Dissertations / Theses on the topic 'Methyl transferase'
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Pandya, Bhavna Kalpesh. "Thiopurine s-methyl transferase gene polymorphism : Clinical correlations." Thesis, University of Manchester, 2010. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.529233.
Full textJiang, Hong, and 姜紅. "Effects of estrogen on human catechol-O-methyl transferase." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2001. http://hub.hku.hk/bib/B31241864.
Full textJiang, Hong. "Effects of estrogen on human catechol-O-methyl transferase." Hong Kong : University of Hong Kong, 2001. http://sunzi.lib.hku.hk/hkuto/record.jsp?B23273744.
Full textHolford, Kenneth C. Borst David Wellington. "Molecular characterization of farnesoic acid o-methyl transferase in the American lobster (Homarus americanus)." Normal, Ill. Illinois State University, 2000. http://wwwlib.umi.com/cr/ilstu/fullcit?p9986727.
Full textTitle from title page screen, viewed May 11, 2006. Dissertation Committee: David Borst (chair), Anthony Otsuka, Radheshyam Jayaswal, Paul Garris, David Williams. Includes bibliographical references (leaves 130-135) and abstract. Also available in print.
Hahn, Eric [Verfasser]. "Der Einfluss des Val158/108Met Polymorphismus der Catechol-O-Methyl-Transferase auf behaviorale Inhibition bei Schizophrenie / Eric Hahn." Berlin : Medizinische Fakultät Charité - Universitätsmedizin Berlin, 2011. http://d-nb.info/1025510348/34.
Full textSalvidge, William. "The role of the histone methyl-transferase, set1, in variable gene expression and cell type proportioning in D. discoideum." Thesis, University of Manchester, 2018. https://www.research.manchester.ac.uk/portal/en/theses/the-role-of-the-histone-methyltransferase-set1-in-variable-gene-expression-and-cell-type-proportioning-in-d-discoideum(d3d7ea3b-7f44-4f8a-ab65-b7d36a295604).html.
Full textEsberard, Barbara Cathalá. "Polimorfismos do gene da tiopurina metiltransferase (TPMT) em pacientes com doenças inflamatórias intestinais: avaliação da prevalência e correlação com efeitos colaterais." Universidade do Estado do Rio de Janeiro, 2013. http://www.bdtd.uerj.br/tde_busca/arquivo.php?codArquivo=6947.
Full textAlthough azathioprine is commonly used for treating patients with inflammatory bowel disease (IBD), there is still concern about potential severe side effects. Determining the Thiopurine-Methyl-Transferase (TPMT) genotype is expected to identify patients predisposition in respect of toxicity prior to azathioprine administration. The aim of this study was to analyze the prevalence of TPMT genotypes and association with drug toxicity in IBD patients from south-eastern Brazil, constituted by a heterogeneous population. We analyzed 146 Crohns disease (CD) and 73 ulcerative colitis (UC) patients, for the presence of the major TPMT genetic variants (TPMP*2, *3A, *3C) by means of specific allele and RFLP PCR. Clinical data were systematically recorded and correlated with the genotype results, and analyzed in multivariate models. Among the side effects recorded from patients taking azathioprine, 14 presented pancreatitis and/or elevation of pancreatic enzymes, while 6 had liver toxicity, and 2 had neutropenia. TPMT polymorphisms were detected in 37/219 patients (8 heterozygous for *2, 11 heterozygous for *3A and 18 heterozygous for *3C). No homozygotic polymorphisms were found. A positive correlation was found between the elevation of pancreatic enzymes and either TPMT*2 or TPMT*3C. The prevalence of polymorphisms in this study (16,89%) was greater than described with caucasian population or other Brazilian studies. Despite the prevalence of genotype *3C, it was not the only polymorphism shown as observed in other populations. Two genetic variants of TPMT gene (*2 and *3C) are associated with azathioprine toxicity in IBD patients from a south-eastern Brazilian population. Genetic testing may help in the selection of the most appropriate medication prior to treatment initiation.
Zhang, Rui. "Association study of adverse events with monoamine oxidase inhibitors and catechol-o-methyl transferase inhibitors in subjects with Parkinson's disease." Thesis, Boston University, 2012. https://hdl.handle.net/2144/31630.
Full textPLEASE NOTE: Boston University Libraries did not receive an Authorization To Manage form for this thesis or dissertation. It is therefore not openly accessible, though it may be available by request. If you are the author or principal advisor of this work and would like to request open access for it, please contact us at open-help@bu.edu. Thank you.
Introduction: Parkinson's disease (PO) is a neurodegenerative disorder. Medication is by far the most effective and important treatment for PO and levodopa is the most effective and commonly used medicine to control motor symptoms in PD. However, its long-term usage often induces several adverse events (AEs). Both combination therapy of monoamine oxidase type B inhibitor. (MAOBI) with levodopa and catechol-0-methyltransferase inhibitor (COMTI) with levodopa were demonstrated to provide benefits to PO patients, such as regulating motor fluctuations and reducing levodopa dose, but are accompanied by increased frequency of dopaminergic AEs. Available data is too limited to directly compare the safety of these combination therapies (MAOBI vs. COMTI). Thus the aim of this study is to investigate whether MAOBI and COMTI have different AE profiles. Methods: All the data used to analyze the AEs of different PO medications were retrieved from "The Boston University Medical Center's Parkinson's Disease and Movement Disorder Database". Ten categories of AEs, i.e. compulsive behavior, dyskinesia, dementia, depression, freezing, hallucinations, motor fluctuations, orthostatic hypotension, other autonomic dysfunction and psychosis, were compared between MAOBI and COMTI groups. Fisher's exact test and multivariable logistic regression models were applied to analyze data. Results: In total 87 subjects were included in the analysis. Out of 10 AEs, presence of dementia was significantly different between the MAOBI and COMTI groups with OR of 6.9 (COMTI vs. MAOBI, 95%CI: 1.3-37.0). Motor fluctuations were also found to be differently distributed in the two medication groups with OR of 3.1 (COMTI vs. MAOBI, 95%CI: 1.0-9.8). Conclusion: COMTI combined with levodopa therapy was more likely to be associated with dementia and motor fluctuations than MAOBI. The results need to be further tested in other independent studies.
2031-01-01
Jacobs, Sarah. "Development of a COMT PCR multiplex to investigate resilience, anxiety and childhood trauma in a South African population." University of the Western Cape, 2020. http://hdl.handle.net/11394/7923.
