Approved for public release; distribution in unlimited. / In this thesis, a new fictitious play (FP) procedure is presented to solve two-person zero-sum (TPZS) Blotto games. The FP solution procedure solves TPZS games by assuming that the two players take turns selecting optimal responses to the opponent's strategy observed so far. It is known that FP converges to an optimal solution, and it may be the only realistic approach to solve large games. The algorithm uses dynamic programming (DP) to solve FP subproblems. Efficiency is obtained by limiting the growth of the DP state space. Blotto games are frequently used to solve simple missile defense problems. While it may be unlikely that the models presented in this paper can be used directly to solve realistic offense and defense problems, it is hoped that they will provide insight into the basic structure of optimal and near-optimal solutions to these important, large games, and provide a foundation for solution of more realistic, and more complex, problems. / Captain, Republic of Korea Air Force

Background: Single photon emission computed tomography (SPECT) with dopamine transporter (DAT) and dopamine D2 receptor (D2R) ligands can visualise the integrity of the nigrostriatal dopamine system. Parkinson’s disease (PD) and the atypical parkinsonian diseases (APD), progressive supranuclear palsy (PSP) and multiple system atrophy (MSA), have similar symptoms and dopamine depletion, but differ in pharmacological response and prognosis. Clinical differentiation between PD and APD is often difficult in the early stages. The aims of the thesis were to evaluate the differential diagnostic and prognostic value of SPECT in early PD, MSA and PSP, to map the pattern of progression with dopamine SPECT, and map the pattern of dopamine SPECT in non-affected elderly volunteers with a prospective approach. Also, we evaluated the methodological aspects of dopamine SPECT with respect to image evaluation tools, reconstruction parameters and gamma cameras. Methods: 172 patients, included in an on-going clinical prospective study on idiopathic parkinsonism, participated in the SPECT study. Also, 31 age-matched healthy controls (HC) were followed within this study. SPECT was done with 123I-FP-Cit (DAT SPECT) and 123I-IBZM (D2R SPECT). Regions of interest (ROI) were used as a standard method for semi-quantitative image analysis. Results: SPECT uptake ratios from different gamma cameras could be equalised through correction equations derived from images of a brain-like phantom, provided that attenuation correction was applied. The ROI method had high reproducibility. SPECT uptake  in HC, measured with the ROI method and a volume based (VOI) method rendered similar trends, but gender and age differences in SPECT uptake were more marked with the VOI method, and less pronounced in DAT SPECT compared to D2R SPECT with both methods. The DAT SPECT uptake was significantly reduced in very early disease stage of PD and APD compared to HC. DATSPECT uptake was more reduced in PD with postural and gait disturbance (PIGD) compared to tremor-dominant PD. Decline in DAT SPECT uptake during the first year was more pronounced in PD and PSP compared to HC. D2R SPECT uptake overlapped between untreated PD and APD. After initiated treatment, the D2R SPECT uptake was significantly higher in MSA patients compared to PD, PSP and HC. Decline in D2R SPECT uptake during the first year was not significantly different between patients or compared to HC. Conclusions: 123I-FP-Cit SPECT is a valuable and sensitive method to detect early stage idiopathic parkinsonism. A different level of uptake between PIGD-PD compared to TD-PD indicates a prognostic potential. It is not possible to differ between PD, MSA and PSP in early stage with 123I-FP-Cit SPECT and no differential diagnostic value was found using 123I-IBZM SPECT in the early, untreated stage of PD, MSA and PSP. A different pattern of uptake of this ligand in MSA compared to PD and PSP during the first years of L-dopa treatment may, however, indicate a diagnostic value during the follow-up period.

Ce travail de thèse porte sur la conception et la réalisation de capteurs optiques ultracompacts et sensibles utilisant le mode d'interrogation en intensité pour la détection d'analytes chimiques et biologiques. Deux approches, l'intégration hybride et l'intégration monolithique, ont été explorées durant cette thèse. Après un descriptif des outils d'analyse et de conception de guides d'onde et de micro résonateurs en anneaux, le manuscrit présente l'intégration hybride d'un laser Fabry-Perot en semiconducteur III-V avec un résonateur en anneau basé sur du matériau SOI. Le laser Fabry-Perot à faible coût fonctionnant en multimode longitudinal a été utilisé comme peigne de référence pour le résonateur en anneau en contact avec un échantillon liquide. L'effet Vernier a été implanté dans le système de détection en utilisant le mode d'interrogation en intensité. La largeur spectrale étroite du laser avec sa densité de puissance élevée ont permis d'obtenir un capteur de plus haute sensitivité en comparaison avec le capteur en double anneaux réalisé précédemment. Une étude numérique d'un capteur composé d'un laser Fabry-Perot et deux résonateurs en anneaux permettant de compenser la fluctuation de température a été ensuite présentée. Concernant l'intégration monolithique, l'interface entre oxyde et non-oxyde après l'oxydation de AlGaAs a été étudiée au Central de Technologies du LPN/CNRS. Un phénomène d'oxydation verticale de GaAs ou AlGaAs avec une faible teneur en aluminium activée par une couche voisine oxydée de AlGaAs avec une forte teneur en aluminium a été identifié expérimentalement. Afin de limiter l'oxydation verticale et de réduire la rugosité des interfaces, des guides d'onde basés respectivement sur une structure intégrant un super-réseau et sur une structure standard ont été fabriqués et caractérisés. L'impact de l'hydrogène sur l'activation du processus d'oxydation de GaAs ou AlGaAs avec une faible teneur en Al a été mis en évidence. Enfin, ce manuscrit décrit la réalisation et la caractérisation d'un laser Fabry-Perot fonctionnant en mode TM. Ce laser constitue une brique important vers l'intégration monolithique d'un capteur extrêmement sensible.

