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1
Deshpande, A. M. „Structure-function analysis of the role of amphiphysin in T-tubule organisation in Drosophila“. Thesis, University of Cambridge, 2005. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.598514.
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To investigate how amphiphysin contributes to T-tubule organisation in Drosophila, I initiated a structure-function analysis of the protein in this process. I assayed the ability of different domains and mutant forms of the protein to rescue the amphiphysin null mutant phenotype. When either an N-terminal fragment that includes the BAR domain, or the SH3 domain, was expressed in an amphiphysin mutant background, there was no obvious rescue of the T-tubule defect. However, expression of full-length protein lacking the first 40 amino acids resulted in some rescue of reticular structures. When full-length amphiphysin, carrying a mutated SH3 domain that does not interact with praline-containing motifs, was expressed in amphiphysin mutants, tubular structures similar to those of wild type were seen, but they failed to localise normally. When full-length amphiphysin, carrying point mutations in the BAR domain that inhibit its binding and tabulating activity, was expressed in amphiphysin mutants, there was an partial rescue of the phenotype. Although amphiphysin is known to dimerise, neither an N-terminal region containing the BAR domain, nor the SH3 domain, had any detectable dominant negative phenotype in a wild type background. I also examined muscle development in embryos, to detect whether amphiphysin expression occurred before or after T-tubule formation. I examined the time course of amphiphysin and Dig (another T-tubule marker) expression in developing muscles. Amphiphysin appeared first on the plasma membrane and as intracellular puncta, then on a reticular network, presumably T-tubules. Dig could be detected on T-tubules only subsequently to this. Therefore, amphiphysin expression in muscles precedes the earliest time at which T-tubules can be detected with any markers available to me.
2
He, Yang. „Modelling the spatio-temporal dynamic of iIntracellular Ca2+ handling system in cardiac cells“. Thesis, University of Manchester, 2017. https://www.research.manchester.ac.uk/portal/en/theses/modelling-the-spatiotemporal-dynamic-of-intracellular-ca2-handling-system-in-cardiac-cells(f1a1b52a-f9f1-4837-aa0f-9d5df1f54d6f).html.
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The intracellular Ca2+ handling system in a cardiac myocyte is of crucial importance. It regulates the contraction and relaxation of the myocyte during the excitation-contraction (EC) coupling. A normal intracellular Ca2+ handling system keeps the contraction of the heart orderly, which represents a powerful force to pump blood to the whole body. However, disarrayed or remodelled cellular structure associated with the intracellular Ca2+ handling system at the subcellular level, such as loss of T-tubule network in diseased conditions, may promote abnormal cardiac EC coupling, leading to genesis of cardiac arrhythmias impairing cardiac mechanical functions. Up to date, it is still incompletely understood how the intracellular Ca2+ handling system is altered by changes in subcellular structures of Ca2+ handling systems. In this thesis, biophysically detailed computational models for the intracellular Ca2+ handling system of a cardiac cell were developed, providing a powerful platform to investigate the spatio-temporal complexity associated with the intracellular Ca2+ handling, and its role in generating abnormal cardiac EC coupling. First, a well-validated single cell model was used to investigate how the diastolic and systolic Ca2+ concentration responded to alterations in the model parameters related to the Ca2+ handling system, from which the mechanisms underlying the rate-dependence of EC coupling were analysed. Then, a novel single cell model, with a 2D presentation of the spatial structures of subcellular Ca2+ handling and membrane action potential, of a sheep atrial myocyte was developed for simulating the abnormal intracellular Ca2+ regulation system due to the loss of T-tubules during atrial fibrillation. Variant scenarios of T-tubule loss were considered to investigate the role of the T-tubule in affecting the intracellular Ca2+ regulation. Furthermore, membrane currents' alterations due to the electrical remodelling arising from atrial fibrillation were considered together with the loss of T-tubule. Three typical types of abnormal Ca2+ cycling phenomenon, namely intracellular Ca2+ alternans, spontaneous Ca2+ sparks and intracellular Ca2+ waves were observed in AF conditions. The relationship between T-tubule loss, AF-remodelling and the genesis of delayed afterdepolarizations (DADs) was also investigated. It was shown that the loss of T-tubule in AF condition played an important role in disturbing the Ca2+ regulation system, which increases the risk for a cell to generate impaired contraction.
3
Sampangi, Sandeep. „Autologous human kidney proximal tubule epithelial cells (PTEC) modulate dendritic cell (DC), T cell and B cell responses“. Thesis, Queensland University of Technology, 2015. https://eprints.qut.edu.au/82033/1/Sandeep_Sampangi_Thesis.pdf.
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This is a comprehensive study of human kidney proximal tubular epithelial cells (PTEC) which are known to respond to and mediate the pathological process of a range of kidney diseases. It identifies various molecules expressed by PTEC and how these molecules participate in down-regulating the inflammatory process, thereby highlighting the clinical potential of these molecules to treat various kidney diseases. In the disease state, PTEC gain the ability to regulate the immune cell responses present within the interstitium. This down-regulation is a complex interaction of contact dependent/independent mechanisms involving various immuno-regulatory molecules including PD-L1, sHLA-G and IDO. The overall outcome of this down-regulation is suppressed DC maturation, decreased number of antibody producing B cells and low T cell responses. These manifestations within a clinical setting are expected to dampen the ongoing inflammation, preventing the damage caused to the kidney tissue.
4
Lemerle, Eline. „Rôle des cavéoles dans la formation des tubules-T et dans la physiopathologie des cavéolinopathies“. Electronic Thesis or Diss., Sorbonne université, 2021. https://accesdistant.sorbonne-universite.fr/login?url=https://theses-intra.sorbonne-universite.fr/2021SORUS010.pdf.
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Dans le muscle squelettique, des invaginations du sarcolemme appelées cavéoles et leur composant principal Cav-3 seraient impliqués dans la formation des tubules transverses, des structures musculaires permettant de propager le potentiel d'action dans la fibre musculaire. Pourtant, ce mécanisme demeure à ce jour inconnu. L’importance des cavéoles et de Cav-3 est accentuée par l’existence de défauts dans l’organisation et la fonction des cavéoles dans le cas de cavéolinopathies, des maladies neuromusculaires autosomiques dominantes dues à des mutations dans le gène CAV-3 et dont les mécanismes physiopathologiques sont à ce jour incompris. L’objectif de mon projet était de comprendre le rôle des cavéoles dans la formation précoce des tubules-T. Une technique de microscopie corrélative combinant de la fluorescence à super résolution et de la microscopie électronique sur répliques de métal a permis d’examiner en détails les composants moléculaires des cavéoles et des tubules-T dans des myotubes extensivement différenciés. J’ai ainsi montré l'organisation des cavéoles sur des plateformes de Bin1 formant ainsi une nouvelle structure en anneaux semblant optimiser la tubulation de la membrane afin d’initier la formation des tubules-T. Ces anneaux ainsi que la tubulation des membranes par Bin1 sont altérés dans le cas de défauts d’expression de Cav-3 et dans les myotubes de patients cavéolinopathes. Mes travaux suggèrent que les anneaux de cavéoles constituent le site d’initiation des tubules-T et apportent les bases d’une caractérisation de la biogénèse des tubules-T dans le muscle squelettique et dans la physiopathologie des cavéolinopathiesIn skeletal muscle, invaginations of the sarcolemma called caveolae and their main component Cav-3 are thought to be involved in the formation of transverse tubules. T-tubules are muscle structures that allow the action potential to be propagated into the muscle fibre. However, the mechanism linking them together remains unknown. The importance of caveolae and Cav-3 is accentuated by the existence of defects in the organisation and function of caveolae in caveolinopathies, autosomal dominant neuromuscular diseases due to mutations in the CAV-3 gene, the pathophysiological mechanisms of which are still not understood. The objective of my project was to understand the role of caveolae in the early formation of T-tubules. A correlative microscopy technique combining super-resolution fluorescence and electron microscopy on metal replicas was used to examine in detail the molecular components of caveolae and T-tubules in extensively differentiated myotubes. I showed the organisation of caveolae on Bin1 platforms forming a novel ring structure that appears to optimise membrane tubulation in the initiation of T-tubule formation. These rings and Bin1-mediated membrane tubulation are impaired in Cav-3 expression defects and in myotubes from caveolinopathic patients. My work suggests that caveolae rings are the site of T-tubule initiation and provides the basis for characterising T-tubule biogenesis in skeletal muscle and in the pathophysiology of caveolinopathies
5
Wagner, Eva [Verfasser], Stephan E. [Akademischer Betreuer] Lehnart, Michael [Akademischer Betreuer] Hoppert und Stefan [Akademischer Betreuer] Jakobs. „Cardiac T-Tubule Membranes - Nanostructure and Remodeling Mechanisms in Disease / Eva Wagner. Gutachter: Michael Hoppert ; Stefan Jakobs. Betreuer: Stephan E. Lehnart“. Göttingen : Niedersächsische Staats- und Universitätsbibliothek Göttingen, 2013. http://d-nb.info/1044768428/34.
