. The TCP was also resorbed more completely in this experimental group. Very little bone was formed in the cases where the defect was filled with TCP alone. The mechanical properties of the regenerate in the group that received the rhBMP-7 and TCP were also significantly superior to those of the cases that received TCP alone. Histologically the overall mean of the percentage regenerated bone volume in the rhBMP-7 and TCP cases was 29.41% ± 6.25, while that for the TCP alone cases was 6.35% ± 3.08. The difference between the groups was statistically significant (p = 0.014). Mechanically the failure moments for the TCP alone cases were found to be very low (0-48mNm) while those for the rhBMP-7 and TCP cases were higher but there was considerable variation between the cases (55-2115mNm). Some of the cases in this group achieved failure moments comparable to normal untreated bone. In conclusion TCP scaffolding and rhBMP-7 can be used successfully for the reconstruction of critical-size mandibular defects in the rabbit model and TCP loaded with rhBMP-7 was significantly superior in its capacity for bone regeneration histologically when compared to TCP alone. The resultant bony regenerate could also at times have mechanical properties similar to those of natural bone. But due to the variability of the mechanical properties further investigations are required before clinical application.

Introduction: 12,000 infrainguinal bypass grafts are performed annually in the UK. Despite improvements in surgical technique, outcomes remain suboptimal: 20% of above knee grafts require intervention to maintain patency by 3 years. Only antiplatelet agents have been demonstrated thus far to improve graft survival. 80% of graft failure is as a result of intimal hyperplasia, an inflammatory process characterised by the proliferation and migration of vascular smooth muscle cells. Toll Like Receptors (TLR), part of the innate immune system, have been implicated in atherosclerosis formation but not investigated in a model of infrainguinal graft failure. When a vein is used as a conduit for infrainguinal bypass graft it has been exposed to ischaemic and hypoxic conditions: preliminary data has demonstrated that ischaemic vascular smooth muscle cell explants are hyperproliferative. Phospholipase C γ (PLC γ) is a signalling pathway with potential links to innate immune pathways and pathways induced by hypoxia and ischaemia. Methods: Human vein tissue was obtained from patients undergoing amputation and coronary artery bypass surgery and used for immunohistochemistry and to obtain vascular smooth muscle cells by explant method. Immunohistochemistry was used to determine the presence of TLR4 and PLC γ in human vein tissue. Specific TLR Ligands were used to determine the functional response of TLR’s in vascular smooth muscle cells as measured by Interleukin 8 ELISA. Radiolabelled Thymidine incorporation was used to measure proliferation of vascular smooth muscle cells in response to TLR4 activation, hypoxia and PLC γ inhibition. Results: TLR4 was demonstrated to be present in human vein tissue, and functionally active in human vascular smooth muscle cells. Furthermore stimulation with the specific ligand of TLR4 caused enhanced proliferation of vascular smooth muscle cells. Hypoxia (5% and 10% Oxygen) significantly enhanced proliferative responses of vascular smooth muscle cells. PLC γ was demonstrated to be present in human vein tissue, and inhibition, using U73122 in vascular smooth muscle cells reduced proliferation. Conclusion: TLR activation and hypoxia appear to enhance the proliferative responses of human vascular smooth muscle cells, a key cellular pathway of intimal hyperplasia formation and infrainguinal graft failure. Inhibition of PLC γ reduces proliferative responses. Further research is required to confirm that PLC γ is a key common pathway mediating enhances of proliferation caused by TLR activation and hypoxia.

