L’automobile occupe une place fondamentale dans notre société, au point qu’on a pu parler de « civilisation de l’automobile ». En dépit des critiques qui lui sont régulièrement adressées, celle-ci n’a cessé de se renforcer, avec toujours davantage de voitures par adulte et une proportion croissante de déplacements effectués en voiture. Cependant, depuis le tournant du millénaire, on assiste à un retournement de tendance. Pour la première fois, la mobilité en voiture baisse dans les grandes agglomérations, tandis que la circulation automobile plafonne à l’échelle nationale. Cette évolution, du reste, n’est pas spécifique à la France mais s’observe dans l’ensemble des pays développés, une tendance parfois désignée sous le terme de « peak car (travel) ». Parmi les explications les plus convaincantes de ce retournement, figurent l’augmentation du prix du carburant, suivie de la récession de 2008. La volonté des ménages de maîtriser leurs budgets-temps de transport y contribue également, dans un contexte d’allongement des déplacements vers le travail et de dégradation des vitesses de déplacements. En outre, la diffusion de l’automobile se rapproche de la saturation. Si à long terme, la croissance du kilométrage moyen par adulte est indexée sur le taux de motorisation, cependant à moyen terme l’utilisation des véhicules fluctue en fonction du pouvoir d’achat énergétique, et un modèle basé sur ces deux variables suggère qu’on observerait une réaction normale à une augmentation exceptionnelle du prix du carburant. Les facteurs de croissance du taux de motorisation tiennent eux-mêmes principalement à la succession de générations de plus en plus motorisées, surtout chez les femmes, compte tenu d’un accès de plus en plus large au permis de conduire, à l’activité professionnelle, et d’une urbanisation de plus en plus diffuse, qui ont augmenté le besoin d’une seconde voiture. Pour modéliser l’auto-mobilité, on propose une approche emboîtée, individuelle et longitudinale, segmentée en fonction du genre. L’auto-mobilité peut en effet être vue au niveau individuel comme une succession de choix emboîtés, puisque la détention du permis conditionne l’accès à un véhicule personnel, de même que la motorisation conditionne l’usage d’un véhicule. L’avantage d’une approche longitudinale réside dans la possibilité de distinguer entre mesures d’hétérogénéité et de sensibilité, qui ne sont pas équivalentes. Pour chaque niveau de choix, l’approche est structurée autour d’une analyse de type âge-cohorte-période. Globalement, les taux de motorisation sont plus hétérogènes chez les femmes, un résultat qui est susceptible de recevoir une double interprétation, économique ou sociétale. On peut le voir en termes d’inégalités de genre. Mais il peut également s’interpréter comme le reflet d’un statut encore intermédiaire du second véhicule, dont l’opportunité serait davantage évaluée au regard des besoins et des contraintes réels du ménage. A l’inverse, l’usage des véhicules est à la fois plus élevé et plus hétérogène chez les hommes, compte tenu de la fonction collective du véhicule principal et des arbitrages internes aux ménages quant aux choix du lieu de résidence et des lieux de travail des conjoints. Pour finir, on estime à partir de modèles sur données de panel des effets marginaux et des élasticités par rapport au revenu, au prix du carburant et à la densité, qui sont ensuite comparées avec la littérature. Dans l’ensemble, les résultats sont cohérents avec l’analyse descriptive, ainsi qu’avec la littérature. Le modèle permet également de rendre compte du déclin tendanciel des élasticités, traduisant l’approche de la saturation. Pour finir, une évaluation a posteriori confirme l’opportunité d’une modélisation séquentielle, indiquant que les choix de motorisation sont indépendants des niveaux d’usage de la voiture. / Car ownership and use are a decisive part of our society, which was sometimes designed as the “civilization of the car”. Despite many critics, the car has become ever-more central in the modern way of life, with an ever-increasing number of cars per adult and proportion of trips realized by car. However, from the beginning of the millennium, there was a reversal in the trend towards ever-more car use. For the first time, the average number of daily trips realized by car has been falling down in French conurbations, and nationwide traffic by car is leveling off. This situation, nonetheless, is not specific to France but is common to many developed countries, and is often referred to as the “peak car (travel)”. The main explanations for such a downturn include rising fuel prices from the late 1990’s, followed by the recession in 2008, but also household’s willingness to control their travel time budgets, in a context of increasing commuting distances and reduced travel speeds. Besides, the diffusion of car ownership is approaching saturation. While on the long-run, average car travel per adult is indexed on motorization, mid-term fluctuations of average car use per vehicle are related to the energetic purchasing power, and a simple model based on these two variables is suggesting that the stagnation of car use from the 2000’s could be a reaction of a usual kind to an exceptional rise in fuel prices. The growth in motorization is itself principally caused by the follow-up of ever-more motorized generations, especially among women, given their increasing access to driving license, job participation and ever-more diffuse land use patterns, which have increased the need for a second car within households. In order to model auto-mobility, a nested, individual and longitudinal approach is implemented, segmented by gender. Auto-mobility can indeed be seen as a follow-up of nested choices, as driving license is necessary for holding a car, while access to a personal vehicle is itself required for car use. The advantage of a longitudinal approach consists in the ability to distinguish between measures of heterogeneity and sensitivity, which can be shown not to be equivalent. For every given level of choice, the approach is based on an age-cohort-period-type analysis. Motorization rates happen to be more heterogeneous among women, a result which is likely to receive an interpretation either of a social or economic nature. According to the first interpretation, it should be regarded as the illustration of gender inequalities. However, it could also be regarded as reflecting the still-intermediary status of the second vehicle, which opportunity is assessed depending upon household’s specific needs and constraints. On the contrary, car use is at the same time higher and more heterogeneous among men, given the collective function of the first vehicle and household’s internal trade-offs in residential and job choices. Finally, average partial effects and elasticities are estimated from panel data models, either with respect to income, fuel prices or density. Generally, results are consistent with the descriptive part, as with the literature. The model also rationally gives account of the decreasing trend for elasticities, which was often noticed in the literature and reflects the approach of saturation. As a conclusion, an a posteriori evaluation of the assumption of a sequential decision process is made, confirming that choices of motorization and car use are mutually independent.

