Rozprawy doktorskie na temat „Particules en cellule (PIC)”
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Monel, Blandine. "Assemblage des particules virales et transmission du VIH de cellule à cellule". Paris 7, 2012. http://www.theses.fr/2012PA077170.
Pełny tekst źródłaDirect cell-to-cell transmission of human immunodeficiency virus (HIV) is a more potent and efficient means of virus propagation than infection by cell-free virus particles, During the first part of my thesis we show that HIV cell-to-cell transmission requires the assembly of enveloped virus particles. Nucleic acids with replication potential can not translocate directly from donor to target cells through envelope glycoprotein (Env)-induced fusion pores, The increased efficiency of this infection route may thus be attributed to the high local concentrations of virus particles at sites of cellular contacts rather than to a qualitatively different transmission process. The truncation of the cytopïasmic tail of Envgp41 inhibits HIV-1 propagation in some cells named non-permissive cells. In some other cell lines (permissive cells), HIV can still propagate. The aim of the second study of my thesis is to characterize the impact of this truncation in the two kinds of cell lines, both on HIV cell-free infectivity and on HTV cell-to-cell transmission. Our results show that, for both transmission modes, the gp41CT truncation of HIV-1 leads to a drastic decrease of infectivity when viruses are produced in non-permissive cells. The replication defect of the HIV-1 gp41CT truncated mutant in non-permissive cells could be explained by an important mortality of the non-infected "bystanders" cells, in addition to the previously shown reduction of Env incorporation into virus particles. Our preliminary results show that contacts established with a cell expressing the truncated Env rapidly induces cell-cell fusion and syncytia formation in non-permissive cells, leading to cell death
Betar, Homam. "Kinetic Effects in Magnetic Reconnection". Electronic Thesis or Diss., Université de Lorraine, 2021. http://www.theses.fr/2021LORR0043.
Pełny tekst źródłaPlasmas are gaseous systems of ions and electrons which interact via electromagnetic fields and display collective properties. Among these, is the notion of the magnetic line "connection". This expresses the fact that, in regimes in which charged particles spiral sufficiently fast along lines of magnetic induction, the latter is linked to the bulk plasma motion and acquire a topological identity which forbids them to break, intersect and reconnect. This topological identity, however, can be locally violated thanks to a number of kinetic effects, such as particle collisions, when the currents in the plasma are sufficiently intense: one speaks of "magnetic reconnection". Magnetic reconnection is an important ingredient of the plasma self-organization and has significance for both space and laboratory plasmas since it is at the basis of natural phenomena like solar flares and polar lights, or of disruptive processes in thermonuclear fusion experiments. A long-standing problem in the study of laboratory and astrophysical plasmas is to understand the mechanisms of acceleration of electrons and ions, as a magnetic field reconnect and release energy. In this work, we studied kinetic effects on reconnection instabilities developing spontaneously in static current sheets (tearing modes) and in combination with a class of kinetic instabilities (Weibel instabilities) that are relevant both to astrophysical plasma jets and to laser-plasma interaction experiments. We performed this study using reduced-fluid and kinetic models and we investigated the competition between tearing-type modes and Weibel-type instabilities by means of both semi-lagrangian full kinetic Vlasov-Maxwell simulations and particles in cell simulations
Malbec, Marine. "La transmission de cellule à cellule du VIH-1 : rôle de la protéine Nef et effet inhibiteur des anticorps neutralisants à large spectre". Paris 7, 2013. http://www.theses.fr/2013PA077191.
Pełny tekst źródłaWe have studied two aspects of HIV-1 cell-to-cell transmission. First, we have investigated the role of Nef in HIV-1 replication and cell transfer. Second, we have examined the effect of a panel of broad neutralizing antibodies (bNAbs) on cell-to-cell transmission and studied the mechanisms involved. Nef is an HIV regulatory protein indispensable for replication and pathogenicity in vivo. Nef is known to down-regulate the surface expression of various cellular molecules, to increase virions infectivity and to affect cellular motility. We have shown that Nef facilitates HIV cell-to-cell transmission and that this function is conserved among lentiviruses. Nef increases levels of the virus structural Gag protein in the cell and promotes Gag localization to the plasma membrane. In the absence of Nef, viral material transferred to target cells is mostly immature. BNAbs are defined by their potency and their breadth, neutralizing a wide'panel of circulating viral strains from a variety of clades. The antiviral activity of these bNAbs is typically measured in cell free infection assay but little is know about their ability to block cell-associated transmission. By examining 15 bNAbs in collaboration with Michel Nussenzweig's group, we demonstrate that only a small subset efficiently prevent HIV cell-to-cell transmission. These bNAbs accumulate at the virological synapse, block the formation of conjugates and inhibit the transfer of viral material to target cells. Infection by cellular contact is likely the main mode of virus dissemination in vivo and the bNAbs identified in our study may represent candidates for therapeutic or prophylactic strategies
Lemercier, Nicolas. "CEMOVIS, développements méthodologiques et étude ultrastructurale de la cellule HT29 : De la cellule aux nucléosomes". Phd thesis, Université Paris Sud - Paris XI, 2012. http://tel.archives-ouvertes.fr/tel-00685425.