Full textAnxiety, resilience and childhood trauma can be categorized as functional behavioural categories, with a wealth of research behind each. The research approach adopted for each, in most cases, is either from a genetic or neuropsychological standpoint, with few studies combining both to better understand all three functional behavioural categories as a multidimensional construct A number of candidate genes have been identified as markers for anxiety, resilience and childhood trauma, of which Catechol-methyl-transferase (COMT) and several respective single nucleotide polymorphisms (SNPs) are included. Although COMT SNPs have been linked to at least one of the functional categories, with a handful of haplotypes identified, to our knowledge no study has investigated the combination of SNPs selected for this study (rs6269, rs4818, rs4680, rs4633, rs737865, rs2075507) as a possible haplotype, specifically in a South African population. The use of SNaPshot for the genotyping of genes is an efficient and reliable means of identifying genotype frequencies and haplotypes in large sample groups, yet when selecting more than two SNPs of interest, the development of a multiplex assay is ideal. The first aim of the study was to design and optimize a multiplex assay to genotype several COMT SNPs. The primer design, multiplex optimization and SNaPshot conditions used showed good working parameters that can be utilized and further improved by optimization. Self-report measures are widely used to measure psychiatric disorders, such as anxiety, and has also been used for the measurement of resilience and childhood trauma. With each functional behavioural category well investigated in its respective domain, there is a need to investigate all three as a collective in a South African population due to the high rate of anxiety and childhood trauma exposure in communities. The second aim of the study was to investigate the prevalence of anxiety, resilience and childhood as functional behavioural categories in the full South African sample group; and the role of sex, through established self-report measures and respective normative data. Additionally, this carried over into investigating the correlation between anxiety, resilience and childhood trauma as a multidimensional construct in both the full South African sample and between sexes. There is a clear relationship which exists between all three functional behavioural categories, as they show a correlation in various dimensions independent of one another. Higher anxiety levels amongst females were reported, with no difference between sexes for resiliency. The empirical data collected from both COMT SNP and self-report measures for male and female where explored and reviewed against current literature for better understanding and insight into the association of COMT SNPs with anxiety, resilience and childhood trauma in a South African population. The results of this study to understand the complexity and association of all three functional behavioural categories as a multidimensional construct will be invaluable and may assist in the identification of possible risk factors which are essential for the promotion of better mental health in society.
Thomas, Sherine Elizabeth. "Targeting Mycobacterium abscessus infection in cystic fibrosis : a structure-guided fragment-based drug discovery approach." Thesis, University of Cambridge, 2019. https://www.repository.cam.ac.uk/handle/1810/289126.
Full textNiehaus, Thomas Daniel. "ELUCIDATING THE BIOCHEMICAL WIZARDRY OF TRITERPENE METABOLISM IN BOTROYCOCCUS BRAUNII." UKnowledge, 2011. http://uknowledge.uky.edu/pss_etds/1.
Full textWasserman, Jacob Israel. "Progress toward the synthesis of structurally novel cytotoxic chlorinated diterpenes and identification of 3-isopropylmalate as an endogenous substrate of a methyl transferase in the yeast S. Cerevisiae." Diss., Restricted to subscribing institutions, 2004. http://proquest.umi.com/pqdweb?did=765405381&sid=1&Fmt=2&clientId=1564&RQT=309&VName=PQD.
Full textAlonso, Hernan, and hernan alonso@anu edu au. "Computer Modelling and Simulations of Enzymes and their Mechanisms." The Australian National University. The John Curtin School of Medical Research, 2006. http://thesis.anu.edu.au./public/adt-ANU20061212.161155.
Full textEklund, Birgitta I. "Role of Multiple Glutathione Transferases in Bioactivation of Thiopurine Prodrugs : Studies of Human Soluble Glutathione Transferases from Alpha, Kappa, Mu, Omega, Pi, Theta, and Zeta Classes." Doctoral thesis, Uppsala : Acta Universitatis Upsaliensis : Universitetsbiblioteket [distributör], 2006. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-7102.
Full textKnuhtsen, Astrid. "Searching for inhibitors of the protein arginine methyl transferases : synthesis and characterisation of peptidomimetic ligands." Thesis, University of British Columbia, 2016. http://hdl.handle.net/2429/57228.
Full textPharmaceutical Sciences, Faculty of
Graduate
Moreno, Daniel Antunes. "Estudo da Expressão dos Genes DNMT1, DNMT3A, DNMT3B, MGMT e Efeitos da Zebularina em Glioblastoma." Universidade de São Paulo, 2012. http://www.teses.usp.br/teses/disponiveis/17/17135/tde-22042013-102215/.
Full textGliomas arise from glial cells and are the most common central nervous system tumors. They are divided in four groups: pilocytic astrocytoma (grade I), difuse astrocytoma (grade II), anaplastic astrocytoma (grade III) and glioblastoma (grade IV or GBM). GBM is the most frequent and aggressive glioma. This type of tumor can occur in any age but its rare in children. Actually, surgery, radiotherapy and temozolomide (TMZ) adjuvant/concomitant chemotherapy has been the standard treatment protocol but the survival is extremely poor. In addition most patients do not respond to TMZ indicating the need for alternative chemotherapeutic agents. Zebularine (ZB) is a DNA metiltransferase inhibitor (DNMTi) stable, slight toxic that has been showed promise effects in cancer including radiosensitivity but little is known about ZB in glioblastoma. The objectives of this study were analyze DNMT1, DNMT3A, DNMT3B, MGMT gene expression profile in 5 samples of normal brain, 6 GBM cell lines and 33 glioma samples (13 grade I, 2 grade II e 18 grade IV), correlate with different gliomas grades and analyze the effects of ZB isolate and in combination with TMZ in irradiated and non irradiated GBM cell lines. Gene expression assays was made using Real Time PCR. Proliferation, clonogenic, radiation and apoptosis assays were realized in three GBM cell lines (U251, SF88, T98G) and one fibroblast cell line (MRC5). We also made proliferation assays in 5 primary cultures of samples of GMB. MGMT and DNMT3A genes showed higher expression in normal brain compared to gliomas and GBM cell lines. DNMT3B gene showed higher expression in GBM cell lines compared with normal brain and DNMT1 showed no significant differences among samples analyzed. We observed decrease of cell proliferation from 50-100µM of ZB and 250-500µM of TMZ on GBM cell lines and from 50µM of ZB for primary GBM samples. It was not observed synergy in the most combinations doses of ZB and TMZ (Calcusyn software). It was observed that 100µM of ZB and 10µM of TMZ decrease colony formation on U251 and SF188 cell lines non irradiated and irradiated with 2, 4, and 6Gy. T98G that express MGMT, did not respond to TMZ but showed response to ZB. It was also observed that 10µM of TMZ is more cytotoxic than 100µM of ZB in fibroblast cell line non irradiated and irradiated with 2Gy. ZB increase apoptosis from 100µM on the three GBM cell lines. Results obtained in this study can indicate that ZB may be an interestig therapeutic target for future studies in glioblastoma.
Challansonnex, Arnaud. "Transferts couplés chaleur/masse dans les matériaux de construction biosourcés : investigation expérimentale et théorique du non-équilibre local." Thesis, Université Paris-Saclay (ComUE), 2019. http://www.theses.fr/2019SACLC022/document.