Premature cardiovascular (CV) death is the commonest cause of death in patients with end stage renal disease (ESRD), which includes those receiving or close to requiring renal replacement therapy. In ESRD patients, CV deaths are most commonly caused by cardiac arrhythmia and sudden cardiac death compared to the general population where myocardial ischaemia and infarction predominate. Higher CV disease burden is due to accumulation of “conventional” risk factors (e.g. hypertension, diabetes mellitus, smoking) and “novel” risk factors (e.g. oxidative stress, proteinuria, anaemia, inflammation) in ESRD patients. In addition, risk factors specific to patients with renal disease have been identified including alteration in left ventricular (LV) structure, called uraemic cardiomyopathy. These structural abnormalities are common in patients with ESRD (between 60-80% of subjects upon initiation of dialysis) and include left ventricular hypertrophy (LVH), systolic dysfunction (LVSD) and dilatation. These changes in LV structure confer adverse CV outcome in ESRD patients and have proven difficult to reverse. Detection of these abnormalities is usually performed using echocardiography, however this technique is inaccurate in ESRD patients due to significant alterations in LV shape and geometric assumptions made during calculation of myocardial mass. Cardiovascular MRI (CMR) negates these assumptions and is the most accurate, reproducible and reliable method of assessing LV dimensions independent of intravascular volume, particularly in patients with altered myocardial architecture. Furthermore, maximal left atrial volume can be measured using CMR. The principle aims of the studies presented in this thesis were to elucidate prognostic and pathophysiological features of uraemic cardiomyopathy using CMR. In a large study (n=246) of haemodialysis patients, the determinants of each LV abnormality of uraemic cardiomyopathy were identified from past clinical history, haemodialysis and blood parameters and other LV measurements. For LV changes, major determinants were clinical features associated with advanced renal disease, namely expansion of intravascular/ extracellular fluid compartment, abnormal bone mineral biochemistry and hypertension. Furthermore, presence of one LV abnormality was one of the strongest predictors of presence of another, perhaps indicating differing stages of uraemic cardiomyopathy development. In a subsequent prognostic study including these patients (n=446), presence of LVSD and LV dilatation on CMR were significantly associated with poorer all cause and CV mortality. Presence of LVH, which is by far the most common structural change, was associated with poorer cardiovascular survival only. In addition, presence of two or three abnormalities (commonly LVH with another abnormality) had a significantly poorer prognosis and independently predicted CV and all cause mortality. This has implications for therapeutic strategies which should aim to slow or reverse cardiac changes of ESRD and prevent progression from one cardiac abnormality to 2 or more. In a further study (n=201) investigating additional prognostic features of ESRD patients with LVH, maximal left atrial volume (LAV) was measured using the bi-plane area length method at end LV systole. Elevated LAV and presence of LVSD were significantly associated with poorer all cause survival and were independent predictors of death. The most likely causes of elevated LAV in ESRD patients are LV diastolic dysfunction and expanded extracellular compartment and may provide a target for therapeutic intervention. The electrophysiological features of uraemic cardiomyopathy were assessed using microvolt T wave alternans (MTWA) which is a novel, non-invasive method of measuring small variations in surface electrocardiogram (ECG) T wave morphology and thus ventricular repolarisation. This technique has been used to stratify other cohorts at elevated risk of sudden cardiac death (such as ischaemic and non ischaemic cardiomyopathy, hypertensive LVH). A study presented in this thesis, compared MTWA results between ESRD (n=200) and hypertensive patients with LVH on echocardiography (n=30). Abnormal MTWA result was significantly more common in ESRD patients compared to hypertensive patients with LVH. Furthermore, abnormal MTWA result was significantly associated with myocardial abnormalities of uraemic cardiomyopathy and a history of macrovascular atheromatous disease in ESRD patients. Despite preservation of LV function on CMR, the frequency of abnormal MTWA result in ESRD patients was similar to previous studies in subjects with heart failure. 31Phosphorus magnetic resonance spectroscopy is a novel, non-invasive technique of estimating cardiac energetic status and high energy phosphate (HEP) metabolism in a myocardial area of interest and has previously been used to assess patients with global myocardial disease (dilated cardiomyopathy, hypertensive LVH). High energy phosphate metabolism was compared between patients with ESRD (n=53) and hypertensive LVH (n=30) and despite similar LV mass between both groups, PCr: ATP (an indicator of HEP metabolism) was significantly reduced in ESRD patients. These findings are most likely due to cardiac interstitial fibrosis and the alteration of tissue composition within the area of interest, and changes in metabolic function within cardiomyocytes of uraemic hearts. Finally, a small study (n=50) investigated the effect of successful renal transplantation on LV mass measured by CMR. On comparison of patients who remained on the renal transplant waiting list, there was no significant difference in LV mass in patients who received a renal transplant. It is likely that previous echocardiography studies that demonstrated significant regression of LVH, measured improvement in fluid control rather that actual reduction in myocardial mass. Future studies investigating benefit of therapeutic intervention may require identification of individuals at higher CV risk and the results of studies presented in this thesis aim to provide information for selecting such ESRD patients. With these results in mind, further prospective studies will be able to carefully select groups of ESRD patients with differing left ventricular, left atrial, electrophysiological and biochemical properties to demonstrate survival benefit with interventional agents. In this way, future therapies for ESRD patients can be tailored to improve cardiovascular survival.