Pełny tekst źródłaBoudhib, Mohamed. "Analyse d’aérosols par méthodes LIBS sans étalonnage et LIBS couplée à une cellule radiofréquence utilisée comme piège à particules". Thesis, Orléans, 2017. http://www.theses.fr/2017ORLE2011/document.
Pełny tekst źródłaNew issues related to process control and workplace surveillance accompany the emergence of nanotechnology industry. This involves the development of new real-time and in-situ characterization techniques. In this context, the NOVA unit from the INERIS institute collaborated with LP3 and GREMI laboratories to study two approaches aiming to enhance the LIBS technic performances. The first approach used a flow cell to determine the relative elemental composition of an aerosol with a calibration-free procedure. The recorded spectra were compared to theoretical spectra calculated for a plasma in the Local Thermodynamic Equilibrium LTE. The best agreement between recorded and computed spectra allowed the determination of the relative composition with a good agreement with the reference value, for an alumina aerosol. The study of the temporal evolution of the plasma allowed the estimation of a temporal range within which the LTE hypothesis was verified. The second approach used a low-pressure radiofrequency plasma generated in an inert gas as a particle trap to analyse aerosols and nanoparticles. The use of such a system allowed the enhancement of particles detection by concentrating them spatially. We determined the optimal parameters for the LIBS analysis using this system. Furthermore, we established the plasma continuum was attenuated even at very low time delays. We evaluated the sampling volume of this new system and compared it to case of LIBS analysis on air. Finally, we estimated the detection limits of this system when analysing nanoparticles
DOORNAERT, BLANDINE. "Impact des particules diesel et des acariens sur les cellules epitheliales bronchiques humaines : alteration des interactions cellule-matrice extracellulaire". Paris 12, 2001. http://www.theses.fr/2001PA120016.
Pełny tekst źródłaKhelifi, Sadjia. "Étude du comportement hydrodynamique de suspensions concentrées de particules d’hématite : sédimentation, comportement rhéologique et écoulement forcé dans une cellule inclinée". Thesis, Université de Lorraine, 2018. http://www.theses.fr/2018LORR0036.
Pełny tekst źródłaThis thesis aims to develop scientific and technological knowledge needed to design a pilot production of steel by electrochemical reduction of hematite particles suspended in an alkaline medium at 110°C in order to provide a reliable and environmentally friendly industrial process, as an alternative to the conventional process based on coal. The mixture considered contains a suspension of hematite of 12% by volume in an aqueous sodium hydroxide solution of 50% by weight. This thesis seeks to study the sedimentation and rheology of hematite suspensions and the hydrodynamic behavior of hematite particles in inclined cell and to quantify the possible phenomeno impact on the cathode
Turkcan, Silvan. "Interaction toxine-cellule étudiée par imagerie de nanoémetteurs individuels". Phd thesis, Ecole Polytechnique X, 2010. http://tel.archives-ouvertes.fr/tel-00608124.
Pełny tekst źródłaSaias, Laure. "Laboratoires-sur-puce pour l'analyse cellulaire : tri de cellules tumorales circulantes et culture de neurones". Paris 6, 2009. http://www.theses.fr/2009PA066684.
Pełny tekst źródłaLyu, Jinming. "Modélisation numérique de la dynamique de particules molles en microcanaux". Thesis, Ecole centrale de Marseille, 2019. http://www.theses.fr/2019ECDM0002.
