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Studium oligomerizace proteinu NKp30 a jeho interakce s B7-H6 / Study of NKp30 oligomerization and its interaction with B7-H6Pažický, Samuel January 2016 (has links)
NK cells are important part of immune system, recognizing and eliminating tumor cells and cells infected by viruses. For the target cell recognition, binding of ligands by activating receptors plays a crucial role. Activating receptor NKp30, protein of family of natural cytotoxicity receptors, is able to bind multiple ligands either present on tumor cell surface or being part of some viruses. B7-H6 is one of the ligands of NKp30 and its specific constitutive expression on some tumor cells and cell lines makes it an interesting biological target. Although the NKp30/B7-H6 complex structure has been solved, structural basis of some important features of their binding is not explained yet. Soluble form of NKp30 receptor binding domain creates oligomers, presence of which is dependent on C-terminus length of its domain and its N-glycosylation; however, structural insight into formation of the oligomers and their significance is not known. Furthermore, binding affinity of NKp30 to its ligands is dependent on presence of its glycosylation and glycosylation type. We have already found out that NKp30 oligomerization is dependent on its glycosylation. In my work, I attempted to gain detailed functional and structural information about oligomerization of NKp30 and its binding to B7-H6 by multimethodical...
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Circuits and systems for CW and pulsed high-field electron spin resonanceBolton, David Robert January 2006 (has links)
This thesis is concerned with the design and realisation of components for a new state of the art 94GHz Electron Spin Resonance (ESR) spectrometer capable of operating in both pulsed and CW modes. The complete spectrometer is designed to provide phase coherent 1kW peak power sub-nanosecond π/2 pulses having variable duration and repetition rate. The mm-wave response of a paramagnetic sample to these pulses is detected with a superheterodyne detector. Such a system would offer a step change in performance, promising unprecedented resolution and sensitivity. These aims should be compared with the performance of commercial (Bruker) instruments capable of delivering 200mW 30ns π/2 pulses. For this type of system, both the long term (thermal) and short term (phase) stability of oscillators and sources employed are extremely important. Consideration of phase noise, frequency, tunability and power output shows that multiplied sources offer substantial benefits compared to fundamental sources. A delay line discriminator method of phase noise measurement, suitable for use with the low frequency oscillators is described and implemented. This is extended to 94GHz using a down convertor with a quasi-optically stabilised Gunn oscillator. These tools are used to select an optimum oscillator-multiplier combination to produce a low noise 94GHz source. Anew method of pulse generation, which has produced +23dBm peak power 250ps rectangular and 115ps Gaussian envelope phase coherent pulses, is described. These are believed to be the shortest phase coherent pulses at 94GHz available. This system will be used to provide ns pulses suitable for amplification to 1kW using a Klystron amplifier. A heterodyne detector has been constructed which employs the same oscillator/multiplier techniques identified above to produce the required local oscillator signal. It is demonstrated that by careful consideration of multiplication factors a system employing one variable and one fixed oscillator allows all the signals required in the spectrometer to maintain phase coherence. It is demonstrated that the complete demodulator responds to pulses on a ns time scale and has a noise temperature of 737K.
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Investigations of current build up in topologically simple magnetic fieldsBocquet, Francois-Xavier January 2005 (has links)
The solar corona is a highly conductive plasma which is dominated by the coronal magnetic field. Observations show that important solar phenomena like flares or the heating of the corona are driven by magnetic energy, probably through the process of magnetic reconnection. The release of magnetic energy by reconnection requires that non-ideal processes take place in contradiction to the high conductivity of the corona. One possibility to overcome this problem is to generate strong electrical currents in strongly localised regions. In this thesis we investigate how such localised currents can be formed by slow ideal evolution of topologically simple magnetic fields. To this purpose numerical simulations are carried out using an Eulerian and a Lagrangian MHD relaxation code. We first use a simple example (twisting of a uniform field) to investigate the advantages and disadvantages of both codes and to discover possible limitations for their application. We show that for the problems addressed in this thesis the Lagrangian code is more suited because it can resolve the localised current densities much better than the Eulerian code. We then focus in particular on magnetic fields containing a so-called Hyperbolic Flux Tube (HPT). A recently proposed analytical theory predicts that HFT's are sites where under certain conditions strong current build-up can be expected. We use our code to carry out a systematic parametric study of the dependence of current growth for a typical HFT configuration. We have also developed a completely new version of the analytical theory which is directly based on the set-up of our numerical simulations. We find that the simulations agree with the analytical prediction in a quantitative way but that the analytical theory underestimates the current growth quite substantially, probably by not taking into account the non-linear character of the full problem.
