Dissertations / Theses on the topic 'T-ray'
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1
Mickan, Samuel Peter. "T-ray biosensing /." Title page, table of contents and abstract only, 2003. http://web4.library.adelaide.edu.au/theses/09PH/09phm6253.pdf.
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Ferguson, Bradley Stuart. "Three dimensional T-Ray inspection systems /." Title page, Table of contents and abstract only, 2004. http://web4.library.adelaide.edu.au/theses/09PH/09phf3521.pdf.
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Meinhold, Mitchell W. 1972. "Aligned T-gate, fabrication using X-ray lithography." Thesis, Massachusetts Institute of Technology, 1996. http://hdl.handle.net/1721.1/43303.
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Thesis (M.S.)--Massachusetts Institute of Technology, Dept. of Electrical Engineering and Computer Science, 1997.Includes bibliographical references (leaves 55-56).
by Mitchell Meinhold.
M.S.
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Gregory, Scott G. "T Tauri stars : mass accretion and X-ray emission." Thesis, St Andrews, 2007. http://hdl.handle.net/10023/336.
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Köhl, Martin [Verfasser], and T. [Akademischer Betreuer] Baumbach. "Analysis of nanostructures based on diffraction of X-ray radiation / Martin Köhl. Betreuer: T. Baumbach." Karlsruhe : KIT-Bibliothek, 2014. http://d-nb.info/1065732163/34.
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Liddington, R. C. "The origins of co-operativity in haemoglobin : An X-ray analysis of the liganded T state." Thesis, University of York, 1986. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.372760.
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Lazarev, Sergey [Verfasser], and Baumbach G. [Akademischer Betreuer] T. "X-ray investigation of defects in III-nitrides and their alloys / Sergey Lazarev. Betreuer: G. T. Baumbach." Karlsruhe : KIT-Bibliothek, 2013. http://d-nb.info/1059803151/34.
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Unlu, Caglar. "Task Parallelism For Ray Tracing On A Gpu Cluster." Master's thesis, METU, 2008. http://etd.lib.metu.edu.tr/upload/12609325/index.pdf.
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Ray tracing is a computationally complex global illumination algorithm that is used for producing realistic images. In addition to parallel implementations on commodity PC clusters, recently, Graphics Processing Units (GPU) have also been used to accelerate ray tracing. In this thesis, ray tracing is accelerated on a GPU cluster where the viewing plane is divided into unit tiles. Slave processes work on these tiles in a task parallel manner which are dynamically assigned to them. To decrease the number of ray-triangle intersection tests, Bounding Volume Hierarchies (BVH) are used. It is shown that almost linear
speedup can be achieved. On the other hand, it is observed that API and network overheads are obstacles for scalability.
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Beasley, Daniel. "3D quantitative elemental mapping of biological tissues using proton induced X-ray emission tomography (PIXE-T) and on/off-axis scanning transmission ion microscopy tomography (STIM-T)." Thesis, University of Surrey, 2006. http://epubs.surrey.ac.uk/843466/.
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A novel experimental set-up was installed at the University of Surrey Ion Beam Centre for the purpose of producing 3D quantitative elemental maps of biological samples by combining simultaneous Proton Induced X-Ray Emission Tomography (PIXE- T), on/off-Axis Scanning Transmission Ion Microscopy-Tomography (STIM-T) and Rutherford Backscatter Spectrometry (RBS). A tomographic sample holder was designed and built and a scattering system developed for On/Off-Axis STIM. 2D PIXE and off-STIM analysis of leukocytes was performed to complement concurrent research and to identify problems with the very recently installed proton microbeam at the Ion Beam Centre. The other major aim was to see if a leukocyte would be a suitable sample for tomographic analysis and to study the damage induced by the beam on biological samples. Instrumental Neutron Activation Analysis (INAA) was performed on hair samples collected from MSc students at the University of Surrey and a database compiled of all elemental analysis of hair performed at the University. This complemented the tomographic analysis performed on a section of a strand of hair. Si, S, Cl, K, Ca, Fe and Zn were mapped using simultaneous PIXE-T, On/Off- Axis STIM-T and RBS.
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Weinhardt, Venera [Verfasser], and T. [Akademischer Betreuer] Baumbach. "3-D imaging based on hard x-ray grating interferometry: theory, development and application / Venera Weinhardt. Betreuer: T. Baumbach." Karlsruhe : KIT-Bibliothek, 2014. http://d-nb.info/1054397279/34.
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Marles-Wright, Jon. "Structural studies on determinants of receptor/ligand binding in the tumour necrosis factor and T cell receptor protein families." Thesis, University of Oxford, 2005. http://ora.ox.ac.uk/objects/uuid:1f6d480a-a641-4778-9ff0-ece1b2d38d5c.
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Protein-protein recognition plays a central role in the surveillance of self and non-self in the mammalian immune system and ultimately in cellular survival within the organism. Two systems of fundamental importance to the immune system are the Tumour Necrosis Factor (TNF) and the T cell receptor (TCR) families. High-throughput methods developed within the Oxford Protein Production Facility have been successfully applied to the production of members of the TNF receptor and ligand superfamilies for structural characterisation. The TNF receptor DR6 was successfully refolded from E.coli inclusion bodies using a rapid-dilution technique and yielded diffraction quality crystals. Data collected from these crystals will be used to obtain an x-ray crystallographic model of DR6. Vascular Endothelial Growth Inhibitor (VEGI) was produced as a soluble recombinant protein in E.coli, and formed a number of poorly diffracting crystals, it is hoped that further trials and optimization of conditions will lead to improved data quality. Lymphotoxin β receptor was produced in a Eukaryotic system. This has shed light on the complications posed by signal peptide cleavage and glycosylation on the production of protein for crystallization trials. TNF superfamily proteins are ideal targets for the design of novel therapeutic agents due to their involvement in a number of disease pathologies. Various methods of molecular docking and small molecule design were applied to the search for potential inhibitors of receptor binding for the TNF ligand proteins TRAIL and BAFF. A number of potential drug leads were identified from the National Cancer Institute drug database. The Natural Killer (NK) T cell restricted TCRs recognise CD1d-presented glycolipid. Determination of the crystal structures of the invariant NK TCR and the NK restricted TCRs 5E and 5B shows that these proteins adopt the canonical structures of class I MHC restricted TCRs. This suggests that the binding of CD1d-glycolipid by these receptors will conform to the same model of binding seen for the class I MHC restricted TCRs.
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Kaufholz, Marthe [Verfasser], and T. [Akademischer Betreuer] Baumbach. "Monitoring the film formation during sputter deposition of vanadium carbide by in situ X-ray reflectivity measurements / Marthe Kaufholz. Betreuer: T. Baumbach." Karlsruhe : KIT-Bibliothek, 2014. http://d-nb.info/1066736936/34.
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Tandl, Dominique [Verfasser], Gerhard [Akademischer Betreuer] Thiel, and Alexander [Akademischer Betreuer] Löwer. "X-ray irradiation triggers via ROS production a canonical Ca2+-dependent immune response in T-lymphocytes / Dominique Tandl ; Gerhard Thiel, Alexander Löwer." Darmstadt : Universitäts- und Landesbibliothek, 2021. http://d-nb.info/1228537410/34.
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Pidchenko, Ivan [Verfasser], and T. [Akademischer Betreuer] Vitova. "Characterization of structural properties of U and Pu in model systems by advanced synchrotron based X-ray spectroscopy / Ivan Pidchenko. Betreuer: T. Vitova." Karlsruhe : KIT-Bibliothek, 2016. http://d-nb.info/1100529543/34.
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Colombo, Salvatore. "Radiation hydrodynamic and magnetohydrodynamic models of plasma flows accreting onto Classical T Tour Stars." Thesis, Sorbonne université, 2019. http://www.theses.fr/2019SORUS608.
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Nous avons étudié le processus d’accrétion dans les CTTSs. D’une part, nous avons examiné la possibilité que l’accrétion du disque vers l’étoile résulte de l’activité coronale; d’autre part, nous avons analysé la structure et la dynamique du plasma de la colonne d’accrétion au niveau de l’impact sur la surface stellaire. Nous avons développé des modèles numériques qui décrivent: un système étoile – disque sous l’influence d’une activité coronale au voisinage de la surface du disque; la zone d’impact d’une colonne d’accrétion sur la surface d’une CTTS. Nous avons examiné si une activité coronale intense, créée par les éruptions au voisinage du disque d’accrétion, pouvait perturber la stabilité du disque interne, déstabiliser cette zone interne, et éventuellement déclencher des phénomènes d’accrétion à des taux d’accrétion comparables à ceux déduits des observations.Lors de notre étude de la zone d’impact de la colonne, nous avons analysé l’effet du rayonnement, produit par le plasma chauffé par le choc d’accrétion, sur la structure de la matière en chute en amont du choc. Pour cela, nous avons perfectionné un module d’hydrodynamique radiative initialement implémenté dans le code PLUTO dans l’hypothèse de l’équilibre thermodynamique local (ETL). Nous avons étendu ce module pour qu’il puisse gérer un régime hors ETL. Ensuite, nous avons étudié si la partie de la colonne d’accrétion en amont du choc pouvait absorber de façon significative le rayonnement créé par la partie de la colonne en aval du choc, de telle sorte que cela puisse créer un préchauffage de la colonne en amont du chocIn this work we investigated the mass accretion process in CTTSs. We studied if accretion from the disk to the star might occur as a result of a coronal activity, and we analyzed the structure and the dynamics of the accretion column plasma in the impact regions. We developed numerical models that describe: a star-disk system subject to the effects of a coronal activity in proximity of the disk surface; the impact of an accretion column onto the surface of a CTTS.We investigated if an intense coronal activity due to flares that occur close to the accretion disk may perturb the stability of the inner disk, disrupt the inner part of the disk, and possibly trigger accretion phenomena with mass accretion rates comparable with those observed in CTTSs. To this end, we modeled a magnetized protostar surrounded by an accretion disk through 3D magnetohydrodynamics simulations.As it concerns the study of accretion impacts, we analyzed the effects of radiation emerg-ing from the shock-heated plasma at the base of accretion columns on the structure of the pre- shock downfalling material. To this end, we upgraded a module handling the local thermodynamic equilibrium (LTE) radiation-hydrodynamics (RHD) in the PLUTO code , which we have extended to handle also the non-LTE regime. Then, we investigated if a significant absorption of radiation arising from the shock heated plasma occurs in the unshocked downfalling material, and if it leads to a pre-shock heating of the accreting gas
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Funke, Peter M. "X-Ray crystal structure of a ribosomal protein S6, S15, S18 : rRNA complex from T. thermophilus, and investigation of conformational changes in 16S rRNA fragments from B. stearothermophilus during ribonucleoprotein assembly." Thesis, Massachusetts Institute of Technology, 2012. http://hdl.handle.net/1721.1/73391.
