Passenger ride vibration comfort is a critical aspect to consider while developing any vehicle and there is a need to understand how the occupants would be affected when driving on different road profile roughness. Hence, road profile generation is critical as road profiles are used as inputs to simulation tools to investigate vehicle dynamic behaviour in depth. At the same time, the optimisation of the vehicle characteristics can be conducted on the various road profiles in order to identify a solution that can provide enhanced ride comfort and improve vehicle handling for all the investigated road profiles. The objective of this thesis is to study ride vibrational comfort and optimise the suspension system for theNational Electric Vehicle Sweden (NEVS) vehicle model for better ride comfort and road holding. Synthetic road profiles are generated by using stochastic processes according to International Organization for Standardization (ISO) 8608 standards. Further, simulations are conducted in MSC ADAMS Car software using the generated synthetic road profiles for a rigid body NEVS vehicle model to study the vertical accelerations. The analysis includes the investigations of the acceleration Power Spectral Density (PSD) and observations are made on the peaks that appear (at Front Seat Rail (FSR) which is the sprung mass of the vehicle and Wheel centre (WC) which is the un-sprung mass of the vehicle) for different road types and vehicle velocities. It is decided that the comfort objective will be used considering the weighted Root Mean Square (RMS) accelerations. Further, the suspension system of the vehicle model is optimised for three different road profiles (A, B, and C) based on the objectives of ride comfort and handling using a suitable vehicle model with the same characteristics as theNEVScar. A multi-objective optimisation technique is used and the optimised results are observed and discussed. Optimal objectives (based on a compromise between ride comfort and road holding) for the suspension system are determined for each investigated road profile. / Vibrationskomfort för passagerare är en kritisk aspekt att tänka på när man utvecklar ett fordon och det finns ett behov av att förstå hur passagerarna kan påverkas när de åker på olika vägprofiler. Därför är vägprofilgenerering avgörande eftersom vägprofiler används som input till simuleringsverktyg för att undersöka fordonets dynamiska beteende. Samtidigt kan optimeringen av fordonets egenskaper utföras på de olika vägprofilerna för att identifiera en lösning som kan ge ökad åkkomfort och förbättra fordonshanteringen för alla undersökta vägprofiler. Syftet med detta examensarbete är att studera körvibrationskomfort och optimera fjädringssystemet för NEVS fordonsmodellen för bättre åkkomfort och väghållning. Syntetiska vägprofiler genereras genom att använda stokastiska processer enligt ISO 8608 standarder. Dessutom utförs simuleringar i MSC ADAMS programvara med hjälp av de genererade syntetiska vägprofilerna för en stelkropps NEVS fordonsmodell för att studera de vertikala accelerationerna. Analysen inkluderar undersökningar av accelerations PSD och observationer görs av topparna som visas (vid FSR och WC) för olika vägtyper och fordonshastigheter. Det beslutas att komfortmålet kommer att utvärderas med hänsyn till endast de vägda RMS accelerationerna. Dessutom är fordonsmodellens hjul upphängningssystem optimerat för tre olika vägprofiler (A, B och C) baserat på målen för åkkomfort och väghållning med hjälp av en lämplig fordonsmodell med samma egenskaper som NEVS bilen. En multi-purpose optimeringsteknik används och de optimerade resultaten observeras och diskuteras. Optimala mål (baserat på en kompromiss mellan åkkomfort och väghållning) för fjädringssystemet bestäms för varje undersökt vägprofil.