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Saying nothing : in defence of syntactic and semantic underdeterminationBowker, Mark January 2016 (has links)
According to the Encoding Model, speakers communicate by encoding the propositions they want to communicate into sentences, in accordance with the conventions of a language L. By uttering a sentence that encodes p, the speaker says that p. Communication is successful only if the audience identifies the proposition that the speaker intends to communicate, which is achieved by decoding the uttered sentence in accordance with the conventions of L. A consequence of the Encoding Model has been the proliferation of underdetermination arguments, each of which concludes against some linguistic theory T, on the grounds that, were T true, audiences would be unable to know what was said by utterances of some particular linguistic form, and therefore unable to know what speakers intended to communicate by these utterance. The result, if we accept the conclusion of these arguments, is radical restriction of the domain of viable linguistic theory. This Thesis defends an alternative model according to which there need be nothing encoded in an uttered sentence – nothing that is said by its utterance – for the audience to retrieve. Rather, there are indefinitely many ways to interpret uttered sentences – indefinitely many routes to the propositions that speaker intend to communicate – which proceed through different interpretations of what is said.
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Análise das células T regulatórias e expressão de moléculas coestimulatórias em células mononucleares de pacientes com Hanseníase com a produção de pacientes com Hanseníase e sua correlação com a produção de citocinas / T regulatory cells and expression of costimulatory molecules in peripheral blood mononuclear cells from patients with leprosy and their correlation with the cytokine secretionNeves, Maria de Lourdes Palermo Fernandes 13 May 2013 (has links)
Introdução: Hanseníase, doença crônica, incapacitante, causada pelo M.leprae, que afeta a pele e os nervos periféricos. Manifesta-se como doença espectral, que exibe dois polos imunologicamente distintos, denominados hanseníase virchowiana (lepromatous - LL), caracterizada por uma resposta celular ineficiente; e hanseníase tuberculoide (Tuberculoid - TT), com resposta imune celular efetiva. A ativação de células T requer a sinalização através de moléculas coestimulatórias expressas em células apresentadoras de antígeno e seus ligantes nas células T. As células T regulatórias (Treg) exercem importante papel no mecanismo de falha do controle da disseminação antigênica nas formas graves das doenças crônicas granulomatosas, mas seu real papel na hanseníase ainda não foi elucidado. Métodos: Estudamos a expressão das moléculas coestimulatórias e células Treg na resposta imune de pacientes nos diferentes espectros da doença. A expressão de células Treg foi quantificada por citometria de fluxo (CD4+CD25+FoxP3+) nas células mononucleares do sangue periférico de pacientes e controles (16 eram virchowianos, 12 tuberculoides e 6 controles) estimulados in vitro com o antígeno do M. leprae e com o mitógeno phytohemaglutinina, bem como nas lesões de pele por imunohistoquímica. A expressão de moléculas coestimulatorias (CD80, CD86, CD28, CTLA-4, PD-1, ICOS) foi avaliada por citometria de fluxo in vitro, a partir do estimulo de células mononucleares provenientes de 14 pacientes virchowianos, 14 tuberculoides e 10 indivíduos saudáveis expostos ao bacilo. A resposta linfoproliferativa, a produção de citocinas (IL10 e IFN-?) in vitro e a expressão in situ de IL-10, TGF? e CTLA-4 também foram determinadas. Resultados: Nós demonstramos que pacientes virchowianos apresentam deficiência na expressão da molécula CD86 na superfície de monócitos, e isso contribui para uma apresentação antigênica ineficiente, favorecendo o estado de anergia observado nesse grupo de pacientes. Observamos ainda, que o bloqueio da expressão dessa molécula, mas não do CD80 inibe a resposta linfoproliferativa ao M.leprae. Ainda no polo virchowiano anérgico, observamos redução da expressão de moléculas coestimulatórias de