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Thesis (S.M.)--Massachusetts Institute of Technology, Dept. of Chemistry, 2012.Cataloged from PDF version of thesis.
Includes bibliographical references (p. 74-80).
The X-ray crystallographic structure of a fragment of the 30S ribosomal subunit from Thermus thermophilus containing ribosomal proteins S6, S15, S18, and a minimal rRNA binding site (T4 RNP) containing two different three-helix junctions was solved to 2.6 A. The protein S15 contains four bundled a-helices and binds the rRNA along the minor groove of helix 22 and contacts elements of both three-helix rRNA junctions. The protein S6 contains a four-stranded [beta]-sheet buttressed by two a-helices and forms a heterodimer with S18, a poorly structured protein with both a-helices and random coil elements. The S6:S18 heterodimer binds across the helix 22, helix 23, helix 23a RNA junction and makes no direct contacts to S15. Time-resolved fluorescence resonance energy (trFRET) methods were used to assess conformational changes in both RNA three-helix junctions in separate model systems from Bacillus stearothermophilus. Helix 21 and helix 23 are shown to stack coaxially onto each end of helix 22 in the absence of either S15 or divalent magnesium ions. S15 and magnesium are both shown to stabilize a reorganization of the helix 20, helix 21, helix 22 RNA junction, whereby helix 20 rotates proximal to helix 22. Single-pair fluorescence resonance energy transfer (spFRET) methods were used to show a conformational change in individual RNA molecules in solution upon addition of either S15 or magnesium. We also observe individual subpopulations of unbound and bound RNA as we titrate S15 around the known protein dissociation constant Kd. We incorporate our structural information into a more detailed model of cooperative binding between S15 and the S6:S18 heterodimer during T4 RNP formation, and address the implica
by Peter M. Funke.
S.M.
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Kebapci, Basak. "Development Of High Performance Uncooled Infrared Detector Materials." Master's thesis, METU, 2011. http://etd.lib.metu.edu.tr/upload/12613070/index.pdf.
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This thesis reports both the optimizations of the vanadium oxide (VOx) thin film as an active infrared detector material by the magnetron sputtering deposition method and its use during fabrication of proper resistors for the microbolometers. Vanadium oxide is a preferred material for microbolometers, as it provides high TCR value, low noise, and reasonable resistance, and a number of high-tech companies have used this material to obtain state-of-the-art microbolometer arrays. This material is first used in microbolometers by Honeywell, who provides its recipe with license agreements, and there is not much information in the literature for its deposition recipe. This is the first study at METU for development of vanadium oxide thin film for microbolometers.
The VOx material deposition studies started by identifying the deposition parameters of the magnetron sputtering system in order to obtain proper VOx resistors for the readout electronics. The obtained recipe includes high temperature deposition
conditions of VOx, however, this causes a diffusion problem on the electrodes, preventing to obtain a good contact to VOx. Also, high oxygen level in the depositions makes a contamination on the electrodes. A number of studies were done to determine a proper electrode material which is proper with the deposition conditions of the VOx.
Characterization of the vanadium oxide samples is done by XRD and XPS measurements to see the relation between the phases and resistivity of the vanadium oxide. It is known that V2O5 phase provides a high TCR and resistivity value, and the XRD results show that this phase is dominant in the highly-oxygen doped or annealed resistors. The TCR and noise measurements are done using resistors implemented with the developed VOx film, after the etching processes of the both VOx and the electrodes are optimized. The contamination on the electrodes is prevented by the help of a newly designed process. The TCR measurement results show that annealing of the resistors affect the TCR values, i.e., increasing the annealing duration increases the TCR values of the resistors. Two different resistors with different deposition conditions are annealed to see the effect of annealing, where TCR results of the resistors are -0.74%/K and -0.8 %/K before annealing. The TCR values of these resistors increase to -1.6 %/K and -4.35 %K, respectively, after annealing in same conditions, showing that both the deposition conditions and annealing change the TCR significantly. Although good TCR values are obtained, the noise values of the VOx resistors are much higher than the expected values, which suggest a further study to determine the cause of this noise.
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Cnudde, Sara Elizabeth. "The x-ray crystallographic structures of the angiogenesis inhibitor angiostatin bound to a peptide from the group A streptococcal surface protein PAM and the metal-bound conantokins con-G and con-T[K7gamma]." Diss., Connect to online resource - MSU authorized users, 2007.
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Zhang, Chong. "Recovery of cerebrovascular morphodynamics from time-resolved rotational angiography." Doctoral thesis, Universitat Pompeu Fabra, 2011. http://hdl.handle.net/10803/51921.
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Over the last decade, there has been a growing interest in assessing cerebral aneurysmal wall motion, because of its potential connections to the biomechanical conditions of the vessel wall, which could eventually aid the prediction of aneurysmal rupture risk. Such quantification could provide a valid surrogate for the vascular wall status and integrity. However, the vast majority of current morphological indices used in the literature to predict growth and rupture in cerebral aneurysms do not take into account the temporal changes that occur during the cardiac cycle. This is because these indices are derived from image modalities that do not provide sufficient temporal and/or spatial resolution to obtain dynamic aneurysm information, which is expected to be similar to or below image resolution. Among currently available vascular imaging techniques, 3D rotational angiography (3DRA) and digital subtraction angiography (DSA) have the highest spatial (and temporal) resolution. Still, for a human operator relying solely on qualitative visual observation, even when using images from these modalities, to objectively analyze the small motion and shape changes of the cerebrovasculature of an individual throughout the cardiac cycle is difficult, if not impossible. Therefore, the availability of a robust morphodynamic analysis tool is needed. In this context, this thesis focuses on developing techniques to estimate, quantify and analyze cerebrovascular wall motion, particularly aneurysmal wall motion, using such modalities. The main contributions of the thesis are: 1) a first methodology to estimate and model patient-specific cerebrovascular morphodynamics over one cardiac cycle, through a proposed multiple 2D to 3D image registration framework; 2) an extension of this methodology to provide robust and efficient estimates of cerebrovascular wall motion for clinical evaluation and for further biomechanical modeling of the cerebrovascular wall; 3) a patient study that demonstrates the validity of the developed techniques from clinical practice, through an analysis of 3DRA and DSA images. Each of these contributions is published in or submitted to a peerreviewed international journal.Durante la última década se ha dado un creciente interés en la evaluación del movimiento de la pared vascular en aneurismas cerebrales. Éste hecho ha sido motivado en gran medida por la relación existente entre dicha motilidad y sus condiciones biomecánicas, pudiendo éstas llegar a ser útiles en la predicción del riesgo de ruptura del aneurisma cerebral analizado. De este modo, de ésta cuantificación, se podría llegar a derivar un indicador indirecto del estado e integridad de la pared vascular. Sin embargo, la gran mayoría de los índices morfológicos utilizados en la actualidad para predecir crecimiento y ruptura de aneurismas cerebrales no consideran los cambios que se producen en el tiempo a lo largo del ciclo cardíaco. Esto se debe a que dichos índices se obtienen a partir de modalidades de imagen que no proporcionan suficiente resolución espacial y/o temporal para obtener información dinámica del aneurisma, cuyo rango de variación se espera sea similar o inferior a la resolución de la imagen. Entre las técnicas de imagen vascular disponibles en la actualidad, la angiografía rotacional 3D (3DRA) y la angiografía de substracción digital (DSA) son las que ofrecen la mayor resolución espacial (y temporal). De todos modos, aún utilizando imágenes de estas modalidades, el análisis objetivo de pequeñas diferencias de forma y movimiento en los vasos cerebrales de un individuo a lo largo de un ciclo cardíaco es difícil, si no imposible para un operador humano utilizando únicamente medidas cualitativas guiadas por inspección visual. Por lo tanto, la disponibilidad de herramientas robustas para el análisis morfodinámico de la vasculatura cerebral resulta necesaria. En este contexto, la investigación de esta tesis se concentra en el desarrollo de técnicas para estimar, cuantificar y analizar el movimiento de las paredes de los vasos cerebrales, con particular énfasis en el movimiento de la pared en aneurismas, utilizando las modalidades indicadas anteriormente. En líneas generales, esta tesis presenta tres contribuciones principales: 1) una primera metodología de estimación y modelado morfodinámico de vasos cerebrales a lo largo de un ciclo cardíaco, utilizando una técnica de registrado de imágenes 2D-3D; 2) una metodología extendida para proporcionar una estimación robusta y eficiente del movimiento de las paredes de los vasos cerebrales para su evaluación clínica y posterior modelado biomecánico de dichas paredes; 3) un estudio sobre una población de pacientes que demuestra la validez de las técnicas desarrolladas en la práctica clínica, a través del análisis en imágenes de 3DRA y DSA. Cada una de estas contribuciones ha sido publicada o se encuentra en fase de revisión en revistas internacionales indexadas.
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Cavarelli, Jean. "Etude cristallographique d'un complexe nucleoproteique forme entre l'aspartyl-trna synthetase de levure et l'acide ribonucleique de transfert specifique de l'acide aspartique." Strasbourg 1, 1987. http://www.theses.fr/1987STR13160.
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Smila-Castro, Ornella. "X-ray absorption spectroscopy studies of electrochemical processes." Thesis, University of Birmingham, 2012. http://etheses.bham.ac.uk//id/eprint/3766/.