The focus of this thesis is on how working class men live with physical interpersonal violence. The place of the research is in Easterhouse, a housing scheme on the outskirts of Glasgow in Scotland. The primary research methods employed are a reflexive engagement with in-depth semi-structured interviews and participant observation. This concern with a reflexive engagement with the research field and the research ‘data’ is theorised using the sociological tools crafted by Pierre Bourdieu; in particular, his stress on reality as fundamentally relational and his use of reflexivity, habitus, the body and fields to construct and understand human agency. In this thesis, these tools are used to open up moments of often `mindless’ violence and to understand what these moments might ‘mean’ to both those who experience this violence, and how this reality can come to be evacuated/excavated in historical and representational forms. To do this, the thesis considers the formation of habitus through time, across generations and indeed how a relationship to time is made and grounded in everyday experience of class relations and culture (and so the amount of resources or capital that can be brought to bear in the context of these relations). In this sense, the thesis endeavours to complicate what is meant by violence and what is mean by the ‘causes’ of physical interpersonal violence by situating moments of violence as elements in a total fact of life. The thesis situates contemporary forms of physical interpersonal violence in the new social, economic and cultural landscape formed post-1979. That is, continuities and discontinuities are assessed in relation to a tradition of having no tradition and the possibilities for historical self-understanding and agency that such a moment could provide. That is, now that working class culture has been ‘stripped down’ to its economic reality the culture of working class life is simultaneously a coming to terms with this ‘nothing’. Paradoxically, then it is in this ‘nothing’ that agency is found and where history, culture and politics can either come to be ‘reclaimed’ – ‘invented’ – or ‘mobilised’.

The thesis aims to propose a framework for poetry translation and its criticism. It is demonstrated how criticism on poetry translation can discuss the source text and target text in a way that they may well be two pieces of prose and miss a very important point: their aesthetic value as poetry. The thesis goes on to investigate an important issue of poetry translation: what makes �·poetry poetry. For if poetry is to be translated into poetry and criticized as poetry, this will be a highly relevant issue. An investigation into both Chinese and Western traditions shows that the common ground shared is that poetry in a poem is something holistic and coming from those aesthetically effective contextual relations from the poem. Gestalt Theory is introduced as the backbone of the framework to embody how those contextual relations function and a new term for the poetry one reads in a poem is coined, poestalt-combining poem and gestalt. The framework then is applied to investigate three issues and its significance to the criticism of poetry translation: Firstly, how poestalt may emerge mid the condition for this to happen, i.e. aesthetic coherence. Secondly, the significance of the creative involvement of the reader/translators, which is an important element of poetry reading/translation. Thirdly, the nature of the contextual relation and poestalt, which is highly related to the former two.issues. With this framework, the thesis shows that the poestalt emerging from the source text is the relevant object of poetry translation and its comparison with the poestalt emerging from the target text is the object for the criticism of poetry translation.

