Le système immunitaire adaptatif joue un rôle de premier plan dans la défense contre les infections. La réponse humorale, impliquant la production d'anticorps, est un élément important de la réponse immunitaire adaptative. Au cours d'une infection, des cellules B spécifiques du système immunitaire prolifèrent et libèrent de grandes quantités d'anticorps qui se lient sélectivement à la protéine cible (antigène) trouvée sur le pathogène invasif, induisant la destruction du pathogène.Cependant, le système immunitaire ne répond pas toujours suffisamment efficacement pour détruire les agents pathogènes, et les mécanismes de tolérance empêchent la génération d'anticorps contre les protéines humaines - comme les marqueurs de surface cellulaire sur les cellules cancéreuses ou les cytokines impliquées dans des maladies inflammatoires et auto-immunes - qui pourraient être des cibles thérapeutiques importantes. Par conséquent, il existe un grand intérêt pour la recherche et le développement d'anticorps spécifiques qui peuvent être utilisés pour le traitement des patients par immunothérapie. En raison de leur grande affinité et de leur liaison sélective aux antigènes, les anticorps monoclonaux (mAbs) sont apparus comme des agents thérapeutiques puissants. Les anticorps monoclonaux dérivés de cellules B individuelles ont une séquence unique et présentent une affinité de liaison pour un antigène spécifique. Cependant, jusqu'à maintenant, la découverte des mAbs a été limitée par l'absence de méthodes à haut débit pour le criblage direct et à grande échelle de cellules B primaires non immortalisées pour découvrir les rares cellules B qui produisent des anticorps spécifiques d'intérêt clinique. Ceci est maintenant possible avec l'émergence et l'amélioration des méthodes de compartimentation in vitro pour l'encapsulation et le criblage de cellules uniques dans des gouttelettes picolitriques. Dans mon projet de doctorat, je décris le développement d'immunodosages et de dispositifs microfluidiques pour le criblage phénotypique direct de cellules individuelles à partir de populations de cellules B enrichies. Ce développement a permis une analyse détaillée de la réponse immunitaire humorale, avec une résolution à l’échelle de la cellule unique. C’est aussi un élément essentiel d'un pipeline de détection d'anticorps couplant le criblage phénotypique de cellules individuelles au séquençage d'anticorps sur cellules uniques. Il est maintenant possible, pour la première fois, de cribler des millions de cellules B individuelles en fonction de l'activité de liaison des anticorps sécrétés et de récupérer les séquences d'anticorps / The adaptive immune system plays a leading role in defense against infection. The humoral response, involving the production of antibodies, is an important component of the adaptive immune response. During an infection, specific B cells of the immune system proliferate and release large amounts of antibodies which bind selectively to the target protein (antigen) found on the invading pathogen, inducing destruction of the pathogen. However, the immune system does not always respond efficiently enough to destroy pathogens, and tolerance mechanisms prevent the generation of antibodies against human protein - such as cell surface markers on cancer cells or cytokines involved in inflammatory and autoimmune disease - that could be important therapeutic targets. Hence, there is great interest in research and development of specific antibodies that can be used for immunotherapy of patients. Due to their high affinity and selective binding to antigens, monoclonal antibodies (mAbs) have emerged as powerful therapeutic agents. Monoclonal antibodies derived from single B cells have a unique sequence and display binding affinity for a specific antigen. However, until now, the discovery of mAbs has been limited by the lack of high-throughput methods for the direct and large-scale screening of non-immortalized primary B cells to uncover rare B cells which produce the specific antibodies of clinical interest. This is now becoming possible with the emergence and improvement of in vitro compartmentalization methods for single-cell encapsulation and screening in picoliter droplets. In my PhD project, I describe the development of binding immunoassays and microfluidic devices for the direct phenotypic screening of single-cells from enriched B cell populations. This development has enabled detailed analysis of the humoral immune response, with single-cell resolution and is an essential component of an antibody-discovery pipeline coupling single-cell phenotypic screening to single-cell antibody sequencing. It is now possible, for the first time, to screen millions of single B cells based on the binding activity of the secreted antibodies and to recover the antibody sequences