Sidescan sonars are tools used in seabed inspection and imagery. As a smaller and cheaper compared to the alternatives tool, it has attracted attention and many studies have been developed to extract information about the seabed altitude from the produced images. The main issue is that sidescan sonars do not provide elevation angle information, therefore a 3D map of the seabed cannot be inferred directly. One of the most recent techniques to tackle this problem is called neural rendering [1], in which the sea surface bathymetry is implicitly represented using a neural network. The purpose of this thesis is (1) to find the minimum altitude change that can be detected using this technique, (2) to check whether the position of the sonar ensonification has any effect on these results, and (3) to check from how many sides is it sufficient to ensonify the region with altitude change in order to detect it confidently. To conduct this research, simulations of missions conducted by an autonomous underwater vehicle with sidescan sonar heads on both sides are done on a map, where different objects from various sizes and shapes are put. Then, neural rendering is used to reconstruct the bathymetry of the maps before and after the object insertion from the sidescan sonar. The reconstructed seabed elevations are then compared and the objects with the smallest size or altitude that were detected (meaning that the predicted height from the model trained on the map with the objects is significantly larger than that of the model trained on the initial map) would be the answer to the first question. Then, those smallest objects are again put on the same map, and now smaller autonomous underwater vehicle missions are used to check how many sides are need so that the objects are still detectable. The conducted experiments suggest that objects with bathymetry elevation in the range of centimeters can be detected, and in some cases ensonification from 2 sides is sufficient to detect an object with confidence. / Sidenskannings-sonarer spelar en avgörande roll i inspektionen av havsbotten och erbjuder kostnadseffektiva alternativ till traditionella verktyg. Bristen på information om elevationsvinklar utgör dock en utmaning för att direkt härleda en 3D-karta över havsbotten. Denna avhandling undersöker tillämpningen av neural rendering [1], en nyligen utvecklad teknik som implicit representerar havsytsbathymetri med neurala nätverk, för att adressera denna begränsning. Målen med denna forskning är tre: (1) att bestämma den minsta detekterbara höjdändringen med hjälp av neural rendering, (2) att bedöma effekten av sonarens ensonifieringsposition på detektionsresultaten och (3) att undersöka det minsta antalet sidor som krävs för pålitlig objektdetektion i områden med höjdändringar. Metoden innefattar simuleringar av autonoma undervattensfordonsuppdrag utrustade med sidenskannings-sonarer på båda sidor. Olika objekt av varierande storlekar och former introduceras på en karta, och neural rendering används för att återskapa bathymetrier före och efter objektets insättning. Analysen fokuserar på att jämföra de återskapade havsbottenhöjderna och identifiera de minsta objekten eller höjdändringarna som är möjliga att detektera med modellen. Därefter återintroduceras dessa minimala objekt på kartan, och mindre uppdrag med autonoma undervattensfordon genomförs för att fastställa det minsta antalet sidor som krävs för pålitlig detektion. Forskningsresultaten indikerar att objekt med höjdändringar i centimeterskalan kan detekteras pålitligt. Dessutom tyder experimenten på att i vissa fall är ensonifiering från endast två sidor tillräckligt för pålitlig objektdetektion. Denna forskning bidrar med värdefulla insikter för att optimera sidenskanningssonarapplikationer för havsbotteninspektion, vilket erbjuder potentiella förbättringar av effektivitet och kostnadseffektivitet för undervattensutforskning och kartläggning.

Die Einwanderung von T-Zellen in ein Gewebe wird durch selektive Wechselwirkungen mit vaskulären Endothelzellen kontrolliert. In der vorliegenden Arbeit wurde der Frage nachgegangen, ob Interaktionen zwischen Lebersinusendothelzellen (LSEC) und CD4+ T-Zellen die gewebespezifische Migration von CD4+ T-Zellen beeinflussen und damit Relevanz für den Verlauf spezifischer Immunantworten haben. Die Präsentation von Antigenen durch zytokinaktivierte LSEC erhöhte die Adhäsion und Transmigration antigenspezifischer CD4+ T-Zellen. Die Daten deuten auf eine Rolle des Lebersinusendothels bei der entzündungsinduzierten, antigenabhängigen Rekrutierung von CD4+ T-Zellen in das Lebergewebe hin. Eine antigenabhängige Aktivierung naiver CD4+ T-Zellen durch LSEC sowie deren Bereitstellung von Retinolsäure induzierte die Expression von darmspezifischen Homingrezeptoren auf CD4+ T-Zellen. LSEC-aktivierte CD4+ T-Zellen migrierten in das Darmgewebe von C57BL/6-Mäusen. Die Ergebnisse legen den Schluss nahe, dass LSEC einen darmspezifischen Homingphänotyp und damit die Migration von in der Leber aktivierten CD4+ T-Zellen in den Darm induzieren. Die Bereitstellung von Chemokinen durch LSEC mittels Transzytose und Immobilisierung verstärkte die Transmigration von CD4+ T-Zellen durch das Endothel. Die Gabe eines Inhibitors der endothelialen Chemokintranszytose während einer Concanavalin A-induzierten Autoimmunhepatitis supprimierte den Verlauf der Hepatitis und führte zu einer verminderten Migration von aktivierten CD4+ T-Zellen in das Lebergewebe. Diese Daten weisen dem Lebersinusendothel eine aktive Beteiligung in der chemokinabhängigen Rekrutierung von CD4+ T-Zellen in die Leber zu. In der vorliegenden Arbeit wurde die Modulation der gewebespezifischen Migration von CD4+ T-Zellen über Antigenpräsentation und Chemokinbereitstellung durch das Lebersinusendothel gezeigt und damit weitere spezifische Aspekte in der Funktion der Leber als immunologisches Organ beschrieben. / T-cell immigration into a tissue is controlled by selective interactions with vascular endothelial cells. The present study addressed the question if interactions between liver sinusoidal endothelial cells (LSEC) and CD4+ T cells influence the tissue-specific migration of CD4+ T cells and thus have relevance for the course of specific immune responses. Antigen presentation by cytokine-activated LSEC increased adhesion and transmigration of antigen-specific CD4+ T cells. These results indicate an involvement of LSEC in the inflammation-induced, antigen-specific migration of CD4+ T cells into the liver tissue. Antigen-specific activation of naive CD4+ T cells by LSEC and their supply of retinoic acid induced expression of gut-specific homing receptors on CD4+ T cells. LSEC-activated CD4+ T cells migrated into the intestine of C57BL/6 mice. The findings presented here imply that LSEC induce a gut-specific homing phenotype resulting in migration of liver-activated CD4+ T cells into the intestine. The active supply of chemokines by LSEC via transcytosis and immobilization enhanced transmigration of CD4+ T cells. Administration of an inhibitor of the endothelial chemokine transcytosis during Concanavalin A-induced autoimmune hepatitis suppressed hepatitis and resulted in reduced migration of activated CD4+ T cells into the liver tissue. The data show the impact of LSEC on the chemokine-dependent recruitment of CD4+ T cells into the liver. In the present study the modulation of the tissue-specific migration of CD4+ T cells by LSEC via antigen presentation and supply of chemokines was demonstrated. Thus, additional functional aspects concerning the immunologic functions of the liver were described.