Full textThe growing interest in biosourced materials in the construction sector is confronted with difficulties in simulating their hygrothermal behavior. Insulating materials such as fiberboard concentrate all the difficulties because they are not very thermally conductive, very hygroscopic and very diffusive to water vapor. Consequently, in transient state, heat and mass coupling is exacerbated, and the phases of water are not in equilibrium locally.In order to highlight this second phenomenon, a new experimental device has been developed. It allows to subject a sample a few centimeters thick to a disturbance of relative humidity on its front face and then to simultaneously measure the evolution of relative humidity on its back face and its mass. In a situation of non-equilibrium, there is a phase shift between these two quantities that the classic coupled transfer formulation cannot predict. In order to obtain a correct prediction, a new formulation was used. It is based on the use of memory functions characterizing microscopic diffusion. In order to demonstrate the predictive capacity of the new formulation, these functions have been determined with gravimetric tests performed on very small samples using a magnetic suspension balance. In parallel, a rigorous analysis of the heat and mass coupling in these materials made it possible to highlight the impact of different macroscopic parameters on their characterization.The use of the new formulation fed by the identified memory functions and the various macroscopic parameters allows an excellent prediction of relative humidity and mass. This new formulation, experimentally validated, can now be used in energy simulation of the building
SCHAEFFER, AURELIE. "Caracterisation fonctionnelle de sterols c-24 et c-24 1 methyl transferases chez arabidopsis et le tabac." Université Louis Pasteur (Strasbourg) (1971-2008), 2001. http://www.theses.fr/2001STR13001.
Full textMullen, Ashley Lynn. "A Polarizable and Transferable Carbon Dioxide Potential for Materials Simulation." Scholar Commons, 2013. http://scholarcommons.usf.edu/etd/4832.
Full textLópez, Hernández Federico. "Identification of the role of [methyl]glucuronic acid on arabinogalactan polysaccharides in Arabidopsis thaliana." Thesis, University of Cambridge, 2018. https://www.repository.cam.ac.uk/handle/1810/276328.
Full textRoten, Conrad Ambros. "I. Zum Mechanismus der Threonin Dehydratase Reaktion : Versuche mit Cyclopropylglycin und Oxiranylglycinen : <> Der stereochemische Verlauf der C- und DNA-Methyl-Transferasen /." Zürich, 1995. http://e-collection.ethbib.ethz.ch/show?type=diss&nr=11138.
Full textKhalid, Rameez. "Progress in Transferable Work-load Projects : Development of a Robust Method for the Evaluation and Forecasting of Distributed Progress." Thesis, Toulouse, INPT, 2009. http://www.theses.fr/2009INPT051G/document.
Full textIn large projects measuring progress is always difficult due to the complexities involved, because the realization is shared among departments of a firm or even between firms disseminated all over the world. Project management and operations research literature is reviewed for discovering various techniques applicable. Widely used tools for progress measurement and forecasting, such as Earned Value Analysis, Progress Plot, Milestone and Resource slip charts, concurrent engineering, can be employed. This thesis is based on a problem of pharmaceutical industry where the effectiveness of a certain medical treatment is examined on patients in a number of countries. The number of variables involved increase the complexity of this problem. The main objective is to analyze the effectiveness of a solution in different situations during the project such that a better project duration and a lower cost can be achieved. Our findings suggest that reallocation of patients among countries produces better results in terms of progress
Viens, Nicolas. "Étude des transferts thermiques lors de la coulée dans le procédé de fonderie à cire perdue." Thesis, Reims, 2016. http://www.theses.fr/2016REIMS039.
Full textDesign casting methodologies are based on the analysis of the energy released by the metal during its solidification. Indeed, the knowledge of this heat transfer permits to faithfully predict local solidification time and to identify last solidified zones. In the case of sand casting, heat exchanges are well known and have been modeled for a long time (Chvorinov). The last, modelize "thermally infinite mold" so in this case whole metal energy threw solidification phase is absorbed by the mold. In contrary, for a shell, a portion of metal energy is transmitted to environment threw the shell, so in this case, the most appropriate model is "a thermally finished mold". Reference experimentations gives a good understanding of energy / thermal mechanisms involved in the casting process and highlight both internal and external shell thermal exchanges complexity (which occur simultaneously during solidification metal). These manipulations allow to use inverse method to estimate hardly measured parameters (such as external heat transfer coefficient or metal-mold interfacial heat transfer), and therefore to build reliable thermal parameters databases used in numerical simulations. Methodology and models developed in this study allow a reliable sizing feed calculation for investment casting. On the long-range, this knowledge could be applied to other foundry processes since the methodology developed on investment casting will be transposed to core molds, die-casting or other molds
Jandaud, Pierre-Olivier. "Étude et optimisation aérothermique d'un alterno-démarreur." Thesis, Valenciennes, 2013. http://www.theses.fr/2013VALE0018/document.
Full textThe goal of this thesis is the aero-thermal study and optimization of a starter-alternator used in hybrid cars. This kind of machines being more powerful than a regular alternator, their cooling is critical. The machine is modeled using lumped method in steady state which uses networks of thermal conductances. The inputs for the model are obtained using correlations from bibliography for the convective heat transfers and three dimensional CFD for the flow rates inside the machine. The numerical results are validated by experimental results with PIV for the fluid results and a machine fitted with thermocouples for the thermal part. In the second part, the thermal code is coupled with an optimization algorithm to obtain an optimal geometry of the machine from a thermal point of view. The method chosen is Particle Swarm Optimization (PSO). The parameters are the sizes of the end-windings, the positions of the fans and the cross section of the rotor channels. For different objectives, different optimal geometries are obtained. The last part of this work aims at the multi-objectives optimization of a heat sink located at the back of the machine. The heat sink has to be thermally efficient but should not affect the flow. Different shapes of fins are also studied
Settar, Abdelhakim. "Etude des transferts thermique et massique au sein d'un échangeur multifonctionnel en présence d'une réaction catalytique." Thesis, Belfort-Montbéliard, 2016. http://www.theses.fr/2016BELF0291.
Full textHydrogen is not a primary energy; we must produce it, transport it and store it before use. It cans be produced by chemical, biological or electrolytic processes from renewable resources or not. Fossil fuels represent the first hydrogen resource, with 96% of total world production, which 48% is made from natural gas containing methane. In this thesis, we focus on the generation of hydrogen by the steam-methane reforming process, which is the most used conversion method. The aims consist first to explore, through numerical studies, the thermal and mass performances of a wall coated steam-methane reformer, wherein a discrete distribution of the catalyst is adopted, combined or not, with an insertion of a highly porous metal foam, and secondly to analyze, by an experimental approach completed by a numerical inverse procedure to estimate the unknown heat flux received by the gas mixture. The geometric configurations adopted in the numerical studies are modeled by the conservation equations and the boundary conditions. The kinetic reaction is governed by a model based on power laws, and the system of equations is solved by the finite volume method. For the estimation of heat flux, an experimental device approachingthe reactor heating system is designed to measure the temperature distribution, and an inverse code based on the function specification method. The results show that the steam methane reforming process performances can be improved by adopting a good distribution of the catalyst on the walls of the reactor fitted on its catalytic region with metal foam. The improvements obtained in terms of methane conversion, compared to a conventional configuration, are of the order of 44.6%. In addition, the combination of experimental and numerical approaches was used to determine the net quantity of heat transferred from the heating system to the steam reformer
Torrijos, Michel. "Evaluation des techniques non conventionnelles d'intensification des transferts d'oxygene en fermentation." Toulouse, INSA, 1987. http://www.theses.fr/1987ISAT0020.
Full textCoundoul, Falilou. "Étude et modélisation des transferts verticaux dans l'interaction biofilm de rivière/couche limite turbulente." Phd thesis, Toulouse, INPT, 2012. http://oatao.univ-toulouse.fr/9268/1/coundoul_partie_1_sur_3.pdf.