Popular Object Oriented size metrics and estimation methods are examined. A case study is conducted. Five of the methods (&ldquo / LOC&rdquo / , &ldquo / OOPS&rdquo / , &ldquo / Use Case Points Method&rdquo / , &ldquo / J.Kammelar&rsquo / s Sizing Approach&rdquo / and &ldquo / Mark II FP&rdquo / ) are applied to a project whose requirements are defined by means of use cases. Size and effort estimations are made and compared with the actual results of the project.

[pt] Neste trabalho apresentamos uma proposta para auxiliar o estudo de funções polinomiais no ensino médio por intermédio das Curvas de Bézier. Para isto introduzimos as curvas de Bézier utilizando o algoritmo de De Casteljau e discutimos suas propriedades. Em seguida aplicamos a formulação das curvas de Bézier não paramétricas para representar funções polinomiais e discutimos alguns resultados observados em sala de aula. / [en] In this work we present a proposal to assist the study of polynomial functions in high school through the Bezier curves. For this we introduce the Bezier curves using the De Casteljau algorithm and discuss its properties. Then apply the formulation of Bezier curves non-parametric to represent polynomial functions and discuss some results observed in the classroom.

Les travaux de cette thèse porte sur le calcul d’un espace d’état navigable d’un véhicule routier, ainsi que sur l’observation et l’estimation de son état, à l’aide des méthodes ensemblistes par intervalles. Dans la première partie de la thèse, nous nous intéressons aux problèmes d’estimation d’état relevant de la dynamique du véhicule. Classiquement, l’estimation se fait en utilisant le filtrage de Kalman pour des problèmes d’estimation linéaires ou le filtrage de Kalman étendu pour les cas non-linéaires. Ces filtres supposent que les erreurs sur le modèle et sur les mesures sont blanches et gaussiennes. D’autre part, les filtres particulaires (PF), aussi connus comme Méthodes de Monte-Carlo séquentielles, constituent souvent une alternative aux filtres de Kalman étendus. Par contre, les performances des filtres PF dépendent surtout du nombre de particules utilisées pour l’estimation, et sont souvent affectées par les bruits de mesures aberrants. Ainsi, l’objectif principal de cette partie de travail est d’utiliser une des méthodes à erreurs bornées, qui est le filtrage par boites particulaires (Box Particle Filter (BPF)), pour répondre à ces problèmes. Cette méthode généralise le filtrage particulaire à l’aide des boites remplaçant les particules. A l’aide de l’analyse par intervalles, l’estimation de certains variables fortement reliées à la dynamique du véhicule comme le transfert de charge latérale, le roulis et la vitesse de roulis est donnée, à chaque instant, sous forme d’un intervalle contenant la vraie valeur simulée. Dans la deuxième partie de la thèse, une nouvelle formalisation du problème de calcul de l’espace navigable de l’état d’un véhicule routier est présentée. Un algorithme de résolution est construit, basé sur le principe de l’inversion ensembliste par intervalles et sur la satisfaction des contraintes. Nous cherchons à caractériser l’ensemble des valeurs de la vitesse longitudinale et la dérive au centre de gravité qui correspondent à un comportement stable du véhicule : pas de renversement ni dérapage. Pour décrire le risque de renversement, nous avons utilisé l’indicateur de transfert de charge latéral (LTR). Pour décrire le risque de dérapage, nous avons utilisé les dérives des roues. Toutes les variables sont liées géométriquement avec le vecteur d’état choisi. En utilisant ces relations, l’inversion ensembliste par intervalles est appliquée afin de trouver l’espace navigable de l’état tel que ces deux risques sont évités. L’algorithme Sivia est implémenté, approximant ainsi cet espace. Une vitesse maximale autorisée au véhicule est déduite. Elle est associée à un angle de braquage donné sur une trajectoire connue. / In this thesis, we aim to characterize a vehicle stable state domain, as well as vehicle state estimation, using interval methods.In the first part of this thesis, we are interested in the intelligent vehicle state estimation.The Bayesian approach is one of the most popular and used approaches of estimation. It is based on the calculated probability of the density function which is neither evident nor simple all the time, conditioned on the available measurements.Among the Bayesian approaches, we know the Kalman filter (KF) in its three forms(linear, non linear and unscented). All the Kalman filters assume unimodal Gaussian state and measurement distributions. As an alternative, the Particle Filter(PF) is a sequential Monte Carlo Bayesian estimator. Contrary to Kalman filter,PF is supposed to give more information about the posterior even when it has a multimodal shape or when the noise follows non-Gaussian distribution. However,the PF is very sensitive to the imprecision due by bias or noise, and its efficiency and accuracy depend mainly on the number of propagated particles which can easily and significantly increase as a result of this imprecision. In this part, we introduce the interval framework to deal with the problems of the non-white biased measurements and bounded errors. We use the Box Particle Filter (BPF), an estimator based simultaneously on the interval analysis and on the particle approach. We aim to estimate some immeasurable state from the vehicle dynamics using the bounded error Box Particle algorithm, like the roll angle and the lateral load transfer, which are two dynamic states of the vehicle. BPF gives a guaranteed estimation of the state vector. The box encountering the estimation is guaranteed to encounter thereal value of the estimated variable as well.In the second part of this thesis, we aim to compute a vehicle stable state domain.An algorithm, based on the set inversion principle and the constraints satisfaction,is used. Considering the longitudinal velocity and the side slip angle at the vehicle centre of gravity, we characterize the set of these two state variables that corresponds to a stable behaviour : neither roll-over nor sliding. Concerning the roll-over risk,we use the lateral transfer ratio LTR as a risk indicator. Concerning the sliding risk, we use the wheels side slip angles. All these variables are related geometrically to the longitudinal velocity and the side slip angle at the centre of gravity. Using these constraints, the set inversion principle is applied in order to define the set ofthe state variables where the two mentioned risks are avoided. The algorithm of Sivia is implemented. Knowing the vehicle trajectory, a maximal allowed velocityon every part of this trajectory is deduced.

