Over the last 20 years, advances in our understanding of the pathophysiology of severe traumatic brain injury (TBI) and in particular the contribution of secondary injury to poor outcome, has served to improve clinical management and reduce the mortality in these patients. However despite many promising preclinical studies there has been a failure to introduce a specific therapeutic intervention to further improve outcome. Inflammation, with cytokine release and leucocyte infiltration, is a significant secondary injury processes. However the inflammatory response to brain injury, its control and modulation remain incompletely described. Chemotactic cytokines, known as chemokines, are mediators of leucocyte recruitment and activation. Expression of chemokines and the resultant recruitment of leucocytes into the brain are generally thought to be integral to the enlargement of cerebral contusions which accompany clinical deterioration following severe TBI. Previous studies indicated that the main neutrophil chemokine, macrophage inflammatory protein-2 (MIP-2/CXCL2) and the monocytic chemokine, monocyte chemoattractant protein-1 (MCP-1/CCL2) are derived from glial. However the origin of these chemokines following TBI, has not been established. Furthermore, little is known about the modulation of these chemokines: The relationship of serum levels of pro-inflammatory mediators such as the human neutrophil chemokine, interleukin-8 (IL-8/CXCL8; a functional homologue of MIP-2/CXCL2), MCP-1/CCL2 and soluble interleukin-6 receptor (sIL-6R) to contusion enlargement has not been investigated. In this thesis, I investigated chemokine expression and modulation both in in-vitro, in-vivo models and in a clinical study. Initially, I compared chemokine expression in rodent and human glial cell cultures and investigated the modulation of chemokine expression by interleukin-6, the glucocorticoid dexamethasone and the immunosuppressant agent FK506. To investigate chemokine expression in-vivo I established the rat lateral fluid percussion injury (LFPI) model of TBI and measured MIP-2/CXCL2 and MCP-1/CCL2 expression in the brain following injury. Inhibition of this expression by dexamethasone and FK506 was then investigated. To identify the cellular source of chemokine expression I developed an immunohistochemical protocol for MIP-2/CXCL2 and MCP-1/CCL2. Finally, in a clinical study of serum chemokine and sIL-6R concentrations after severe TBI, I examined the relationship between these inflammatory mediators and clinical deterioration. Rat glia (microglia and astrocytes) produce chemokines with a response profile that was qualitatively similar to that of human derived cells. These chemokines were increased in the ipsilateral hemisphere following TBI. Surprisingly, immunohistochemical studies identified marked chemokine expression localised to cells with the morphology of degenerating neurones in contused tissue, rather than in glia. Furthermore, while dexamethasone significantly inhibited both MIP-2/CXCL2 and MCP-1/CCL2 expression in a rat astrocyte derived cell line, only MCP-1/CCL2 expression was reduced by steroid treatment in-vivo. Clinically, serum IL-8/CXCL8, MCP-1/CCL2 or sIL-6R were not significantly different in patients that deteriorated due to contusion enlargement from those that remained stable. However these inflammatory mediators were significantly increased in those patients that died. These studies indicate that astrocytes may not be the major source of chemokines following TBI and highlight the need for caution when inferring pathophysiological mechanisms from in-vitro studies.

Switched mode, Class-D power amplification allows for high efficiency power amplification of an audio signal. This thesis investigates its application to high power car audio systems where there is a demand for efficient high power amplification. Examination of the present car audio power amplifiers, which comprise a switched mode power supply combined with a linear output stage, has shown that there is significant scope for improvement in efficiency and power density. A novel power stage in which the attributes of a switched-mode power supply and full bridge output stage is presented. It is demonstrated that elimination of the intermedjate DC supply results in an amplifier which has a significantly lower part count, size and cost compared to conventional designs. Two different modulation schemes are explored (PWM and PDM) with a view to finding the most suitable for the new power stage. The theoretical performances of the modulators are verified by practical measurements. The design of high order DeltaSigma modulators is difficult as they show unstable behaviour and an alternative design methodology has been presented to ease this task. The mechanisms which introduce distortion in a practical amplifier are discussed, and for the case of a PWM driven output stage, a new model is presented to predict the effect of dead time on harmonic distortion. This form of distortion is shown to be the dominant cause of open loop non-linearity. The use of feedback is also investigated and yields a factor of 20 improvement in amplifier total harmonic distortion . The design throughout has been supported with practical results and these have illustrated the importance for careful circuit layout in high frequency switching systems.