sinalização positiva (CD28, CD86) na superfície dos linfócitos. Em contraste, nos pacientes tuberculoides notamos um aumento da expressão de moléculas de sinalização negativa (CTLA-4 e PD-1), que pode representar uma provável modulação da resposta imune exacerbada, regulando dessa forma os efeitos deletérios da hiperreatividade celular. Notavelmente, os contatos também expressão em menor intensidade CD86 e CD28, mas não se observou expressão exacerbada de CTLA-4 ou PD-1, sugerindo que eles provavelmente desenvolvem resposta imune balanceada sem que haja necessidade de sinalização imunossupressora. Observamos ainda, que o antígeno do M.leprae induz uma significativa redução da resposta linfoproliferativa, mas um aumento significativo de células Treg no sangue e na pele dos pacientes virchowianos, quando comparado ao grupo tuberculoide. Em paralelo, notamos o aumento da expressão de moléculas anti-inflamatórias (IL-10 e CTLA-4) nas lesões cutâneas desses pacientes virchowianos. Conclusão: Nossos resultados sugerem que células Treg e moléculas coestimulatórias desempenham papel importante na patogênese da hanseníase, especialmente no polo virchowiano, em que favoreceria a anergia e a multiplicação bacilar / Introduction: Leprosy, caused by the bacillus Mycobacterium leprae, is a chronic, incapacitating disease that affects the peripheral nerves and skin. Leprosy manifests as a spectral disease, exhibiting two polar sides, namely, lepromatous leprosy (LL) characterised by impaired T-cell responses and tuberculoid leprosy in which T-cell responses are strong. Proper T-cell activation requires signalling through costimulatory molecules expressed by antigen presenting cells and their ligands on T-cells. T regulatory cells (Tregs) play an important role in the mechanism of host\'s failure to control pathogen dissemination in severe forms of different chronic granulomatous diseases, but their role in leprosy has not yet been elucidated. The objective of this study was to investigate the influence of costimulatory molecules and Tregs cels on the immune responses of subjects along the leprosy spectrum. Patients and Methods: Tregs were quantified by flow cytometry (CD4+ CD25+ Foxp3+) in peripheral blood mononuclear cells (PBMC) of patients (16 lepromatous, 12 tuberculoids and controls (n = 6) stimulated in vitro with a M. leprae antigenic preparation and phytohemagglutinin as well as in skin lesions by immunohistochemistry. The expression of the costimulatory molecules (CD80, CD86, CD28, CTLA-4, PD-1, ICOS) was evaluated in in vitro-stimulated peripheral blood mononuclear cells isolated from 14 lepromatous and 14 tuberculoid patients, and 10 healthy individuals exposed to the bacillus. The lymphoproliferative (LPR), interleukin-10 (IL-10), and interferon-g (IFN-g) responses of the in vitro-stimulated peripheral blood mononuclear cells and the in situ expression of IL-10, transforming growth factor-b (TGF-b), and cytotoxic T-lymphocyte antigen 4 (CTLA-4) were also determined. Results: We show that lepromatous patients have defective monocytes\' CD86 expression, likely contributing to the impairment of the antigen presentation process and to their anergy. Accordingly, anti-CD86 blocking monoclonal antibody, but not anti-CD80 antibody, inhibited the lymphoproliferative response to Mycobacterium leprae. Consistent with the lepromatous pole anergy, there was reduced T-cells\' expression of the positive signaling costimulatory molecules CD28 and CD86 in these patients. Tuberculoid patients, on the other hand, had increased expression of the negative signaling CTLA-4 and PD-1 molecules, probably representing a means of modulating exacerbated immune response and avoiding immunopathology. Interestingly, contacts exhibited proper CD86 and CD28 expression, but not exacerbated CD152 and PD-1 expression, suggesting that they tend to develop a balanced immunity without requiring immunosuppressive costimulatory signaling. We also observed that M. leprae antigens induced significantly lower lymphoproliferation but significantly higher Treg numbers in lepromatous than tuberculoid patients and contacts. Mitogen-induced lymphoproliferation and Treg frequencies were not significantly different between the three groups. Tregs were also more frequent in situ in multibacillary patients, and this was paralleled by increased expression of the anti-inflammatory molecules IL-10 and CTLA-4, but not TGF. Conclusion: Our results suggest that Tregs and costimuatory molecules play a major role in the pathogenesis of leprosy, especially the lepromatous pole, in which they would act to favor the anergy and the unrestricted multiplication of the bacilli