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Electron transfer is a key part of many chemical, biological and physical processes, that is commonly studied by electrochemical methods, which give insight into reaction mechanisms but no structural information. It is necessary to combine electroanalysis with another technique to gain essential knowledge of metal-ligand bond length and oxidation states. X-ray absorption spectroscopy (XAS) can provide these data for species in dilute solution and, if combined with electrochemistry, could potentially provide powerful insight into electron transfer reactions. This dissertation describes the development and application of techniques for the study of electrochemical intermediates by XAS. Chapters 2 and 3 introduce the theory and practice of electrochemistry and spectroscopy with emphasis on XAS. Chapter 4 describes the development of variable-temperature spectroelectrolysis cells for the study of electrochemical intermediates. In Chapter 5, the electrochemical behaviour of Cp\( \ast \)Rh(CO)\(_2\), is investigated as an organometallic compound representative of the redox chemistry studied in this thesis. Chapter 6 describes a new approach to the study of electrochemical intermediates in which a miniature electrolysis cell is combined with a microdispenser so that electrochemical intermediates can be generated and then dispensed, quenched at low temperature prior to study by XAS. Chapter 7 contains final conclusions.
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Rodríguez, Sanmartín Daniel. "Smart piezoelectric devices for X-ray optics applications." Thesis, University of Birmingham, 2011. http://etheses.bham.ac.uk//id/eprint/3193/.
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The development of active/adaptive X-ray optics, utilising piezoelectric actuation for the focussing of X-rays in large and small scale applications, has been studied as part of the UK Smart X-Ray Optics (SXO) consortium. For laboratory based X-ray sources utilising micro structured optical arrays (MOAs), a novel spider actuator structure, compatible with silicon wet etching of MOAs, has been developed. Test spider samples (20x20x0.100mm) have been bent to a 6.5cm radius using unimorph actuators, and to a 3cm radius without failure. FEA models predicted that a 4.5cm radius and +/-3mrad tip/tilt control of the MOAs could be obtained using unimorph actuators with segmented electrodes and optimized thickness, which would enable a tandem pair MOA configuration of suitable focal length. A first generation prototype Wolter I optic for future high resolution X-ray telescopes exhibited kinks in the reflecting surface corresponding to the gaps between piezoelectric devices. FEA models have been used to develop second generation prototypes in which the gaps have been minimised or filled. These incorporate a brick wall arrangement of curved unimorph piezoelectric actuators (32x75x0.190mm) with radii from 160-200mm +/-6mm, manufactured using a VPP technique and laser machining for precise dimensional control. Keywords: Smart X-ray optics (SXO), micro-structured optical arrays (MOAs), Wolter I X-ray optics, piezoelectric actuators, finite element analysis (FEA), viscous plastic processing (VPP).
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Powrie, Fiona Margaret. "Functional analysis of rat T cell subsets." Thesis, University of Oxford, 1989. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.238190.
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Mi, Na. "Synchrotron X-ray studies of atmospheric pitting corrosion of stainless steel." Thesis, University of Birmingham, 2013. http://etheses.bham.ac.uk//id/eprint/4558/.
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Atmospheric pitting corrosion of stainless steel was studied to determine pit growth mechanisms and kinetics. Inkjet printing of chloride was used to investigate the growth of atmospheric corrosion pits. It has been shown that the pit size increases with increasing chloride deposition density, as well as increases with increasing deposit diameter. Atmospheric pit growth was characterised in situ and in real time with synchrotron X-ray microtomography. Most pits were found to have open mouths and shallow depths. Growth of a deep pit was also observed in a pre-existing defect. Pit growth in depth does not appear to be under diffusion control. Electrochemical kinetics of the metal dissolution reaction including the Tafel slope as well as the critical metal ion concentration for pit propagation were studied with lD artificial pits in high chloride concentration solutions relevant to atmospheric conditions. The diffusion-limited current density and ratio of the critical metal ion concentration for pit propagation to the saturation concentration were found to decrease with increasing chloride concentration. However, there is no significant effect of the chloride concentration on the Tafel slope. The pitting potential and repassivation potential were measured on abraded wires and were found to decrease with increasing chloride concentration. Salt layer formation has been observed on ID artificial pits in 1 M and 6 M solutions with synchrotron XRD. The dominant phase of the salt layer was found to be FeCl\(_2\)•4H\(_2\)0. The formation of FeCl\(_2\)•2H\(_2\)0 was also observed, predominantly at higher applied potentials. This work can be used to provide a basis for developing a model to predict pitting corrosion of stainless steel under atmospheric corrosion conditions, for example in the case of storage of stainless steel intermediate nuclear waste containers.
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Crocker, Glenn. "A study of surface receptors on rat T lymphocytes." Thesis, University of Oxford, 1991. http://ora.ox.ac.uk/objects/uuid:5c74a70b-1f5e-4c78-904f-7c4ff1b543a8.
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A double immunolabelling technique was developed to study microscopically the interactions between CD4, CD45 and the T cell receptor on the surface of rat T cells induced by the phenomenon of co-capping. It was found that both CD4 and CD45 passively co-cap with the actively capped T cell receptor, that the T cell receptor and CD45 passively co-cap with CD4, but that neither CD4 nor the T cell receptor co-cap with CD45. Co-crosslinking and active capping of CD45 with either the T cell receptor or CD4 prevented CD4 or the T cell receptor respectively, from passively co-capping. These experiments were extended to study the effects of particular antibody crosslinking conditions on T cell proliferation and tyrosine phosphorylation. A correlation was found to exist between receptor distribution and the effects of particular antibody combinations on proliferation and tyrosine phosphorylation. The significance of this with respect to T cell activation is discussed. Finally, an observation is reported concerning the failure of some cell lines to cap antibody-crosslinked surface molecules. Preliminary investgations into the nature and extent of the phenomenon are described.
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Law, Deborah Ann. "The role of the CD2 antigen in T-lymphocyte interactions." Thesis, University of Oxford, 1989. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.236192.
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Arthur, R. P. "In vitro functional studies of rat T helper cell heterogeneity." Thesis, University of Oxford, 1985. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.355759.
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Hernández-Hoyos, Gabriela. "Studies of the T cell lineage in the BB rat." Thesis, University of Cambridge, 1996. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.627489.
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Ghahari, Seyed Majid. "In situ synchrotron x-ray characterisation and modelling of pitting corrosion of stainless steel." Thesis, University of Birmingham, 2012. http://etheses.bham.ac.uk//id/eprint/3269/.
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Pit propagation in stainless steels under electrochemical control was investigated using in situ synchrotron X-ray microtomography, which was used to confirm that the lacy covers commonly found for pits in stainless steels grow through perforation of the metal surface by upward growth of rapidly dissolving lobes from the main pit. In situ synchrotron X-ray radiography has been used to observe the evolution of 2D pits growing at the edge of stainless steel foils under electrochemical control in chloride solutions. Pit growth shape, kinetics and stability under current and potential control at various bulk chloride concentrations have been studied. It was found that the pit depth tends to grow under diffusion control, whereas lateral development is influenced by solution conductivity. The impact of the perforated cover on the pit growth and stability was examined and its formation was found to be similar to the observations from 3D by X-ray microtomography. A method for extracting the key dissolution kinetic parameters from radiographs has been developed. The local anodic current density along the boundary of a pit was directly measured from the rate of advance of the pit into the metal. Then the local metal ion concentration and potential drop inside the pit cavity was back-calculated using transport equations and the requirement to maintain charge neutrality, establishing the relationship between local current density, interfacial potential and metal ion concentration in the solution. The predictive model for pit propagation in stainless steel developed by Laycock and co-workers was examined, its sensitivity to key growth parameters was evaluated, and a modified version of the model was developed based on the kinetic parameters extracted from the radiographic measurements.
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Vanpeene, Victor. "Étude par tomographie RX d'anodes à base de silicium pour batteries Li-ion." Thesis, Lyon, 2019. http://www.theses.fr/2019LYSEI023/document.
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De par sa capacité spécifique théorique dix fois plus élevée que celle du graphite actuellement utilisé comme matériau actif d'anode pour les batteries Li-ion, le silicium peut jouer un rôle important dans l'augmentation de la densité d'énergie de ces systèmes. La réaction d'alliage mise en place lors de sa lithiation se traduit cependant par une forte expansion volumique du silicium (~300 % contre seulement ~10 % pour le graphite), conduisant à la dégradation structurale de l'électrode, affectant notablement sa tenue au cyclage. Comprendre en détail ces phénomènes de dégradation et développer des stratégies pour limiter leur impact sur le fonctionnement de l'électrode présentent un intérêt indéniable pour la communauté scientifique du domaine. L'objectif de ces travaux de thèse était en premier lieu de développer une technique de caractérisation adaptée à l'observation de ces phénomènes de dégradation et d'en tirer les informations nécessaires pour optimiser la formulation des anodes à base de silicium. Dans ce contexte, nous avons utilisé la tomographie aux rayons X qui présente l'avantage d'être une technique analytique non-destructive permettant le suivi in situ et en 3D des variations morphologiques s'opérant au sein de l'électrode lors de son fonctionnement. Cette technique a pu être adaptée à l'étude de cas du silicium en ajustant les volumes d'électrodes analysés, la résolution spatiale et la résolution temporelle aux phénomènes à observer. Des procédures de traitement d'images adéquates ont été appliquées afin d'extraire de ces analyses tomographiques un maximum d'informations qualitatives et quantitatives pertinentes sur leur variation morphologique. De plus, cette technique a pu être couplée à la diffraction des rayons X afin de compléter la compréhension de ces phénomènes. Nous avons ainsi montré que l'utilisation d'un collecteur de courant 3D structurant en papier carbone permet d'atténuer les déformations morphologiques d'une anode de Si et d'augmenter leur réversibilité en comparaison avec un collecteur de courant conventionnel de géométrie plane en cuivre. Nous avons aussi montré que l'utilisation de nanoplaquettes de graphène comme additif conducteur en remplacement du noir de carbone permet de former un réseau conducteur plus à même de supporter les variations volumiques importantes du silicium. Enfin, la tomographie RX a permis d'étudier de façon dynamique et quantitative la fissuration et la délamination d'une électrode de Si déposée sur un collecteur de cuivre. Nous avons ainsi mis en évidence l'impact notable d'un procédé de "maturation" de l'électrode pour minimiser ces phénomènes délétères de fissuration-délamination de l'électrodeBecause of its theoretical specific capacity ten times higher than that of graphite currently used as active anode material for Li-ion batteries, silicon can play an important role in increasing the energy density of these systems. However, the alloying reaction set up during its lithiation results in a high volume expansion of silicon (~300% compared with only ~10% for graphite) leading to the structural degradation of the electrode, which is significantly affecting its cycling behavior. Understanding in detail these phenomena of degradation and developing strategies to limit their impact on the functioning of the electrode are of undeniable interest for the scientific community of the field. The objective of this thesis work was first to develop a characterization technique adapted to the observation of these degradation phenomena and to draw the necessary information to optimize the formulation of silicon-based anodes. In this context, we have used X-ray tomography which has the advantage of being a non-destructive analytical technique allowing in situ and 3D monitoring of the morphological variations occurring within the electrode during its operation. This technique has been adapted to the case study of silicon by adjusting the analyzed electrode volumes, the spatial resolution and the temporal resolution to the phenomena to be observed. Appropriate image processing procedures were applied to extract from these tomographic analyzes as much qualitative and quantitative information as possible on their morphological variation. In addition, this technique could be coupled to X-ray diffraction to complete the understanding of these phenomena. We have shown that the use of a carbon paper structuring 3D current collector makes it possible to attenuate the morphological deformations of an Si anode and to increase their reversibility in comparison with a conventional copper current collector of plane geometry. We have also shown that the use of graphene nanoplatelets as a conductive additive to replace carbon black can form a conductive network more able to withstand the large volume variations of silicon. Finally, the X-ray tomography allowed studying dynamically and quantitatively the cracking and delamination of an Si electrode deposited on a copper collector. We have thus demonstrated the significant impact of a process of "maturation" of the electrode to minimize these deleterious phenomena of cracking-delamination of the electrode
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Dorneles, Cristina Manera. "Tomografia computadorizada de t?rax em crian?as : podemos fazer um exame com a dose semelhante a de um raio x de t?rax e sem anestesia?" Pontif?cia Universidade Cat?lica do Rio Grande do Sul, 2016. http://tede2.pucrs.br/tede2/handle/tede/7688.