Motivated by results of linear algebra over fields, rings and tropical semirings, we present a systematic way to understand the behaviour of matrices with entries in an arbitrary semiring. We focus on three closely related problems concerning the row and column spaces of matrices. This allows us to isolate and extract common properties that hold for different reasons over different semirings, yet also lets us identify which features of linear algebra are specific to particular types of semiring. For instance, the row and column spaces of a matrix over a field are isomorphic to each others' duals, as well as to each other, but over a tropical semiring only the first of these properties holds in general (this in itself is a surprising fact). Instead of being isomorphic, the row space and column space of a tropical matrix are anti-isomorphic in a certain order-theoretic and algebraic sense. The first problem is to describe the kernels of the row and column spaces of a given matrix. These equivalence relations generalise the orthogonal complement of a set of vectors, and the nature of their equivalence classes is entirely dependent upon the kind of semiring in question. The second, Hahn-Banach type, problem is to decide which linear functionals on row and column spaces of matrices have a linear extension. If they all do, the underlying semiring is called exact, and in this case the row and column spaces of any matrix are isomorphic to each others' duals. The final problem is to explain the connection between the row space and column space of each matrix. Our notion of a conjugation on a semiring accounts for the different possibilities in a unified manner, as it guarantees the existence of bijections between row and column spaces and lets us focus on the peculiarities of those bijections. Our main original contribution is the systematic approach described above, but along the way we establish several new results about exactness of semirings. We give sufficient conditions for a subsemiring of an exact semiring to inherit exactness, and we apply these conditions to show that exactness transfers to finite group semirings. We also show that every Boolean ring is exact. This result is interesting because it allows us to construct a ring which is exact (also known as FP-injective) but not self-injective. Finally, we consider exactness for residuated lattices, showing that every involutive residuated lattice is exact. We end by showing that the residuated lattice of subsets of a finite monoid is exact if and only if the monoid is a group.