Le virus de l’hépatite murine de type 3 (MHV3) est un excellent modèle animal pour l’étude des différents désordres immunologiques lors d’infections virales. L’hépatite aiguë fulminante induite par ce virus chez la souris susceptible C57BL/6 se caractérise par la présence de plusieurs foyers nécrotiques et inflammatoires dans le foie associée à une immunodéficience en lymphocytes B et T, tuant les souris entre 3 et 5 jours post-infection. L’évolution rapide de cette maladie virale suggère un débalancement dans les mécanismes de l’immunité naturelle sous le contrôle des cellules NK et NK-T et un bris de l’équilibre entre la tolérance hépatique et la réponse inflammatoire. Afin d’élucider les rôles respectifs des différents mécanismes de la défense innée impliqués dans le développement de l’hépatite aiguë, des infections in vivo ont été réalisées chez des souris C57BL/6 avec la souche pathogène L2-MHV3 ou avec des variants du virus MHV3. Ces derniers possèdent des tropismes différents pour les cellules endothéliales sinusoïdales hépatiques et les cellules de Kupffer, tels que les virus faiblement atténué 51.6-MHV3, fortement atténué CL12-MHV3 et non pathogène YAC-MHV3. Ces études in vivo ont montré une diminution des cellules NK spléniques et myéloïdes suite à une infection avec le virus MHV3. Cette chute en cellules NK spléniques reflète un recrutement de ces cellules au niveau du foie. Par contre, les cellules NK se sont avérées permissives à la réplication virale entraînant un processus d’apoptose suite à la formation de syncétia induits par le virus. Les niveaux de recrutement et d’apoptose des cellules NK et NK-T dans le foie reflètent la pathogénicité des variants MHV3 durant les trois premiers jours de l’infection virale bien que les cellules NK recrutées au niveau du foie maintiennent leur activité cytotoxique. L’ajout des IL-12 et IL-18, qui sont normalement diminués lors de l’hépatite aiguë, provoque une production synergique d’IFN-g par les cellules NK, résultant d’une interaction entre l’activation de la voie p38 MAPK et la réplication virale. Par ailleurs, le récepteur viral CEACAM1a (carcinoembryonic antigen cell adhesion molecule 1a) serait essentiel à cette synergie, mais exercerait aussi une action inhibitrice dans la production de l’IFN-g. D’autre part, les niveaux de production des cytokines immunosuppressives IL-10, TGF-b et PGE2, impliquées dans la tolérance hépatique et particulièrement produites par les cellules de Kupffer et les cellules endothéliales sinusoïdales, sont en relation inverse avec le degré de pathogénicité des variants du virus MHV3. Finalement, le virus pathogène L2-MHV3 déclenche la production de cytokines inflammatoires par les macrophages, tels que l’IL-6 et le TNF-a. L’induction de ces cytokines par les macrophages serait indépendante de la présence de la molécule CEACAM1a. Cette stimulation est plutôt reliée à la fixation des particules virales sur des récepteurs TLR2, en association avec les régions riches en héparanes sulfates. Tous ces résultats mettent en évidence de nouveaux mécanismes par lesquels le virus MHV3 peut diminuer l’efficacité des mécanismes de l’immunité naturelle sous le contrôle des cellules NK et NK-T intrahépatiques, suite à une stimulation de l’inflammation résultant du bris de la tolérance hépatique. / Mouse hepatitis virus type 3 (MHV3) is an excellent model to study immunological disorders related to viral infections. The fulminant acute hepatitis induced in susceptible C57BL/6 mice is characterized by the presence of necrotic and inflammatory foci in the liver associated with B and T cell immunodeficiencies leading to the death of the animals in 3 to 5 days post-infection. The fulminance of this viral infection suggests a deficiency in the natural immunity mechanisms under control of NK and NK-T cells and an imbalance between the hepatic tolerance and the inflammatory responses. To understand the different mechanisms involved in the acute hepatitis, in vivo infections have been done in C57BL/6 mice with either the pathogenic L2-MHV3, or with its attenuated variants: the weak attenuated 51.6-MHV3, the highly attenuated CL12-MHV3 or the non-pathogenic YAC-MHV3 viruses, possessing different tropisms for liver sinusoidal endothelial cells and Kupffer cells. The results demonstrate that splenic and myeloid NK cells are impaired during a MHV3 infection. This impairment is due to a recruitment of these cells in the liver and a virus-induced apoptotic phenomenon. The recruitment and the subsequent apoptosis of NK and NK-T cells during the first three days of infection are in relation with the pathogenicity of the MHV3 