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Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior - CAPES
Objective: To evaluate the technical quality of low-dose computed tomography without contrast and without the use of anesthesia in the diagnosis of lung diseases in children Materials and Methods: It reviewed 86 chest CT scans performed due to clinical indications of acute or chronic inflammatory lung diseases, cancer or congenital malformations in patients from 1 to 18 years of age who were subjected to a low dose of radiation dose bellow the dose recommended by the ALARA and using interactive image reconstruction filters performed without the use of anesthesia or sedation. The exams will be evaluated by two reviewers and age, gender, the radiation dose, image quality and image noise will be assessed. Image analysis will be quantitative. The variables will be the outside Roi diameter of trachea divided by the Roi of trachea, the percentage of axial images with motion artifacts, and identification of the tracheal, the main and segmental bronchi? 20 segments, the main and lobar pulmonary arteries and the ascending aorta artery. The presence of pleural effusion and the identification of paratracheal and subcarinal lymph node chains will also be assessed. Data will be analyzed by for mean, standard deviation and the correlation of the data will be analyzed by tests of Pearson and Spearman, considering significant a p<0.05. Results: The average age of the patients was 5.5 years. LSD as well with the LID, LSE and LIE were displayed in all tests. The middle lobe in almost all (n = 85) apical segment and the medial basilar segment were seen in almost all of the scans (n = 84). The aorta and pulmonary arteries were distinguished on all tomography examinations. The percentage of images with motion artifact introduced an average of 0.8 with IC: 0-2.9 (P25-P75) with p < 0.001. The noise of the image showed an average of 45.5 with 12.4DP. How much ROI the trachea and main bronchi were seen in all the CT scans. The image quality was considered excellent and blurring that didn't compromise the evaluation in almost all the tests. The DLP in mGy dose presented an average of 27.5 with DP ? 11.1. Conclusion: The dose used was significantly lower than the one used in children and allowed the visualization of lung structures in almost all patients, enabling the final diagnosis of cystic fibrosis, bronchiolitis and congenital malformations without difficulty of diagnosis by image artifact
Objetivo: Avaliar a qualidade t?cnica da Tomografia Computadorizada de baixa dose sem contraste e sem anestesia no diagn?stico de doen?as pulmonares em crian?as e adolescentes. Materiais e m?todos: Estudo descritivo retrospectivo em que foram analisadas 86 Tomografias Computadorizadas de t?rax em pacientes pedi?tricos e adolescentes. Os exames foram realizados por indica??o clinica de suspeita de patologias pulmonares com baixa dose de radia??o e com filtro de reconstru??o interativa da imagem sem uso de anestesia ou seda??o. Estes exames foram analisados por dois avaliadores independentes e as vari?veis medidas foram idade, o sexo, a dose de radia??o, a qualidade da imagem, o ru?do de imagem, o ROI externo dividido pelo um ROI na traqueia, identifica??o da traqueia, dos br?nquios principais e segmentares-20 segmentos , das art?rias pulmonares principais e lobares, aorta ascendente, presen?a de derrame pleural, cadeias linfonodais paratraqueais e subcarinal Todas as imagens tamb?m foram medidas quanto a artefato de movimento e foram descritos em porcentagem comparando com o total de imagens. Os dados foram analisados com m?dia, desvio padr?o. Para a an?lise da correla??o foram usados os ?ndices de Pearson e de Spearman considerando um p < 0,01 como significativo. Resultados: A visualiza??o da traqueia e dos br?nquios principais foi poss?vel em 100% dos exames. Os linfonodos paratraqueais e os subcarinais foram visto em todos os exames na bronquiolite e na malforma??o cong?nita. Os lobos superior, m?dio e inferior direito foram visualizados na totalidade das Tomografias Computadorizadas com baixa dose de radia??o nos pacientes com fibrose c?stica e bronquiolite. Na malforma??o cong?nita os lobos superior e inferior direitos foram visualizados em todos exames. Os lobos superior e inferior esquerdos foram identificados em todas as an?lises por TC. Os segmentos apicais foram vistos em 100% das imagens na FC, BO e malforma??o cong?nita.O segmento basilar apical foi visto em todas as imagens na FC. As art?rias aorta e pulmonar foram distinguidas no total dos exames Em nenhum exame houve comprometimento da qualidade da imagem. Na malforma??o cong?nita a percentagem de imagem com excelente qualidade e borramento leve sem comprometimento da avalia??o foram encontradas em todos os exames tomogr?ficos. A porcentagem de artefato de imagem foi de 0,3% na fibrose c?stica, 1,3 % na bronquiolite e 1,1% na malforma??o cong?nita. Conclus?o A dose utilizada foi significativamente menor do que a utilizada em crian?as e permitiu a visualiza??o das estruturas pulmonares em quase todos os pacientes possibilitando o diagn?stico final da fibrose c?stica, da bronquiolite e das malforma??es cong?nitas sem dificuldade de diagn?stico por artefato de imagem.
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Wiefelspütz, Achim [Verfasser]. "Frequenzevaluation von Ras- und Influenza-spezifischen T-Zellen bei Pankreaskarzinompatienten / Achim Wiefelspütz." Berlin : Medizinische Fakultät Charité - Universitätsmedizin Berlin, 2009. http://d-nb.info/1023581000/34.
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Catchpole, Brian. "Antigen presentation to autoreactive T cells in experimentally-induced arthritis in the rat." Thesis, Royal Veterinary College (University of London), 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.314347.
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CASTEDO, MARIA(DOLORES. "Fonction des cellules t cd4#+ autoreactives dans deux modeles d'autoimmunite chez le rat." Paris 7, 1993. http://www.theses.fr/1993PA077234.
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Nous avons etudie le role de cellules t cda#+ autoreactives dans deux modeles de desordres immuns induits chez le rat: 1) l'un, specifique d'organe, induit par immunisation de rats shr avec de la renine de souris emulsionnee dans de l'adjuvant de freund, est caracterise par la production d'autoanticorps anti-renine et par l'apparition d'une nephrite interstitielle, 2) l'autre, induit par des toxiques (hgcl#2 ou sels d'or), est caracterise par une maladie systemique de type lupus, autoregulee, chez le rat bn, et par une immunosuppression non specifique mediee par des cellules t cd8#+ chez le rat lewis. De l'ensemble de ces travaux, il ressort que des cellules t autoreactives qui produisent des cytokines de type th2 peuvent cooperer avec des lymphocytes b syngeniques de rat shr naif pour induire une reponse specifique d'un autoantigene (autoimmunite anti-renine). Ceci implique que les lymphocytes b anti-renine presentent spontanement des peptides de la renine aux cellules t. De meme, des cellules t autoreactives de type th2 sont a l'origine d'une activation polyclonale chez le rat bn expose a des toxiques. L'emergence de cellules de type th1 joue un role preponderant dans la generation de cellules cytotoxiques specifiques d'alloantigenes chez les rats bn lors de la phase de remission, et dans l'emergence de cellules suppressives cd8#+ chez le rat lewis injecte avec hgcl#2
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Green, Harry M. Bjorkman Pamela Jane. "Novel methods for studying Ras/Erk MAP kinase signaling in developing T cells /." Diss., Pasadena, Calif. : Caltech, 2006. http://resolver.caltech.edu/CaltechETD:etd-10242005-165226.
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Fujiki, Masato. "Induced Tolerance to Rat Liver Allografts Involves the Apoptosis of Intragraft T Cells and the Generation of CD4[+]CD25[+]Foxp3[+] T Regulatory Cells." Kyoto University, 2011. http://hdl.handle.net/2433/142102.
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Xystrakis, Emmanuel. "Caractérisation des réponses alloréactives des lymphocytes T séparés en fonction de l'expression de l'antigène CD45RC : rôle potentiel dans l'allogreffe de moelle osseuse." Toulouse 3, 2004. http://www.theses.fr/2004TOU30002.
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Trinquand, Amélie. "Leucémies Aigues Lymphoblastiques T et signalisation TCR." Thesis, Sorbonne Paris Cité, 2015. http://www.theses.fr/2015PA05S008.