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6
Afrin, Sadia. „Defining a 3-dimensional (3D) in vitro model to study immune cell and renal cell interactions“. Thesis, Queensland University of Technology, 2015. https://eprints.qut.edu.au/84754/1/Sadia_Afrin_Thesis.pdf.
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This study aimed to develop a 3-Dimensional (D) hydrogel system for the co-culture of autologous human renal and immune cells. Previous studies have shown that human renal epithelial cells are able to modulate autologous immune cell responses. However, these studies were undertaken in a standard 2D culture system. The 3D model was developed to re-capitulate these observations within a more physiological relevant in vivo like environment.
7
Metzger, Sabrina Kinzie. „Modeling of excitation in skeletal muscle“. Wright State University / OhioLINK, 2021. http://rave.ohiolink.edu/etdc/view?acc_num=wright1620983611677044.
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8
Payne, J. G. „Residual stresses in welded tubular T-joints“. Thesis, University of Cambridge, 1986. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.384523.
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9
Neira, Dorivalda Santos Medeiros. „Fibras de sisal (Agave sisalana) como isolante t?rmico de tubula??es“. Universidade Federal do Rio Grande do Norte, 2005. http://repositorio.ufrn.br:8080/jspui/handle/123456789/15545.
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Previous issue date: 2005-12-16Conselho Nacional de Desenvolvimento Cient?fico e Tecnol?gico
In the last decades there was a significant increasing of the numbers of researchers that joint efforts to find alternatives to improve the development of low environmental impact technology. Materials based on renewable resources have enormous potentials of applications and are seen as alternatives for the sustainable development. Within other parameters, the sustainability depends on the energetic efficiency, which depends on the thermal insulation. Alternative materials, including vegetal fibers, can be applied to thermal insulation, where its first goal is to minimize the loss of energy. In the present research, it was experimentally analyzed the thermal behavior of fiber blankets of sisal (Agave sisalana) with and without surface treatment with oxide hidroxide (NaOH). Blankets with two densities (1100/1200 and 1300/1400 g/m2) were submitted to three rates of heat transfer (22.5 W, 40 W and 62.5 W). The analysis of the results allowed comparing the blankets treated and untreated in each situation. Others experiments were carried out to obtain the thermal conductivity (k), heat capacity (C) and the thermal diffusivity (α) of the blankets. Thermo gravimetric analyses were made to the verification of the thermal stability. Based on the results it was possible to relate qualitatively the effect of the heat transfer through the sisal blankets subjected to three heat transfer rates, corresponding to three temperature values (77 ?C, 112 ?C e 155 ?C). To the first and second values of temperature it was verified a considerable reduction on the rate of heat transfer; nevertheless, to the third value of temperature, the surface of the blankets (treated and untreated) in contact with the heated surface of the tube were carbonized. It was also verified, through the analyses of the results of the measurements of k, C e α, that the blankets treated and untreated have values near to the conventional isolating materials, as glass wool and rock wool. It could be concluded that is technically possible the use of sisal blankets as constitutive material of thermal isolation systems in applications where the temperature do not reach values greater than 112 ?C
Nas ?ltimas d?cadas, t?m sido grandes os esfor?os dos pesquisadores na busca por alternativas sustent?veis e conhecimentos sobre como se poder? continuar promovendo o desenvolvimento sem que isso ocorra de forma agressiva ao ambiente. Materiais oriundos de fontes renov?veis possuem grande potencial de aplicabilidade e s?o vistos como alternativas para um desenvolvimento sustent?vel. Dentre outros par?metros, a sustentabilidade depende da efici?ncia energ?tica e essa, por sua vez, depende de isolantes t?rmicos. Materiais alternativos, entre eles as fibras vegetais, podem ser aplicadas para fins de isolamento t?rmico, cujo principal objetivo ? minimizar as perdas de energia. Na presente pesquisa, analisou-se experimentalmente a aplicabilidade de mantas de fibras de sisal (Agave sisalana), in natura e com tratamento superficial com hidr?xido de s?dio (NaOH), ? isola??o t?rmica. Foram utilizadas mantas de duas gramaturas (1100/1200 e 1300/1400 g/m2) submetidas a tr?s taxas de transfer?ncia de calor (22,5 W, 40 W e 62,5 W). A an?lise dos resultados obtidos permitiu comparar a capacidade de isola??o das mantas tratada e in natura em cada situa??o. Ensaios foram realizados para determina??o da condutividade t?rmica (k), capacidade calor?fica (C) e a difusividade t?rmica (α) das mantas; a estabilidade t?rmica foi verificada por meio de an?lise termogravim?trica (TGA). Com base nos resultados, foi poss?vel relacionar qualitativamente o efeito da transfer?ncia de calor atrav?s das mantas de sisal submetidas a tr?s condi??es de aquecimento, correspondentes a tr?s valores de temperatura (77 ?C, 112 ?C e 155 ?C). Nas duas condi??es iniciais, verificou-se que as mantas de sisal proporcionaram uma significativa redu??o da taxa de transfer?ncia de calor. Na terceira condi??o (155 ?C), contudo, as superf?cies das mantas (tratadas e in natura) em contato com a superf?cie aquecida do tubo ficaram carbonizadas. Por meio das an?lises dos resultados das medi??es de k, C e α, constatou-se que as mantas tratadas e in natura apresentaram valores bem pr?ximos aos de materiais isolantes comerciais (l? de vidro e l? de rocha). P?de-se concluir que mantas de sisal podem ser empregadas como material constituinte de sistemas de isola??o t?rmica para aplica??es em que a temperatura n?o ultrapasse 112 ?C
10
Li, Qince. „Mathematical modelling of intracellular Ca2+ alternans in atrial and ventricular myocytes“. Thesis, University of Manchester, 2012. https://www.research.manchester.ac.uk/portal/en/theses/mathematical-modelling-of-intracellular-ca2-alternans-in-atrial-and-ventricular-myocytes(54ff4d2a-f820-43b6-a572-4706850f28ec).html.