variants. In spite of the fact that hepatic recruited NK cells are still cytotoxic, these cells undergo apoptosis due to viral replication via the formation of syncytia. Addition of IL-12 and IL-18, which are impaired during the acute hepatitis, promote a synergistic IFN-g production by NK cells depending of both the p38 MAPK pathway and the viral replication. Moreover, the specific viral receptor CEACAM1a (carcinoembryonic antigen cell adhesion molecule 1a) is essential for this response but also exerts an inhibitory action. Levels of the immunosuppressive cytokines IL-10, TGF-b and PGE2, mainly produced by Kupffer cells and sinusoidal endothelial cells, and implicated in the natural hepatic tolerance, are in inverse correlation with the pathogenicity of the MHV3 variants. Finally, viral infection promotes the secretion of IL-6 and TNF-a by macrophages, triggered by the fixation of viral particules to TLR2 and heparan sulfate receptors rather than the engagement of CEACAM1a receptor and viral replication. In conclusion, our results suggest new mechanisms by which the MHV3 virus disturbs the innate immunity under control of NK and NK-T cells, as well as the cytokines involved in the hepatic tolerance to the detriment of the inflammatory response.

Les cellules endothéliales (EC) constituent une première barrière physique à la dissémination de virus pléiotropiques circulant par voie hématogène mais leur contribution à la défense innée anti-virale est peu connue. Des dysfonctions des EC de la barrière hémato-encéphalique (BMEC) et des sinusoïdes hépatiques (LSEC) ont été rapportées dans des neuropathologies et des hépatites aiguës ou chroniques d’origine virale, suggérant que des atteintes à leur intégrité contribuent à la pathogenèse. Les sérotypes de coronavirus de l’hépatite murine (MHV), se différenciant par leur capacité à induire des hépatites et des maladies neurologiques de sévérité variable et/ou leur tropisme pour les EC, représentent des modèles viraux privilégiés pour déterminer les conséquences de l’infection des EC sur la pathogenèse virale. Lors d’infection par voie hématogène, le sérotype MHV3, le plus virulent des MHV, induit une hépatite fulminante, caractérisée par une réponse inflammatoire sévère, et des lésions neurologiques secondaires alors que le sérotype moins virulent, MHV-A59, induit une hépatite modérée sans atteintes secondaires du système nerveux central (SNC). Par ailleurs, le sérotype MHV3, à la différence du MHV-A59, démontre une capacité à stimuler la production de cytokines par la voie TLR2. Les variants atténués du MHV3, les virus 51.6-MHV3 et YAC-MHV3, sont caractérisés par un faible tropisme pour les LSEC et induisent respectivement une hépatite modérée et subclinique. Compte tenu de l’importance des LSEC dans le maintien de la tolérance hépatique et de l’élimination des pathogènes circulants, il a été postulé que la sévérité de l’hépatite et de la réponse inflammatoire lors d’infections par les MHV est associée à la réplication virale et à l’altération des propriétés tolérogéniques et vasculaires des LSEC. Les désordres inflammatoires hépatiques pourraient résulter d’une activation différentielle du TLR2, plutôt que des autres TLR et des hélicases, selon les sérotypes. D’autre part, compte tenu du rôle des BMEC dans la prévention des infections du SNC, il a été postulé que l’invasion cérébrale secondaire par les coronavirus est reliée à l’infection des BMEC et le bris subséquent de la barrière hémato-encéphalique (BHE). À l’aide d’infections in vivo et in vitro par les différents sérotypes MHV, chez des souris ou des cultures de BMEC et de LSEC, nous avons démontré, d’une part, que l’infection in vitro des LSEC par le sétotype MHV3, à la différence des variants 51.6- et YAC-MHV3, altérait la production du facteur vasodilatant NO et renversait leur phénotype tolérogénique en favorisant la production de cytokines et de chimiokines inflammatoires. Ces dysfonctions se traduisaient in vivo par une réponse inflammatoire incontrôlée et une dérégulation du recrutement intrahépatique de leucocytes, favorisant la réplication virale et les dommages hépatiques. Nous avons aussi démontré, à l’aide de souris TLR2 KO et de LSEC dont l’expression du TLR2 a été abrogée par des siRNA, que la sévérité de l’hépatite et de la réponse inflammatoire induite par le sérotype MHV3, dépendait en partie de l’induction et de l’activation préférentielle du TLR2 par le virus dans le foie. D’autre part, la sévérité de la réplication virale au foie et des désordres dans le recrutement leucocytaire intrahépatique induits par le MHV3, et non par le MHV-A59 et le 51.6-MHV3, corrélaient