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Análise das células T regulatórias e expressão de moléculas coestimulatórias em células mononucleares de pacientes com Hanseníase com a produção de pacientes com Hanseníase e sua correlação com a produção de citocinas / T regulatory cells and expression of costimulatory molecules in peripheral blood mononuclear cells from patients with leprosy and their correlation with the cytokine secretionMaria de Lourdes Palermo Fernandes Neves 13 May 2013 (has links)
Introdução: Hanseníase, doença crônica, incapacitante, causada pelo M.leprae, que afeta a pele e os nervos periféricos. Manifesta-se como doença espectral, que exibe dois polos imunologicamente distintos, denominados hanseníase virchowiana (lepromatous - LL), caracterizada por uma resposta celular ineficiente; e hanseníase tuberculoide (Tuberculoid - TT), com resposta imune celular efetiva. A ativação de células T requer a sinalização através de moléculas coestimulatórias expressas em células apresentadoras de antígeno e seus ligantes nas células T. As células T regulatórias (Treg) exercem importante papel no mecanismo de falha do controle da disseminação antigênica nas formas graves das doenças crônicas granulomatosas, mas seu real papel na hanseníase ainda não foi elucidado. Métodos: Estudamos a expressão das moléculas coestimulatórias e células Treg na resposta imune de pacientes nos diferentes espectros da doença. A expressão de células Treg foi quantificada por citometria de fluxo (CD4+CD25+FoxP3+) nas células mononucleares do sangue periférico de pacientes e controles (16 eram virchowianos, 12 tuberculoides e 6 controles) estimulados in vitro com o antígeno do M. leprae e com o mitógeno phytohemaglutinina, bem como nas lesões de pele por imunohistoquímica. A expressão de moléculas coestimulatorias (CD80, CD86, CD28, CTLA-4, PD-1, ICOS) foi avaliada por citometria de fluxo in vitro, a partir do estimulo de células mononucleares provenientes de 14 pacientes virchowianos, 14 tuberculoides e 10 indivíduos saudáveis expostos ao bacilo. A resposta linfoproliferativa, a produção de citocinas (IL10 e IFN-?) in vitro e a expressão in situ de IL-10, TGF? e CTLA-4 também foram determinadas. Resultados: Nós demonstramos que pacientes virchowianos apresentam deficiência na expressão da molécula CD86 na superfície de monócitos, e isso contribui para uma apresentação antigênica ineficiente, favorecendo o estado de anergia observado nesse grupo de pacientes. Observamos ainda, que o bloqueio da expressão dessa molécula, mas não do CD80 inibe a resposta linfoproliferativa ao M.leprae. Ainda no polo virchowiano anérgico, observamos redução da expressão de moléculas coestimulatórias de sinalização positiva (CD28, CD86) na superfície dos linfócitos. Em contraste, nos pacientes tuberculoides notamos um aumento da expressão de moléculas de sinalização negativa (CTLA-4 e PD-1), que pode representar uma provável modulação da resposta imune exacerbada, regulando dessa forma os efeitos deletérios da hiperreatividade celular. Notavelmente, os contatos também expressão em menor intensidade CD86 e CD28, mas não se observou expressão exacerbada de CTLA-4 ou PD-1, sugerindo que eles provavelmente desenvolvem resposta imune balanceada sem que haja necessidade de sinalização imunossupressora. Observamos ainda, que o antígeno do M.leprae induz uma significativa redução da resposta linfoproliferativa, mas um aumento significativo de células Treg no sangue e na pele dos pacientes virchowianos, quando comparado ao grupo tuberculoide. Em paralelo, notamos o aumento da expressão de moléculas anti-inflamatórias (IL-10 e CTLA-4) nas lesões cutâneas desses pacientes virchowianos. Conclusão: Nossos resultados sugerem que células Treg e moléculas coestimulatórias