Pełny tekst źródłaVesicles are a model system for understanding the dynamical behavior of a closed soft particle such as red blood cells (RBCs) in flows. The inextensible lipid bilayer membrane of a vesicle admits resistance to the bending elasticity, and its large surface-area-to-volume ratio allows the vesicle to exhibit remarkable shape changes in the dynamics even in a simple flow. Significant progress has been made over the past decades in understanding vesicle dynamics in unbounded Stokes flows. This manuscript deals with the numerical investigation of shape transition and lateral migration of 3D vesicles in wall-bounded Stokes flows by means of an isogeometric finite-element method (FEM) and boundary-element method (BEM). Starting from a previously reported isogeometric FEM-BEM simulations of the dynamics of soft particles (drops, capsule, and vesicle) in Stokes flows in free space, the original code is developed to account for microchannel walls of arbitrary cross-section. The present work focuses on the dynamics of a vesicle that is transported through a circular tube in a pressure-driven flow. First, we investigate typical vesicle shapes, different lateral migration modes, and flow structure onto vesicle membrane versus three independent dimensionless parameters, namely, the reduced volume, the confinement, and the (bending) capillary number. Shape transitions and the phase diagram of stable shapes for several reduced volumes are obtained in the (confinement, capillary number) space, showing an extension of the set of vesicle morphologies and rich vesicle dynamics owing to the intricate interplay among the tube wall, hydrodynamic stresses, and membrane bending. Secondly, we study, via an axisymmetric BEM, the hydrodynamics under high confinements in which the shape of the vesicle is expected to maintain axisymmetry. A particular emphasis is given to the prediction of the vesicle mobility and the extra pressure drop caused due to the presence of the vesicle, the latter having implications in the rheology of a dilute suspension. In addition, based on the numerical results of limiting behavior of quantities of interest near maximal confinement, we give various scaling laws to infer, for example, the vesicle velocity, its length, and the thickness of lubrication film. Finally, we present a coupled, hybrid continuum–coarse-grained model for the study of RBCs in fluid flows. This model is based on a combination of the vesicle model with a network of springs with fixed connectivity, representing the cytoskeleton. Numerical results show that this two-component vesicle–cytoskeleton model isable to extract the mechanical properties of RBCs and predict its dynamics in fluid flows
Gueroult, Renaud. "Étude d'une source d'ions obtenue par extraction et accélération à partir d'une source plasma filaire". Phd thesis, Palaiseau, Ecole polytechnique, 2011. https://pastel.hal.science/docs/00/64/68/21/PDF/these.pdf.
Pełny tekst źródłaIn this study we first model a DC low pressure wire plasma source and then characterize the properties of an ion gun derived from the plasma source. In order to study the properties of the derived ion gun, we develop a particle-in-cell code fitted to the modelling of the wire plasma source operation, and validate it by confrontation with the results of an experimental study. In light of the simulation results, an analysis of the wire discharge in terms of a collisional Child-Langmuir ion flow in cylindrical geometry is proposed. We interpret the mode transition as a natural reorganisation of the discharge when the current is increased above a threshold value which is a function of the discharge voltage, the pressure and the inter-electrodes distance. In addition, the analysis of the energy distribution function of ions impacting the cathode demonstrates the ability to extract an ion beam of low energy spread around the discharge voltage assuming that the discharge is operated in its high pressure mode. An ion source prototype allowing the extraction and acceleration of ions from the wire source is then proposed. The experimental study of such a device confirms that, apart from a shift corresponding to the accelerating voltage, the acceleration scheme does not spread the ion velocity distribution function along the axis of the beam. It is therefore possible to produce tunable energy (0-5 keV) ion beams of various ionic species presenting limited energy dispersion (~ 10 eV). The typical beam currents are about a few tens of micro-amperes, and the divergence of such a beam is on the order of one degree. A numerical modelling of the ion source is eventually conducted in order to identify potential optimizations of the concept
Carrière, Christian. "Etude par mutagenèse du rôle de la polyprotéine Gag du virus de l'immunodéficience humaine (HIV-1) dans le processus d'assemblage des particules virales". Montpellier 1, 1995. http://www.theses.fr/1995MON1T005.
Pełny tekst źródłaGueroult, Renaud. "Étude d'une source d'ions obtenue par extraction et accélération à partir d'une source plasma filaire". Phd thesis, Ecole Polytechnique X, 2011. http://pastel.archives-ouvertes.fr/pastel-00646821.
Pełny tekst źródłaDrouin, Mathieu. "Vers la simulation particulaire réaliste de l'interaction laser-plasma surcritique : conception d'un schéma implicite avec amortissement ajustable et fonctions de forme d'ordre élevé". Phd thesis, Cachan, Ecole normale supérieure, 2009. https://theses.hal.science/tel-00442715/fr/.