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Les Leucémies Aigues Lymphoblastiques T (LAL-T) sont des hémopathies malignes causées par la prolifération de cellules immatures T bloquées à un stade donné de leur différenciation. Leur oncogenèse est multigénique. Une anomalie de type A (à l’origine du blocage de différenciation) ainsi que des anomalies de type B (gains de fonctions de type prolifération, métabolisme, résistance à l’apoptose…) sont souvent retrouvées chez le même patient. Ces leucémies reproduisent individuellement les différentes étapes de la maturation thymique humaine. En fonction de l’immunogénétique (phénotype et réarrangement des loci des TCR), 3 groupes de LAL-T sont ainsi identifiables : les LAL-T immatures (correspondant aux formes non T-restreintes), les LAL-T corticales (bloquées autour de la b-sélection) et les LAL-T matures TCR/CD3+. Mon travail de thèse a consisté à déterminer à quel point l’activation et la signalisation du TCR pouvaient être impliquées dans la biologie de cette hémopathie. Nous avons utilisé le modèle transgénique Marilyn TCR-HY et montré in vitro (lignée TLX+) et in vivo (modèle de leucémogénèse TEL-JAK2) que l’activation du TCR par la reconnaissance de son peptide spécifique (DBY, peptide présent uniquement dans les souris mâles) empêche le développement et le maintien de la leucémie. L'induction de la signalisation du TCR par des anticorps monoclonaux dirigés contre la chaîne de signalisation CD3e (anti-CD3e humain, OKT3 ; anti-CD3e murin, 145-2C11) entraîne également une mort massive des cellules leucémiques en induisant un programme d'expression génique et de phosphoproteomique ressemblant à la sélection négative thymique. In vitro dans des LAL-T primaires, la stimulation du complexe CD3/TCR par un anticorps anti-CD3 entraîne la mort cellulaire des LAL-T CD3/TCR+ et non des TCR/CD3- quelque soit leur mécanisme oncogénétique sous-jacent. Finalement, le traitement anti-CD3 in vivo empêche la leucémogenèse chez les souris transplantées avec des LAL-T murines et humaines. Ces données fournissent un fort rationnel en faveur d’une thérapie ciblée, basée sur le traitement anti-CD3 des LAL-T matures CD3/TCR+. Ce travail démontre aussi que des étapes-clés du développement (comme la sélection négative) peuvent être des cibles thérapeutiques et sont actionnables malgré l’accumulation d’altérations géniques et épigénétiques dans les cellules cancéreuses. Par ailleurs, j’ai étudié la fréquence et l’impact pronostique des anomalies de la signalisation du TCR/pré-TCR dans une grande série protocolaire de LAL-T de l’adulte (GRAALL-2003 et -2005). Les voies de prolifération RAS/MAPK et PI3K/PTEN/AKT participent à la signalisation du TCR/pré-TCR et ont été rapportées comme dérégulées dans des séries de LAL-T pédiatriques. Dans notre série, j’ai identifié des délétions/mutations perte de fonction de PTEN (12 %) ou des mutations activatrices de KRAS/N-RAS (11%) montrant que les anomalies du pré-TCR/TCR sont fréquentes dans les LAL-T puisqu’elles sont retrouvées dans 23% des cas. Les anomalies de RAS/PTEN sont associées à un pronostic défavorable. Leur impact pronostique en fonction du statut mutationnel NOTCH1/FBXW7 (N/F) a également été étudié et montre que les anomalies de RAS/PTEN abrogent le bon pronostic des mutations N/F. Ce travail permet de proposer une classification oncogénétique basée sur les anomalies de N/F et RAS/PTEN. Cette classification définit les patients de bas risque comme ceux ayant N/F muté mais sans anomalie de RAS et PTEN (51 %) et les hauts risques qui regroupent tous les autres patients (49 %). Cette classification oncogénétique est dorénavant utilisée dans le nouveau protocole GRAALL-2014 des LAL-T de l’adulteT-cell acute lymphoblastic leukemias (T-ALL) are rare lymphoid neoplasms characterized by the proliferation of T lymphoblasts arrested at specific stages of maturation. Leukemic transformation of maturating thymocytes is caused by a multistep pathogenesis involving numerous genetic abnormalities that drive normal T cells into uncontrolled cell growth and clonal expansion. Depending on immunogenetic, T-ALLs are classified in 3 groups: immature, cortical (blocked around b-selection) and mature (CD3/TCR+) T-ALL. My work was to determine if activation and TCR signalling are involved in the biology of this disease. We demonstrate in T-ALL that, irrespective of the complex oncogenic abnormalities underlying tumor progression, experimentally induced, persistent TCR signalling has anti-leukemic properties and enforces a molecular and phosphoproteomic program resembling thymic negative selection, a major developmental event in normal T cell development. Using mouse models of T-ALL, we show that induction of TCR signalling by high affinity self-peptide/MHC or treatment with monoclonal antibodies to the CD3e chain (anti-CD3) causes massive leukemic cell death. Importantly, anti-CD3 treatment hampered leukemogenesis in mice transplanted with either mouse or patient-derived T-ALLs. These data provide a strong rationale for targeted therapy based on anti-CD3 treatment of TCR-expressing T-ALL patients and demonstrate that endogenous developmental checkpoint pathways are amenable to therapeutic intervention in cancer cells. Besides, I studied frequency and prognostic impact of anomalies concerning pre-TCR/TCR signalling in a large cohort of adult T-ALL included in GRAALL trials. RAS/MAPK and PI3K/PTEN/AKT pathways are involved in pre-TCR/TCR signalling and are reported as deregulated in pediatric T-ALL. I identified deletion/mutation loss-of-function of PTEN (12%) and activating mutations of KRAS/N-RAS (11%) in 23% of patients. These anomalies predict poor outcome and abrogate the good prognosis of NOTCH1/FBXW7 mutations. We proposed a purely genetic stratification of patients based on N/F/RAS/PTEN status, identifying low-risk patients (51%) with N/F mutations without RAS/PTEN anomalies and high-risk patients (49%) composed by the remaining cohort. This stratification will be used for the next protocol of adult-T-ALL
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Lanzarotti, Nina. "Régulation de la réponse immunitaire T par l’apoptose et hyperactivation de la voie RAS." Thesis, Paris 5, 2014. http://www.theses.fr/2014PA05T038/document.
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L'apoptose lymphocytaire joue un rôle essentiel dans le contrôle de la réponse immunitaire et de la prolifération cellulaire. De nombreuses voies interviennent dans sa régulation, dont certaines dépendantes de l’oncogène RAS. Un défaut d'apoptose lymphocytaire induit l'apparition de maladies auto-immunes et lympho-prolifératives comme l'Autoimmune LymphoProliferative Syndrome (ALPS). L'ALPS fait suite à des anomalies du principal récepteur membranaire de mort FAS, pivot de l'apoptose lymphocytaire. Le RAS-Associated Lymphoproliferative Disease (RALD) est une entité décrite récemment, se rapprochant de l'ALPS par la symptomatologie et la physiopathologie sous-jacente. Cependant, dans le RALD, le défaut d'apoptose lymphocytaire n’est pas lié à des mutations de FAS mais à une hyperactivation de la voie RAS, mettant ainsi en lumière le rôle essentiel de cette voie dans la régulation du processus en question. Dans les Leucémies Myélo-Monocytaires Juvéniles Chroniques (JMML), les mêmes mutations que celles observées dans les RALD sont trouvées, sur les mêmes populations cellulaires. Il existe une hétérogénéité clinique et biologique au sein des JMML, certaines étant indolentes (LS-JMML) et d'autres sévères (S-JMML). A cette hétérogénéité au sein même des JMML s'ajoute celle observée entre JMML et RALD. L'objectif de ce travail a été de comprendre les tenants des différences phénotypiques observées, au travers du scope de l'apoptose des lymphocytes T activés, en comparant les trois entités résultant de mutations activatrices de RAS dans des cellules pluripotentes hématopoïétiques : RALD, LS-JMML et S-JMML. Nous rapportons des conséquences distinctes pour des mutations identiques ou équivalentes, avec différentes voies de l'apoptose touchées, différenciant les phénotypes induits. Ce travail a permis de démontrer que l’hyperactivation de la voie RAS seule n’entraîne pas nécessairement une dérégulation de la réponse immunitaire T. Des événements additionnels aux mutations présentes sont nécessaires au développement des symptômes. Ces événements ont bien des conséquences sur l'apoptose lymphocytaire, au niveau post-traductionnel, qu’ils concernent la voie RAS ou non. Les différences observées entre les trois phénotypes sur le plan expérimental pourraient être une aide au pronostic. De plus, ce travail ouvre la voie à l'identification en détails des facteurs additionnels et voies défaillantes et permettrait ainsi d'obtenir des thérapeutiques spécifiques actuellement inexistantesLymphocytes apoptosis is essential in maintaining homeostasis and avoiding abnormal proliferation. When defective, autoimmune diseases as the Autoimmune LymphoProliferative Syndrome (ALPS), due to mutations of the death receptor FAS, can occur. Several pathways are important actors influencing the apoptosis cascade, including the RAS proto-oncogene signaling. The RAS Associated Lymphoproliferative Disease (RALD) is a newly described entity, similar to ALPS but with RAS mutations instead of FAS mutations, enlightening the primary role of RAS in apoptosis regulation. Interestingly, the same RAS mutations as observed in RALD are also the cause of a malignant proliferation, the Juvenile Myelo Monocytic Leukemia (JMML). In the case of JMML, RAS mutations can lead either to a mild (LS-JMML) or a severe (S-JMML) phenotype. Thus, three different phenotypes can be caused by the same oncogenic RAS mutations. In order to better understand and characterize the influence of oncogenic RAS mutations in lymphocytes’ apoptosis we studied it in patients presenting with RALD, LS-JMML and JMML. We showed that isolated RAS hyperactivity is not sufficient to induce an immune deregulation. Additional factors are required to do so. These factors influence both mitochondrial and extrinsic apoptosis pathways at a post-transcriptional level. They are due to probable genetic events, and their identification can lead to new therapeutic strategies. Furthermore, activated lymphocytes’ in vitro apoptosis assessment can help differentiating the three phenotypes and thus facilitate prognosis prediction
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Oliveira, Marinez Josefina Casarotto de. "Desenvolvimento de t?cnica de resson?ncia nuclear magn?tica r?pida e de respira??o livre em pacientes com fibrose c?stica." Pontif?cia Universidade Cat?lica do Rio Grande do Sul, 2017. http://tede2.pucrs.br/tede2/handle/tede/7760.