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During excitation-contraction coupling, Ca2+ transient induced by the depolarization of membrane potential is the trigger of mechanical contraction in cardiac myocytes, which is responsible for the pumping function of the heart. However, mechanisms underlying intracellular Ca2+ regulation and the coupling between Ca2+ transient and membrane potential are not completely understood. Abnormalities in intracellular Ca2+ regulation have been observed during heart failure and cardiac arrhythmias, such as intracellular Ca2+ alternans and T-tubule disorganization. In this project, intracellular Ca2+ dynamics in different types of cardiac myocytes were investigated by using computer modelling. For atrial myocytes, a biophysically detailed computer model was developed to describe the observations of Ca2+ alternans and Ca2+ wave propagation in cardiac myocytes lacking T-tubules. The model was validated by its ability to reproduce experimental observed Ca2+ wave propagation under normal condition and the influences on spatial Ca2+ distribution by modifying various aspects of Ca2+ cycling, such as Ca2+ influx, SR Ca2+ uptake and SR Ca2+ release in cardiac myocytes lacking T-tubules. Mechanisms underlying the genesis of Ca2+ alternans in this type of cell were investigated by the model. Furthermore, a spontaneous second Ca2+ release was observed in response to a single voltage stimulus pulse with enhanced Ca2+ influx as well as SR Ca2+ overload. For the ventricular myocytes, an existing canine model was used to study the genesis of APD and intracellular Ca2+ alternans under various conditions. The genesis of Ca2+ alternans was investigated by analyzing the relationship between systolic Ca2+ concentration and SR Ca2+ content. On the other side, the roles of SR Ca2+ regulation and action potential restitution in the genesis of intracellular Ca2+ and APD alternans were also examined under various conditions. In addition, it was shown that spatially discordant Ca2+ alternans was generated when the Ca2+-dependent inactivation of ICa,L was strong. It tended to be concordant for weak Ca2+-dependent inactivation of ICa,L. For the sinoatrial node cells, a mathematical model was developed to simulate stochastic opening of unitary L-type Ca2+ channel and single RyR channel, thereby reproducing experimental observed local Ca2+ release during diastolic depolarization phase of the action potential. Simulation results of ionic channel block and modifications of SR Ca2+ regulation suggested a limited role of intracellular Ca2+ in the automaticity of central SA node cells.
11
Cheng, Shumin. „Non-destructive evaluation of cracking in tubular T-joints using vibration procedures“. Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1997. http://www.collectionscanada.ca/obj/s4/f2/dsk2/ftp02/NQ34244.pdf.
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12
Saad, Sariffuddin Bin. „Finite element determination of the static strength of cracked tubular T-joints“. Thesis, University of Nottingham, 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.362919.
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13
Toussaint, Anne. „Implication de l'amphiphysine2/BIN1 et des tubules-T/triades dans les myopathies à centralisation des noyaux“. Strasbourg, 2010. http://www.theses.fr/2010STRA6227.
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Les myopathies centronucléaires (CNM) sont des maladies congénitales caractérisées par une faiblesse musculaire et des fibres musculaires à noyaux centraux. La forme sévère néonatale liée à l’ X est due à des mutations dans le gène MTM1. Des mutations dans le gène DNM2, ont été identifiées dans la forme modérée (adulte) autosomique dominante. Les formes intermédiaires autosomiques récessives sont infantiles, et j’ai identifié, en M2, des mutations dans le gène codant pour l’amphiphysine 2/BIN1, une protéine du remodelage membranaire et de la formation des tubules-T dans le muscle. En thèse, j’ai montré que ces mutations menaient soit à la perte de formation de tubules membranaire, soit à l’altération du recrutement de DNM2 à ces tubules. J’ai mis en évidence que le domaine PI participait au rôle spécifique de BIN1 dans le muscle squelettique, en le dirigeant aux tubules-T/triades, et que la perte de ce domaine jouait aussi un rôle dans phénotype musculaire des dystrophies myotoniques (collaboration). L’étude de BIN1 et de marqueurs de la triade chez les souris MTM1-KO, ainsi que chez des patients atteints de CNM, a révélé une altération systématique de l’organisation de BIN1 et des triades. J’ai ainsi pu mettre en évidence l’existence 1) d’un lien fonctionnel MTM1/BIN1; 2) d’un mécanisme pathologique commun aux trois formes de CNM faisant intervenir les triades et BIN1, ce dernier pouvant représenter un lien moléculaire dans la maladie; 3) de désorganisations spécifiques de BIN1 et des triades selon le gène muté. Enfin, j’ai montré que DNM2 était distribuée à la ligne Z dans le muscle squelettique, malgré l’altération de sa localisation chez les patients atteints de CNMCentronuclear myopathies (CNM) are congenital disorders characterized by hypotonia and muscular fibres with central nuclei. The severe X-linked form is neonatal and due to mutations MTM1 (XLMTM). Mutations in DNM2 were identified in the autosomal dominant form. The intermediate autosomal recessive forms appear during childhood. During my M2, I identified mutations in the gene that codes amphiphysin 2/BIN1, a protein involved in membrane remodelling and T-tubules biogenesis in skeletal muscle. During my thesis, I showed that theses mutations led to either the loss of membrane tubules, or the defect in recruitment of DNM2 to these tubules. I highlighted that PI domain was implicated in the specific role of BIN1 in skeletal muscle that directs to T-tubule/triads. Moreover I showed, in collaboration, that le loss of the PI domain played a role in the muscular phenotype of myotonic dystrophy. The study BIN1 and triads markers in MTM-KO mice, beside in patients suffering of CNM, revealed an automatic alteration in BIN1 and triads organization. Then I highlighted the presence of 1) a functional link between MTM1 and BIN1; 2) a common pathological mechanism between the three CNM forms, where triads and BIN1 participate, and where this last one could represent a molecular link in the disease; 3) of specific disorganization of BIN1 and triads according the mutated gene. Finally, I showed that DNM2 was distributed to the Z-line in skeletal muscle, although a defect in DNM2 localization in the patients with CNM
14
Llewelyn-Parry, A. „Behaviour and strength of stiffened tubular T- and DT-joints in offshore structures“. Thesis, Swansea University, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.637938.
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This thesis addresses the understanding of the static strength and behaviour of internally ring stiffened T- and DT-joints under axial brace loading. Initial numerical work verifies the appropriateness of the Finite Element (F.E.) modelling technique and the use of the F.E. Method as an analysis tool. This was achieved through a validation study on both unstiffened and ring stiffened T-joints and on unstiffened DT-joints. There follows four substantial parametric studies on ring stiffened T- and DT-joints which investigate the effect of the variation of the stiffener dimensions of plain and T-shaped stiffeners along with the joint geometrical parameters β and γ on the strength and behaviour of the stiffener and the stiffened joint. Also the number and position of the ring stiffeners are investigated. Findings of the study enabled, where appropriate, the proposal of two methods of strength prediction for the ring stiffener. One uses Plastic Theory to postulate a ring model which is based on a five- or six-hinge failure mechanism for the stiffener, resulting in a virtual Work Equation. For this method it is assumed that a portion of the chord interacts with the stiffener in producing the strength enhancement. The stiffener cross-section is then considered as a T- and an I-section for the plain and T-shaped stiffeners respectively. The other is an empirical equation based on the variation of the non-dimensional stiffener strength with the various influencing non-dimensional parameters. It has been shown that the theoretical method can be compromised when the stiffener parameters exceed the validity range of the predictive method whereas the empirical method appears to be more robust to extrapolation of the validity ranges. Both methods provide accurate predictions of stiffener strength when compared to the newly created FE database and existing test and numerical results.