Full textGhannam, Boutros. "Modélisation ultra-rapide des transferts de chaleur par rayonnement et par conduction et exemple d'application." Phd thesis, Ecole Nationale Supérieure des Mines de Paris, 2012. http://pastel.archives-ouvertes.fr/pastel-00958145.
Full textSarret, Frédéric. "Simulation numérique de dépôts céramiques plasma." Thesis, Bordeaux, 2014. http://www.theses.fr/2014BORD0066/document.
Full textThis PhD thesis is a contribution to the numerical simulation of the plasma sprayedcoating build-up by APS process (Atmospheric Plasma Spraying). This work focuses onthe build-up of a representative volume of the coat considering a great range of phenomenonappearing in APS process such as gas flow properties, kinetic (multiphase flow,wettability) and thermal (heat transfers, thermal contact resistance, solidification) duringthe impact and steaking of particles. An original numerical method, named VOF-SM(Volume Of Fluid - Sub Mesh) is developped. The simulation of the impact of an unsteadyand turbulent ArH2 plasma flow is carried out in order to define the gas flow closeto the wall and heat transferred to the substrate by the plasma. Specific phenomena of theimpact of particles were incorporated into the CFD code (Thétis) and validated independentlyby caparison with analytical solutions, then together combined by the comparisonto a millimeter size impact experimental data. Finally, a study of successive impacts ofYttria-Stabilized Zirconia particles onto a steel substrate was carried out by thermal andkinetic approach similarities to overcome the difficulty of resolving small scales
Tawk, Rony. "Optimisation topologique des transferts de masse et de chaleur en écoulement bi-fluide laminaire : application aux échangeurs de chaleur." Thesis, Paris Sciences et Lettres (ComUE), 2018. http://www.theses.fr/2018PSLEM017/document.
Full textHeat exchangers are devices widely used in various energy systems. The present research work focuses on the design of single-phase bi-fluid heat exchangers by using topology optimization methods. Unlike conventional size and shape optimization methods, topology optimization methods allow greater design freedom and do not require prior definition of the exchanger geometry. Hence, bi-fluid topology optimization consists of freely reorganizing two fluids and one solid in the optimization domain. Both fluids should connect inlet sections to outlet sections while avoiding any fluid mixture inside the domain. SIMP method “Solid Isotropic Material with Penalization” is used within the framework of this thesis. This method includes various algorithms that were formulated and tested : finite volume method was selected for solving the direct physical problem, discrete adjoint method was used for the calculation of the gradient of the objective function, and the method of moving asymptotes was adopted to guide the numerical optimization. Simulation results have allowed the definition of various heat exchanger shapes in 2D. The number of inlet and outlet as well as the flow rates of each fluid have been varied. The works have shown the ability of this method to design innovative shapes of heat exchangers. Hence, the thesis establishes the basis of a new design methodology of heat exchangers
Rodiet, Christophe. "Mesure de Température par Méthodes Multi-Spectrales et Caractérisation Thermique de Matériaux Anisotropes par Transformations Intégrales : « Aspects Théoriques et Expérimentaux »." Thesis, Université de Lorraine, 2014. http://www.theses.fr/2014LORR0283/document.
Full textThis thesis consists of two relatively independent parts, the first part focuses on methods of temperature measurement using Multi-Spectral (passive optical pyrometry) methods, and the second on the Thermal Characterization by integral transforms at high temperature of orthotropic materials. In each of these two parts, methods / models developed were treated from a theoretical point of view, numerical and experimental. In the multi-spectral part, a method of temperature measurement to take into account a spectral variation of the overall measurement chain (including the emissivity) was introduced. Moreover, a method of determining the optimal wavelengths in the sense of minimizing the standard deviation of temperature, has been developed. Finally, it has also been shown that the optimal wavelengths for mono-spectral and bi-spectral measurements could be determined with similar laws to Wien's displacement law. In the Thermal Characterization part, different methods and models have been developed. The proposed methods perform the estimation of longitudinal and transverse diffusivities on all harmonics simultaneously. Furthermore, they allow overcoming the thermal coupling due to the presence of a sample holder, and / or making pseudo-local measurements of diffusivities. Finally, the concepts of correlation between parameters and duration of harmonics exploitability were also discussed.This thesis consists of two relatively independent parts, the first part focuses on methods of temperature measurement using Multi-Spectral (passive optical pyrometry) methods, and the second on the Thermal Characterization by integral transforms at high temperature of orthotropic materials. In each of these two parts, methods / models developed were treated from a theoretical point of view, numerical and experimental. In the multi-spectral part, a method of temperature measurement to take into account a spectral variation of the overall measurement chain (including the emissivity) was introduced. Moreover, a method of determining the optimal wavelengths in the sense of minimizing the standard deviation of temperature, has been developed. Finally, it has also been shown that the optimal wavelengths for mono-spectral and bi-spectral measurements could be determined with similar laws to Wien's displacement law. In the Thermal Characterization part, different methods and models have been developed. The proposed methods perform the estimation of longitudinal and transverse diffusivities on all harmonics simultaneously. Furthermore, they allow overcoming the thermal coupling due to the presence of a sample holder, and / or making pseudo-local measurements of diffusivities. Finally, the concepts of correlation between parameters and duration of harmonics exploitability were also discussed
Azzouz, Ali. "Conception d'un thermoanemometre et application a l'evaluation des transferts thermiques lors de l'ouverture d'une chambre froide industrielle." Paris, CNAM, 1988. http://www.theses.fr/1988CNAM0096.
Full textSans, Morgan. "Caractérisation des propriétés thermophysiques de mousses céramiques à haute température." Electronic Thesis or Diss., Université de Lorraine, 2019. http://www.theses.fr/2019LORR0192.
Full textSince the end of the twentieth century, research and development has increasingly focused on the use of solid ceramic foams for a myriad of high-temperature applications because of their advantageous thermal, mechanical, chemical or optical properties. In a global energy context that is tending to reduce the consumption of fossil fuels and greenhouse gas emissions, they appear to be a promising solution due to their ability to absorb, recover and convert a large radiative flux. In particular, they are the subject of growing interest in the field of solar thermal energy, while LEMTA is interested in these materials as a recover of fatal heat present in high-temperature industrial processes (glassware, cement, metallurgy, etc.). However, some studies have shown that improving current and future systems requires a better understanding of the relationship between the structural/thermal/optical properties associated with these heterogeneous media (geometry, porosity, pore diameter, conductivity, emissivity, etc.) and heat transfers. The objectives of this work are to provide relevant modelling and characterization tools that allow the description of conductive, convective (forced) and radiative heat transfers. Three characterization methods are studied and detailed in this manuscript. 1. In the case of conductive and radiative transfer, the main difficulty lies in the ability to separate the contribution of each heat transfer mode. In order to exceed these limits, a transitional method based on the principle of the flash method was used. The ceramic foam, placed between two ceramic soleplates and in the centre of a tubular furnace, is thermally excited while the thermal elevation is measured on the side opposite the latter. In parallel, a direct model resolving the Energy Balance Equation by the Finite Volume Method while the Radiative Transfer Equation by an optimized reciprocal Monte Carlo method was implemented. The latter method allows, while maintaining reasonable calculation time, to solve radiation transfers more generally than the method usually used. A simultaneous identification of equivalent phononic conductivity and optical thickness was performed on a wide variety of structured and stochastic foams composed of SiC or SiSiC up to 800 °C. Compared to simplified models such as Rosseland's, this study provides a better understanding of the validity of the diffusion approximation and guides the choice of modeling and parameters to be used. 2. Another difficulty lies in the ability to numerically solve a coupled problem directly on the 3D heterogeneous geometry of the porous medium. A Monte Carlo method allowing the resolution of both transfer modes in a single algorithm has been employed. The flash method was performed thanks to the latter in a entirely numerical manner. It allows the solution to be obtained quickly with the increase in radiation transfer. The proposed procedure allowed the identification of the equivalent properties of structured foams (Kelvin's cells). 3. A method for characterizing axial and radial thermal dispersion coefficients has been implemented. the experimental bench is composed of 5 sections of 20 cm SiC foams separated by flanges for temperature measurement. A hot air flow is applied to the porous medium at equilibrium with the ambient temperature. In parallel, a one-temperature model allows a 2D axisymmetric and multilayer resolution of the thermal problem. The application of an inversion algorithm allows the estimation of the two coefficients for different flow rates
Hugo, Jean-michel. "Transferts dans les milieux cellulaires à forte porosité : applications à l'optimisation structurale des échangeurs à ailettes." Thesis, Aix-Marseille, 2012. http://www.theses.fr/2012AIXM4767/document.