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Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior - CAPES
Introduction-objective: Cystic fibrosis is the most common genetic disease in the Caucasian population. The reduction in life expectancy is due to progressive lung disease, characterized by severe changes in the pulmonary structure, more precisely, bronchiectasis and air catabolization. Computed tomography of the chest is considered the most sensitive method to monitor lung disease in cystic fibrosis. The main disadvantage is the patient's exposure to radiation. Magnetic resonance imaging of the chest, a radiation-free technique, has been introduced as an alternative to computed tomography. Magnetic resonance has been compared to computed tomography in several studies using various sequences, but none have used the combined sensing, parallel imaging, and golden-angle radial sampling technique. The aim of this study was to evaluate the combined golden-angle radial technique of magnetic resonance imaging in patients with cystic fibrosis in relation to conventional magnetic resonance imaging and computed tomography of the chest. Cystic fibrosis has been compared to computed tomography in several studies using various sequences, but none have used the combined sensing, parallel imaging, and golden-angle radial sampling technique. The aim of this study was to evaluate the combined radial-angle golden-angle technique of magnetic resonance imaging in patients with cystic fibrosis in relation to conventional magnetic resonance imaging and computed tomography of the chest. Methods: Computed tomography and magnetic resonance of the chest were performed in 29 patients with cystic fibrosis who were followed at the pediatric pulmonology outpatient clinic of the S?o Lucas Hospital of the Pontifical Catholic University of Rio Grande do Sul. The Cartesian K-space sampling and, after the free-breathing magnetic resonance techniques, using the Golden_Angle Radial Sparse Parallel technique. Magnetic resonance imaging and computed tomography of the chest were evaluated by two independent observers using the Helbich-Bhalla score. Intraclass correlation coefficient and Bland-Altman analysis were used to assess agreement and reproducibility in the Helbich-Bhalla severity score. No patient was sedated or used contrast medium. Results: Intraclass correlation coefficients and the Bland-Altman graphical model between the Helbich-Bhalla scores and the evaluated methods, computed tomography, magnetic resonance and free breating magnetic resonance , showed very strong correlations in all comparisons of the total scores (ICCCT -RM = 97%, ICCCT-FB-RM = 96% and ICCCT-FB-RM = 99%). The association of the Helbich-Bhalla score of both computed tomography and magnetic resonance with pulmonary function tests were significant, mainly in relation to the severity of bronchiectasis and thickening of the bronchial walls. Conclusion: This study demonstrated that the new technique of free-breathing magnetic resonance and combination of compressed sensing, parallel imaging and radial golden-angle sampling, showed a good concordance with computed tomography in the assessment of pulmonary alterations in cystic fibrosis. The combined golden-angle radial technique can be used in clinical practice to monitor fibrocystic lung disease, and demonstrates particular value for patients who can not hold their breath during the examination.
Introdu??o-objetivo: Fibrose c?stica ? a doen?a gen?tica mais comum na popula??o caucasiana. A redu??o da expectativa de vida ? devido ? doen?a pulmonar progressiva, caracterizada por mudan?as severas na estrutura pulmonar, mais precisamente, bronquiectasias e alcaponamento de ar. A tomografia computadorizada de t?rax ? considerada o m?todo mais sens?vel para monitorar a doen?a pulmonar na fibrose c?stica. A principal desvantagem ? a exposi??o do paciente ? radia??o. A resson?ncia magn?tica de t?rax, t?cnica livre de radia??o, tem sido introduzida como uma alternativa ? tomografia computadorizada. A resson?ncia magn?tica tem sido comparada ? tomografia computadorizada em v?rios estudos usando v?rias sequ?ncias, mas, nenhuma utilizou a t?cnica de sensoriamento comprimido, imagem paralela e amostragem golden-angle radial combinada. O objetivo deste estudo foi avaliar a t?cnica de golden-angle radial combinada de resson?ncia magn?tica de t?rax em pacientes com fibrose c?stica em rela??o ? tomografia computadorizada e a resson?ncia magn?tica convencional de t?rax. M?todos: Foram realizados exames de tomografia computadorizada e resson?ncia magn?tica de t?rax em 29 pacientes com fibrose c?stica que eram acompanhados no ambulat?rio de pneumologia pedi?trica do Hospital S?o Lucas da Pontif?cia Universidade Cat?lica do Rio Grande do Sul. Os exames, foram realizados utilizando, primeiro, a amostragem de K-espa?o cartesiano e, ap?s, as t?cnicas de resson?ncia magn?tica com respira??o livre, utilizando a t?cnica Golden_Angle Radial Sparse Parallel. As imagens de resson?ncia magn?tica e tomografia computadorizada de t?rax foram avaliadas por dois observadores independentes utilizando o escore de Helbich-Bhalla. Coeficiente de correla??o intraclasse e an?lise de Bland-Altman foram usados para avaliar a concord?ncia e a reprodutibilidade no escore de severidade de Helbich-Bhalla. Nenhum paciente foi sedado ou usado meio de contraste. Resultados: Os coeficientes de correla??o intraclasse e o modelo gr?fico de Bland-Altman entre os escores de Helbich-Bhalla e os m?todos avaliados, tomografia computadorizada, resson?ncia magn?tica e resson?ncia magn?tica de respira??o livre, evidenciaram, em todas as compara??es dos escores totais, correla??es muito fortes (ICCCT-RM = 97%; ICCCT-FB-RM = 96% e ICCCT- FB-RM=99%). A associa??o do escore de Helbich-Bhalla, tanto da tomografia computadorizada como das imagens de resson?ncia magn?tica, com os testes de fun??o pulmonar foram significativas, principalmente, em rela??o ? severidade das bronquiectasias e espessamento das paredes br?nquicas. Conclus?o: Este estudo demonstrou que a nova t?cnica de resson?ncia magn?tica com respira??o livre e combina??o de sensoriamento comprimido, imagem paralela e amostragem golden-angle radial, mostrou uma boa concord?ncia com a tomografia computadorizada na avalia??o das altera??es pulmonares na fibrose c?stica. A t?cnica de golden-angle radial combinada pode ser utilizada na pr?tica cl?nica para acompanhamento de doen?a pulmonar fibroc?stica, e demonstra particular valor para os pacientes que n?o conseguem suspender a respira??o durante o exame.
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Hansson, Johan. "Activation and differentiation of cytotoxic T lymphocytes identification of district CTL subsets in the rat /." Lund : Dept. of Tumor Immunology, the Wallenberg Laboratory, 1994. http://catalog.hathitrust.org/api/volumes/oclc/39158589.html.
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Braun, Monika. "Einfluss des onkogenen RAS-Signalweges auf die Tumorerkennung durch zytotoxische T-Lymphozyten und NK-Zellen." Diss., lmu, 2008. http://nbn-resolving.de/urn:nbn:de:bvb:19-96419.
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Scudamore, Charles Henry. "Allograft enhancement in a rat heart transplant model : effect of T and B cell immunization." Thesis, University of British Columbia, 1985. http://hdl.handle.net/2429/24916.
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Acute and chronic rejection continue to be the most important problems in maintaining a functioning organ allograft. Despite advances in immunosuppression, organs are still damaged or destroyed by the recipient's immune system. In order to protect the transplanted organ it is necessary to overwhelm the host's immune system and thus expose the host to the complications of invasion from fungi, bacteria, protazoa, reduction in oncologic surveillance, and reduction of stem cell production.
Donor specific immunosuppression would provide graft protection and allow maintenance of the host's immunologic competence.
Graft enhancement has been described for many years. Current practice uses this principle by pretransfusing prospective kidney transplant recipients with type specific blood. Previous work has supported the concept that this clinical effort can be produced by certain cells in the blood, specifically, lymphocytes.
To study the effects of preimmunization with T or B lymphocytes and platelets in a rat heterotopic heart transplant model, the following experiments were performed. Experiment 1: The effect of pretransplant immunization with lxlO7 donor specific T cells or B cells showed that T cells have little affect on rejection of heterotopic heart allograft and B cells caused prolongation of graft function. This effect is species specific and not due to a pure anti-idiotype phenomenon.
Experiment 2: The effect of heating the purified T and B cells at 56°C for 30 minutes is known to denature the presenting protein antigens on the cell membranes without destroying the cell membrane.
After pretransplant immunization, seven days prior to heterotopic heart transplant in the rat model, the previously observed prolongation of graft survival after nonheated B cell immunization was still present but not as marked.
Experiment 4: The effect of pretransplant immunization of donor specific T and B cells treated by heating to 85°C for 10 minutes followed by heterotopic heart graft showed that there was a significant prolongation of the engrafted heart following immunization with the denatured B cells. Cellular proteins are denatured by this pretreatment but polysaccharides are not.
Experiment 5: The effect of pretransplant immunization with purified donor specific platelets followed by heterotopic heart rat transplant showed no prolongation or shortening of graft survival.
It is concluded that, in the heterotopic rat heart transplant model, immunization with purified T cells 7 days prior to transplant has little effect on rejection. When B cells are immunized in the same way, graft survival is prolonged. If the cells are heated to 56°C for 30 minutes this effect is reduced but not eliminated. This effect indicates that denaturation of protein HLA antigens on the presenting cell surface reduces the enhancing effect of the intact antigens on B cells. By denaturing, the presenting B cell protein graft enhancement is still present, suggesting the phenomenon of graft enhancement is not totally dependent on protein antigens but may have a contribution from mucopolysaccharides or other carbohydrates.
Donor specific purified platelet pretransplant immunizations produced no statistically significant prolongation of either PV6 or F₁ heart grafts. This observation is consistent with the findings that purified T cell immunization do not produce graft enhancement.Surgery, Department of
Medicine, Faculty of
Graduate
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Infante, Elvira. "Role of Rap and Rho GTPases in T-acute lymphoblastic leukaemia cell adhesion and migration." Thesis, King's College London (University of London), 2013. https://kclpure.kcl.ac.uk/portal/en/theses/role-of-rap-and-rho-gtpases-in-tacute-lymphoblastic-leukaemia-cell-adhesion-and-migration(e1c1aff6-96a7-4dc6-9ee5-355bb41b01ee).html.