International Telemetering Conference Proceedings / October 17-20, 1994 / Town & Country Hotel and Conference Center, San Diego, California / With the development of the airborne telemetry technique, it will be demanded that the transmitting sets on the missiles are more reliable and smaller. A frequency modulation (FM) oscillator stabilized with a dielectric resonator (DR), which can operates in the S-band directly, is presented. The FM oscillator is of simple circuit, reliable operation in the stabilization, small size, light weight and low cost. It will have a certain prospect of application in the airborne telemetry transmitting sets.

In metozoans, most of the key events that lead to cell activation and inhibition are controlled by tyrosine phosphorylation. Extracellular signals are transmitted by membrane bound receptors, which have intrinsic kinase activity or themselves recruit intracellular kinases to specialised inhibitory or activating phosphorylation motifs. In this way, the pattern of kinase activation creates its own turnover and can rapidly generate amplified signals by positive feedback, or recruit inhibitory proteins to counteract the signals. This process of inhibition is also constitutive since it requires continuous counter-inhibition by phosphatases at the cell surface and intracellularly even in the absence of ligands. The absence of phosphatase activity results in unbridled protein phosphorylation and form this and other data it has been proposed that the triggering of the T cell receptor and other co-receptors may result simply by physical exclusion of the large phosphatases such as CD45 from the vicinity of the receptors. Superagonist monoclonal antibodies may work in a similar way, by binding receptors close to the plasma membrane and excluding extracellular phosphatases. The work described in this thesis seeks to discover if antibody superagonists can be generated against the T cell inhibitory cell surface receptor PD-1 and test if this approach can attenuate the immune response. Using in vitro assays of lymphocyte activation and a mouse model expressing human PD-1, this study characterises a series of anti-PD-1 antibodies and shows how patterns of inhibitory activity varying according to binding sites. The inhibitory effects of the anti-PD1 antibodies are seen in the humoral, cellular and transplant immune responses. Agonistic anti-PD1 antibodies induce regulatory T cells and may have role in suppression of autoimmune disease. The thesis suggests that superagonism may be harnessed clinically to dampen the immune response, through activation of inhibitory receptors.

La lumière comprimée est un état du champ électromagnétique pour lequel le bruit, mesuré selon une certaine quadrature est inférieur au bruit du vide. Dans cet ouvrage, nous étudions la possibilité de générer de la lumière micro-onde à partir d’un transistor à effet de champ commercial. D’une part, nous observons le bruit de grenaille du canal drain-source à basse fréquence, ce qui suggère que le canal est cohérent. Ensuite, nous exploitons cette cohérence et procédons à une expérience standard de compression par le bruit de grenaille. D’autre part, nous prédisons, à l’aide d’un modèle simple, la possibilité de comprimer le bruit par modulation de la résistance du canal drain-source pour des mesures de bruit à hautes fréquences. Nous concluons en proposant une mise en œuvre de cette méthode.

In RF communications with a rotorcraft such as a helicopter, the rotor blades can impart a modulation onto the received signal called Rotor Blade Modulation (RBM). This modulation is caused by the reflection of a signal off the rotating blades. The reflected signal is Doppler shifted based on where the signal is reflected along the length of the blade as well as the angle between the axis of rotation and the emitter. RBM is known to degrade the performance of RF communications on rotorcraft and can be used in radar applications to detect and classify aircraft, but there is little on its usefulness in other areas. This thesis looks at the ability to utilize the RBM phenomenon on the rotorcraft itself to geo-locate and track a signal emitter on the ground. To do this a 3D RF ray tracing program was developed in C++ to produce simulations of RBM signals. The developed program is based on optical ray tracing algorithms with modified physical propagation effects for RF signals, and swapping lights and cameras for RF transmitters and receivers respectively. The ray tracer was then run over a realistic set of physical parameters to determine their effects on the received signal; this includes transmitter azimuth and elevation angle, receiver position, blade pitch, etc. along with their combinations. The simulations of the azimuth and elevation angle produce predictable modulations on the received signal. Based on the trends in the signal's modulation, a DSP algorithm was distilled down that accurately determines the azimuth and elevation angle of the transmitter from simulated signal data.