desempenham papel importante na patogênese da hanseníase, especialmente no polo virchowiano, em que favoreceria a anergia e a multiplicação bacilar / Introduction: Leprosy, caused by the bacillus Mycobacterium leprae, is a chronic, incapacitating disease that affects the peripheral nerves and skin. Leprosy manifests as a spectral disease, exhibiting two polar sides, namely, lepromatous leprosy (LL) characterised by impaired T-cell responses and tuberculoid leprosy in which T-cell responses are strong. Proper T-cell activation requires signalling through costimulatory molecules expressed by antigen presenting cells and their ligands on T-cells. T regulatory cells (Tregs) play an important role in the mechanism of host\'s failure to control pathogen dissemination in severe forms of different chronic granulomatous diseases, but their role in leprosy has not yet been elucidated. The objective of this study was to investigate the influence of costimulatory molecules and Tregs cels on the immune responses of subjects along the leprosy spectrum. Patients and Methods: Tregs were quantified by flow cytometry (CD4+ CD25+ Foxp3+) in peripheral blood mononuclear cells (PBMC) of patients (16 lepromatous, 12 tuberculoids and controls (n = 6) stimulated in vitro with a M. leprae antigenic preparation and phytohemagglutinin as well as in skin lesions by immunohistochemistry. The expression of the costimulatory molecules (CD80, CD86, CD28, CTLA-4, PD-1, ICOS) was evaluated in in vitro-stimulated peripheral blood mononuclear cells isolated from 14 lepromatous and 14 tuberculoid patients, and 10 healthy individuals exposed to the bacillus. The lymphoproliferative (LPR), interleukin-10 (IL-10), and interferon-g (IFN-g) responses of the in vitro-stimulated peripheral blood mononuclear cells and the in situ expression of IL-10, transforming growth factor-b (TGF-b), and cytotoxic T-lymphocyte antigen 4 (CTLA-4) were also determined. Results: We show that lepromatous patients have defective monocytes\' CD86 expression, likely contributing to the impairment of the antigen presentation process and to their anergy. Accordingly, anti-CD86 blocking monoclonal antibody, but not anti-CD80 antibody, inhibited the lymphoproliferative response to Mycobacterium leprae. Consistent with the lepromatous pole anergy, there was reduced T-cells\' expression of the positive signaling costimulatory molecules CD28 and CD86 in these patients. Tuberculoid patients, on the other hand, had increased expression of the negative signaling CTLA-4 and PD-1 molecules, probably representing a means of modulating exacerbated immune response and avoiding immunopathology. Interestingly, contacts exhibited proper CD86 and CD28 expression, but not exacerbated CD152 and PD-1 expression, suggesting that they tend to develop a balanced immunity without requiring immunosuppressive costimulatory signaling. We also observed that M. leprae antigens induced significantly lower lymphoproliferation but significantly higher Treg numbers in lepromatous than tuberculoid patients and contacts. Mitogen-induced lymphoproliferation and Treg frequencies were not significantly different between the three groups. Tregs were also more frequent in situ in multibacillary patients, and this was paralleled by increased expression of the anti-inflammatory molecules IL-10 and CTLA-4, but not TGF. Conclusion: Our results suggest that Tregs and costimuatory molecules play a major role in the pathogenesis of leprosy, especially the lepromatous pole, in which they would act to favor the anergy and the unrestricted multiplication of the bacilli
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On taxes, labour market distortions and product imperfectionsBokan, Nikola January 2010 (has links)