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T-acute lymphoblastic leukaemia (T-ALL) is a common childhood cancer. Multiple genetic mutations have been identified in T-ALL patients. The most common is the mutation of the NOTCH 1 oncogene occurring in more than 50% of patients. Poor prognosis has often been shown to correlate with the migration and accumulation of T-ALL cells in the tissues. Rap and Rho family GTPases play key roles in T cell adhesion and migration and are often involved in cancer progression. Most of these proteins are post-translationally isoprenylated to facilitate their anchorage to membranes, where they function to stimulate signal transduction processes. In the first part of these studies, statins were used to reduce prenylation of GTPases, and to investigate whether the resulting alteration of GTPase membrane targeting affects T-ALL cell migration. Statins inhibited adhesion, chemotaxis and transendothelial migration of T-ALL cell lines. A similar effect was observed with geranylgeranyl transferase inhibitors and siRNA depletion of Raplb but not Rap la, RhoA, Racl, Rac2 and Cdc42. These results suggest that statins and Raplb depletion could be used to reduce tissue invasion in T-ALL. In contrast to other Rho family proteins, the atypical Rho GTPases RhoU and RhoV are not prenylated but undergo palmitoylation for membrane targeting. They are expressed at higher levels in primary T-ALL samples compared to primary T cells, and RhoU expression was shown to be unregulated by Notch 1. In the second part of these studies downregulation of RhoU and Notch 1 by siRNA reduced adhesion and migration of T-ALL cell lines. Interestingly, similar functional effects were observed upon siRNA depletion of RhoV. RhoU and RhoV partially co-localized and moved dynamically between endosomes and the plasma membrane, suggesting they act together to regulate membrane trafficking. These results indicate that RhoU and RhoV could contribute to T-ALL invasion by regulating T-ALL cell adhesion and migration.
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Moreau, Thierry. "Etude structurale et fonctionnelle du T-kininogène de rat (Thiostatine) et de ses fragments protéolytiques." Tours, 1988. http://www.theses.fr/1988TOUR4003.
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Les kininogènes représentent les membres les plus évolués de la superfamille des cystatines. Leur structure particulière fait qu'ils sont potentiellement porteurs d'activités diverses (précurseur de kinine, inhibiteur d eprotéase, initiateur de la coagulation, marqueur de l'inflammation. . . ). Notre principal objectif a été d'établir les relations structure-fonctions pour ce type de molécule. Le T-kininogène de rat, choisi comme modèle expérimental dans cette étude, est particulièrement sensible à une protéolyse limitée, confinée à des zones particulières de la molécule et identique pout toutes les protéases testées. La nature et l'expression des fonctions potentielles est dépendante de cette susceptibilité à la protéolyse. Contrairement aux autres kininogènes, le T-kininogène n'est pas hydrolysé par les kallicréines et sa fonction de précurseur de kinine est donc hypothétique. D'autres protéases à sérine d'origine cellulaire ou tissulaire diverse sont cependant capables de libérer une kinine à partir fdu T-kininogène mais seulemetn après avoir induit une fragmentation de la molécule. Cette fragmentation permet la libération de peptides dont les propriétés inhibitrices sont semblables à celles de la molécule active. L'activation de certaines de ces enzymes de traitement protéolytique (processing enzymes) pendant l'inflammation, ainsi que l'augmentation de synthèse du T-kininogène dans ces mêmes conditions, laissant supposer que la génération de fragments actifs est un phénomène essentiel dans l'expression des fonctions des kininogènes et en particulier dans le contrôle de l'activité des protéases à système.
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Kamsu, Ngounve Jeanine. "Cyto-architecture de la formation hippocampique du rat et de l’homme par IRM 7 T." Caen, 2013. http://www.theses.fr/2013CAEN3168.
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Le dépistage précoce de lésions de la formation hippocampique dans des maladies telles que l’épilepsie, la maladie d’Alzheimer, la dépression reste un challenge pour les imageurs IRM cliniques actuels. La formation hippocampique est une structure cérébrale possédant une cyto-architecture originale avec une organisation lamellaire. Elle est également traversée par un faisceau trisynaptique excitateur unique. Étant donné que certaines couches de l'hippocampe sont spécifiquement touchées et de façon précoce dans certaines pathologies comme le stratum radiatum et lacunosum moléculaire de la région CA1 dans la maladie d’Alzheimer ou la couche granulaire du gyrus denté dans la dépression, il est devenu impératif de dépister plus précocement ces anomalies afin d’améliorer le diagnostic de ces pathologies. Grâce à une séquence T2 haute résolution optimisée nous permettant une analyse du signal et des mesures du volume des couches hippocampiques et une séquence en tenseur de diffusion, nous avons pu visualiser cette cyto-architecture par couches sur des échantillons d’hippocampe de rat ainsi que chez l’homme à partir d’une IRM 7T assez répandue dans les centres de recherche. Notre séquence T2 nous a permis de mesurer l'épaisseur de la couche granulaire sur des cerveaux de rats et la séquence du tenseur de diffusion nous a permis d' isoler le circuit tri-synaptique chez le rat et l’homme. Ces séquences réalisées ex-vivo sont préliminaires aux séquences in-vivo qui, optimisées, ouvriront, nous l’espérons, des perspectives dans le dépistage précoce par IRM de processus neuropathologiques survenant dans certains modèles animaux ou au sein de l’hippocampe chez l’hommeEarly detection of lesions of the hippocampal formation in diseases such as epilepsy, Alzheimer's disease, depression remains a challenge for current clinical MRI scanners. The hippocampal formation is a cerebral structure with a multi-layered organization and is also crossed by an original excitatory synaptic circuit. Given that specific layers of the hippocampus are affected early in the development of some pathologies, such as the stratum radiatum and lacunosum moleculare of CA1 region in Alzheimer's disease or the granular cell layer of the dentate gyrus with depression, it has become imperative to obtain more precise images of the hippocampal structure in order to improve our understanding and the early detection of microstructural changes which could occur in the hippocampus. With an optimized High Resolution T2 sequence allowing us a signal analysis and volume measurements of hippocampal layers and a diffusion tensor sequence, we could visualize this lamellar cyto-architecture of rat and human hippocampus samples with a widely spread 7T MRI scanner. Our T2 sequence allowed us to measure the thickness of the granular cell layer of the hippocampal formation and the diffusion tensor sequence allowed us to isolate the tri- synaptic circuit in rats and humans. These optimized sequences open perspectives on in vivo studies of animal models or pathological human hippocampus
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van, de Looij Yohan. "Imagerie spirale du tenseur de diffusion à 7-T : application au cerveau du rat traumatisé." Université Joseph Fourier (Grenoble), 2006. http://www.theses.fr/2006GRE10288.
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L'objet de cette thèse était de mettre en place une séquence robuste d'imagerie rapide du tenseur de diffusion par RMN sur un imageur petit animal 7-T. Nous avons mis en place une séquence Twice Refocused Spin Echo afin de s'affranchir des problèmes de courants de Foucault. Nous avons préféré une acquisition spirale de l'espace-k à EPI pour son insensibilité aux artefacts de mouvement et de flux très importants en diffusion. Nous avons développé un logiciel sous Matlab pour la reconstruction des images du tenseur de diffusion et la visualisation des cartes d'anisotropie et cartes couleurs. Enfin nous avons utilisé un logiciel développé à l'INRIA de Nice-Sofia Antipolis (MedfNRfA OTf Track) pour visualiser l'affichage des vecteurs propres et effectuer le « fiber tracking » à partir des datas collectées sur notre imageur 7-T sur cerveau de rat. Une fois la technique et les méthodes de reconstructions validées sur différents fantômes et sur cerveau de rat sain, nous l'avons appliqué à un modèle de rat traumatisé étudié au sein du laboratoire et traumatisé selon la méthode impact-accélération. L'objet de l'étude était de caractériser l'œdème cérébral post traumatique de manière précoce grâce à l'imagerie du tenseur de diffusion. Cette technique nous a permis de caractériser le type d'œdème cérébral post-traumatique par des modifications de la diffusivité moyenne. Des modifications d'an isotropie dans le corps calleux du cerveau de rat traumatisé ont montré la présence de lésions axonales diffuses. Enfin, l'imagerie fiber tracking a permis de détecter des lésions axonales au centre du corps calleux du cerveau de rat traumatiséThe purpose of this thesis was to implement a robust fast diffusion tensor imagines sequence on a 7-T small bore system. We implemented a Twice Refocused Spin Echo sequence in order to cancel eddy currents problems on our system. Spiral k-space acquisition was preferred to EPI for its insensitivity to motion and flow artifacts, very important in diffusion imaging. We developed software (in Matlab) to reconstruct spiral diffusion weighted and tensor images as weil as maps of tensor derived parameters: anisotropy indices, and color maps. We used a free software (MedfNRfA OTI Track) developed by P. Fillard from INRIA Nice-Sofia Antipolis in order to track white matter fibers in the rat brain. After preliminary calibrations as weil as validations on different phantoms and healthy rat brain, the implemented sequence was applied to traumatic rat brain injury. Ln this model, developed in our laboratory, the traumatism was induced by impact-acceleration method. The aim of this study was to early characterize post-traumatic cerebral edema by the mean of diffusion tensor imaging. Variations of mean diffusivity in the traumatic rat brain provided information about the type of cerebral edema induced by traumatic brain injury. Modifications of anisotropy indices in corpus callosum of traumatic rat brain provided evidence for presence of diffuse axonal injury. Fiber tracking in the corpus callosum of rat brain showed axonal rupture on the center of traumatic rat corpus callosum
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Moreau, Thierry. "Etude structurale et fonctionnelle du T-kininogène de rat, thiostatine, et de ses fragments protéolytiques." Grenoble 2 : ANRT, 1988. http://catalogue.bnf.fr/ark:/12148/cb37616636p.
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Casemayou, Audrey. "Vav1 contrôle le développement des lymphocytes T régulateurs et des maladies d'origine immune." Toulouse 3, 2010. http://thesesups.ups-tlse.fr/1583/.