Full textThis work is composed of two parts: the first one deals with the design of fins-and-tubes and metal foam heat exchangers; the second one deals with the relationship between foams morphology and their effective thermophysical properties. The first part is dedicated to Mota heat exchanger performance enhancement. We develop a multi-scale method to optimize both local heat transfer surfaces and global architecture of classical and foam units. We develop, using this method, new heat exchanger and we characterize it numerically and experimentally. An increase of 50% of energetic efficiency is obtained and new geometries are nowadays produced and commercialized. The second part deals with the analysis of transport phenomena in metal foams and the determination of their effectives properties. We develop an approach based on pore scale numerical simulation of conjugate heat transfer – validated by experimental results obtained on set-up developed for this study. We have generated 900 virtual samples obtained by deformation a periodic unit cell (Kelvin cell). Full effective properties tensors are determined. The influence of cell shape and classical geometrical parameters on physical properties is then studied. To conclude, in the last chapter, we present natural perspectives involved by this work: Geometrical optimization of heat exchanger architecture and foams morphology depending on the application; The use of a multi-scale approach to design modern –foam- heat exchangers
Spiesser, Christophe. "Méthode de simulation appropriée aux systèmes complexes : preuve de concept auto-adaptative et auto-apprenante appliquée aux transferts thermiques." Thesis, Ecole nationale des Mines d'Albi-Carmaux, 2017. http://www.theses.fr/2017EMAC0005/document.
Full textAs computing power increases, engineers and designers tackle increasingly complex problems using simulation (multiphysics, multiscale, intricated geometries ...). In this context, discretization-based quadratures (FDM, FEM, FVM) show their limit: the need of a great number of sub-domains which induces prohibitive consumption of RAM and CPU power. The Monte Carlo method appears to be more appropriate, but the difficulty to build probabilistic models of complex systems forms a bottleneck. A systemic approach is proposed to alleviate it and is implemented to create a proof-of-concept dedicated to the coupled heat transfer simulation. After a successful validation step against analytical solutions, this tool is applied to illustrative cases (emulating heat transfer in buildings and in solar heating systems) in order to study its simulation capabilities.This approach presents a major beneficial behavior for complex systems simulation: the computation time only depends on the influential parts of the problem. These parts are automatically identified, even in intricate or extensive geometries, which makes the simulation self-adaptive. In addition, the computational performance and the system scale ratio are completely uncorrelated. Consequently, this approach shows an exceptional capacity to tackle multiphysics and multiscale problems. Each temperature is estimated using exploration paths. By statistically analyzing these paths during the process, the tool is able to generate a reduced predictive model of this physical quantity, which is bringing a self-learning capacity to the simulation. Its use can significantly improve optimization and control of processes, or simplify inverse measurements. Furthermore, based on this model, an uncertainty propagation analysis has been performed. It quantifies the effect of uncertainties affecting boundary conditions on the temperature. Finally a Particle Swarm Optimization (PSO) process, based on simulations done by the framework, is successfully carried out
Vu, Van Huyen. "Modélisation hybride et multi-échelle pour la simulation des écoulements et des transferts thermiques dans les micro-canaux." Thesis, Paris Est, 2016. http://www.theses.fr/2016PESC1163/document.
Full textThe main objective of this thesis is to model the multi-scale heat and fluid flows in micro-/nano channels. This method must be able of capturing at the same time the fluid/solid interaction at the small scale but also the flows induced by the inlet/outlet boundary conditions at the large scale. To this aim, we have adopted an approach coupling the continuum model in the bulks of the channel and the discrete model at the vicinity of the wall, based on an atomistic representation of the fluid and the solid.The Navier-Stokes and energy equations, coupled with an equation of state, are approximated by a finite volume method and the molecular dynamics simulations are used to finely represent the interaction between the fluid and the solid. This hybrid method requires information transmission between the former two regions: averaged quantity in molecular dynamics simulations are imposed as boundary conditions for the continuous model and constrained dynamics, coupled with a thermostat Langevin, is used to control in the molecular level. A set of small molecular dynamics blocks, smartly distributed all along the wall/fluid interface, allows to treat flow and heat transfers in a long micro/nano-channel with a reasonable computational cost.After a validation step, the hybrid multi-scale simulations of complex fluid flows in the channel composed of the platinum wall have been conducted for argon in incompressible liquid or compressible gaseous phase with and without phase change in the vicinity of the wall
El, Jannoun Ghina. "Adaptation anisotrope précise en espace et temps et méthodes d’éléments finis stabilisées pour la résolution de problèmes de mécanique des fluides instationnaires." Thesis, Paris, ENMP, 2014. http://www.theses.fr/2014ENMP0077/document.
Full textNowadays, with the increase in computational power, numerical modeling has become an intrinsic tool for predicting physical phenomena and developing engineering designs. The modeling of these phenomena poses scientific complexities the resolution of which requires considerable computational resources and long lasting calculations.In this thesis, we are interested in the resolution of complex long time and large scale heat transfer and fluid flow problems. When the physical phenomena exhibit sharp anisotropic features, a good level of accuracy requires a high mesh resolution, hence hindering the efficiency of the simulation. Therefore a compromise between accuracy and efficiency shall be adopted. The development of space and time adaptive adaptation techniques was motivated by the desire to devise realistic configurations and to limit the shortcomings of the traditional non-adaptive resolutions in terms of lack of solution's accuracy and computational efficiency. Indeed, the resolution of unsteady problems with multi-scale features on a prescribed uniform mesh with a limited number of degrees of freedom often fails to capture the fine scale physical features, have excessive computational cost and might produce incorrect results. These difficulties brought forth investigations towards generating meshes with local refinements where higher resolution was needed. Space and time adaptations can thus be regarded as essential ingredients in this recipe.The approach followed in this work consists in applying stabilized finite element methods and the development of space and time adaptive tools to enhance the accuracy and efficiency of the numerical simulations.The derivation process starts with an edge-based error estimation for locating the regions, in the computational domain, presenting sharp gradients, inner and boundary layers. This is followed by the construction of nodal metric tensors that prescribe, at each node in the spatial mesh, mesh sizes and the directions along which these sizes are to be imposed. In order to improve the efficiency of computations, this construction takes into account a fixed number of nodes and generates an optimal distribution and orientation of the mesh elements. The approach is extended to a space-time adaptation framework, whereby optimal meshes and time-step sizes for slabs of time are constructed in the view of controlling the global interpolation error over the computation domain
Baud, Germain. "Conception de récepteurs solaires à lit fluidisé sous flux radiatif concentré." Thesis, Toulouse, INPT, 2011. http://www.theses.fr/2011INPT0106/document.