Les oxydes non-stoechiométriques de type Ruddlesden-Popper, tel que Pr2NiO4+δ, peuvent être dopés en trous par substitution du strontium au praséodyme ou par insertion d’oxygène. Ces modes de dopage s’accompagnent de mises en ordre complexes impliquant la distribution des ions oxygène excédentaires, des ordres de charge et/ou de spin. Le diagramme de phase de Pr2-xSrxNiO4+δ a été exploré par diffraction des rayons X (en laboratoire et par rayonnement synchrotron) ainsi que neutronique. Pour la phase Pr2NiO4.25, nous avons mis en évidence une sur-structure incommensurable avec des réflexions satellites au 6ème ordre, produisant un spectre de diffraction très complexe avec 4 individus et 8 domaines incommensurables. Par diffractions synchrotron et neutronique, un ordre de charge de type échiquier a été identifié dès la température ambiante, suivi en dessous de 170 K par un ordre de type rubans ; un ordre de spin incommensurable s’établit au-dessous de 99 K. Ce travail a permis de révéler un ensemble complexe de phases ordonnées structuralement et électroniquement, gouvernées par des variations subtiles de stoechiométrie en strontium et oxygène. / Non-stoichiometric oxides from the Ruddlesden-Popper series, such as Pr2NiO4+δ, can be hole-doped by substituting strontium to praseodymium or by oxygen insertion. This leads to complex structural ordering involving oxygen-, charge- and spin ordering. The complex phase diagram of Pr2-xSrxNiO4+δ was explored using X-ray (laboratory and synchrotron) as well as neutron diffractions. For the doped phase of highest oxygen content (Pr2NiO4.25), we could evidence an incommensurate structure with satellite reflections of 6th order, yielding a very complex diffraction pattern of up to four twin-individuals and eight incommensurate domains. Checkerboard-type charge ordering was identified already at ambient temperature, while stripe charge ordering was observed below 170 K by synchrotron and neutron diffraction; incommensurate spin ordering appears below 99 K. This thesis reveals the existence of many complex oxygen and electronically ordered phases going along with small variations of the oxygen/strontium stoichiometry.

Thesis deal with complete proposition of internet sites and e-commerce. Thesis includes first analyse of all web functions, scheme of e-commerce, scheme of graphic layout, e-commerce implementation by the help of web programming languages and databases. Part of thesis is first initiation of internet sites, debugging, administration systém, technical and content updating. There is also economical evaluation, influence on the company, service of e-commerce and off-set evaluation whole system.

This doctoral thesis deals with possibilities of using advanced methods of decision-making - Soft Computing, in company’s ordering cycle management. The main aim of the thesis is to propose an artificial neural network model with an optimal architecture for ordering cycle management within the supply chain management. The proposed model will be employed in an organization involved in retailing to ensure smooth material flow. A design and verification of artificial neural networks model for sales prediction is also part of this doctoral thesis as well as a comparison of results and usability with standard and commonly used statistical methods. Furthermore, the thesis deals with finding a suitable artificial neural network model with architecture capable of solving the lot-size problem according to specified inputs. Methods of statistical data processing, economical modelling and advanced decision-making (Soft Computing) were utilized during the model designing process.