avec une invasion virale subséquente du SNC, au niveau de la BHE. Nous avons démontré que l’invasion cérébrale du MHV3 était associée à une infection productive des BMEC et l’altération subséquente des protéines de jonctions serrées occludine, VE-cadhérine et ZO-1 se traduisant par une augmentation de la perméabilité de la BHE et l’entrée consécutive du virus dans le cerveau. Dans l’ensemble, les résultats de cette étude mettent en lumière l’importance du maintien de l’intégrité structurale et fonctionnelle des LSEC et des BMEC lors d’infections virales aigües par des MHV afin de limiter les dommages hépatiques associés à l’induction d’une réponse inflammatoire exagérée et de prévenir le passage des virus au cerveau suite à une dissémination par voie hématogène. Ils révèlent en outre un nouveau rôle aggravant pour le TLR2 dans l’évolution de l’hépatite virale aigüe ouvrant la voie à de nouvelles avenues thérapeutiques visant à moduler l’activité inflammatoire du TLR2. / Endothelial cells (EC) act as a physical barrier against invasion by pleiotropic blood borne viruses but their contribution in innate antiviral defense is poorly known. Dysfunctions in blood-brain barrier EC (BMECs) and liver sinusoidal EC (LSECs) have been reported in viral neuropathologies and hepatitis, suggesting that loss of ECs integrity may contribute to the pathogenesis. Mouse hepatitis coronaviruses (MHV), differing in their ability to induce severe to subclinical hepatitis and neurological diseases and / or their tropism for ECs, are relevant viral models to study the consequences of EC infection in viral pathogenesis. Following hematogenous infection, the MHV3 serotype, the most virulent MHV, induces fulminant hepatitis, characterized by severe inflammatory response, followed by neurological damage whereas the less virulent MHV-A59 serotype induces milder hepatitis but does not invade the central nervous system (CNS). In addition, MHV3, in contrast to MHV-A59, shows ability to induce TLR2-dependent cytokine response. The attenuated MHV3 variants, 51.6-MHV3 and YAC-MHV3, are characterized by a weak tropism for LSECs and induce moderated and subclinical hepatitis respectively. Given the importance of LSECs in hepatic tolerance and the elimination of circulating pathogens, it has been postulated that the severity of hepatitis and inflammatory response induced by MHVs correlates with infection and alterations in vascular and tolerogenic properties of LSECs. Hepatic inflammatory disorders may result from differential activation of TLR2, rather than other TLRs and helicases, according to serotypes. Moreover, given the role of BMECs in preventing CNS infections, it has been postulated that secondary cerebral invasion by coronaviruses is related to infection of BMECs and subsequent breakdown of the blood-brain barrier (BBB). Through in vitro and in vivo infections of isolated BMECs, LSECs or mice with the different MHVs, we demonstrated, first, that in vitro productive infection of LSECs by the highly virulent MHV3 serotype, in contrast to 51.6- et YAC-MHV3 variants, altered their production of vasoactive factors and overthrew their intrinsic tolerogenic properties by promoting inflammatory cytokines and chemokines production. These disturbances were reflected in vivo by an uncontrolled inflammatory response and a deregulation of intrahepatic leukocyte recruitment, favoring viral replication and liver damages. We demonstrated, using TLR2 KO mice and LSECs treated with siRNA for TLR2 that the abnormal inflammatory response induced by MHV3 depended in part on preferential induction and activation of TLR2 by the virus on the surface of hepatic cells. Moreover, the severity of the primary viral replication in the liver and disorders in intrahepatic leucocyte recruitment induced by MHV3, but not by MHV-A59 and 51.6-MHV3, correlated with a subsequent brain invasion at the BBB level. Such invasion was related to productive infection of BMECs and subsequent IFN--dependent disruption of tight junction proteins occludin, VE-cadherin and ZO-1, resulting in an increase of BBB permeability and further viral entry into the CNS. Overall, the results of this study highlight the importance of structural and functional integrity of LSECs and BMECs during acute viral infections by MHVs to limit liver damages associated with viral-induced exacerbation of inflammatory response and prevent brain invasion by MHVs following viral spread through the bloodstream. They also reveal a new worsening role for TLR2 in the evolution of acute viral hepatitis paving the way for new therapies targeting TLR2-induced inflammatory activity.