15
Castaneda, Adrian Lance. „Selective histone deacetlyase inhibition decreases disease in lupus-prone mice“. Thesis, Virginia Tech, 2016. http://hdl.handle.net/10919/72952.
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Histone deacetylase 6 (HDAC6) is a cytoplasmic enzyme that acetylates several proteins that are involved in the immune response. HDAC6 inhibition has been shown in various models to decrease inflammation by altering various proteins involved in the dysregulation of B and T cell responses. In our current studies we sought to determine if HDAC6 inhibition would decrease disease in lupus-prone mice using two murine mouse models of SLE: MRL/lpr mice and NZB/W F1 mice. Both mouse models were fed a rodent diet formulated with the selective HDAC6 inhibitor ACY-738 (N-hydroxy-2-(1-phenylcycloproylamino) pyrimidine-5-carboxamide). NZBW mice received 18 weeks of treatment starting at 16-weeks-of-age and had an average of 57.3 +/- 14.6 ng/mL of ACY-738 in the plasma. MRL/lpr mice received 7 weeks of treatment starting at 11-weeks-of-age and had an average of 78.5 +/- 17.3 ng/mL of ACY-738 in the plasma. Controls received either dexamethasone 5x a week or were left untreated. As the mice aged, body weight, urine protein, and blood sera was collected weekly. Spleen cells were isolated following euthanasia for flow cytometry and kidneys were also collected for histological analyses. We found that in both mouse models that mice treated with ACY-738 had reduced splenic weight and IgG immunoglobulin isotypes. MRL/lpr mice that were treated with ACY-738 had a reduction in the number of IL-17+, ROR-gamma-t TH17 cells. NZBW/ F1 mice that received ACY-738 treatment also had a reduction in the TH17 cells and we observed a significant reduction in kidney pathology. Selective HDAC6 targeting may warrant future investigations as a potential therapeutic target for the treatment of SLE.Master of Science
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Neves, Elierton Evangelista das. „Blendas de isolante t?rmico para aplica??o em tubula??es de vapor na ind?stria do petr?leo“. PROGRAMA DE P?S-GRADUA??O EM ENGENHARIA MEC?NICA, 2016. https://repositorio.ufrn.br/jspui/handle/123456789/22215.
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O prop?sito deste trabalho ? descrever os procedimentos de desenvolvimento de um material alternativo para isolamento t?rmico a alta temperatura de tubula??es de distribui??o e inje??o de vapor mediante o reaproveitamento do refugo de materiais isolantes comerciais tais como o silicato de c?lcio e a l? de rocha associados em forma de blendas com o rejeito de perfura??o de po?os de petr?leo terrestre. Este trabalho dividiu-se em tr?s principais partes, a primeira refere-se ? coleta e prepara??o das amostras de materiais como encontrado em campo, ou seja, materiais que j? foram submetidos ?s altas temperaturas de processo, a segunda foi o planejamento com o aux?lio do software comercial para planejamento de experimentos Design-Expert? V10 e execu??o dos ensaios de determina??o da condutividade t?rmica para as composi??es planejadas com o uso do equipamento medidor de condutividade t?rmica KD2-Pro da empresa Decagon Devices, Inc., os resultados destes ensaios foram realimentados no Design-Expert? V10 para gera??o de um modelo matem?tico com sa?da gr?fica das curvas de n?vel que representam as blendas tern?rias e por fim executou-se uma simula??o num?rica em regime permanente com o uso do software comercial Ansys? para comprovar teoricamente a aplicabilidade do novo material como isolante t?rmico para conserva??o de energia e prote??o pessoal. Os resultados obtidos na simula??o num?rica apontaram que foi atingida uma temperatura m?dia m?xima de 57,3?C e 59,3?C nos ensaios experimentais na superf?cie de uma prote??o mec?nica em alum?nio do isolamento t?rmico projetado com uma espessura 38,1 mm e aplicado a uma tubula??o de a?o carbono di?metro nominal tr?s polegadas sch. 80 quando submetida a uma temperatura de 313?C.
The purpose of this work is to describe the procedures for the development of an alternative material used for thermal insulation in high temperatures of steam injection pipes through the reuse of waste commercial insulation materials such as calcium silicate and rock wool associates of blends forms with waste of on-shore oil well drilling. This work was divided into three main parts, the first relates to the collection and preparation of samples of materials as found in the field, i.e., materials that have been subjected to high temperatures process, the second was design of experiment and planning with the aid commercial software for DOE Design-Expert? V10 and execution of the determination of thermal conductivity tests for compositions designed using the thermal conductivity meter equipment KD2-Pro of the company Decagon Devices, Inc., the results of these tests were fed back into the Design- Expert? V10 to generate a mathematical model with graphical output of contour lines representing the ternary blends and finally was executed a computational simulation on a steady state basis with the use of commercial software Ansys? to theoretically prove the applicability of the new material as insulation for energy conservation and personal protection. The results of the computational simulation showed that a maximum average temperature of 57,3?C and 59,3?C to the experimental results in the external surface of mechanical protection of thermal insulation designed with a total thickness of 38.1 mm applied in a carbon steel pipe with nominal diameter of 3 inches and schedule 80 when subjected to the temperature of 313?C.
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Saberi, Sina. „Analysis of Unreinforced and Reinforced Tubular T-Joints Structures with Open Source Finite Element Software“. Master's thesis, Alma Mater Studiorum - Università di Bologna, 2021.
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Tubular Joints play quite a vital role in most of the marine structures. It is obvious that having full control about the capacity and strength of tubular joints would be very worthy to have good knowledge about the total performance of the structure. In recent years the application of the finite element method has become very popular in the analyses of different types of welded circular tubular joints. The rapid development of FE programs and computation facilities has extended the analyses in the study of stress distribution and load-displacement behavior of a joint to the assessment of the ultimate capacity. This thesis presents a numerical investigation using open source finite element analysis on tubular joints that are the main structural components of steel offshore structures. The studied joint is reinforced and unreinforced T-joint. In nowadays, several types of reinforcement are available to enhance the strength of tubular joints. Thus, for a better understanding of the static strength of joints, two common types of reinforcement plate (doubler and collar) were investigated. In this regards twelve T-Joint specimens subjected to axial brace load (6 in compression and 6 in tension) have been studied, with the different geometric, material property, and reinforced plate. In addition, different types of shell and solid finite elements are considered in this investigation. The shell elements are the linear triangular and quadrilateral elements and the solid elements are the linear tetrahedral and hexahedral elements. Also, this study was performed to investigate and report the usefulness of the open-source software programs Code\_Aster and Salome-Meca in implementing static finite element modeling of tubular joints.
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Pekalski, Marcin. „Renal allograft regjection : The role of TGFB in the differentiation on intragraft T cells and tubular epithelium“. Thesis, University of Newcastle Upon Tyne, 2009. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.506537.
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Jantakananuruk, Nattikarn. „Performance, Temperature and Concentration Profiles in a Non-Isothermal Ammonia-Fueled Tubular SOFC“. Digital WPI, 2019. https://digitalcommons.wpi.edu/etd-theses/1295.