Kronecker structured representations are used to cope with the state space explosion problem in Markovian modeling and analysis. Currently an open research problem is that of devising strong preconditioners to be used with projection methods for the computation of the stationary vector of Markov chains (MCs) underlying such representations. This paper proposes a block SOR (BSOR) preconditioner for hierarchical Markovian Models (HMMs) that are composed of multiple low level models and a high level model that defines the interaction among low level models. The Kronecker structure of an HMM yields nested block partitionings in its underlying continuous-time MC which may be used in the BSOR preconditioner. The computation of the BSOR preconditioned residual in each iteration of a preconditioned projection method becoms the problem of solving multiple nonsingular linear systems whose coefficient matrices are the diagonal blocks of the chosen partitioning. The proposed BSOR preconditioner solvers these systems using sparse LU or real Schur factors of diagonal blocks. The fill-in of sparse LU factorized diagonal blocks is reduced using the column approximate minimum degree algorithm (COLAMD). A set of numerical experiments are presented to show the merits of the proposed BSOR preconditioner.

Hierarchical Markovian Models (HMMs) are composed of multiple low level models (LLMs) and high level model (HLM) that defines the interaction among LLMs. The essence of the HMM approach is to model the system at hand in the form of interacting components so that its (larger) underlying continous-time Markov chain (CTMC) is not generated but implicitly represented as a sum of Kronecker products of (smaller) component matrices. The Kronecker structure of an HMM induces nested block partitionings in its underlying CTMC. These partitionings may be used in block versions of classical iterative methods based on splittings, such as block SOR (BSOR), to solve the underlying CTMC for its stationary vector. Therein the problem becomes that of solving multiple nonsingular linear systems whose coefficient matrices are the diagonal blocks of a particular partitioning. This paper shows that in each HLM state there may be diagonal blocks with identical off-diagonal parts and diagonals differing from each other by a multiple of the identity matrix. Such diagonal blocks are named candidate blocks. The paper explains how candidate blocks can be detected and how the can mutually benefit from a single real Schur factorization. It gives sufficient conditions for the existence of diagonal blocks with real eigenvalues and shows how these conditions can be checked using component matrices. It describes how the sparse real Schur factors of candidate blocks satisfying these conditions can be constructed from component matrices and their real Schur factors. It also demonstrates how fill in- of LU factorized (non-candidate) diagonal blocks can be reduced by using the column approximate minimum degree algorithm (COLAMD). Then it presents a three-level BSOR solver in which the diagonal blocks at the first level are solved using block Gauss-Seidel (BGS) at the second and the methods of real Schur and LU factorizations at the third level. Finally, on a set of numerical experiments it shows how these ideas can be used to reduce the storage required by the factors of the diagonal blocks at the third level and to improve the solution time compared to an all LU factorization implementation of the three-level BSOR solver.

<p>Ako je&nbsp; Lalgebarska mreža i&nbsp; a kodistributivan elemenat u L, onda sve klase kongruencije&nbsp; (pa indukovane homomorfizmom&nbsp; ma : xi&mdash; &gt;&nbsp; a&nbsp;&nbsp; A x imaju najveće elemente. Najveći elemenat klase kojoj&nbsp; x E Lpripada je označen sa&nbsp; x.Ako je&nbsp; *a binarna op&shy;eracija definisana sa x *ay = (x A y)&nbsp; V&nbsp; (x A y),onda je istraživana struktura&nbsp; (L, *a), i odgovarajući poset ( L, &lt;&raquo;). Kao primer takve strukture posmatrana je algebra slabih kongruencija&nbsp; (CwA, *a), gde je *a specijalna grafička kompozicija. Dobijeni rezultati daju prirodne posledice u strukturi slabih kongruencija. Data je primena ovih rezultata u univerzalnoj algebri. Njihovom primenom karakterizuje se CEP i Hamiltonovo svojstvo. Dat je potreban i dovoljan uslov da poset (L, &lt; -) bude mreža i ovi rezultati su primenjeni na mrežu slabih kongruencija.</p> / <p>If&nbsp; Lis an algebraic lattice and&nbsp; a codistributive element in&nbsp; L,then all the classes of the congruences&nbsp; 4&gt;a determined by the homomorphism&nbsp; ma :&nbsp; x&nbsp; \&mdash; &gt;&nbsp; a Ax&nbsp;&nbsp; have top elements. The top element of the class which to belongs an&nbsp; x&nbsp;&nbsp; &euro;&nbsp; Lis denoted by&nbsp; x.&nbsp;&nbsp; If *a is a binary operation defined by&nbsp; x&nbsp; *ay=&nbsp; (xA y)&nbsp; V&nbsp; (xA y),then we investigate the<br />structure&nbsp; (L,*a), and the corresponding poset&nbsp; (L, &lt; t ). Asan example of such a structure we observe an algebra of weak congruences ( C w A , * a),where *a is a special graphical composition. We obtain natural conse&shy; quences of the mentioned results to the structure weak congruences. An application in universal algebra is presented, for example, we characterized CEP and Hamiltonian property. Necessary and sufficient conditions for a poset&nbsp; (L,&lt;*) to be a lattice are given, and the results are applied in the case of weak congruence lattices.</p>