Pełny tekst źródłaLaser-plasma interaction and electronic transport are pure kinetic processes thus requiring to solve the complete Vlasov-Maxwell system of equations. This thesis focuses on PIC (‘‘Particle-In-Cell'') methods, and is intended to widen the operating regime of such methods. First, we present the linear stability analysis of an explicit PIC algorithm including spatial and temporal step size effects. This study highlights the aliasing instability, which we link to the more intricate issue of numerical heating in PIC codes in the overcritical regime. We show the beneficial influence of using an increasingly high order weight function to drop this heating, thereby allowing to reach overcritical regimes relevant for comparison with experiments. Implicit PIC codes are not submitted to the constraints affecting their explicit counterparts. Particularly we can relax the need to solve high frequency electronic modes. Such a property is extremely valuable when we model the interaction between a high intensity laser and a highly overcritical plasma. Here, we give the relativistic extension of the direct implicit method, provided with an adjustable damping parameter and high order weight functions. This formalism was implemented in the code ELIXIRS, 2D in space and 3D in velocity. This code was validated for various plasma physics configurations, among them one or two electronic temperatures plasma expansions, high intensity laser-plasma interaction, and also beam-plasma instabilities in the relativistic regime. Especially, we prove the capability of the code to catch the main characteristics of the aforementioned phenomena, despite a crude spatio-temporal discretisation, thus providing significant gains of computation time
Rodriguez, Vincent. "Etude de la formation de jets issus de la dispersion d'un anneau de particules solides par onde de choc". Thesis, Aix-Marseille, 2014. http://www.theses.fr/2014AIXM4750/document.
Pełny tekst źródłaThe dispersion of particles by a blast or a shock wave induces the formation of coherent structures which take the form of particle jets. All the experiments conducted so far have been performed in three-dimensional geometry. In the present study, a blast wave, issuing from the discharge of a planar shock wave at the exit of a conventional shock tube, is generated in the center of a granular medium ring initially confined inside a Hele-Shaw cell. With the present experimental set-up, under impulsive acceleration, a solid particle jet formation is clearly obtained and observed in a quasi-two-dimensional configuration, for the first time. From fast flow visualizations, we highlighted that the selection of the number of jets is unsteady. We noticed, in all instances, that the jets are initially generated inside the particle ring and thereafter expelled outward. This point has not been observed in three-dimensional experiments. The influence of many parameters such as density and diameter of particles, the generated pressure and the geometry of the ring, has been studied. Empirical relationships were deduced from the experimental curves. Moreover, we observed in detail the formation of very thin perturbations created around the external surface of the dispersed particle layer. This phenomenon is independent of the main jet formation and solely depends on the nature of particles
Ouzilou, Laurent. "Analyse des étapes précoces de l'infection de cellules in vitro par le poliovirus (PV) : transcytose du PV à travers les entérocytes et caractérisation des particules 147S produites en amont de la décapsidation par un mutant du PV responsable d'infections persistantes". Paris 7, 2002. http://www.theses.fr/2002PA077136.
Pełny tekst źródłaDrouin, Mathieu. "Vers la simulation particulaire réaliste de l'interaction laser-plasma surcritique : conception d'un schéma implicite avec amortissement ajustable et fonctions de forme d'ordre élevé". Phd thesis, École normale supérieure de Cachan - ENS Cachan, 2009. http://tel.archives-ouvertes.fr/tel-00442715.
Pełny tekst źródłaGuyot, Julien. "Particle acceleration in colliding laser-produced plasmas". Thesis, Sorbonne université, 2019. http://www.theses.fr/2019SORUS616.
Pełny tekst źródłaEnergetic charged particles are ubiquitous in the Universe and are accelerated by galactic and extragalactic sources. Understanding the origin of these "cosmic rays" is crucial in astrophysics and within the framework of high-energy-density laboratory astrophysics we have developed a novel platform on the LULI laser facilities to study particle acceleration in the laboratory. In the experiments, the collision of two laser-produced counter-propagating plasmas generates a distribution of non-thermal particles with energies up to 1 MeV. The aim of this work is to provide a theoretical framework to understand their origin. Magneto-hydrodynamic simulations with test particles show that the plasma collision leads to the growth of bubble and spike structures driven by the magnetic Rayleigh-Taylor instability and the generation of strong electric fields. We find that particles are accelerated to energies up to a few hundred of keV in less than 20 ns, by repeated interactions with these growing magnetic Rayleigh-Taylor perturbations. The simulations and a stochastic acceleration model recover very well the experimentally measured non-thermal energy spectrum. In conclusion, we have identified in the laboratory a new particle acceleration mechanism that relies on the growth of the magnetic Rayleigh-Taylor instability to stochastically energize particles. This instability is very common in astrophysical plasmas, with examples including supernovae remnants and coronal mass ejections, and we suggest that it may contribute to the energization of particles in these systems
Doche, Antoine. "Particle acceleration with beam driven wakefield". Thesis, Université Paris-Saclay (ComUE), 2018. http://www.theses.fr/2018SACLX023/document.