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Ammonia has emerged as an attractive potential hydrogen carrier due to its extremely high energy density (hydrogen density), ease of storage and transportation as a liquid, and carbon-free nature. Direct utilization of ammonia in high-temperature solid oxide fuel cells (SOFCs) has been demonstrated over the past decade. Concurrence of in situ endothermic ammonia decomposition and exothermic electrochemical hydrogen oxidation permit efficient heat integration. In this study, the experimental analyses of axial temperature and concentration profiles along the tubular SOFC (t-SOFC) fed directly with ammonia are performed to investigate the coupled ammonia decomposition and hydrogen oxidation reactions as well as the effect of polarization. Fast ammonia decomposition over the Ni catalyst is evident at the inlet of t-SOFC and complete ammonia conversion is confirmed above 600ºC. It is found that direct ammonia-fueled t-SOFC and an equivalent hydrogen-nitrogen fueled t-SOFC provide identical performances. With 100 SCCM of ammonia fuel feed, a maximum power of 12.2 W and fuel utilization of 81% are obtained at 800ºC in a t-SOFC with active area of 32 cm2. The temperature and concentration profiles validate that the efficient heat integration inside ammonia-fueled t-SOFC is feasible if t-SOFC is operated at the temperature of 700ºC and below. The 23-hour performance test and SEM-EDS images of the fresh and used Ni-YSZ cermet surfaces confirm uniform performance and good durability of ammonia t-SOFC.
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Jung, Gonghyun. „Plasticity-Based Distortion Analysis for Fillet Welded Thin Plate T-Joints“. The Ohio State University, 2003. http://rave.ohiolink.edu/etdc/view?acc_num=osu1047434566.
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Law, Becker M. P. „The functional characterisation of human innate lymphocytes in renal fibrosis and chronic kidney disease“. Thesis, Queensland University of Technology, 2019. https://eprints.qut.edu.au/132513/1/Becker%20Meng-Po_Law_Thesis.pdf.
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This thesis by publication is a step forward in understanding the function of discrete immune cell populations in kidneys with chronic inflammation and fibrosis. We have successfully identified various human immune cells of the innate immune system as critical drivers of chronic kidney disease. The findings of this thesis sheds light on novel functions of innate immune cells and opens opportunities for the development of novel kidney therapies.
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Ha, Hong Clinical School St Vincent's Hospital Faculty of Medicine UNSW. „Role of T cells and cytokines in the induction of tolerance to renal tubular antigen in active Heymann nephritis“. Awarded by:University of New South Wales. Clinical School - St Vincent's Hospital, 2007. http://handle.unsw.edu.au/1959.4/40871.
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Idiopathic Membranous nephropathy (MN) is a common cause of nephrotic syndrome in humans, and many patients progress to end-stage kidney disease. The best available animal model of MN is active Heymann nephritis (HN) in which rats are immunized with renal tubular antigen (RTA) in complete Freund's adjuvant (CFA). Rats develop heavy proteinuria, a key measure of glomerular damage, and the disease is histologically identical to human MN. It has been thought that HN is mediated by antibody-based mechanisms. More recent evidence demonstrates a critical role for cytotoxic T cells. This thesis aims to further examine the role of T cell responses in active HN. First, the effect of the anti-CD3 monocIonal antibody (mAb) G4.18 was investigated. Anti-CD3 given 4 weeks after immunization prevented the development of proteinuria, delayed anti-RTA antibody responses, and reduced glomerular infiltration of CD8+ T cells and macrophages, but did not affect glomerular deposition of IgG or complement. Increased mRNA expression of the Th2 cytokines IL-4 and IL-5 was detected in draining lymph nodes. These findings suggest that immune deviation to a Th2 response reduces glomerular injury in HN. Second, the role of CD4+ T cells in immune tolerance was examined. Rats were given RTA in incomplete Freund's adjnvant (lFA) to induce tolerance to RTA, and three weeks later were immunized with RTA in CFA. Anti-CD4 mAb therapy at the time of RTA1IFA treatment had no effect on subsequent proteinuria or anti-RTA autibodies. Third, the role of IL-4 in this model of immune tolerance was examined. Anti-IL-4 mAb therapy blocked the induction of tolerance, and led to the development of proteinuria. Finally, the effect of treatment with IL-4 and IL-5 was examined. Treatment with these cytokines separately or together after immunization blocked the development of proteinuria, without a consistent effect on anti-RTA antibodies. These results demonstrate a central role for T cell regulation in HN, and show that immune deviation to a Th2 response is protective against glomerular injury. The findings may have implications in the future for focused therapeutic intervention in human idiopathic MN.
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Yang, Chao. „Syntheses and Bioactivities of Targeted and Conformationally Restrained Paclitaxel and Discodermolide Analogs“. Diss., Virginia Tech, 2008. http://hdl.handle.net/10919/28942.
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Paclitaxel was isolated from the bark of Taxus brevifolia in the late 1960s. It exerts its biological effect by promoting tubulin polymerization and stabilizing the resulting microtubules. Paclitaxel has become one of the most important current drugs for the treatment of breast and ovarian cancers.
Studies aimed at understanding the biologically active conformation of paclitaxel bound on β–tubulin are described. In this work, the synthesis of isotopically labeled taxol analogs is described and the REDOR studies of this compound complexed to tubulin agrees with the hypothesis that palictaxel adopts T-taxol conformation. Based on T-taxol conformation, macrocyclic analogs of taxol have been prepared and their biological activities were evaluated. The results show a direct evidence to support T-taxol conformation.
(+) Discodermolide is a polyketide isolated from the Caribbean deep sea sponge Discodermia dissoluta in 1990. Similar to paclitaxel, discodermolide interacts with tubulin and stabilizes the microtubule in vivo. Studies aimed at understanding the biologically active conformation of discodermolide bound on β–tubulin are described. In this work, the synthesis of fluorescent labeled discodermolide analogs is described and their biological activities were evaluated. Synthetic approaches to fluorescent labeled and isotopically labeled discodermolide analogs discodermolide are also described.Ph. D.
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Zhao, Jielu. „Design, Syntheses and Biological Activities of Paclitaxel Analogs“. Diss., Virginia Tech, 2011. http://hdl.handle.net/10919/77272.
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The conformation of paclitaxel in the bound state on the protein has been proposed to be the T-taxol conformation, and paclitaxel analogs constrained to the T-taxol conformation proved to be significantly more active than paclitaxel in both cytotoxicity and tubulin polymerization assays, thus validating the T-taxol conformation as the tubulin-binding conformation. In this work, eight compounds containing an aza-tricyclic moiety as a mimic of the baccatin core of paclitaxel have been designed and synthesized as water-soluble simplified paclitaxel analogs, among which 3.50-3.52 and 3.55 were conformationally constrained analogs designed to bind to the paclitaxel binding site of tubulin, based on their similarity to the T-taxol conformation. The open-chain analogs 3.41-3.43 and 3.57 and the bridged analogs 3.50-3.52 and 3.55 were evaluated for their antiproliferative activities against the A2780 cell lines. Analogs 3.50-3.52 and 3.55 which were designed to adopt the T-taxol conformation showed similar antiproliferative activities compared to their open-chain counterparts. They were all much less active than paclitaxel. In the second project, a series of paclitaxel analogs with various thio-containing linkers at C-2′ and C-7 positions were designed and synthesized in our lab. These analogs were attached to the surfaces of gold nanoparticles by CytImmune Sciences for the development of mutifunctional tumor-targeting agents. The native analogs and the gold bound analogs were evaluated for their antiproliferative activities against the A2780 cell line. All the compounds tested showed comparable or better activities than paclitaxel. Stability studies were performed for selected analogs in hydrolysis buffer, which showed that the analogs released paclitaxel in buffer over time. In the third project, the synthesis of a conformationally constrained paclitaxel analog which was designed to mimic the REDOR-taxol conformation was attempted. Two synthetic routes were tried and significant progress was made toward the synthesis of the conformationally constrained analog. However, both of the current synthetic routes failed to produce the key intermediate that would serve as the precursor for a ring-closing metathesis reaction to furnish the macrocyclic ring.Ph. D.