In this work we studied magnetic properties of molecular magnets of the new heteropolyanion {Cu20}, dodecanuclear cluster {Ni12}, and the heterometallic {Cr7M} wheels, in which one of the CrIII ions of Cr8 has been replaced by a Fe, Cu, Zn, Ni, ion with this extra-spin acts as local probe for the spin dynamics.Such systems have been synthesized recently and they are well described using the Heisenberg spin Hamiltonian with a Zeeman term of an applied magnetic field along the z-axis. Using the numerical exact diagonalization method, we have calculated the energy spectrum and the eigenstates for different compounds,and we have used them for reexamining the available experimental susceptibility data to determine the values of exchange parameters.We have studied the thermodynamic properties such magnetization, susceptibility, heat-capacity. At low temperature regions molecular magnets act as individual quantum nanomagnets and can display super-paramagnetic phenomena like macroscopic quantum tunneling, ground state degeneracy, level-crossing. A crucial issue for understanding these phenomena is the coupling between magnetic molecular levels and the environment such as nuclear spins. We have modeled the behavior of the proton spin lattice relaxation rate as a function of applied magnetic field for low temperatures as it is measured in Nuclear Magnetic Resonance (NMR) experiments.

BaVS3 est un système quasi-unidimensionnel constitué de chaînes de vanadium. C'est aussi un système multi-bandes dans lequel plusieurs types d'électrons coexistent au voisinage du niveau de Fermi (les bandes dz2 et e(t2g)), qui sont fortement corrélés. Ce système s'appuie donc à la fois sur la physiques des systèmes unidimensionnels et sur celle des systèmes à électrons fortement corrélés. La transition métal-isolant de BaVS3, qui fut l'objet de nombreuses études, a récemment été interprété comme s'apparentant à une onde de densité de charge des électrons dz2 : celle-ci s'accompagne d'une quadrimérisation de la chaîne de vanadium et de l'apparition d'une sur-structure indexée (1,0,1/2)O dans le réseau réciproque. La composante commensurable de la sur-structure selon l'axe des chaînes ne peut s'expliquer qu'en considérant une redistribution des électrons entre les différentes bandes au voisinage du niveau de Fermi sous l'effet des corrélations électroniques. La transition métal-isolant disparaît en un point critique quantique sous pression à 2 GPa. D'un autre point de vu, une autre instabilité isolante d'un autre type, indexée (1/3,1/3,0.8)H avait été observée dans des échantillons substitués chimiquement. Cette thèse en deux temps s'est d'abord intéressée à la compétition entre les deux phases (1,0,1/2)O et (1/3,1/3,0.8)H dans deux séries d'échantillons chimiquement modifié BaVS3-δ et Ba1-xSrxVS3. Cette étude permet de montrer que la phase (1/3,1/3,0.8)H est associée à un ordre de charge des électrons e(t2g) et de conclure sur le rôle des modifications chimiques en temps qu'impuretés quand au mécanisme d'apparition de la seconde phase, par opposition à une théorie de "pression chimique". Le deuxième temps de cette thèse présente l'étude structurale de la transition métal-isolant sous pression. Cette étude à nécessité la mise en place d'un dispositif de diffraction sous pression à basse température avec mesure in-situ de la pression. Cette étude a montrée que la modulation structurale reste commensurable sur les 3/4 du diagramme de phase puis devient incommensurable lorsque l'on s'approche du point critique quantique. Ceci permet d'interpréter l'évolution de la transition métal-isolant sous pression en terme de locking à la commensurabilité, et donne une information sur la physique du composé au voisinage du point critique quantique. / BaVS3 is a quasi one dimensional system made of vanadium