This diploma thesis deals with a car in a relation to accounting and tax laws. This thesis is divided into two basic parts, theoretical and practical. The theoretical part is concerned with a car perception in accounting and the influence of tax laws on the car perception. The theoretical part is divided into three main parts. The first part is focused on a general view of vehicles in accounting, for example, vehicle valuations, acquisitions, depreciation, valuation changes and disposals of vehicles. The other part is focused on specifications of the vehicle perception in a tax evidence of individual entrepreneurs. In the third part there are described the vehicle perception in business corporations. It is focused on a value-added tax, mainly on a value-added tax in cross-border buying and selling of vehicles. Furthermore, there are analyzed a deferred tax and issues of cars in a relation to employers and employees. In the theoretical part there is dealt with the usage of vehicles for private purposes. In the practical part there is analyzed the usages of company cars by an employee for private purposes. There is compared a rent and a free of charge usage. In this part there is also verified whether the law is followed in practice. There are stated atypical transactions. These include using grants to acquire a car, updating of a depreciation plan and disposing of a vehicle by its sale to a foreign entity.

This thesis deals by the design of 1/4 car model for testing vehicle dampers, which can be used to simulate the real suspension of a vehicle wheel (up to a maximum car weight of 1,970 kg) and the so-called linear wheel suspension. A linear mathematical 1/4 car model with 2 DOF (Degrees Of Freedom) and data from literature search are used to design and derive the basic parameters of the device. The thesis contains a description of the linear mathematical model and its outputs (acceleration of the sprung mass and forces acting on the sprung mass), description of designed device, descriptions of created simulations (static, modal and harmonic analysis in ANSYS Workbench 2020 R2) and conceptual design of the modifications this device for another possible use for testing of bicycles.