One of the fundamental limitations of mobile radio communications is their time-varying fading channel. This thesis addresses the efficient use of channel state information to improve the communication systems, with a particular emphasis on practical issues such as compatibility with the existing wireless systems and low complexity implementation. The closed-loop transmit diversity technique is used to improve the performance of the downlink channel in MIMO communication systems. For example, the WCDMA standard endorsed by 3GPP adopts a mode of downlink closed-loop scheme based on partial channel state information known as mode 1 of 3GPP. Channel state information is fed back from the mobile unit to the base station through a low-rate uncoded feedback bit stream. In these closed-loop systems, feedback error and feedback delay, as well as the sub-optimum reconstruction of the quantized feedback data, are the usual sources of deficiency. In this thesis, we address the efficient reconstruction of the beamforming weights in the presence of the feedback imperfections, by exploiting the residual redundancies in the feedback stream. We propose a number of algorithms for reconstruction of beamforming weights at the base-station, with the constraint of a constant transmit power. The issue of the decoding at the receiver is also addressed. In one of the proposed algorithms, channel fading prediction is utilized to combat the feedback delay. We introduce the concept of Blind Antenna Verification which can substitute the conventional Antenna Weight Verification process without the need for any training data. The closed-loop mode 1 of 3GPP is used as a benchmark, and the performance is examined within a WCDMA simulation framework. It is demonstrated that the proposed algorithms have substantial gain over the conventional method at all mobile speeds, and are suitable for the implementation in practice. The proposed approach is applicable to other closed-loop schemes as well. The problem of (long-range) prediction of the fading channel is also considered, which is a key element for many fading-compensation techniques. A linear approach, usually used to model the time evolution of the fading process, does not perform well for long-range prediction applications. We propose an adaptive algorithm using a state-space approach for the fading process based on the sum-sinusoidal model. Also to enhance the widely-used linear approach, we propose a tracking method for a multi-step linear predictor. Comparing the two methods in our simulations shows that the proposed algorithm significantly outperforms the linear method, for both stationary and non-stationary fading processes, especially for long-range predictions. The robust structure, as well as the reasonable computational complexity, makes the proposed algorithm appealing for practical applications.

One of the fundamental limitations of mobile radio communications is their time-varying fading channel. This thesis addresses the efficient use of channel state information to improve the communication systems, with a particular emphasis on practical issues such as compatibility with the existing wireless systems and low complexity implementation. The closed-loop transmit diversity technique is used to improve the performance of the downlink channel in MIMO communication systems. For example, the WCDMA standard endorsed by 3GPP adopts a mode of downlink closed-loop scheme based on partial channel state information known as mode 1 of 3GPP. Channel state information is fed back from the mobile unit to the base station through a low-rate uncoded feedback bit stream. In these closed-loop systems, feedback error and feedback delay, as well as the sub-optimum reconstruction of the quantized feedback data, are the usual sources of deficiency. In this thesis, we address the efficient reconstruction of the beamforming weights in the presence of the feedback imperfections, by exploiting the residual redundancies in the feedback stream. We propose a number of algorithms for reconstruction of beamforming weights at the base-station, with the constraint of a constant transmit power. The issue of the decoding at the receiver is also addressed. In one of the proposed algorithms, channel fading prediction is utilized to combat the feedback delay. We introduce the concept of Blind Antenna Verification which can substitute the conventional Antenna Weight Verification process without the need for any training data. The closed-loop mode 1 of 3GPP is used as a benchmark, and the performance is examined within a WCDMA simulation framework. It is demonstrated that the proposed algorithms have substantial gain over the conventional method at all mobile speeds, and are suitable for the implementation in practice. The proposed approach is applicable to other closed-loop schemes as well. The problem of (long-range) prediction of the fading channel is also considered, which is a key element for many fading-compensation techniques. A linear approach, usually used to model the time evolution of the fading process, does not perform well for long-range prediction applications. We propose an adaptive algorithm using a state-space approach for the fading process based on the sum-sinusoidal model. Also to enhance the widely-used linear approach, we propose a tracking method for a multi-step linear predictor. Comparing the two methods in our simulations shows that the proposed algorithm significantly outperforms the linear method, for both stationary and non-stationary fading processes, especially for long-range predictions. The robust structure, as well as the reasonable computational complexity, makes the proposed algorithm appealing for practical applications.