This thesis aims to provide new and useful insights into the effects that various tax, labour and product market reforms have on the overall economic performance. Additionally, it aims also to provide insights about the optimal monetary and fiscal policy behaviour within the economy characterized with various real labour market frictions. We analyze the benefits of tax reforms and their effectiveness relative to product or other labour market reforms. A general equilibrium model with imperfect competition, wage bargaining and different forms of tax distortions is applied in order to analyze these issues. We find that structural reforms imply short run costs but long run gains; that the long run gains outweigh the short run costs; and that the financing of such reforms will be the main stumbling block. We also find that the effectiveness of various reform instruments depends on the policy maker's ultimate objective. More precisely, tax reforms are more effective for welfare gains, but market liberalization is more valuable for generating employment. In order to advance our understanding of the tax and product market reform processes, we then develop a dynamic stochastic general equilibrium model which incorporates search-matching frictions, costly ring and endogenous job destruction decisions, as well as a distortionary progressive wage and a at payroll tax. We confirm the negative effects of marginal tax distortions on the overall economic performance. We also find a positive effect of an increase in the wage tax progressivity and product market liberalization on employment, output and consumption. Following a positive technology shock, the volatility of employment, output and consumption turns out to be lower in the reformed economy, whereas the impact effect on inflation is more pronounced. Following a positive government spending shock the volatility of employment, output and consumption is again lower in the reformed economy, but the inflation response is stronger over the whole adjustment path. We also find detrimental effects on employment and output of a tax reform which keeps the marginal tax wedge unchanged by partially offsetting a decrease in the payroll tax by an increase in the wage tax rate. If this reform is anticipated one period in advance the negative effects remain all over the transition path. We investigate the optimal monetary and fiscal policy implication of the New-Keynesian setup enriched with search-matching frictions. We show that the optimal policy features deviation from strict price stability, and that the Ramsey planner uses both inflation and taxes in order to fully exploit the benefits of the productivity increase following a positive productivity shock. We also find that the optimal tax rate and government liabilities inherit the time series properties of the underlying shocks. Moreover, we identify a certain degree of overshooting in inflation and tax rates following a positive productivity shock, and a certain degree of undershooting following a positive government spending shock as a consequence of the assumed commitment of policy maker.
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Momentum accounting na gestão pública:um estudo de caso em organização militar prestadora de serviços da Marinha do Brasil/Rodrigo Barreiros LealLeal, Rodrigo Barreiros January 2011 (has links) (PDF)
Orientador: Profa. Dra. Aracéli Cristina de Sousa Ferreira / Dissertação (mestrado) - Universidade Federal do Rio de Janeiro, Faculdade de Administração e Ciências Contábeis, 2011. / Este estudo buscou verificar como é possível aplicar a teoriamultidimensional da contabilidade (momentum accounting) em uma Organização Militar Prestadora de Serviços da Marinha do Brasil(OMPS). Em linhas gerais, o cerne da referida teoria está no fato de / This study attempts to check how can apply the theory ofmultidimensional accounting (momentum accounting) in a Brazilian Navy Industrial Military Organization (BNIMO). In general, the core ofthis theory is the fact that accounting does not recognize the i / Made available in DSpace on 2018-02-14T18:06:18Z (GMT). No. of bitstreams: 0
Previous issue date: 2011. Added 1 bitstream(s) on 2019-02-13T19:07:14Z : No. of bitstreams: 1
0000099b.pdf: 1246657 bytes, checksum: 69a8d70caff034cdba4642816499c3c3 (MD5)
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Mécanismes d'immunoévasion dans les leucémies aiguës myéloïdes : la molécules B7-H1Berthon, Céline 17 September 2012 (has links) (PDF)