As high-k dielectrics are introduced into commercial Si CMOS (Complimentary Metal Oxide Semiconductor) microelectronics, the 40 year channel/dielectric partnership of Si/SiO2 is ended and the door opened for silicon to be replaced as the active channel material in MOSFETs (Metal Oxide Semiconductor Field Effect Transistor). Germanium is a good candidate as it has higher bulk carrier mobilities than silicon. In addition, Si and Ge form a thermodynamically stable SiGe alloy of any composition, allowing Ge to be implemented as a thin layer on the surface of a standard Si substrate. This thesis is a practical investigation on several aspects of Ge CMOS technology. High-k dielectric Ge p-MOSFETs are electrically characterised. A large variation in interface state densities is demonstrated to be responsible for a threshold voltage shift and this is proportional to reciprocal peak mobility due to the Coulomb scattering of carriers by charged states. A theoretical mobility is fitted to that measured at 4.2 K and confirms that interface states are the main source of interface charged impurities. The model demonstrates a reduction in the interface charged impurity density in p-MOSFETs that underwent a PMA (Post Metallisation Anneal) in hydrogen atmosphere and that the anneal also reduces the RMS (Root Mean Square) dielectric/semiconductor interface roughness, from an average of 0.60 nm to 0.48 nm. High-k strained Ge p-MOSFETs are electrically characterised and have peak mobilities at 300 K (470 cm2 V-1 s-1) and 4.2 K (1780 cm2 V-1 s-1) far in excess of those measured for the unstrained Ge p-MOSFETs (285 cm2 V-1 s-1,785 cm2 V-1 s-1 respectively). Strained Ge n-MOSFETs perform significantly worse than standard Si P, - MOSFETs primarily due to a high source/drain resistance. A 10 nm thick SiGe-01 (On Insulator) layer with a Ge composition of 58% is obtained from a 55 nm Si0_88Ge1o2. initial layer on 100 nm Si-Ol substrate via the germanium condensation technique. For the first time, germanium is demonstrated to diffuse through the BOX (Buried OXide) during Ge-condensation and into the underlying Si substrate. An order of magnitude increase in the calculated ITOX (Internal Thermal OXidation) rate of the BOX in the final stages of Ge-condensation is hypothesised to be responsible for stopping this diffusion.

Shape-from-shading is a classical problem in computer vision. The aim is to recover 3D surface shape from a single image of an object, based on a photometric analysis of the pattern of shading. Since the amount of light reflected by a surface is a function of the direction of the incident light and the viewer, relative to the local surface normal, image intensity conveys information about surface orientation and hence, indirectly, surface height. This thesis aims to relax some of the assumptions typically made in the shape-from-shading literature. Our aim is to move shape-fromshading away from the overly simplistic assumptions which have limited its applicability to images captured in lab conditions. In particular, we focus on assumptions of surface smoothness, point source illumination and reconstruction in the surface normal domain. In Chapter 3, we relax the assumption of a smooth surface. We exploit a psychology-inspired heuristic that pixels need only have a similar surface orientation if they are both in close proximity and have a similar intensity. This leads to an adaptive smoothing process which is able to preserve fine surface structure. We adapt a geometric shape-from-shading framework to overcome the problem of normals “flipping” between solutions which alternately satisfy data-closeness and smoothness terms. Under the classical assumption of point source illumination, we show that our method significantly outperforms a number of previously reported methods. In Chapter 4, we relax the assumption of illumination being provided by a single point light source. Specifically, we consider environment illumination in which lighting is represented by a spherical function which describes the incident radiance from all directions in the scene. We use the well known result that Lambertian reflectance acts like a low pass filter and hence the convolution of environment lighting and surface reflectance can be efficiently represented using a low order spherical harmonic. With an order-1 approximation, we show how the image irradiance equation can be solved as a quadratically-constrained linear least squares optimisation. The global optimum is found using the method of Lagrange multipliers. The order-2 case is non-convex and prone to converge on local minima if solved using local optimisation. We reformulate the problem as a bilinear system of equations which leads to an efficient and robust solution method. In both cases, we incorporate a structure-preserving smoothness constraint based on ideas from Chapter 3 to regularise the problem. In Chapter 5, we continue with the relaxed illumination assumption (i.e. we model environment illumination), but we develop algorithms which operate in the domain of surface height rather than surface normals. This has the advantage of reducing the dimensionality of the problem at the expense of increased complexity. Moreover, integrability is implicitly enforced via the problem formulation. We describe two contributions. The first is a linear method for recovering surface height directly from images formed by taking ratios between colour channels. In this case, the nonlinear normalisation term is factored out. This allows us to form a linear system of equations relating image intensity and surface height via a finite difference approximation to the surface gradient. Finally, we relax the assumption that the object must be globally convex (i.e. contains no self occlusions). We show that self occluded intensity can be related to unoccluded intensity via a quadratic inequality constraint. This is too weak a constraint to be used for shape-from-shading on its own. However, we use it to develop an occlusion-sensitive surface integration algorithm. We show that the problem can be formulated as a convex optimisation and solved using semidefinite programming.