This thesis deals with modeling, simulation and implementation of Load Commutated SCR based current source Inverter (LCI) fed squirrel cage induction motor drive with sinusoidal voltage and sinusoidal current. In the proposed system, the induction motor is fed by an LCI. A three level diode clamped voltage source inverter (VSI) is connected at the motor terminal with ac chokes connected in series with it. The VSI currents are controlled in such a manner that it injects the reactive current demanded by the induction motor and the LCI for successful commutation of the SCRs in the LCI. Additionally, it absorbs the harmonic frequency currents to ensure that the induction motor draws sinusoidal current. As a result, the nature of the motor terminal voltage is also sinusoidal. The concept of load commutation of the SCRs in the LCI feeding an induction motor load is explained with necessary waveforms and phasor diagrams. The necessity of reactive compensation by the active filter connected at the motor terminal for the load commutation of the thyristors, is elaborated with the help of analytical equations and phasor diagrams. The requirement of harmonic compensation by the same active filter to achieve sinusoidal motor current and motor voltage, is also described. Finally, to achieve the aforementioned induction motor drive, the VA ratings of the active filter (VSI) and the CSI with respect to VA rating of the motor, are determined theoretically. The proposed drive scheme is simulated under idealized condition. Simulation results show good steady state and dynamic response of the drive system. Load commutation of the SCRs in the LCI and the sinusoidal profile of motor current and voltage, have been demonstrated. As in LCI fed synchronous motor drives, a special mode of operation is required to run up the induction motor from standstill. As the SCRs of the LCI are load commutated, they need motor terminal voltages for commutation. At standstill these voltages are zero. So, a starting strategy has been proposed and adopted to start the motor with the aid of the current controlled VSI to accelerate until the motor terminal voltages are high enough for the commutation of the SCRs in the LCI. The proposed drive is implemented on an experimental setup in the laboratory. The IGBT based three level diode clamped VSI has been fabricated following the design of the standard module in the laboratory. A generalized digital control platform is also developed using a TMS320F2407A DSP. Two, three phase thyristor bridges with necessary firing pulse circuits have been used as the phase controlled rectifier and the LCI respectively. Appropriate protection scheme for such a drive is developed and adopted to operate the drive. Relevant experimental results are presented. They are observed to be in good agreement with the simulation results. The effect of capacitors connected at the output of the LCI in the commutation process of the SCRs in the LCI is studied and analyzed. From the analysis, it is understood that the capacitors form a parallel resonating pair with filter inductor and the motor leakage inductance, which results in an undesired oscillation in the terminal voltage during each of the commutation intervals leading to commutation failure. So, in the final system, the capacitors are removed to eliminate any chance of commutation failure of the SCRs in the LCI. It is shown by experiment that the commutation of the SCRs takes place reliably in the absence of the capacitors also. The commutation process is studied and analyzed without the capacitors to understand the motor terminal voltage waveform of the experimental results.

Le virus de l’hépatite murine de type 3 (MHV3) est un excellent modèle animal pour l’étude des différents désordres immunologiques lors d’infections virales. L’hépatite aiguë fulminante induite par ce virus chez la souris susceptible C57BL/6 se caractérise par la présence de plusieurs foyers nécrotiques et inflammatoires dans le foie associée à une immunodéficience en lymphocytes B et T, tuant les souris entre 3 et 5 jours post-infection. L’évolution rapide de cette maladie virale suggère un débalancement dans les mécanismes de l’immunité naturelle sous le contrôle des cellules NK et NK-T et un bris de l’équilibre entre la tolérance hépatique et la réponse inflammatoire. Afin d’élucider les rôles respectifs des différents mécanismes de la défense innée impliqués dans le développement de l’hépatite aiguë, des infections in vivo ont été réalisées chez des souris C57BL/6 avec la souche pathogène L2-MHV3 ou avec des variants du virus MHV3. Ces derniers possèdent des tropismes différents pour les cellules endothéliales sinusoïdales hépatiques et les cellules de Kupffer, tels que les virus faiblement atténué 51.6-MHV3, fortement atténué CL12-MHV3 et non pathogène YAC-MHV3. Ces études in vivo ont montré une diminution des cellules NK spléniques et myéloïdes suite à une infection avec le virus MHV3. Cette chute en cellules NK spléniques reflète un recrutement de ces cellules au niveau du foie. Par contre, les cellules NK se sont avérées permissives à la réplication virale entraînant un processus d’apoptose suite à la formation de syncétia induits par le virus. Les niveaux de recrutement et d’apoptose des cellules NK et NK-T dans le