Full textThe aim of this work is to evaluate the position and the potential of solar fluidized bed receivers compared to other methods for the solar heating of gases at high temperature. To this end, a thorough knowledge of the heat transfer and hydrodynamic of the receiver is necessary. To acquire this knowledge, we modeled the heat transfer in the receiver with a focus on the radiative transfer by taking into account the multiple scattering of light in the particle medium, the effect of walls on radiative heat transfer and the directionality of the concentrated solar radiation. The accurate determination of the distribution of particles within the fluidized bed has been a critical parameter for the calculation of heat transfer. With these models, later refined by a confrontation with experimental references, we have studied the effect of geometry on heat transfer in the receiver. This study highlighted the necessity to use a switching section fluidization column and the importance to optimize the pair : solar concentrator / receiver to avoid any overheating at the walls of the receiver. Moreover, it appears that the homogenization of the temperature in the fluidized bed of the receiver increase its performance
Trovalet, Lionel. "Résolution numérique des transferts par rayonnement et conduction au sein d'un milieu semi-transparent pour une géométrie 3D de forme complexe." Thesis, Nancy 1, 2011. http://www.theses.fr/2011NAN10142/document.
Full textThis work deals with the numerical solution of coupled radiative and conductive heat transfer in participating media in complex 3D geometries. Thermal radiation is simulated by a numerical code developed during this thesis. This code solves the radiative transfer equation (RTE) by a modified finite volume method (FVM) with a cell-vertex formulation applied to unstructured tetrahedral meshes. It uses a closure relation based on an exponential scheme, a marching order map and an innovative matrix solution for the FVM applied to the RTE. The model is applied to absorbing-emitting, grey or non-grey media bounded by black or opaque walls with diffuse reflection. The mesh used for the radiation-conduction coupling is the one used by the finite element code for the conduction. The validation of the radiative code and the coupling are carried out through several test cases taken from the literature. Grey and isothermal media with different geometries are considered, and the effects of the spatial and angular discretizations are observed through a sensitivity study. Three closure schemes have been studied on a transparent medium in order to show their influence on the accuracy and false scattering. Studies of coupled heat transfer are carried out on radiative equilibrium problems and coupled radiation-conduction problems in steady or transient states with the dimensionless equations. Finally a non-grey medium such glass is also studied, considering conduction and radiation in steady state with a spectral band model for radiation
Benabdelkader, Mohammed el Amine. "Sources et transferts des éléments majeurs et traces dans le bassin versant de la Tafna (Algérie) : approches géochimiques et hydrochimiques." Thesis, Toulouse, INPT, 2019. http://www.theses.fr/2019INPT0046.
Full textSemi-arid Mediterranean characterized by floods and sever low water and anthropogenic increasing, the North African wadis are exposed to important environment impacts. Traces metal elements contamination (ETM including rare earth elements) continues to increase and contributes to degrade aquatic environment. Traces metals elements concentrations and mobility, different processes (hydro)biogéochimiques as well as their transfer downstream, are thus affected. In this context, to evaluate the impact of these pressures, the Tafna was used as a model in this thesis to evaluate the water and sediments quality of the basin, to identify the sources and the behavior of the ETM in different hydrological conditions. ETM (Pb, Cd, Zn, Cu, Cr, Co, Ni, As), the REE (La-Yb) and the major elements, COP, COD, as well as the physicochemical parameters, were studied during several hydrological campaigns contrasting, for 10 stations and two dams, from upstream to downstream of the watershed. The results obtained show that the chemical composition of the water is influenced by lithology (presence of calcite and evaporitic minerals) which contributes to the water enrichment by Na, Mg, B, Cl, SO4, as well as by Ca and CO3 through dissolution process. The hydrological conditions and the different geochemical processes of adsorption/desorption, precipitation/dissolution, dilution influence the content and mobility of ETM in water and sediments, particularly in relation to the presence of carbonate and evaporitic formations. Enrichment and origins of sediment contamination were assessed using a combination of geochemical and isotopic indicators. High contamination in some ETM (Pb> Cd> Zn> Cu) and low enrichment for others (Al, Fe, Cr, Co, Ni) was demonstrated. Multiple local contamination sources were identified (industrial, agricultural and domestic wastes) and more diffuse pollution, notably from atmospheric deposition (gasoline, ores, aerosols). During floods, through the remobilization of particles accumulated, dams can be either secondary sources of contamination or dilution of contamination by particles from highly erosive upstream zones. Geomorphology plays a major role in slowing the transfer contamination to downstream (by sedimentation), but in high water condition there is remobilization and transfer of ETM to the Mediterranean. The elements with natural origin (Co, Ni, Cr, As) are correlated with Al, Fe and Mn, suggesting a control by oxides or clays, those of anthropogenic origin with phosphorus (Cd and Zn) or sulfur (Cu), mainly related to agricultural inputs. Cadmium and Pb are the most extractable metals upstream and downstream, but their availability is not strictly related to the degree of contamination. REE profiles in sediments are controlled by particle size and geochemical characteristics (including anomalies). Light rare earths elements were associated with clay minerals and heavy rare earths elements with coarse silt; the medium and heavy rare earths were the most extractable. Dams are wells for light rare earths from retained sediments and influence the traditional fractionation of REE erosion patterns from upstream to downstream. By highlighting the natural processes impact (hydrological, geochemical and erosion) and anthropogenic disruptions (discharges, dams) by the REE and various geochemical and isotopic tools combined, this innovative work for semi-arid carbonate systems could be used for other similar basins subjected to various pressures (erosion and anthropization). Repository recommendations and a set of geochemical and statistical data and tools are provided
Lancial, Nicolas. "Effets de la rotation sur la dynamique des écoulements et des transferts thermiques dans les machines électriques tournantes de grande taille." Thesis, Valenciennes, 2014. http://www.theses.fr/2014VALE0021/document.