Tato práce popisuje simulátor TORCS a optimalizační algoritmy, jenž jsou využívány při tvorbě autonomních řidičů pro tento simulátor. Hlavním cílem je navržení nového autonomního řidiče, který se bude schopen s použitím přírodou inspirovaných optimalizačních technik vyrovnat již dříve navrženým řešením. Chování implementovaného řešení lze rozdělit do dvou hlavních částí, které jsou využívány v různých rozdílných etapách závodu. Zahřívací kolo je využito pro vytvoření modelu trati, ze kterého je posléze získána optimální trajektorie pomocí genetického algoritmu. Této trajektorie je potom využíváno v samotné kvalifikaci či závodě pro zajetí co nejrychlejšího kola. Z důvodu složitosti problému optimalizace celé trajektorie je nutno tuto trajektorii rozdělit na menší úseky nazývané segmenty, přičemž každý z nich je potom optimalizován odděleně. Jednotlivé optimalizované segmenty jsou následně spojeny dohromady, aby opět utvořily trajektorii pro celou trať. Protože některé přechody mezi segmenty mohou být nesouvislé, je zde znovu aplikován genetický algoritmus pro jejich vyhlazení. Během závodu je tato trajektorie následována, přičemž se z ní odvíjí i maximální možná rychlost v daném úseku. V práci jsme ukázali, že vzorkování trati s následnou optimalizací pomocí genetického algoritmu trvá pouze zlomek času vyhrazeného pro zahřívací kolo. Nejen díky tomuto se řešení jeví jako vhodné pro závody autonomních řidičů a může být dále rozšířeno.

Background: The CD19 chimeric antigen receptor (CAR) adoptive T-cell therapy for B-cell leukemia is a promising treatment for relapsed or refractory malignities. The overall response rate of CD19 CAR-T cells in clinical trials was greater than 80% for patients with B-cell acute lymphoblastic leukemia (B-ALL) and non-Hodgkin's lymphoma (NHL). However, CAR-T cell therapy of leukemias and solid tumors has been limited by a lot of factors such as antigen loss of tumor escape variants, reduced proliferation, persistence and tumor-infiltration of CAR-T cells in vivo, immunosuppressive tumor environment, absence of ideal antigens and on-target, off-tumor toxicities. Therefore, new strategies improving the safety and efficacy of CAR-T cells, including further T-cell modification to overcome the immune suppression, are tested. Aims: (i) Bispecific CARs designed to express two antigen-binding domains prevent of antigen escape. (ii) T-cells were genetically modified to express CAR along with an inducible IL-21 gene cassette driven by NFAT-responsive promoter. IL-21 directly enhances CAR-T cell activity and anti-tumor effects. (iii) Applying suicide epitope modification in CAR enables significantly increasing the therapeutic safety of CAR-T cells. Methods: CARs were constructed by using molecular biology...

Cancer immunotherapies utilize the capabilities of the immune system to efficiently target malignant cells. In recent years, chimeric antigen receptor (CAR) equipped T cells showed promising results against B cell lymphomas. Autologous CAR-T cells require patientspecific manufacturing and thus extensive production facilities, resulting in high priced therapies. Along with potentially severe side effects, these are the major drawbacks of CAR-T cells therapies. Natural Killer (NK) cells pose an alternative for CAR equipped immune cells. Since NK cells can be safely transferred from healthy donors to cancer patients, they present a suitable platform for an allogeneic “off-the-shelf” immunotherapy. However, administration of activated NK cells in cancer therapy has until now shown poor anti-cancer responses, especially in solid tumors. Genetic modifications such as CARs promise to enhance recognition of tumor cells, thereby increasing anti-tumor effects and improving clinical efficacy. Although the cell biology of T and NK cells deviates in many aspects, the development of CAR-NK cells frequently follows within the footsteps of CART cells, meaning that T cell technologies are simply adopted to NK cells. In this review, we underline the unique properties of NK cells and their potential in CAR therapies. First, we summarize the characteristics of NK cell biology with a focus on signaling, a fine-tuned interaction of activating and inhibitory receptors. We then discuss why tailored NK cellspecific CAR designs promise superior efficacy compared to designs developed for T cells. We summarize current findings and developments in the CAR-NK landscape: different CAR formats and modifications to optimize signaling, to target a broader pool of antigens or to increase in vivo persistence. Finally, we address challenges beyond NK cell engineering, including expansion and manufacturing, that need to be addressed to pave the way for CAR-NK therapies from the bench to the clinics.