Loss of adaptive variation arising from population declines and fragmentation is a primary concern in conservation. However, many conservation programmes assess only neutral genetic variation. Whilst assessments of neutral variation are informative about demographic history, inbreeding and genetic structure, they do not provide information on adaptive variation. The Major Histocompatibility Complex (MHC) is a group of genes that has been extensively studied and are known to be important in effective immune responses. Given the threat posed by infectious diseases to wildlife, the MHC is increasingly being assessed in endangered species. African wild dogs (Lycaon pictus, hereafter wild dog) are an endangered canid that has suffered extensive declines in the wild and now persist as small and fragmented populations totalling less than 8,000 individuals. The purpose of this study was to assess how neutral and MHC marker data genetic data can be used to assist conservation of this species. As such, I assessed sequence diversity across ~300bp of mitochondrial DNA, patterns of polymorphism and heterozygosity at 10 neutral microsatellite loci, compared to sequence variation and haplotype diversity at the MHC. Wild dogs were found to be genetically depauperate at the MHC compared to other canids. Patterns of variation indicate a historical loss of variation, followed by more recent diversification. However, it was also shown that evolutionary history contributes to differences in diversity between species. The spatial and temporal structure of MHC diversity was found to be largely correlated with neutral markers, which may suggest that selection is unable to counter strong genetic drift in such small populations. Overall, genetic diversity of both neutral and MHC markers appeared to be largely determined by demographic stability and size of populations. Habitat fragmentation and loss were associated with genetic isolation of wild dog populations, which showed strong structuring. However, the barriers to, or corridors for, dispersal of wild dogs were not always clear. The European captive breeding population was found to have comparable diversity metrics to wild populations, and was found to contain a large proportion of the MHC variation from the Southern African populations from which they were originally sourced. Careful genetic management is now required to correct the severe over- and underrepresentation of some founder lineages in this captive population to reduce inbreeding and loss of genetic variation.

This thesis views the Angolan civil war as a conflict that resulted from both internal and external political factors. The war, fought in the period 1975-1976 between the MPLA and the FNLA-UNITA coalition to succeed Portuguese colonialism in Angola, involved the intervention of external powers on behalf of both sides. This study examines, in part, the relationships that were established between these international powers and the Angolan movements. Due to the way in which these external relationships modified the nature of the internal political dispute, they became an intricate part of the origins of the conflict itself. The internationalization of the Angolan civil war was predicated, however, on an internal political conflict that emerged from a dynamic interaction of the effects of both Portuguese colonialism and divergent currents of Angolan anti-colonialism. While the particularities of Portuguese colonialism and the Salazarist regime played their part in establishing some of the conditions within which Angolan anti-colonialism emerged, the latter was also a product of specific political choices on the part of the movements involved. In this interaction there can also be found the roots of the conflict between the Angolan movements. This internal conflict was further exacerbated when the parties to it hoped to bolster their respective positions by establishing relationships with external powers. The establishment of these relationships was in part achieved by appealing to external rivalries, in particular to that of the competition between the superpowers, but also to regional rivalries, such as that between Congo and Zaire and wider continental divisions. The interaction between the internal conflict and these external rivalries is shown to have contributed significantly to the origins of the civil war. This thesis maintains its focus tightly on the specific question of the origins of the Angolan civil war. Those developments that led to the war, rather than the conflict itself are its main concern.