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Breda, Philippe Christophe [Verfasser]. „Renal proximal tubular epithelial cells exert immunomodulatory function by driving inflammatory CD4+ T cell responses : Renale proximale Tubulusepithelzellen üben durch Auslösen von inflammatorischen T-Zell-Antworten eine immunmodulatorische Funktion aus / Philippe Christophe Breda“. Hamburg : Staats- und Universitätsbibliothek Hamburg Carl von Ossietzky, 2020. http://d-nb.info/1221276344/34.
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Liu, Changhui. „Syntheses and Bioactivities of Targeted and Conformationally Restrained Taxol Analogs“. Diss., Virginia Tech, 2004. http://hdl.handle.net/10919/11186.
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Taxol (1) was first isolated from the bark of the Pacific yew about 35 years ago by Drs. Wall and Wani. Although its development as an anticancer agent was delayed by numerous reasons, including its scarcity and insolubility, the discovery of its tubulin-assembly activity and other factors motivated oncologists to overcome these problems. It has since become one of the most important current drugs for the treatment of several cancers, including breast and ovarian cancers.
Like almost all anticancer drugs taxol does have some toxic side effects and many tumors also show significant resistance to therapy with taxol. Drug targeting studies aimed at improving its selectivity and efficacy is described. Two targeting methods, the estrogen receptor (ER) directed targeting and colloidal gold (cAu)directed targeting, were used in our research. In this dissertation, a series of estradiol-taxol conjugates (ETCs) were synthesized. They were active in four cytotoxicity assays and tubulin polymerization assay, but less active than taxol. One of them showed the desired selectivity for ER positive cancer cells.
Recently, several studies have attempted to elucidate the bioactive binding conformation of taxol on microtubules. Three models have been proposed for this conformation. The T-taxol conformation was proposed by Dr. Snyder based on electron crystallographic density and molecular modeling. In this dessertation, a series of cyclopropyl-containing taxol analogs and macrocyclic taxol lactones were synthesized. The bioassay results showed they are less active than taxol. The molecular modeling studies suggested that the cyclopropyl-containing taxol analogs could not adopt the T-taxol conformation, which would result in the loss of bioactivities. It is an indirect evidence to support T-taxol conformation. As for macrocyclic taxol lactones, it is proposed that they would have a close contact between the ester moiety on the C-3' phenyl ring and Phe272 of the β-tubulin protein when they adopt T-taxol conformation. It will push the macrocyclics out of the binding pocket and lead to the lost of bioactivities.Ph. D.
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Pit?goras, Tatiana Zotti. „O emprego da eletroestimula??o associada ? t?cnica de tubula??o na regenera??o do nervo ci?tico de ratos wistar ap?s transec??o sem perda de subst?ncia“. Pontif?cia Universidade Cat?lica do Rio Grande do Sul, 2018. http://tede2.pucrs.br/tede2/handle/tede/8213.
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Introduction: Peripheral nerve transection injuries are common and occur frequently in clinical practice and are responsible for serious problems such as pain, loss of sensibility and motor, and permanent sequelae. Great advances were obtained in the treatment of peripheral nerve lesions due to greater knowledge about their physiology and the development of techniques such as microsurgery. The results of electrical stimulation are encouraging and suggest its use as an alternative treatment. Objective: To evaluate, in vivo, the use of electrostimulation (EE) associated with the tubulization technique on the repair of sciatic nerve injury in Wistar rats. Materials and Methods: Ninety male Wistar isogenic rats weighing between 200 and 300 grams were divided into three groups of 30 rats (electrostimulation associated with the tubing technique (EE), tubing suture (ST) and suture(SUT), which were subdivided into three other groups with ten animals according to the evaluation time, with three, six and nine weeks postoperative. Regeneration was assessed by ?walking track? analysis and histological analysis in which determination of the area and number of Schwann cells in the nerve samples. Results: In the functional evaluation, the group that received only one EE with 20 Hz, 3 V for one hour presented a superior result, statistically significant when compared to those stimulated more than once, however when comparing the three different types of treatment at the end of the nine weeks there was statistically significant superiority in the treated with standard suture. Regarding the number of cells, no statistically significant result was found in either group. The findings related to the nerve area, in those submitted to EE at three weeks, when compared to the other groups in the same period, were significant, and in the comparison within the same group, those with suture and tube at six weeks obtained a regenerated nerve with area in a statistically significant way.
Introdu??o: Traumatismos por transec??o de nervo perif?rico s?o comuns e ocorrem, frequentemente, na pr?tica cl?nica, sendo respons?veis por problemas graves como dor, perda de sensibilidade e motricidade, al?m de sequelas permanentes. Grandes avan?os foram obtidos no tratamento das les?es dos nervos perif?ricos, devido ao maior conhecimento sobre sua fisiologia e ao desenvolvimento de t?cnicas como a microcirurgia. Os resultados da estimula??o el?trica s?o encorajadores e sugerem seu uso como alternativa de tratamento. Objetivo: Avaliar, in vivo, o uso da eletroestimula??o (EE) associada ? t?cnica de tubuliza??o sobre o reparo de les?o de nervo ci?tico, em ratos Wistar. Materiais e m?todos: Noventa ratos isog?nicos da ra?a Wistar, machos, adultos, pesando entre 200 e 300 gramas de massa corporal, foram divididos em tr?s grupos de 30 ratos (eletroestimula??o associada ? t?cnica de tubuliza??o (EE), sutura com tubuliza??o (ST) e sutura padr?o (SUT). Os tr?s grupos foram ainda subdivididos em tr?s grupos com 10 animais, de acordo com o tempo de avalia??o (tr?s, seis e nove semanas de p?s-operat?rio). A regenera??o foi avaliada atrav?s da an?lise da marcha e an?lise histol?gica, em que houve a determina??o da ?rea e do n?mero de c?lulas de Schwann nas amostras de nervo. Resultados: Na avalia??o funcional, o grupo que recebeu somente uma EE com 20 Hz e 3V por uma hora apresentou um resultado superior se comparado com os estimulados mais de uma vez. Entretanto, ao se comparar os tr?s diferentes tipos de tratamento ao final das nove semanas, os ratos com sutura padr?o apresentaram resultados melhores. Com rela??o ao n?mero de c?lulas, n?o foi encontrado resultado estatisticamente significativo em nenhum dos grupos. Em rela??o aos achados relacionados ? ?rea do nervo, naqueles submetidos ? EE com tr?s semanas, quando comparados aos outros grupos no mesmo per?odo, houve signific?ncia, sendo que na compara??o dentro do mesmo grupo, aqueles com sutura e tubo com seis semanas, obtiveram um nervo regenerado com ?rea maior.
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Metaferia, Belhu B. „Synthesis of Taxol™ Analogs as Conformational Probes“. Diss., Virginia Tech, 2002. http://hdl.handle.net/10919/28428.