Whiplash is a neck injury caused by the sudden differential movement between the head and torso. Whiplash injuries are most commonly reported as a consequence of rear impacts in car accidents. They are regarded as minor injuries, but can still lead to long-term disablement and discomfort in the neck. Whiplash injuries can be mitigated by better car seat designs. For this purpose, head restraint geometry must be improved first, and then the dynamic performance of the whole seat must be assessed at all crash seventies. A biofidelic human-body model is a key requirement in designing whiplash mitigating car seats. This thesis presents the development of a 50th percentile male multi-body human model and several energy absorbing car seat designs. The human-body model is specifically designed for rear impact and validated using the responses of seven volunteers from Japanese Automobile Research Institute (JARI) sled tests, which were performed at an impact speed of 8 kph with a rigid seat and without head restraint and seat belt. A generic multi-body car seat model is also developed to implement various seatback and recliner properties, anti-whiplash devices (A WDs) and head restraints. Using the same driving posture and the rigid seat in the JARI sled tests as the basic configuration, several anti-whiplash seats are designed to allow different types of motion for the seatback and seat-pan. The major findings of this research are: -The human-body model simulates the effects of muscle contraction and its overall response is superior in comparison to the currently used models and dummies. -A criterion called the S-shape index (SSI) is developed based on the intervertebral angles of the upper and lower cervical spine. -The car seat design concepts are able to control and use crash energy effectively with the aid of anti-whiplash devices for a wide range of crash seventies. -In order to reduce whiplash injury risk, this study advocates energy absorbing car seats which can also provide head restraint contact as early as possible.

Målet med examensarbetet har varit att samla information åt ett tekniskt konsultföretag för att öka deras kunskap om autonoma system och fordonskommunikation. Statusen på arbetet kring dessa aktiva säkerhetssystem hos olika aktörer och hur systemen implementeras i dagens och framtidens fordon har undersökts genom omfattande litteraturstudier, intervjuer och marknadsanalyser. De autonoma systemen kan samla information från omgivningen genom sensorer och bidra till ett jämnare trafikflöde, ökad säkerhet, lättare bilar och bättre miljö. Genom fordonskommunikationen kan fordon kommunicera med varandra samt infrastrukturen och garantera en säker bilfärd. År 2030 utgörs innerstaden av autonom, elektrifierad kollektivtrafik för att transportera människor på begäran, samtidigt som personbilar till viss del förbjuds. Potentiella behov för människan i en fullt autonom bil har identifierats och diverse produktutvecklingsmetoder har tillämpats för att utforma två konceptuella lösningar för en framtida bilinteriör. Lösningarna visar interaktionen mellan människa och system eftersom underhållning och bekvämlighet blir viktigt i en fullt autonom bil. Respektive lösning är statsägd och rymmer fyra passagerare. I lösningarna är sittplatserna placerade på ett sätt som underlättar kommunikation mellan passagerarna. Passagerarna kan underhållas eller informeras individuellt eller gemensamt via text, ljud och bild. / The goal with this thesis project has been to collect information for a technical consulting company in order to increase their knowledge about autonomous systems and vehicular communication. The status of how various operators work with active safety systems and how the systems are implemented in current and future vehicles has been investigated through extensive literature studies, interviews and market research. The autonomous systems can collect information from the surrounding through sensors and contribute to better traffic efficiency, increased safety, lighter cars and a better environment. Through vehicle communication, the vehicle can communicate with each other in order to guarantee a safe ride. In 2030 the inner city constitutes of autonomous, electrified public transport to transport people on demand, meanwhile private cars are prohibited. Potential needs for the human in a fully, autonomous car has been identified and various product development methods has been applied in order to develop two conceptual solutions for a future car interior. The solutions show the interaction between human and system since entertainment and comfort becomes important in a fully, autonomous car. Each solution is state-owned and holds four passengers. In the solutions, the seats are placed in regard to facilitate communication between the passengers. The passengers can be entertained or informed individually or collectively by text, sound and images.