Pełny tekst źródłaPlasma wakefield accelerators (PWFA) or laser wakefield accelerators (LWFA) are new technologies of particle accelerators that are particularly promising, as they can provide accelerating fields of hundreds of Gigaelectronvolts per meter while conventional facilities are limited to hundreds of Megaelectronvolts per meter. In the Plasma Wakefield Acceleration scheme (PWFA) and the Laser Wakefield Acceleration scheme (LWFA), a bunch of particles or a laser pulse propagates in a gas, creating an accelerating structure in its wake: an electron density wake associated to electromagnetic fields in the plasma. The main achievement of this thesis is the very first demonstration and experimental study in 2016 of the Plasma Wakefield Acceleration of a distinct positron bunch. In the scheme considered in the experiment, a lithium plasma was created in an oven, and a plasma density wave was excited inside it by a first bunch of positrons (the drive bunch) while the energy deposited in the plasma was extracted by a second bunch (the trailing bunch). An accelerating field of 1.36 GeV/m was reached during the experiment, for a typical accelerated charge of 40 pC. In the present manuscript is also reported the feasibility of several regimes of acceleration, which opens promising prospects for plasma wakefield accelerator staging and future colliders. Furthermore, this thesis also reports the progresses made regarding a new scheme: the use of a LWFA-produced electron beam to drive plasma waves in a gas jet. In this second experimental study, an electron beam created by laser-plasma interaction is refocused by particle bunch-plasma interaction in a second gas jet. A study of the physical phenomena associated to this hybrid LWFA-PWFA platform is reported. Last, the hybrid LWFA-PWFA scheme is also promising in order to enhance the X-ray emission by the LWFA electron beam produced in the first stage of the platform. In the last chapter of this thesis is reported the first experimental realization of this last scheme, and its promising results are discussed
Fourrier, Joris. "Les accélérateurs à champ fixe et gradient alterné FFAG et leur application médicale en protonthérapie". Phd thesis, Grenoble 1, 2008. http://www.theses.fr/2008GRE10161.
Pełny tekst źródłaRadiotherapy uses particle beams to irradiate and kill cancer tumors while sparing healthy tissues. Bragg peak shape of the proton energy loss in matter allows a ballistic improvement of the dose deposition compared with X rays. Thus, the irradiated volume can be precisely adjusted to the tumour. This thesis, in the frame of the RACCAM project, aims to the study and the design of a proton therapy installation based on a fixed field alternating gradient (FFAG) accelerator in order to build a spiral sector FFAG magnet for validation. First, we present proton therapy to define medical specifications leading to the technical specifications of a proton therapy installation. Secondly, we introduce FFAG accelerators through their past and on-going projects which are on their way around the world before developing the beam dynamic theories in the case of invariant focusing optics (scaling FFAG). We describe modelling and simulation tools developed to study the dynamics in a spiral scaling FFAG accelerator. Then we explain the spiral optic parameter search which has leaded to the construction of a magnet prototype. Finally, we describe the RACCAM project proton therapy installation starting from the injector cyclotron and ending with the extraction system
Fourrier, Joris. "Les accélérateurs à champ fixe et gradient alterné FFAG et leur application médicale en protonthérapie". Phd thesis, Université Joseph Fourier (Grenoble), 2008. http://tel.archives-ouvertes.fr/tel-00338177.
Pełny tekst źródłaFaugier, Loreline. "Modeling airflow related to train movement in subway stations : small-scale model and numerical simulations compared to on-site measurements". Electronic Thesis or Diss., La Rochelle, 2023. http://www.theses.fr/2023LAROS022.