Full textEDF operates a large number of electrical rotating machines in its electricity generation capacity. Thermal stresses which affect them can cause local heating, sufficient to damage their integrity. The present work contributes to provide methodologies for detecting hot spots in these machines, better understanding the topology of rotating flows and identifying their effects on heat transfer. Several experimental scale model were used by increasing their complexity to understand and validate the numerical simulations. A first study on a turbulent wall jet over a non-confined backward-facing step (half-pole hydrogenerator) notes significant differences compared to results from confined case : both of them are present in an hydrogenerator. A second study was done on a small confined rotating scale model to determinate the effects of a Taylor-Couette-Poiseuille on temperature distribution and position of hot spots on the heated rotor, by studying the overall flow regimes flow. These studies have helped to obtain a reliable method based on conjugate heat transfer (CHT) simulations. Another method, based on FEM coupled with the use of an inverse method, has been studied on a large model of hydraulic generator so as to solve the computation time issue of the first methodology. It numerically calculates the convective heat transfer from temperature measurements, but depends on the availability of experimental data. This work has also developped new no-contact measurement techniques as the use of a high-frequency pyrometer which can be applied on rotating machines for monitoring temperature
Passerat, de Silans Alain. "Transferts de masse et de chaleur dans un sol stratifié soumis à une excitation atmosphérique naturelle : comparaison : modèles-expérience." Grenoble INPG, 1986. http://www.theses.fr/1986INPG0061.
Full textTaurines, Kevin. "Modelling and experimental analysis of a geothermal ventilated foundation." Thesis, Lyon, 2017. http://www.theses.fr/2017LYSEI100/document.
Full textThis thesis deals with the thermal and energy analysis of a geothermal ventilated fonudation. Similarly to earth-to-air heat exchangers (EAHE) this foundation enables, according to the season, to preheat or to cool down the air for the hygienic air change. Considering the energy consumption constraints and the buildings users thermal comfort desire, these systems appears to be relevant. The principle of this foundation is simple: to force the air to circulate in a hollowed beam buried into the ground (1 to 3m depth) so that it takes advantage - via convection - to the thermal inertia of the ground. The difference lays on the fact that the channel is not a plastic or aluminium pipe but it a part of the building structure, namely the reinforced concrete foundation. This induces a significant space gain, usually devoted to the pipe burying. From a thermal point of view, the foundation exchanges heat with both the soil beneath the building, and with the soil exposed to the weather thermal loads. Furthermore, the depth - imposed by structural and economical purposees - is lower than that of traditional EAHE. In addition to the fact that concrete is a porous material, the humidity content may strongly influence the thermal performance of the foundation. The current work thus proposes to study the complex thermal behaviour of this foundation in two ways. The first is experimental: an retirement home equipped with two foundation has been intensively instrumented and data recorded over more than one year. The other is numerical: two models validated against the experimental data have been developed. The first is intended to be a designing tool, the second a tool to allow a fine comprehension of the physical phenomenon and take into account coupled heat and moisture transfers
Gérard-Marchant, Pierre. "Caractérisation hydro-dynamique des transferts d'eau en conditions non saturées dans un milieu déformable à faible perméabilité : application aux matériaux de centre de stockage de déchets." Université Joseph Fourier (Grenoble), 1998. http://www.theses.fr/1998GRE10155.
Full textIbarrart, Loris. "Description en espaces de chemins et méthode de Monte Carlo pour les transferts thermiques couplés dans les structures fluides et solides, une approche compatible avec l'informatique graphique." Thesis, Ecole nationale des Mines d'Albi-Carmaux, 2020. http://www.theses.fr/2020EMAC0009.
Full textThe present manuscript deals with the coupling of thermal heat transfers. More precisely, it adresses this coupling by making use of the Monte Carlo method and the sampling of random paths. This choice was made in the perspective of building algorithms that do not present constraints regarding the complexity of the studied geometry. Indeed, the combined use of this kind of statistical approaches, and acceleration tools coming from the image synthesis community, already allowed for an exact resolution of radiative transfer in arbitrary geometries. Regarding diffusive heat transfers, exact results using random paths are only achievable in academic configurations. Thus, approximate random paths are commonly used to account for this kind of thermal transport. Among the possible choices, we will use random paths built on ray tracing, therefore allowing to benefit once again from all the advantages of the tools developed in computer graphics. A proof of concept of the insensitivity of the computation time of the resolution of thermal transfers in porous exchangers to the number of pores by making use of conducto-convecto-radiative random paths will be presented. Beyond this result, an analysis of the behaviour of this method in ducts heat exchangers will allow to clarify when this kind of insensitivity can indeed be observed. This analysis will induce the concept of thermal thickness, by analogy with optical thickness for radiative transfer
Ferraz, Bastos José Luis. "Extension de la méthode nodale à la modélisation des transferts couples conduction/convection dans un canal : application à la thermique du bâtiment et aux cartes électroniques." Poitiers, 1988. http://www.theses.fr/1988POIT2310.
Full textZinebi, Fatiha. "Mécanismes amino-acidergiques cellulaires impliqués dans l'hyperexcitabilité du système nerveux central de mammifère sous haute pression d'hélium : étude électrophysiologique in vitro des transferts synaptiques et électrotoniques dans l'Hippocampe de rat." Aix-Marseille 1, 1988. http://www.theses.fr/1988AIX11141.
Full textGondre, Damien. "Numerical modeling and analysis of heat and mass transfers in an adsorption heat storage tank : Influences of material properties, operating conditions and system design on storage performances." Thesis, Lyon, 2016. http://www.theses.fr/2016LYSEI022/document.
Full textThe development of energy storage solutions is a key challenge to enable the energy transition from fossil resources to renewable energies. The need to store energy actually comes from a dissociation between energy sources and energy demand. Storing energy meets two principal expectations: have energy available where and when it is required. Low temperature heat, for dwellings and offices heating, represents a high share of overall energy consumption (i.e. about 35 %). The development of heat storage solutions is then of great importance for energy management, especially in the context of the growing part of renewable energies. Adsorption heat storage appears to be the best trade off among available storage technologies in terms of heat storage density and performances over several cycles. Then, this PhD thesis focuses on adsorption heat storage and addresses the enhancement of storage performances and system integration. The approach developed to address these issues is numerical. Then, a model of an adsorption heat storage tank is developed, and validated using experimental data. The influence of material thermophysical properties on output power but also on storage density and system autonomy is investigated. This analysis enables a selection of particularly influencing material properties and a better understanding of heat and mass transfers. The influence of operating conditions is also underlined. It shows the importance of inlet humidity on both storage capacity and outlet power and the great influence of discharge flowrate on outlet power. Finally, it is shown heat storage capacity depends on the storage tank volume, while outlet power depends on cross section area and system autonomy on bed length. Besides, the conversion efficiency from absorbed energy (charge) to released energy (discharge) is 70 %. But during the charging process, about 60 % of incoming heat is not absorbed by the material and directly released. The overall conversion efficiency from energy provided to energy released is as low as 25 %. This demonstrates that an adsorption heat storage system cannot be thought of as a self-standing component but must be integrated into the building systems and control strategy. A clever use of heat losses for heating applications (in winter) or inlet fluid preheating (in summer) enhances global performances. Using available solar heat for system preheating is an interesting option since a part is instantly retrieved at the outlet of the storage tank and can be used for direct heating. Another part is stored as sensible heat and can be retrieved a few hours later. At least, it has the advantage of turning the adsorption storage tank into a combined sensible-adsorption storage tank that offers short-term and long-term storage solutions. Then, it may differ avoidable discharges of the sorption potential and increase the overall autonomy (or coverage fraction), in addition to optimizing chances of partial system recharge
Hans, Stéphane. "Modélisation des transferts couplés de chaleur, de soluté et de quantité de mouvement lors de la refusion à l'arc sous vide (VAR) : application aux alliages de titane." Vandoeuvre-les-Nancy, INPL, 1995. http://www.theses.fr/1995INPL023N.