During the period 1920-1930, British Protestant missionaries engaged in many cultural activities in China. This study is designed to analyze their special role in China's national development and modernization. The opening chapter mainly introduces the significance of the missionary social gospel and describes its theological tenets. It also examines the origins of the movement for cooperation among the Protestant missions and the features of the main British missions. The thesis then turns to the areas in which the missions displayed their leading social concerns, deriving from their policies. Chapters 2 & 3 describe the major contributions of the missionary medical services, analysing both primary medical work (direct medical care) and secondary medical work (education, research, translations and publications, public health). During the 1920s the Protestant missions were the most important force in medicine in China. Chapter 4 assesses the educational activities of British missionaries and their importance in the circumstances of China in the 1920s in triggering and moulding social change. Above all, the missionaries helped China to perfect her modem educational system and to understand Western learning and culture to much higher standards than previously. The following two chapters analyse the missionaries' role as social welfare workers and social reformers. Their work in this field included popular education, moral welfare, industrial welfare, famine relief, and rural reform, and constituted one of the most outstanding episodes in mission cultural activities. Chapter 7 discusses the British missionaries' influence in the movement of Chinese women's emancipation. In the 1920s many ordinary Chinese women, who had been untouched by the Revolution of 1911, were mobilized by missionary women's work. In contradiction to many traditional accounts, especially those of Chinese scholars, the final chapter assesses the positive cultural achievements of the Protestant missionaries and their unique role in promoting China's progress and modernization.

Since c.1945, there has been an 'explosion' of small-scale industrial activity in Ghana. This thesis attempts to explain why this has happened. First, developments in small industries during the colonial period are analyzed. Using new sources of data, it is argued that indigenous industries survived this period and were of significant importance by the end of British rule in 1957. Next, changes in the size and sophistication of these industries in the postcolonial period are quantified. It is estimated that, between 1960 and 1984, the number of workers employed in this sector more than doubled. There was also a clear increase in the small industry sector's sophistication. A significant part of the thesis concerns government policy towards small industries since c.1945. Extensive use is made of newly-released archival material, particularly from the Nkrumah years (1951 to 1966). It is argued that, in general, government policies cannot explain Ghana's small industry expansion: although some governments have championed the cause of small industrialists, their small industry development programmes have been relatively small. Also, some government policies actually have prevented small industry growth. Given that the state cannot be accountable for the 'explosion' of small-scale industrial activity, this thesis considers other possible reasons for this phenomenon. This is done by examining previous studies of the small industry sector and using new material from a survey of 40 small-scale industrialists conducted in 1996. It is argued that Ghana's small-scale industrial 'explosion' can be understood as one of the consequences of Ghana's pattern of economic development until the early 1960s, followed by a period of prolonged and rapid economic collapse during the 1970s and early 1980s.

The aim of this study was to explore children's play, looking at developmental domains of play and gender differences in aggressive play. Chapter One reviewed existing literature on types and functions of play. Five developmental domains of play that incorporate types and functions were proposed, namely sensorimotor, cognitive, socio-communicative, imaginative/ creative and emotional. Chapter Two involved an observational study of children's play. An attempt was made to explore the existence and occurrence of the developmental domains that were proposed in Chapter One. Results suggested that the domains exist in this sample of children's play. Children statistically spent the most time in sensorimotor and imaginative/ creative play, compared to the other types of play. No statistical difference was found in gender with respects to time spent playing in the domains. Clinical implications are discussed. Future research is required to create more valid and reliable criteria for the domains and age-related norms. Chapter Three investigated gender differences in the duration of aggressive play. An observational study of children's play was carried out. The duration of time of aggessive play in each child's play was recorded and analysed. Results showed that boys displayed statistically more aggressive play than girls in this sample. Clinical implications are discussed. Chapter Four reviews the previous three chapters, looking at methodological limitations, observations of the research process and personal reflections.