Proline-rich antimicrobial peptides (PrAMPs) are promising candidates for the treatment of infections caused by highpriority human pathogens. Their mode of action consists of (I) passive diffusion across the outer membrane, (II) active transport through the inner membrane, and (III) inhibition of protein biosynthesis by blocking the exit tunnel of the 70S ribosome. We tested whether in vitro data on ribosomal binding and bacterial uptake could predict the antibacterial activity of PrAMPs against Gram-negative and Gram-positive bacteria. Ribosomal binding and bacterial uptake rates were measured for 47 derivatives of PrAMP Onc112 and compared to the minimal inhibitory concentrations (MIC) of each peptide. Ribosomal binding was evaluated for ribosome extracts from four Gram-negative bacteria. Bacterial uptake was assessed by quantifying each peptide in the supernatants of bacterial cultures. Oncocin analogues with a higher net positive charge appeared to be more active, although their ribosome binding and uptake rates were not necessarily better than for Onc112. The data suggest a complex mode of action influenced by further factors improving or reducing the antibacterial activity, including diffusion through membranes, transport mechanism, secondary targets, off-target binding, intracellular distribution, and membrane effects. Relying only on in vitro binding and uptake data may not be sufficient for the rational development of more active analogues.

No / The pharmacology of bimatoprost, a synthetic prostaglandin-amide, was examined in prostaglandin F2¿ (PGF2¿)-sensitive preparations. Bimatoprost potently contracted the rabbit isolated uterus (pEC50=7.92±0.16). In contrast, bimatoprost exhibited weak excitatory activity in human myometrium from pregnant and nonpregnant donors, mouse uterus, rat uterus, and endothelium-intact rabbit jugular veins, and did not stimulate DNA synthesis in mouse fibroblasts. The possibility that the effects of bimatoprost may reflect partial agonism at prostanoid FP receptors was examined and the contractile effects of full agonists, 17-phenyl PGF2¿ (FP) and U-46619 (TP, a control), were determined in the absence and presence of 1 ¿M bimatoprost on the mouse uterus. Analyses of the agonist¿agonist functional studies showed no antagonism, indicating that bimatoprost is not a partial agonist. Bioassay metabolism studies of bimatoprost and latanoprost (FP receptor agonist prodrug) in the rabbit uterus were conducted using recipient mouse uterus. Results indicated that the potent responses to bimatoprost in the rabbit uterus are produced by the intact molecule and not by its putative free acid metabolite, 17-phenyl PGF2¿. Some hydrolysis of latanoprost to latanoprost free acid appears to have occurred in the rabbit uterus, according to biological detection. The pharmacology of bimatoprost could not be explained by its interaction with known prostanoid FP receptors and was independent of species-, tissue-, or preparation-related factors. The potent contractile effects of bimatoprost in the rabbit uterus provide further pharmacological evidence for the presence of a novel receptor population that preferentially recognises bimatoprost.

Les ligands orthostériques transmettent un signal complexe aux cellules en se fixant à l'intérieur de la pochette de liaison de leur récepteur cible. Le changement conformationel qui en résulte modifie l'efficacité du récepteur à recruter et activer les seconds messagers en amont des voies de signalisation, soit les protéines G hétérotrimériques dans le cas des récepteurs couplés aux protéines G (GPCRs). Ces variations entraînent une vaste gamme de modifications dans le milieu intracellulaire. Par exemple, l'activation de la protéine G q provoque entre autres l'activation de la phospholipase C? (PLC? ), la production d'inositol 1,4,5-trisphosphate (1P3), puis l'activation des protéines kinases C (PKC). L'activation de la protéine G s , pour sa part, stimule l'activité de l'adénylate cyclase (AC), ce qui entraîne la production d'AMPc et l'activation de la protéine kinase A (PKA). Un ligand n'influence pas nécessairement deux voies de signalisation indépendantes de façon similaire, ce qui lui confère la propriété de sélectivité fonctionnelle. Dans ce travail, nous avons caractérisé le profil pharmacologique de ligands orthostériques du récepteur FP de la PGF2? à l'aide d'un clone HEK-293-SL exprimant le récepteur FP de façon stable. La mesure de la production d'IP3 a permis d'évaluer la voie de la PLC alors que la mesure de la production d'AMP c a permis d'évaluer la voie de l'AC. Pour chacune d'entre elles, le fluprostenol s'est comporté comme un agoniste complet moins puissant que l'agoniste naturel. Le composé synthétique Al-8810 s'est comporté comme un agoniste partiel de la voie de la PLC, alors qu'il s'est avéré être un antagoniste de la voie de l'AC. Ces résultats démontrent que l'activité d'un ligand vis-à-vis un récepteur dépend du groupe d'effecteurs observé, ce qui illustre le concept de sélectivité fonctionnelle des ligands. L'étude des composés allostériques THG113 et THG113.824 démontre que ces derniers n'influencent pas la signalisation déclenchée en aval du récepteur FP par son agoniste naturel. Ces résultats suggèrent qu'ils agiraient comme antagoniste des effets de la PGF 2? par un mécanisme indépendant du récepteur FP. [Symboles non conformes]