Full textMartínez, Ramos Inmaculada. "Papel de EF-Tu en la interacción de Pseudomonas aeruginosa con los queratinocitos humanos." Doctoral thesis, Universitat de les Illes Balears, 2015. http://hdl.handle.net/10803/291564.
Full textIntroducció: Pseudomonas aeruginosa és un patogen oportunista que causa una gran varietat d’infeccions, entre les quals destaquen les infeccions respiratòries agudes i cròniques i les infeccions de ferides per cremada. A un treball previ, vàrem utilitzar anticossos específics per detectar la presència de l’epítop de fosforilcolina a la superfície del bacteri associat al factor d’elongació Tu (EF-Tu). Vàrem identificar que el gen eftM (Elongation Factor Tu Modifying enzime) és el responsable de la incorporació de fosforilcolina a EF-Tu. A més a més demostrarem que aquest epítop és clau per la colonització inicial del tracte respiratori per P. aeruginosa i el desenvolupament de pneumònia. En aquesta tesi hem investigat la contribució de la fosforilcolina a la interacció de P. aeruginosa amb els queratinocits epidèrmics humans i a les infeccions de ferides per cremades causades per aquest patogen. Contingut de la recerca: La proteïna EF-Tu recombinant purificada d’un aïllament clínic i d’un mutant isogènic desproveït del gen eftM funcional va ser analitzat per espectrometria de masses. L’anàlisi comparativa va demostrar que el producte de eftM és una metiltranferasa (EftM) que incorpora tres grups metil al residu 5 de lisina de EF-Tu donant lloc a un epítop estructuralment igual a la fosforilcolina. Mitjançant la combinació de tècniques de fraccionament cel·lular, microscopia electrònica i immunologia, hem demostrat que EftM trimetila EF-Tu al citoplasma, el qual és posteriorment transportat a la membrana externa, deixant el residu 5 trimetilat expossat cap a l’exterior. Els assajos d’invasió i transmigració amb cultius de queratinocits humans polaritzats infectats amb la soca parental o el mutant d’eftM demostraren que la trimetilació d’ EF-Tu facilita la migración de P. aeruginosa a través de la barrera epitelial. Això és degut al fet que la soca parental és capaç d’alterar, de forma més eficient que el mutant, la permeabilitat de la barrera epitelial mitjançant la reducció de l’expressió de ZO-1, una proteïna clau per a la integritat de l’epiteli. Els assajos amb un antagonista del receptor del factor activador de plaquetes (PAFR) demostraren que aquest receptor actua com a intermediari en la interacció de P. aeruginosa amb els queratinòcits a través d’EF-Tu trimetilat. No obstant això, la reducció de ZO-1 no és deguda directament a la interacció EF-Tu-PAFR, sino que està induïda per l’activació, per part de P. aeruginosa, del factor de transcripció cel·lular NF-κB. Finalment, els experiments a un model murí d’infecció per cremada demostraren que la mutació d’eftM redueix la virulència i la capacitat de disseminació de P. aeruginosa. Conclusions: S’ha identificat el gen eftM, que codifica una nova metiltransferasa que incorpora tres grups metil al residu 5 de lisina d’EF-Tu. EftM està molt conservat i àmpliament distribuït entre espècies i és necessari i suficient per metilar EF-Tu a P. aeruginosa o a altres sistemes heteròlegs. EF-Tu està a la membrana externa exposant la regió N-terminal trimetilada cap a l’exterior. Aquesta trimetilació facilita la invasió i transmigració bacteriana a través de queratinocits humans mitjançant la interacció amb PAFR. P. aeruginosa redueix els nivells de proteïna ZO-1, incrementant la permeabilitat paracel·lular de la barrera epitelial, procés mitjançat per l’activació de NF-κB. La mancança d´EftM redueix la virulència de P. aeruginosa a un model murí d’infecció de cremada. La nova metiltransferasa podria ser una nova diana pel disseny de fàrmacs contra P. aeruginosa.
Introduction: Pseudomonas aeruginosa is an opportunistic pathogen responsible of a wide range of infections including acute and chronic respiratory infections and wound burn infections. In a previous study, we used specific antibodies to detect the presence of the phosphorylcholine epitope on the bacterial surface linked to the elongation factor Tu (EF-Tu). We identified the gene eftM (Elongation Factor Tu Modifying enzime) as the responsible of the modification of EF-Tu with phosphorylcholine. In addition, we demonstrated that this epitope is crucial for initial colonization of the respiratory tract by P. aeruginosa and for development of pneumonia. In this Thesis we have investigated the contribution of the phosphorylcholine in the interaction of P. aeruginosa with the human epidermic keratinocytes and in the burn wound infections caused by this pathogen. Research: A tandem mass spectrometry analysis was choosen to compare recombinant EF-Tu purified from a clinical isolate and from an isogenic eftM deficient mutant. Comparative analysis shown that the product of eftM, is a methyltransferase (EftM) that transfers three methyl groups to the lysine residue 5 of EF-Tu resulting in a chemical structure similar to phosphorylcholine. Through a combination of approaches, including sub-cellular fractionation, electronic microscopy and immunological techniques, we demonstrated that EftM trymethylates EF-Tu in the cytoplasm, which is subsequently transported to the outer membrane, leaving the trimethylated residue 5 exposed outwards. Invasion and transmigration experiments with cultured human polarized keratinocytes infected with the wild-type strain or the eftM mutant demonstrated that the trimethylation of EF-Tu mediates the migration of P. aeruginosa through the epithelial barrier. Accordingly, the wild-type strain increased the paracellular permeability and reduced the expression of ZO-1, a key protein for the integrity of the epithelial barrier, more efficiently than the mutant. An antagonist of the platelet activating factor receptor (PAFR) reduced the invasion and transmigration of the wild type strain but had no effect on the mutant suggesting that PAFR on the keratinocytes mediates the interaction with the modified EF-Tu. However, reduction of ZO-1 is not directly due to the interaction EF-Tu-PAFR, but is due to the activation of the transcription factor NF-κB induced by P. aeruginosa. Finally, we demonstrated the mutation of eftM impaired the virulence and the dissemination capacity of P. aeruginosa in murine model of wound burn infection. Conclusions: We have identified the gen eftM, encoding a novel methyltransferase, which links three methyl groups to the lysine residue 5 of EF-Tu. EftM is conserved and widely distributed among different species and is sufficient and necessary to methylate EF-Tu in P. aeruginosa and other heterologous systems. EF-Tu is on the outer membrane exposing the N-terminal trimethylated region outward. Trimethylation of EF-Tu promotes invasion and transmigration of the microorganisms via PAFR. Activation of NF-κB by P. aeruginosa induces the reduction of ZO-1 and increase the paracellular permeability of the epithelial barrier. Mutation of eftM reduces the virulence of P. aeruginosa in a murine model of wound burn infection. This opens up new avenues for the development of new drugs targeting this new methyltransferase.