The viability of any electric vehicle is critically dependent on it having an acceptable range between charges, a feature which is ultimately dictated by the capacity of the battery energy store. Considerable improvements in vehicle range are possible, however, by ensuring the most effective use of this limited energy resource through the minimisation of the losses in the electric drive-train, i.e. the combined machine and power electronic controller. A particular consideration is that, for the majority of the time, the electric drive-train will be operating at part load. The thesis investigates the operation of induction motor based electric traction drive-trains, with a view to minimising the system loss over typical driving cycles. The study is based around a 26kW induction motor and IGBT inverter drive, which is typical of the technology used to power a small urban vehicle. A potential advantage of an induction motor based drive-train is the ability to vary the level of excitation field in the motor, and therefore the balance of iron and copper loss. The control of the supply voltage magnitude necessitates the use of some form of modulation on the output of the power converter. The method of modulation employed will influence the harmonic content of the supply to the motor, the level of parasitic harmonic loss in the machine and the switching losses of the power semiconductors. A theoretical study supported by experimental work on a DSP controlled drive is presented and used to determine the most appropriate modulation strategy at a given operating point to achieve an optimal balance between the motor copper, iron and harmonic loss and inverter switching and conduction loss. It is shown that compared to the established method of constant flux and fixed inverter switching frequency control, a significant reduction in the traction system loss can be achieved. Some different modulation schemes involve varying amounts of computational overhead in a DSP, the implementation of candidate modulation and control schemes has also been investigated to ensure the defined scheme is practically realisable.

QC 351 A7 no. 53 / The optical performance of three stereomicroscopes commonly used for photo - interpretation is described in terms of magnification, field of view, and square wave response (SqWR). For a given field size, the SqWR can be used to compare the amount of information in the image of each microscope. The SqWR was determined by scanning a square wave test target at four field positions for each of four field sizes (corresponding to magnifications of 6, 12, 25, and 50X). The measured SqWR was used to evaluate the relative ability of each microscope to perform two typical photointerpretation tasks: (1) detailed viewing of a target, and (2) scanning or searching for a target. For these tasks the Wild M -5 stereomicroscope was found to be somewhat better than the Bausch and Lomb 240 stereomicroscope, and both were found to be superior to the Olympus SZ III stereomicroscope. The SqWR curves are included and can be used to compare the stereo - microscopes for various photointerpretation tasks.

A digital modulation method using Chirp-Slope Keying (CSK) is developed for coherent underwater acoustic communications. Effective signal detection is a critical stage in the implementation of any communications system; we will see that CSK solves some significant challenges to reliable detection. This thesis is primarily based on analyzing the effectiveness of CSK through simulations using Matlab's Simulink for underwater communications. The procedure begins with modulating a chirp's slope by random binary data with a linear-down-slope chirp representing a 0, and a linear-up-slope chirp representing a 1. Each received symbol is demodulated by multiplying it with the exact linear-up-slope chirp and then integrating over a whole period (i.e., integrate and dump). This slope-detection technique reduces the need for the extensive recognition of the magnitude and/or the frequencies of the signal. Simulations demonstrate that CSK offers sturdy performance in the modeled ocean environment, even at very low signal-to-noise ratio (SNR). CSK is first tested using the fundamental communication channel, Additive White Gaussian Noise (AWGN) channel. Simulation results show excellent BER vs. SNR performance, implying CSK is a promising method. Further extensive analysis and simulations are performed to evaluate the quality of CSK in more realistic channels including Rayleigh amplitude fading channel and multipath.