Pełny tekst źródłaAir quality and ventilation efficiency in underground subway stations are concerns for health and safety. The piston effect, caused by trains passing through the station, contributes significantly to air movements. Models are often used to study and predict airflow in these environments due to challenges in on-site measurements. However, the differences between measured and modeled data are rarely discussed. This thesis focuses on developing models for train-induced airflow on platforms of underground subway stations. A 3D Computational Fluid Dynamics (CFD) model with a dynamic mesh is implemented to simulate the station. A small-scale model at 1:95 scale with Particle Image Velocimetry (PIV) is also used. Both models include the train's realistic movement, deceleration, stop, and departure phases. To validate the models, extensive on-site measurements are conducted, recording velocity magnitude at various platform positions. The results are compared using correlation and peak shape parameters. They show that models can capture the key elements of piston wind in the station: both the numerical and experimental results reveal that differences can be found between locations close to each other, that are the consequence of flow features developing at a fraction of the platform scale in the horizontal plane; and that local velocity changes occur over short time intervals scaling with the train velocity. However, finer predictions about the value of velocity magnitude are less reliable as they are bounded by simplifications of the geometry, of the boundary conditions and by scaling considerations. Despite these limitations, the models provide insights into flow patterns and are used to investigate how changes in station blockage ratio and train speed affect velocity magnitude and air exchanges in the station. The study concludes that the models are valuable tools for exploring platform airflow, but caution is needed in interpreting fine-scale velocity predictions
Lanoiselée, Yann. "Revealing the transport mechanisms from a single trajectory in living cells". Thesis, Université Paris-Saclay (ComUE), 2018. http://www.theses.fr/2018SACLX081/document.
Pełny tekst źródłaThis thesis is dedicated to the analysis and modeling of experiments where the position of a tracer in the cellular medium is recorded over time. The goal is to be able to extract as much information as possible from a single experimentally observed trajectory. The main challenge is to identify the transport mechanisms underlying the observed movement. The difficulty of this task lies in the analysis of individual trajectories, which requires the development of new statistical analysis tools. In the first chapter, an overview is given of the wide variety of dynamics that can be observed in the cellular medium. In particular, a review of different models of anomalous and non-Gaussian diffusion is carried out. In the second chapter, a test is proposed to reveal weak ergodicity breaking from a single trajectory. This is a generalization of the approach of M. Magdziarz and A. Weron based on the time-averaged characteristic function of the process. This new estimator is able to identify the ergodicity breaking of continuous random walking where waiting times are power law distributed. By calculating the average of the estimator for several subdiffusion models, the applicability of the method is demonstrated. In the third chapter, an algorithm is proposed to recognize the different phases of an intermittent process from a single trajectory (e.g. active/passive transport within cells, etc.).This test assumes that the process alternates between two distinct phases but does not require any hypothesis on the dynamics of each phase. Phase changes are captured by calculating quantities associated with the local convex hull (volume, diameter) evaluated along the trajectory. It is shown that this algorithm is effective in distinguishing states from a large class of intermittent processes (6 models tested). In addition, this algorithm is robust at high noise levels due to the integral nature of the convex hull. In the fourth chapter, a diffusion model in a heterogeneous medium where the diffusion coefficient evolves randomly is introduced and solved analytically. The probability density function of the displacements presents exponential tails and converges towards a Gaussian one at long time. This model generalizes previous approaches and thus makes it possible to study dynamic heterogeneities in detail. In particular, it is shown that these heterogeneities can drastically affect the accuracy of measurements made by time averages along a trajectory. In the last chapter, single-trajectory based methods are used for the analysis of two experiments. The first analysis carried out shows that the tracers exploring the cytoplasm show that the probability density of displacements has exponential tails over periods of time longer than the second. This behavior is independent of the presence of both microtubules and the actin network in the cell. The trajectories observed therefore show fluctuations in diffusivity, indicating for the first time the presence of dynamic heterogeneities within the cytoplasm. The second analysis deals with an experiment in which a set of 4mm diameter discs was vibrated vertically on a plate, inducing random motion of the disks. Through an in-depth statistical analysis, it is demonstrated that this experiment is close to a macroscopic realization of a Brownian movement. However, the probability densities of disks’ displacements show deviations from Gaussian which are interpreted as the result of inter-disk shocks. In the conclusion, the limits of the approaches adopted as well as the future research orientation opened by this thesis are discussed in detail
Doineau, Raphaël. "Development of droplet-based microfluidic technology for high-throughput single-cell phenotypic screening of B cell repertoires". Thesis, Sorbonne Paris Cité, 2017. http://www.theses.fr/2017USPCC263/document.
Pełny tekst źródłaThe 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