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Taxol™, isolated from the bark of Taxus brevifolia in the late 1960s, and the semisynthetic analog Taxotere™ have proven clinical importance for the treatment of ovarian and breast cancer. Taxol™ exerts its biological effect by binding to polymerized tubulin and stabilizing the resulting microtubules. Studies aimed at understanding the biologically active conformation of taxol and its binding environment on β-tubulin are described. This knowledge is important because it could lead to the design of structurally less complicated drugs with better efficacy and better bioavailability. Moreover, the information can be extended to other natural products that possess microtubule-stabilizing properties similar to Taxol™. In this work, the synthesis of a triply labeled taxol analog is described as well as REDOR studies of this compound complexed to tubulin are in progress. Macrocyclic analogs of taxol have been prepared and their biological activities were evaluated. Chemical modeling of these analogs and their activities agrees with the hypothesis that Taxol™ adopts T-shaped conformation. Difficulties were encountered with the key ring-closing metathesis strategy, suggesting that a more flexible and efficient macrocyclization method will be needed to synthesize additional macrocyclic analogs.Ph. D.
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Nizer, Adriano. „Avaliação da influência do esforço normal no banzo no comportamento de ligações tubulares em aço“. Universidade do Estado do Rio de Janeiro, 2014. http://www.bdtd.uerj.br/tde_busca/arquivo.php?codArquivo=7761.
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A demanda pelo uso de perfis tubulares em estruturas na construção civil tem tido grande avanço no Brasil, apesar de ser, há muito tempo, amplamente empregado na Europa e países desenvolvidos. O lançamento de uma norma técnica brasileira específica para dimensionamento de perfis tubulares confirma esta tendência, havendo então a necessidade de uma maior divulgação e execução de estudos e trabalhos de pesquisa para uma melhor compreensão e desenvolvimento desta tecnologia. O presente trabalho apresenta uma análise da influência da aplicação de esforço normal no banzo no comportamento de ligações tubulares do tipo T. No desenvolvimento deste trabalho, foram realizados seis ensaios em laboratório com ligações do tipo T com perfis do tipo RHS para o banzo e SHS para o montante, sendo utilizados perfis conformados a frio para composição das ligações ensaiadas. Do total dos ensaios foram executados dois ensaios sem aplicação de esforço normal no banzo; dois com aplicação de esforço normal de compressão e dois com aplicação de esforço normal de tração. A resistência última das ligações nos ensaios foi obtida por meio do Critério de Deformação Limite proposto por diversos pesquisadores. Estes resultados foram comparados com os resultados obtidos em modelos numéricos em elementos finitos desenvolvidos no programa ANSYS 12.0, sendo considerado nestes modelos as não-linearidades geométricas e de material. Estes resultados também foram comparados com os resultados teóricos obtidos com base nas prescrições constantes nas normas Eurocode 3; norma brasileira NBR 16239 e do CIDECT. Conclui-se com este estudo que os resultados obtidos tanto nos ensaios experimentais quanto nos modelos numéricos ficaram a favor da segurança quando comparados com os valores teóricos obtidos pelas normas Eurocode 3 e NBR 16239:2013 e CIDECT com o banzo sem aplicação de esforço normal e com aplicação de esforço normal de compressão de até 60% e 80 % da carga de plastificação do banzo, respectivamente, para o Eurocode 3/NBR16239:2013 e para o CIDECT. As resistências obtidas para as ligações com a aplicação de esforço normal de tração no banzo foram superiores aos resultados teóricos no caso estudado.The demand for the use of hollow sections structures in construction has had great progress in Brazil, despite being a long time widely used in Europe and developed countries. The release of a Brazilian Technical Standard specific for design of hollow sections, confirms this trend, and the need for increased dissemination and implementation of studies and research for a better understanding and development of this technology. This paper presents an analysis of the influence of chord normal stresses on the behavior of hollow sections connections, specifically for a T tubular joint. The experimental program consisted of six tests where two experiments were executed without chord axial forces, two were performed with compressive axial forces and two tension axial forces. The tested joints ultimate strengths were determined using deformation limit criteria proposed by several researchers. These results were then compared to the results obtained from a finite element numerical model developed 12.0 ANSYS program that included geometrical and material nonlinearities. These results were also compared to the design provisions present at the Eurocode 3; Brazilian standard NBR 16239:2013 and CIDECT. This assessment indicated that the results obtained in both experimental tests and in the numerical models were in favor of security when compared to the theoretical values obtained by all the investigated standards for chords without axial forces and with compressive axial forces corresponding to 60% and 80% of the chord plastic resistance, respectively, according to Eurocode 3/NBR16239:2013 and CIDECT. The obtained resistances for the joints applying tensile axial force on the chord were superior to the predicted theoretical results in the studied cases.
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Veber, Romain. „Néogenèse lymphoïde au cours du lupus : mécanismes fondamentaux et pistes thérapeutiques“. Thesis, Strasbourg, 2018. http://www.theses.fr/2018STRAJ092.
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Le lupus érythémateux disséminé est une maladie auto-immune systémique chronique dont les atteintes sont multiples, l’atteinte rénale constituant la plus sévère. Une conjonction de facteurs génétiques et environnementaux conduit au développement de la maladie qui se traduit par une rupture de tolérance au soi. L’un des signes biologiques majeurs est la production d’auto-anticorps dirigés contre des composants nucléaires qui, en se déposant dans divers tissus dont les reins, génèrent une inflammation chronique conduisant au dysfonctionnement de l’organe. Le dépôt d’autoanticorps s’accompagne d’infiltrats de cellules immunitaires, qui, dans ce type d’inflammation, peuvent se transformer en structures lymphoïdes ectopiques fonctionnelles appelées Organes Lymphoïdes Tertiaires (OLT). Des OLT sont retrouvés dans diverses pathologies et participent à la génération locale de réponses immunitaires bénéfiques (infections/cancers) ou délétères (maladies auto-immunes). Mon projet de thèse a porté sur la mise en évidence d’OLT dans les reins au cours du lupus et sur l’étude des mécanismes permettant leur formation. Nous avons tout d’abord caractérisé les infiltrats inflammatoires présents dans les reins de souris NZB/W, modèle murin spontané de lupus. Ces infiltrats sont hautement organisés et constituent des OLT fonctionnels, potentiellement impliqués dans la néphrite lupique. Nous nous sommes ensuite intéressés aux mécanismes de mise en place de ces OLT et avons identifié les lymphocytes T et le récepteur aux chimiokines CXCR3 comme des éléments clés de ce processus et de la pathologie lupique. Les données obtenues apportent une meilleure compréhension fondamentale de la néogenèse lymphoïde au cours du lupus et ouvrent la voie vers de nouvelles stratégies thérapeutiques permettant de traiter la néphrite lupiqueSystemic lupus erythematosus (SLE) is a chronic systemic autoimmune disease with multiple outcomes, with renal damage being the most severe. A combination of genetic and environmental factors leads to the development of the disease, which results in a break of immune tolerance. One of the major biological signs is the production of autoantibodies to nuclear components that, by depositing in various tissues including the kidneys, generate chronic inflammation leading to organ dysfunction. Deposition of autoantibodies is accompanied by immune cell infiltrates, which in this type of inflammation can be transformed into functional ectopic lymphoid structures called Tertiary Lymphoid Organs (TLO). TLO are found in various diseases and participate in the local generation of beneficial (infections / cancers) or deleterious (autoimmune diseases) immune responses. My thesis project focused on the demonstration of TLO in the kidneys during lupus and on the study of the mechanisms allowing their formation. We first characterized the inflammatory infiltrates present in the kidneys of NZB/W mice, a spontaneous murine model of lupus. These infiltrates are highly organized and constitute functional TLO that are potentially implicated in lupus nephritis. We then investigated the mechanisms of development of these TLO and identified T lymphocytes and the CXCR3 chemokine receptor as key components of this process and lupus pathology. The data obtained provide a better understanding of lymphoid neogenesis during lupus and pave the way for new therapeutic strategies to treat lupus nephritis
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Wagner, Eva. „Cardiac T-Tubule Membranes - Nanostructure and Remodeling Mechanisms in Disease“. Doctoral thesis, 2012. http://hdl.handle.net/11858/00-1735-0000-0001-BB48-1.