Chimeric antigen receptors (CARs) are artificial molecules composed of an antibody derived antigen recognition domain which is fused with the signal transduction domain derived from the physiological TCR. CAR technology used to transduce patients T-cells and endow them with the specificity to a certain surface antigen, has been a major breakthrough in cancer immunotherapy in the last decade. This strategy has been most successful for treating hematologic malignancies. Various CAR approaches and applications are currently tested mainly in the United States where many clinical trials have been launched. In contrast, in the Czech Republic, there are only a few teams focused on this topic with no clinical trials going on. During my work on this diploma thesis and in close collaboration with MUDr. Pavel Otáhal, PhD., who is working on implementation of CAR technology into the Czech clinics for the treatment of B-cell malignancies, individual functional CARs were prepared and tested. CAR expressing Jurkat T-cell lines were generated using a lentiviral vector transduction system. CAR functionality was determined by two different assays. We have shown that individual CARs are able to recognize the B-cell lineage specific antigens CD19 and CD20 and significantly up-regulate the activation molecule CD69 upon...

L'adoption récente et généralisée des systèmes d'automatisation des véhicules, avec l’incorporation de la connectivité entre voitures, a encouragé l’utilisation des techniques comme le Contrôle Croisière Adaptatif Coopératif (CACC) et la conduite en convoi. Ces techniques ont prouvé l’amélioration du flux de trafic et la sécurité de la conduite, tout en réduisant la consommation d’énergie et les émissions CO_2. Néanmoins, la robustesse et la stabilité stricte du convoi, malgré les délais de communication et l’hétérogénéité des convois, restent des sujets de recherche en cours. Cette thèse a pour sujet la conception, l’analyse et validation de systèmes de contrôle pour le car-following automatisé et coopératif, en ciblant l’augmentation de ses avantages et son usage, en se concentrant sur la robustesse et la stabilité du convoi même sur des séries de véhicules hétérogènes avec des retards de communication. Une structure feedforward/feedback est développée, dont sa modularité est fondamentale pour la mise au point des approches avec des objectifs différents mais complémentaires. L’architecture permet non seulement l’adoption d’une stratégie d’espacement pour la range entière de vitesse, mais elle peut aussi être employée dans le cadre d’un CACC basé sur une machine d’état pour la conduite en convoi sur des environnements urbains avec des capacités de freinage d’urgence et de rejoint du convoi. Des différents algorithmes pour la conception de systèmes de contrôle feedback pour la régulation des distances sont présentés, pour quoi le calcul d’ordre fractionnaire démontre fournir des réponses fréquentielles de boucle fermé plus précises et satisfaire des besoins plus exigeantes. La performance est assurée malgré l’hétérogénéité avec la proposition de deux approches feedforward différents. Le premier est basé sur une topologie en considérant que le véhicule précédent dans la boucle, tandis que le deuxième inclut le véhicule leader pour améliorer la performance de suivi. Les algorithmes proposés sont validés avec des études de stabilité dans le domaine du temps et fréquence, ainsi que simulations et expérimentations réelles. / Recent widespread adoption of vehicle automation and introduction of vehicle-to-vehicle connectivity has opened the doors for techniques as Cooperative Adaptive Cruise Control (CACC) and platooning, showing promising results in terms of traffic capacity and safety improvement, while reducing fuel consumption and CO_2 emissions. However, robustness and strict string stability, despite communication delays and string heterogeneity is still an on-going research field. This thesis deals with the design, study and validation of control systems for cooperative automated car-following, with the purpose of extending their benefits and encourage their employment, focusing on robustness and string stability, despite possible V2V communication delays and string heterogeneity. A feedforward/feedback hierarchical control structure is developed, which modularity is fundamental for the proposal of approaches that target different but complementary performance objectives. The architecture not only permits the adoption of a full speed range spacing policy that target multiple criteria, but can also be employed in a state machine-based CACC framework for urban environments with emergency braking and platoon re-joining capabilities in case of pedestrian interaction. Different feedback control design algorithms are presented for the gap-regulation, for which the fractional-order calculus is demonstrated to provide more accurate closed loop frequency responses and satisfy more demanding requirements. Desired performance is ensured in spite of string heterogeneity through the proposal of two feedforward methods : one based on predecessor-only topology, while the second includes the leader vehicle information on feedforward to gain tracking capabilities. Proposed control algorithms are validated through time and frequency-domain stability studies, simulation and real platforms experiments.