Un des mécanismes d'évasion des cellules tumorales au système immunitaire fait intervenir la famille des molécules de type B7. Ces molécules de costimulation ont aussi un rôle dans les mécanismes de tolérance immunitaire. La molécule B7-H1 (PD-L1 ou CD274) inhibe directement les lymphocytes T cytotoxiques (CTL) et est fortement exprimée à la surface de nombreux types de cellules tumorales. Les mécanismes de régulation de son expression ne sont pas bien connus. Il existe une augmentation d'expression de cette molécule après stimulation par l'IFNγ et récemment les ligands des Toll-Like-Receptor (TLR) 2, 4 et 9 ont été impliqués dans sa régulation au niveau du myélome multiple. L'implication possible des TLR dans l'expression de B7-H1 suggère un rôle possible de pathogènes dans l'échappement des tumeurs au système immunitaireIl n'existe aucune donnée dans la littérature sur l'expression des TLR au niveau des cellules blastiques de patients atteints de leucémies aigues myéloblastique (LAM). Nous avons dans un premier temps étudié l'expression des TLR dans les LAM et l'inductibilité de l'expression de la molécule B7-H1 par les ligands des TLR en cytométrie en flux. Nos résultats montrent que les TLR sont exprimés dans les LAM, avec une grande variabilité suivant les patients. On observe une augmentation significative de l'expression de B7-H1 après stimulation par le LPS (ligand TLR4) alors qu'elle n'est pas significative pour les autres ligands (PGN et ODN). Comme dans les tumeurs solides et le myélome multiple, l'expression de B7-H1 est augmentée par l'IFN γ. Des tests de lyse CTL sont en cours afin de confirmer le rôle fonctionnel de cette expression de B7-H1 via les TLR dans les LAM.Une autre partie de l'étude a été réalisée sur deux lignées murines leucémiques : DA1-3B et WEHI-3B, afin de disposer de modèles expérimentaux d'expression de B7-H1. On retrouve sur ces deux modèles l'augmentation d'expression de B7-H1 après stimulation par l'IFN γ et les ligands des TLR. L'utilisation de différents inhibiteurs chimiques des voies de signalisation suggère le rôle des voies MEK/ERK et de la voie JAK/STAT dans l'expression de cette molécule. La voie PI3kinase/Akt semble au contraire jouer un rôle inhibiteur. Le travail se poursuit avec la transfection de transdominants négatifs des différentes voies et de mutants constitutivement actifs. L'objectif à terme est de tester des stratégies d'immunothérapies des LAM par blocage pharmacologique de l'expression de B7-H1.
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Controle de qualidade de biodieseis de macaúba e algodão e suas misturas com o diesel usando Espectrometria no Infravermelho Médio e Cartas de Controle Multivariadas / Quality control of macaúba and cotton biodiesels and their diesel blends usind MID Spectrometry and Multivariate Control ChartsGuimarães, Eloiza 23 February 2018 (has links)
CNPq - Conselho Nacional de Desenvolvimento Científico e Tecnológico / A Lei nº 13.033/2014 estabelece a adição de 7 ± 0,5% (v/v) de biodiesel ao óleo diesel utilizado no sistema viário e proíbe a adição de óleos vegetais ou quaisquer solventes nesta mistura. No entanto, há casos de adição irregular de óleos vegetais e/ou residuais no diesel devido, principalmente, ao baixo custo destas matérias-primas em comparação com o produto final ou contaminado durante seu transporte e armazenamento. Assim, são necessárias análises que forneçam respostas imediatas e eficientes para garantir a qualidade dos combustíveis comercializados. Nesse sentido, o presente trabalho propõe o monitoramento da qualidade das misturas biodiesel/diesel (7% de biodiesel e 93% de diesel) usando a Espectrometria no Infravermelho Médio associada a Cartas de Controle Multivariadas baseadas no sinal analítico líquido (NAS). Os biodieseis foram produzidos a partir de óleos de macaúba e algodão usando metanol e etanol. Para cada modelo, foram desenvolvidas três cartas (gráficos): a Carta NAS, que corresponde ao analito de interesse (nesse caso o biodiesel), a carta interferente, relacionadas às contribuições de outros componentes na amostra (diesel), e a carta resíduo correspondendo à variação não sistemática nos espectros (ruído instrumental). Foram analisadas 1508 amostras utilizadas na calibração e validação de seis modelos (biodieseis etílicos e metílicos de algodão, biodieseis metílicos da amêndoa da macaúba, biodieseis metílicos e etílicos do mesocarpo da