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Dyachok, Oksana. „Modulation Of Cardiac Inward-Rectifier K+ Current IK1 By Intracellular K+ And Extracellular K+“. 2011. http://hdl.handle.net/10222/14391.
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The inwardly-rectifying K+ current (IK1) is important for heart cell function because it sets the resting potential, influences cell excitability, and promotes repolarization of the action potential. My objective was to investigate the modulation of IK1 by extracellular K+ (K+o) and intracellular K+ (K+i). IK1 was recorded from whole-cell-configured guinea-pig ventricular myocytes that were dialyzed with Na+-free EGTA-buffered pipette-filling solution and bathed with Na+ or NMDG+ solution that contained agents that inhibit non-IK1 currents.
Lowering K+o from standard 5.4 to 2 and 1 mM shifted the reversal potential (Erev) of IK1 in accord with calculated K+ equilibrium potential (EK), and altered IK1 amplitude in accord with conductance (GK1)? ?K+o. Surprisingly, myocytes bathed with 0-mM K+ solution had a small outward IK1 at holding potential (Vhold) ?85 mV. This IK1 was attributed to channel-activation by T-tubular K+ (K+T) whose concentration is sensitive to the flow of T-tubular IK1. K+T in myocytes bathed with 0-mM K+ solution was ? 3.2 mM at Vhold ?85 mV, but ? 0.3 mM following large K+T-depleting flows of inward IK1 at ?160 mV. Results consistent with interplay of IK1 and K+T were also obtained in experiments on myocytes bathed with 2-, 5.4-, and 15-mM K+ solution.
Myocytes were dialyzed with pipette solutions that contained 0-140 mM K+ to investigate modulation by K+i. When IK1 at Vhold was kept small, Erev varied with pipette K+ in a near-Nernstian manner (i.e., Erev ? EK); however, when IK1 (Vhold) was large and inward, Erev was markedly negative to nominal EK. Findings in experiments that involved shifting Vhold, changing K+o, and application of Ba2+ and Cs+ suggest that the magnitude/direction of IK1 strongly affects the concentration of K+ in submembrane cytoplasm. Classical GK1-voltage parameters GK1max and V0.5 (but not slope factor) were affected by decreases in K+i: GK1max declined by ? 25% per decade decrease in K+i, and V0.5 shifted approximately as 0.5 ? EK-shift. The latter findings are discussed and compared with those of earlier studies on the dependence of inwardly-rectifying K+ conductance on K+i.
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Brandenburg, Sören. „Über die differentielle Regulation von Ionenkanälen in spezifischen Nanodomänen atrialer und ventrikulärer Kardiomyozyten“. Doctoral thesis, 2017. http://hdl.handle.net/11858/00-1735-0000-0023-3E50-C.
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Chow, Brenda Marilyn. „Functional Characterization of Amphiphysin in Drosophila melanogaster“. Thesis, 2012. http://hdl.handle.net/1807/33961.
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Amphiphysin (Amph) is a multi-domain protein that has been implicated in synaptic vesicle (SV) endocytosis. In vertebrates, Amph1 associates with SVs and binds to known endocytic proteins, such as dynamin and clathrin. Overexpression of the vertebrate Amph1 SH3 domain is sufficient to inhibit SV endocytosis in the lamprey synapse. However, these in vitro and overexpression studies may not reflect Amph function in vivo. To investigate Amph function in vivo, I used Drosophila melanogaster as a model organism. I discovered that Drosophila Amph was broadly expressed throughout all developmental stages and was also highly expressed in specialized membranes such as the postsynaptic membrane at the larval neuromuscular junction and the t-tubule membranes of muscles. amph mutants were viable and had normal synaptic transmission, results that were inconsistent with a role for Amph in SV endocytosis. However, amph mutants had impaired locomotion, which may reflect a defect in the t-tubule network, a membrane system that is specialized to couple muscle membrane excitation to muscle contraction. To further explore this idea, I undertook a structure-function approach to ask if different Amph functional domains could rescue the t-tubule and locomotory defects observed in amph mutants. Partial rescue was observed for most constructs, suggesting that Amph function was dependent on more than one domain. To further elucidate how Amph functions at the t-tubule network, I used different in vitro methods to investigate novel protein partners for Amph. A GST pull-down approach identified actin as a potential Amph partner, consistent with studies in yeast. However, I could not confirm a direct interaction between Amph and actin in Drosophila. Another candidate partner was the actin-nucleating protein, Wiskott Aldrich Syndrome Protein, WASP. Although WASP and Amph could be coimmunoprecipitated in vitro, WASP was not expressed at the t-tubule membrane, and Wasp mutants had normal t-tubule morphology. Clearly, Amph is essential for normal t-tubule morphology and future work is needed to further define the function of Amph at the t-tubule network.
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Mercier, Frédéric. „L'implication des tubules T dans la repolarisation ventriculaire chez la souris“. Thèse, 2007. http://hdl.handle.net/1866/8071.
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Musa, Idris. „Fatigue design of concrete-filled steel tubular T- and K-joints“. Thesis, 2019. http://hdl.handle.net/1959.7/uws:51918.
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Steel tubular members are widely used in offshore structures and in infrastructure entities such as oil platforms and bridges. The tubular members are exposed to repetitive loading from sea waves, wind and traffic. Repetitive loading causes deterioration of the structural members through crack initiation and propagation which is called ‘fatigue’. Fatigue strength has always taken most attention in the design of steel tubular members. Due to geometric discontinuity at the connected steel tubular members, high stress concentration exists at the joint. The location of high stresses is usually the location of fatigue crack initiation. In the last century, a large amount of research was conducted on empty (non-filled) steel tubular joints which resulted in the development of various fatigue design guidelines. At the beginning of the current century, researchers have effectively used concrete filled steel tubes to reduce stress concentration at the joint. With regard to the fatigue strength of welded steel tubular joints, there is still lack of understanding and further research is required. In this study, a comprehensive study, which covers experimental and numerical analysis, on the fatigue performance of CHS-to-CFCHS T- and K-joints based on the hot spot stress method has been conducted. In the experimental program, three CHS-to-CFCHS T-joints have been tested experimentally under axial tension, axial compression, in-plane bending and out-of-plane bending in the brace. SCF measurements in the three specimens under the three loading formats have been performed and compared with those for empty T-joints. Additionally, a CHS-to-CFCHS K-joint specimen was tested under balanced axial loading. SCF measurements around the brace-chord intersection have been performed. The experimental program was followed by an extensive numerical analysis study. A large number of finite element CHS-to-CFCHS T- and K-joints models were developed. The effect of the joint geometric parameters on the maximum SCF in CHS-to-CFCHS T- and K-joints has been studied and compared with those for empty T- and K-joints. Parametric equations for predicting the maximum SCF in CHS-to-CFCHS T-joints under the three basic loading formats and in CHS-to-CFCHS K-joints under balanced axial loading have been derived.
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Cheng, Shumin. „Non-destructive evaluation of cracking in tubular T-joints using vibration procedures /“. 1998.
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