This study investigated a methodology for an on-line condition monitoring of tool wear during milling. Based on a comprehensive literature survey, a novel method called 'feature filtered fuzzy clustering' is proposed and developed. Different from the existing fuzzy clustering techniques used for the condition monitoring of machine faults and tool awear, this method can make a realistic identification and classification of tool wear under various cutting conditions by the classification of the features on which the effects of cutting conditions were removed. To realise this method, the relationships between the cutting conditions and the features under three pre-defined wear states corresponding to three clustering centres (initial, normal, severe) were established by experiemnts, which were undertaken under the conditions defined by experiemental design, and non-linear multiple regression analysis. During experiments, a sensor fusion strategy was applied in order to get information from different aspects of the milling process. A mathematical model for fuzzy clustering based on the conception of distance has been verified by experiments using inserts both with artificially created flank wear and accelerated natural flank wear during milling in a CNC tool. In order to obtain appropriate features, the effectiveness of applying different physical parameters, i.e. cutting forces, power consumption of the spindle motor, AE RMS and AE pseudo ring-down count, for monitoring of tool wear has been investigated. Employing data fusion approach and its effect on the classification results has been investigated. Also the feasibility of applying Fourier and Walsh transforms to cutting force signals during monitoring of tool wear has been investigated.

This thesis investigates the dynamics of the local Universe with particular reference to discovering the source of the Local Group (LG) motion. A redshift survey of the Great Attractor (GA) region, thought responsible for a significant fraction of the LG motion, is presented. Over 3053 galaxies, located in both clusters and filaments, were targeted using the 2dF on the AAT. Velocity distributions and mass estimates for nine clusters are reported. Together with redshifts from the literature, this survey reveals the dominant feature in the core of the GA to be a large filament extending from Abell S0639 (l= 281º, b=+11º) towards a point at I ~ 5º b ~ -50º , encompassing the Cen-Crux, CIZA J1324.7-5736, Norma and Pavo II clusters. A new model of the local velocity field out to ՅՕՕh(^-1) Мрc is derived from the combined REFLEX, BCS and CIZA surveys: the RBC catalogue. This is the first all-sky, X-ray selected galaxy cluster sample. The reconstruction includes an intrinsic correction for the bias of clusters in tracing the total density field. The velocity fields from both this reconstruction and that of the PSCz survey are compared to the observed peculiar velocities of 98 local type la supernovae (SNIa). The best fits are respectively found for values of βRBC(= Ω(^0.6)m /(^b)RBC) = 0.39±0.20 and βι = 0.55±0.06. These results are found to be robust to culls of the SNIa sample by distance, host-galaxy extinction and the reference frame in which the comparison is carried out. As the PSCz preferentially samples late-type galaxies, the derived density field under- Samples the contributions from regions of greatest over density, precisely the regions traced by the RBC survey. When combined in the ratio 78% PSCz, 22% RBC these two complimentary reconstructions are a better fit to the ресuliar velocities of the same SNIa sample than either one alone. Compared to galaxy surveys, which only see contributions to the LG motion from structures within -60h(^-1) Мрc, previous cluster surveys have argued that sources at much greater distances (~150h(^-1) Mpc) influence local dynamics. However, the RBC reconstruction presented here shows similar contributions from the same depths as the PSCz, which is partly attributed to the intrinsic bias correction and inclusion of the Virgo cluster in the RBC. The extended GA region, defined as the volume enclosed by 250 < / <350º, 一45 < ь < 45º and 2000