foie reflètent la pathogénicité des variants MHV3 durant les trois premiers jours de l’infection virale bien que les cellules NK recrutées au niveau du foie maintiennent leur activité cytotoxique. L’ajout des IL-12 et IL-18, qui sont normalement diminués lors de l’hépatite aiguë, provoque une production synergique d’IFN-g par les cellules NK, résultant d’une interaction entre l’activation de la voie p38 MAPK et la réplication virale. Par ailleurs, le récepteur viral CEACAM1a (carcinoembryonic antigen cell adhesion molecule 1a) serait essentiel à cette synergie, mais exercerait aussi une action inhibitrice dans la production de l’IFN-g. D’autre part, les niveaux de production des cytokines immunosuppressives IL-10, TGF-b et PGE2, impliquées dans la tolérance hépatique et particulièrement produites par les cellules de Kupffer et les cellules endothéliales sinusoïdales, sont en relation inverse avec le degré de pathogénicité des variants du virus MHV3. Finalement, le virus pathogène L2-MHV3 déclenche la production de cytokines inflammatoires par les macrophages, tels que l’IL-6 et le TNF-a. L’induction de ces cytokines par les macrophages serait indépendante de la présence de la molécule CEACAM1a. Cette stimulation est plutôt reliée à la fixation des particules virales sur des récepteurs TLR2, en association avec les régions riches en héparanes sulfates. Tous ces résultats mettent en évidence de nouveaux mécanismes par lesquels le virus MHV3 peut diminuer l’efficacité des mécanismes de l’immunité naturelle sous le contrôle des cellules NK et NK-T intrahépatiques, suite à une stimulation de l’inflammation résultant du bris de la tolérance hépatique. / Mouse hepatitis virus type 3 (MHV3) is an excellent model to study immunological disorders related to viral infections. The fulminant acute hepatitis induced in susceptible C57BL/6 mice is characterized by the presence of necrotic and inflammatory foci in the liver associated with B and T cell immunodeficiencies leading to the death of the animals in 3 to 5 days post-infection. The fulminance of this viral infection suggests a deficiency in the natural immunity mechanisms under control of NK and NK-T cells and an imbalance between the hepatic tolerance and the inflammatory responses. To understand the different mechanisms involved in the acute hepatitis, in vivo infections have been done in C57BL/6 mice with either the pathogenic L2-MHV3, or with its attenuated variants: the weak attenuated 51.6-MHV3, the highly attenuated CL12-MHV3 or the non-pathogenic YAC-MHV3 viruses, possessing different tropisms for liver sinusoidal endothelial cells and Kupffer cells. The results demonstrate that splenic and myeloid NK cells are impaired during a MHV3 infection. This impairment is due to a recruitment of these cells in the liver and a virus-induced apoptotic phenomenon. The recruitment and the subsequent apoptosis of NK and NK-T cells during the first three days of infection are in relation with the pathogenicity of the MHV3 variants. In spite of the fact that hepatic recruited NK cells are still cytotoxic, these cells undergo apoptosis due to viral replication via the formation of syncytia. Addition of IL-12 and IL-18, which are impaired during the acute hepatitis, promote a synergistic IFN-g production by NK cells depending of both the p38 MAPK pathway and the viral replication. Moreover, the specific viral receptor CEACAM1a (carcinoembryonic antigen cell adhesion molecule 1a) is essential for this response but also exerts an inhibitory action. Levels of the immunosuppressive cytokines IL-10, TGF-b and PGE2, mainly produced by Kupffer cells and sinusoidal endothelial cells, and implicated in the natural hepatic tolerance, are in inverse correlation with the pathogenicity of the MHV3 variants. Finally, viral infection promotes the secretion of IL-6 and TNF-a by macrophages, triggered by the fixation of viral particules to TLR2 and heparan sulfate receptors rather than the engagement of CEACAM1a receptor and viral replication. In conclusion, our results suggest new mechanisms by which the MHV3 virus disturbs the innate immunity under control of NK and NK-T cells, as well as the cytokines involved in the hepatic tolerance to the detriment of the inflammatory response.

The mechanisms behind cardiovascular disease (CVD) initiation and progression are not fully elucidated. It is hypothesized that blood flow patterns regulate endothelial cell (EC) function to affect the progression of CVDs. A system that subjects ECs to physiologically-relevant shear stress waveforms within microfluidic devices has not yet been demonstrated, despite the advantages associated with the use of these devices. In this work, a bioreactor was designed to fulfill this need. Waveforms from regions commonly affected by CVDs including were derived. Pump motion and fluid flow profiles were validated by actuator motion tracking, particle image velocimetry, and flowmeters. While several relevant waveforms were successfully replicated, physiological waveforms could not be produced at physiological frequencies owing to actuator velocity and accuracy limitations, as well as dampening effects in the system. Overall, this work lays the foundation for designing a system that provides insight into the role of shear stress in CVD pathogenesis.