Le LETI possède un savoir-faire permettant de réaliser des micro modulateurs spatiaux de lumière (Spatial Light Modulators, SLMs) réalisés en technologie microélectronique sur silicium, ayant des très grandes résolutions et de très petits pas de pixels. Le LETI souhaite utiliser une technologie LCD particulière (la technologie IPS) dont d’une part les performances électro-optiques dans le domaine des micro-écrans ne sont pas connues mais d’autre part permet de garder des coûts réduits et de réduire le nombre d’étapes de fabrication. L’objectif de cette thèse est d’évaluer sur la base de simulations puis de réalisations techniques, les performances d’un micro-SLM IPS utilisé en modulation de phase et d’amplitude.Les recherches effectuées au cours de cette thèse portent sur 4 axes d’études. Le premier axe consiste à la recherche et à l’essai d’un logiciel spécifique (LCDMaster) permettant de simuler des cellules à cristaux liquides ainsi que des électrodes flottantes. Le second axe consiste à étudier en fonction du design du pixel et des différents modes d’alignements des cristaux liquides (Homogène, vertical et twisté) avec un pilotage de type IPS, les performances en modulation de phase. Les meilleurs résultats sont obtenus pour un alignement vertical fournissant un déphasage de 2 Pi. De plus, les performances d’un dispositif d’optique adaptative intégrant le SLM étudié ont été investiguées. Le troisième axe d’étude, consiste avec le même logiciel à investiguer sur les performances d’un SLM à cristaux liquide avec un pilotage de type IPS utilisant un alignement homogène en modulation d’amplitude (étude statique et dynamique). Cette étude permet également d’étudier les possibilités de diminution du temps de réponse de la cellule. Cette étude a aboutie à deux designs de SLM. Le premier design avec deux niveaux d’électrodes séparés par un isolant permettant de reproduire un effet type « cage de faraday ». La seconde a permis de diminuer de manière drastique le temps de réponse. Le quatrième axe de recherche consiste à tester des prototypes basés sur ces deux designs pour vérifier les performances obtenues en simulation grâce à un banc de caractérisation électro-optique. Des résultats concordants ont étés obtenus et de nouveaux types de SLM à pilotage IPS proposant un temps de rafraichissement rapides se rapprochant de l’état de l’art ont donc pu être désignés et caractérisés. / LETI possesses an expertise allowing to realize Spatial Light Modulators (SLMs) made in microelectronic technology on silicon, having very high resolutions and very small pixel steps. LETI wishes to use a specific LCD technology (IPS technology), on the one hand the electro-optical performances in the field of micro-display had to be investigated but on the other hand allows to keep costs down and reduce the number of manufacturing steps. The objective of this thesis is to evaluate on the basis of simulations and technical achievements, the performance of a micro-SLM IPS used in phase modulation and amplitude.Our investigations have been carried out on four major areas of study. The first axis is the search and testing of a specific software (LCDMaster) to simulate liquid crystal cells and floating electrodes. The second axis according to different designs of pixel and the different liquid crystal alignment modes (Homogeneous, vertical and twisted) with an IPS type control, to investigate the performances in modulation phase. The best results were obtained for a vertical alignment providing a phase shift of 2π. In addition, the performance of an adaptive optics device integrating the studied SLM has been investigated. The third axis of study focused on the performance investigation of a liquid crystal SLM with an IPS-type control using a homogeneous alignment in amplitude modulation (static and dynamic study). This study also makes it possible to study the possibilities of reducing the response time of the cell. It resulted in two SLM designs. The first design with two levels of electrodes separated by an insulator to reproduce a Faraday type effect. The second has drastically reduced the response time. The fourth area of research consists in testing prototypes based on these two designs to validate the performances obtained in simulation. Concordant results have been obtained and new types of IPS-controlled SLMs with state-of-the-art refreshing times have thus been designated and characterized.