macaúba, e também de B7 comercial). Na etapa de calibração foram usadas 103 amostras dentro das especificações de qualidade, amostras estas usadas para estabelecerem os limites estatísticos para cada carta. A etapa de validação se deu com amostras dentro e fora das especificações de qualidade (1405 amostras). A validação com amostras fora dos padrões de qualidade foi feita de duas maneiras: em relação ao teor de biodiesel no diesel e à presença de adulterantes no biodiesel, no diesel e na mistura. A presença de adulterantes se deu por substituição parcial do biodiesel por óleos de soja, milho e residual, substituição parcial do diesel por óleo lubrificante, querosene e gasolina e por adição direta dos adulterantes citados na mistura biodiesel/diesel (B7) na faixa de 3,5 a 43,5% (v/v) correspondendo a uma faixa de adulteração de 0,2 a 30% (v/v) na mistura. Assim, foi possível separar as amostras conformes e não conformes tanto em relação ao teor de biodiesel no diesel quanto à presença de adulterantes, uma vez que as amostras dentro das especificações ficaram dentro dos limites estabelecidos e as amostras fora das especificações saíram do limite em pelo menos uma das cartas. Desta maneira, os resultados mostraram que o método descrito neste trabalho é uma alternativa viável, eficiente e rápida no controle de qualidade de biocombustível. / The Law No. 13.033/2014 establishes the addition of 7 ± 0.5% (v/v) of biodiesel to the diesel used in the road system and prohibits the addition of vegetable oils or any solvents to this mixture. However, there are cases of irregular addition of vegetable and/or waste oils in diesel, mainly due to the low cost of these raw materials when compared to the final or contaminated product during transportation and storage. Thus, analyzes are necessary to provide immediate and efficient responses in order to ensure the quality of the marketed fuels. In this sense, the present study proposed the quality monitoring of biodiesel/diesel blends (7% biodiesel and 93% diesel) through the use of the Medium Infrared Spectrometry associated with Multivariate Control Charts based on the liquid analytical signal (NAS). Biodiesel was produced from macaúba (acrocomia aculeate) and cotton oils using methanol and ethanol. For each model, three charts were developed: the NAS Chart, which corresponds to the analyte of interest (in this case biodiesel); the interfering chart, related to the contributions of other components in the sample (diesel); and the waste chart, corresponding to non-systematic variation in spectra (instrumental noise). A total of 1508 samples were used for the calibration and validation of the six models (ethyl and cotton biodiesel, macaúba almond (acrocomia aculeate) methyl biodiesel, macaúba mesocarp (acrocomia aculeate) methyl and biodiesel, and also commercial B7 biodiesel). At the calibration stage, 103 samples were used within the quality specifications, these samples were used to establish the statistical limits for each chart. The validation step was carried out with samples within and out of the quality specifications (1405 samples). The validation with non-standard quality samples was carried out in two ways: in relation to the biodiesel content in diesel and the presence of adulterants in biodiesel, diesel and blend. The presence of adulterants was due to the partial replacement of biodiesel by soybean, corn and residual oils; the partial replacement of diesel by lubricating oil, kerosene and gasoline; and by direct addition of the adulterants mentioned in the biodiesel/diesel blend (B7) in the range of
3.5 to 43.5% (v/v) corresponding to an adulteration range of 0.2 to 30% (v/v) in the blend. Thus, it was possible to separate the conforming and non-conforming samples, both regarding the biodiesel content in diesel and the presence of adulterants, since the samples within the specifications were within the established limits, and the samples out of the specifications have exceeded the limit in least one of the charts. Thus, the results have showed that the method described in this study is a viable, efficient and fast alternative to the biofuel quality control. / Tese (Doutorado)
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