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Les maladies auto-immunes et allergiques sont des maladies multifactorielles. Elles résultent d'interactions complexes entre des facteurs génétiques et environnementaux. L'identification des gènes impliqués dans la sensibilité à ces maladies est rendue difficile par l'hétérogénéité génétique des populations et la variabilité de l'environnement. Notre laboratoire a développé un modèle de choix sans équivalent chez la souris pour étudier le contrôle génétique de ces maladies immunes multifactorielles en pathologie expérimentale. Ce modèle est représenté par deux souches de rats, Lewis (LEW) et Brown-Norway (BN), qui sont génétiquement prédisposés à développer des types de réponses immunes différentes. Ces différences sont associées à des sensibilités opposées vis-à-vis des maladies auto-immunes et des manifestations allergiques. Le rat LEW est sensible, et le rat BN résistant, aux maladies auto-immunes de type 1, comme l'encéphalomyélite auto-immune expérimentale (EAE), modèle de sclérose en plaques (SEP). En revanche, le rat BN développe des désordres allergiques de type 2 après injections chroniques de sels de métaux lourds, alors que le rat LEW est résistant à l'induction de ces désordres. Les études génétiques dans ce modèle ont identifié à l'extrémité acrocentrique du chromosome 9, une région contrôlant la sensibilité à l'inflammation du système nerveux central (locus Eae4) et aux manifestations allergiques induites par les sels de métaux lourds (locus Iresp3). La co-localisation de ces loci suggère que cette région contient un gène ou cluster de gènes jouant un rôle majeur dans l'homéostasie du système immunitaire. Au cours de ma thèse, la dissection génétique de ces loci à l'aide de lignées et sous-lignées congéniques de rats m'a permis d'affiner la localisation du locus Iresp3 à 117 kb et du locus Eae4 à 1cM. J'ai montré que la région de 117 Kb contrôle la proportion et le nombre absolu des lymphocytes T régulateurs Foxp3+ (Treg) (locus Fort1). Par cartographie haplotypique de six souches de rats, le polymorphisme codant pour la mutation p. Arg63Trp dans l'exon 1 de Vav,1 a été associé au niveau d' expression des cytokines de type 1, et à la proportion des Treg au sein des LT CD4. Les études cellulaires réalisées in vitro ont montré que le polymorphisme R63W a un impact fonctionnel et quantitatif majeur sur la protéine Vav1. Le variant Vav1-63W est associé à une faible quantité protéique, à une hyperphosphorylation des tyrosines et a une augmentation de l'activité "facteur d'échange guanidique" de Vav1. Nous avons aussi montré que ce variant est associé à une réduction du flux calcique dans les LT activés, phénomène probablement lié à une réduction de l'activité adaptatrice du Vav1. Enfin, l'étude du gène orthologue chez l'homme a montré une association entre un haplotype de l'intron 1 de VAV1 et la sensibilité à la sclérose en plaques (SEP). Ce travail souligne l'intérêt des recherches translationnelles allant des modèles expérimentaux à la pathologie humaine. Les résultats obtenus ouvrent de nouvelles possibilités d'études sur le rôle des voies cellulaires mettant en jeu Vav1 dans les cellules du système immunitaire avec à terme de possibles retombées pour le traitement des maladies immunes, notamment de la SEPAutoimmune and allergic diseases are multifactorial diseases resulting from complex interactions between genetic and environmental factors. Human genetic studies are hampered by the genetic heterogeneity of human population and the variability of environment. Our team has developed a rat model to investigate the genetic control of immune diseases. This model is based on two rat strains, BN and LEW, which are different for their immune responses. These differences are associated with opposite susceptibility to autoimmune and allergic diseases. LEW rats are susceptible, and BN rats resistant, to type-1-mediated autoimmune diseases, like experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS). Conversely, BN rats are susceptible, and LEW rats resistant, to type-2-mediated allergic disorders induced by heavy metal injections. Genetic studies in this model have identified at the acrocentric tip of chromosome 9 (c9), a region that controls the susceptibility to central nervous system inflammation (locus Eae4) and the susceptibility to heavy metal-triggered immune disorders (locus Iresp3). This region also controls the level of CD45RC expression on T cells. This level defines subsets of T lymphocytes (CD45RChigh and CD45RClow) that are characterized by different cytokinic profiles and functions. The colocalization of these three loci suggests that this region contains a gene or set of genes that plays a major role in the control of immune system homeostasis. During my thesis, genetic dissection of these loci using rat congenic and sub-congenic lines led to narrow down Iresp3 and Cdexp1 to a 117 kb region and Eae4 to a 1cM region that includes Iresp3 and Cdexp1. We further demonstrated that, in basal conditions, the 117 kb region controls the absolute number and proportion of regulatory Foxp3+ T cell population (Treg) (locus Fort1). The haplotypic maps of six rat strains allowed us to associate R63W polymorphism in exon 1 of Vav1 with a decreased expression of type 1 cytokines and an increased proportion and number of Treg. . In vitro studies showed that the R63W polymorphism impacts the cellular amount of Vav1 protein and its function. In fact, the Vav1-63W variant was responsible for a 4 fold reduction of Vav1 protein and for Vav1 constitutive activation, revealed by its tyrosine hyperphosphorylation and increased guanine nucleotide exchange factor activity. Moreover, Vav1-63W is increased by 4 fold as compared to Vav1-63R. Vav1-63W is also associated with a decrease of calcium flux after TCR engagement, which may be related to the decrease in the total amount of Vav1 and thus to the decrease of cellular Vav1 adaptor capacity. Finally, human studies of the orthologous gene showed the association of an haplotype in intron 1 of VAV1 with MS. This work demonstrates the power of translational researches going from animal models to human pathology and suggests that alterations in Vav1 signaling could be a new target for the management and treatment of immune diseases such as MS
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Martins, Andr? Olimpio. "Cortisol e testosterona salivares como biomarcadores de estresse e recupera??o em atletas de corrida de aventura." UFVJM, 2013. http://acervo.ufvjm.edu.br/jspui/handle/1/789.
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Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior (Capes)
Conselho Nacional de Desenvolvimento Cient?fico e Tecnol?gico (CNPq)
Funda??o de Amparo ? Pesquisa do estado de Minas Gerais (FAPEMIG)
A Corrida de aventura ? uma competi??o praticada em contato com a natureza, na qual o competidor utiliza obst?culos naturais para a pr?tica de v?rias modalidades esportivas combinadas. O cortisol salivar (CT) pode ser utilizado como biomarcador do estresse e estados catab?licos. A concentra??o salivar de testosterona (TT) pode representar um marcador de estado anab?lico do, j? que seus efeitos fisiol?gicos est?o relacionados com o repara??o tecidual. A propor??o entre a atividade anab?lica/catab?lica pode ser dada pela an?lise da raz?o testosterona/cortisol (T/C). O objetivo deste trabalho foi quantificar as concentra??es de CT e TT de participantes de uma corrida de aventura, para determina??o do impacto fisiol?gico deste tipo de prova. O estresse e a recupera??o dos atletas foram inferidos pela an?lise da concentra??o de CT e TT e da T/C, 1 semana antes da competi??o (dia 1), 1 dia antes da competi??o (dia 2), no dia da competi??o (dia 3) e 1 dia ap?s a competi??o (dia 4). Frequ?ncia card?aca e VO2m?x foram registrados para avalia??o da intensidade de esfor?o da prova. As concentra??es de CT para o dia 2 e 3, n?o se elevaram em rela??o ?s concentra??es apresentadas no dia 1. Entretanto, no dia 4, as concentra??es de CT foram superiores em compara??o ?s concentra??es dos dias 1, 2 e 3. O ritmo TT normal foi observado nos 04 dias analisados e n?o foi observada varia??o nas concentra??es de TT. A raz?o T/C apresentou-se diminu?da no dia 4 em compara??o ao dia 1. Os resultados mostraram que a T/C apresentou-se reduzida em mais de 75% no dia 4. Conclus?es: 1. Corrida de aventura ? um evento multiesportivo de alta intensidade de esfor?o f?sico e desafia homeostase e alostase corporais; 2. O esfor?o do treinamento e da competi??o possivelmente mostrou-se desajustado ao preparo f?sico dos atletas analisados, j? que, o ritmo CT observado, tanto no per?odo pr?, quanto no p?s-competi??o, indicou estados de exaust?o e catabolismo intenso, respectivamente. Contudo, mais analises s?o necess?rias para compreender se o esfor?o da competicao foi realmente desajustado para o organismo do atleta ou se o esfor?o f?sico n?o foi intenso o suficiente para evocar uma resposta dos eixos end?crinos analisados.
Disserta??o (Mestrado) ? Programa Multic?ntrico de P?s-gradua??o em Ci?ncias Fisiol?gicas, Universidade Federal dos Vales do Jequitinhonha e Mucuri, 2013.
ABSTRACT Adventure racing is a competition practiced in contact with nature where the competitor uses natural obstacles to practice various combined sports. The salivary cortisol (CT) can be used as a biomarker of stress and catabolic states. The concentration of salivary testosterone (TT) may represent a marker of anabolic status since its physiological effects are related tissue repair. The ratio of the anabolic activity/catabolic can be given by analysis of the testosterone/cortisol ratio (T/C). The aim of this study was to quantify the CT and TT concentrations of the participants of an adventure race to determine the physiological impact of such test. Stress and recovery of athletes were inferred by analyzing the TC and TT and T / C concentration of: 1 week before competition (day 1), 1 day before competition (day 2), competition day (day 3) and 1 day after competition (day 4). VO2max and heart rate were recorded to assess the intensity of effort of competition. The concentrations of CT to day 2 and 3 did not increase compared to the concentrations showed on day 1. However, on day 4, the TC concentrations were higher compared to concentrations on days 1, 2 and 3. The TT regular rhythm was observed in 04 days and there was no variation in the concentration of TT. The ratio T/C appeared reduced at day 4 compared to day 1. The results showed that T/C appeared reduced by more than 75% in 4 days. Conclusions: 1. Adventure Racing is a multisport event of high intensity physical exertion and challenges homeostasis and allostasis body; 2. The stress of training and competition possibility proved inadequate to the physical preparation of athletes analyzed, since, CT rhythm observed in both pre and post-competition showed states of exhaustion and intense catabolism, respectively. 3. However, more analyses is necessary to understand if the competition was wrong to the athletic`s organism or if the effort was not intense enough to stimulate an answer from the endocrine axis analyzed.