chains. It is also a multi-band system in which different kinds of electrons coexist near the Fermi level (the dz2 and e(t2g) bands), which are strongly correlated. This system belongs thus either to the one dimensional physics and to the strongly correlated electron physics. The metal - insulator transition in BaVS3, which has been extensively studied, was recently interpreted relying on a Peierls-like theory for the dz2 band : the transition involves a quadrimerisation of the vanadium chain, which corresponds to a super-structure indexed (1,0,1/2)O in the reciprocal lattice. This commensurate indexation can only be explained by a redistribution of electrons between the different bands near the Fermi level, because of electronic correlations. The metal - insulator transition disappears in a quantum critical point at 2 GPa. On another point of view, another insulating instability of another type, indexed (1/3,1/3,0.8)H, was seen in chemically substituted compounds. This Ph. D. Thesis articulates in two times. The first point deals with chemically substituted samples series BaVS3-δ and Ba1-xSrxVS3. This study shows that the (1/3,1/3,0.8)H phase is associated to a charge ordering of the e(t2g) electrons and permit to conclude on the role of chemical modification as impurities, concerning the apparition mechanism of this other insulating phase, contrary to a "chemical pressure" theory. The second point presents the structural study under pressure of the metal - insulator transition. To conduct this study, a low temperature X-ray diffraction under pressure experiment , including in-situ pressure measurements, was set up. This study showed that the structural modulation remains commensurate on the 3/4th of the phase diagram and then becomes incommensurate on approaching the quantum critical point. This allows an interpretation of evolution of the metal - insulator transition under pressure in terms of commensurate locking, and gives a clue concerning the physics near the quantum critical point.

This research study aims to investigate the capacity of single photons to carry information through polarization and time ordering and proposes a protocol called Beyond Pulse Position Modulation (BPPM) to improve photon-based communication reliability over longer distances with limited power. Such a protocol may be used in any communication scenario where energy efficiency is important, e.g., in satellite communication or where pulse position modulation (PPM) typically is used. The study compares various metrics such as information bits per symbol, photon, and time bin to evaluate the system’s efficiency and conducts a comparative analysis of BPPM, Pulse Position Modulation (PPM), On-Off Keying (OOK), andGeneral protocol’s effectiveness. (The simulations were conducted using the Python programming language with Visual Studio Code IDE.) / Denna forskningsstudie syftar till att undersöka informationskapaciteten hos enstaka fotoner då dessa kodats med avseende på polarisering och tidsordning. Ett nytt protokoll som kallas Beyond Pulse Position Modulation (BPPM) använder felkorrigering för att förbättra kommunikationstillförlitligheten över längre avstånd med begränsad effekt. Ett sådant protokoll kan användas i vilket kommunikationsscenario som helst där energieffektivitet är viktigt, t.ex. vid satellitkommunikation eller där pulspositionsmodulering (PPM) vanligtvis används. Studien jämför olika mätvärden som informationsbitar per symbol, per foton och per tidslucka för att utvärdera systemets effektivitet och genomför en jämförande analys av BPPM, Pulse Position Modulation (PPM), On-Off Keying (OOK) och ett protokoll med fixt antal fotoner per block avseende protokollens effektivitet. (Simuleringarna utfördes med Python-programmeringsspråket med Visual Studio Code IDE.)