My master thesis is focused on design and realization fully automated system which will be used for the characterization of the organic FET structure, based on DPP derivatives with follow optimization of the characterization process. Program „MeasFET“ has been created at the LabVIEW surroundings that drives hardware gadgets was build-up during last year. Furthermore, initial tests were taken for optimalization process of charge carrier mobility measurements in derivatives DPP.

In traditional electronics, inorganic materials such as silicon and germanium are used as semiconductors due to their outstanding semiconducting properties. Unfortunately, inorganic materials are rigid due to their high crystalline nature, and processing these materials is complex and expensive. Furthermore, traditional semiconducting materials do not have favorable mechanical properties in applications such as wearable devices and large-area applications with complicated shapes. Conjugated conducting polymers (CCPs) are being explored as alternative materials to conventional semiconductors due to their mechanical properties and high conductivity. CCPs offer properties such as solution and low-temperature processability, flexibility, thermal and optical properties that traditional semiconductors could not provide. These characteristics are essential in Organic Light-Emitting Diodes (OLEDs), Organic Field-Effect Transistors (OFETs), and Photovoltaic (PVs) devices. This dissertation focuses on synthesizing rhodamine- and diketopyrrolopyrrole- containing CCPs. Chapter I focuses on the synthesis, and characterization of polyrhodamine (PRho), a semiconducting conjugated polymer containing the rhodamine core in the polymer’s backbone. PRho was synthesized by the Buchwald-Hartwig polycondensation and characterized for its optical and electrochemical properties. We have discovered that the polymer is electrochemically reversible and stable up to 1000 cycles as recorded by cyclic voltammetry between -0.4 and 1.0 V vs. Ag/AgCl and stable to extreme acidic and basic conditions without noticeable degradation. Remarkably, the polymer has a conductivity in the semiconductor range of 8.38 x 10-2 S cm–1 when treated with 20% HCl. Chapter II focuses on the synthesis and characterization of four different alkenyl flanked diketopyrrolopyrrole (DPP) polymers ( PDPPVTV, PDPPVTT, PDPPV3T, and PDPPV4T) synthesized via Stille polycondensation. Different pi-conjugated segments (alkenyl/ PDPPVTV, thiophene/ PDPPVTT, thienothiophene/ PDPPV3T, and dithienothiophene/ PDPPV4T) were used to tune the optoelectrical properties of the polymers. The effect of the alkenyl groups and different pi-conjugated segments on the optoelectrical and charge mobility properties were determined by UV/visible spectroscopy, cyclic voltammetry, and FET characteristics. Three of the four polymers, except PPP4T, showed good solubility in chloroform. All the polymers showed high thermal stabilities in TGA and semi-crystalline nature in X-Ray diffraction patterns. PDPPVTV and PDPPVTT exhibited hole mobilities of 1.8 x 10-3 cm2 V-1 s-1 and 0.25 cm2 V-1 s-1, respectively. .

During the development of multicellular organisms, organs grow to well-defined shapes and sizes. The proper size and patterning of tissues are ensured by signaling molecules as e.g. morphogens. Secreted from a restricted source, morphogens spread into the adjacent target tissue where they form a graded concentration profile. Upon binding of the morphogens to receptors on the cell surfaces, the morphogenetic signal is transduced inside the cell via the phosphorylation of transcription factors, which subsequently regulate the expression of different target genes. Thus, cell fates are determined by the local concentration of such morphogens. In this work, we investigate three key aspects of morphogenetic signaling processes in growing tissues. First, we study the mechanics of tissue growth via cell division and cell death. We examine the rearrangements of cells on large scales and times by developing a continuum theory which describes the growing tissue as an active complex fluid. In our description we include anisotropic stresses generated by oriented cell division, and we show that average cellular trajectories exhibit anisotropic scaling behaviors. Our description is used to study experimentally measured shape changes of the developing wing disk of the fruit fly Drosophila melanogaster. Second, we focus on the spreading of morphogens in growing tissues. We show that the flow field of cell movements due to oriented cell division and cell death causes a drift term in the morphogen transport equation, which captures the stretching and dilution of the concentration profile. Comparing our theoretical results to recent experiments in the Drosophila wing disk, we find that the transport of the morphogen Dpp is mainly intracellular. We moreover show that the decay length of the Dpp gradient increases during development as a result of changing degradation rate and diffusion coefficient, whereas the drift of molecules due to growth is negligible. Thus growth does not affect the decay length of the gradient, but the decay length of the gradient might affect the tissue growth rate as discussed in this work. Finally, we develop a microscopic theoretical description of the intracellular transduction machinery of morphogenetic signals within an individual cell. Our description captures the kinetics of the trafficking of proteins between different cellular compartments in response to receptor-bound signaling molecules. Analyzing experimental data at the Drosophila neuromuscular junction, we show that the morphogenetic signaling is modulated by synaptic signaling via neuronal action potentials.

Morphogens are signaling molecules that play a key role in animal development. They spread from a restricted source into an adjacent target tissue forming a concentration gradient. The fate of cells in the target tissue is determined by the local concentration of such morphogens. Morphogen transport through the tissue has been studied in experiments which lead to the suggestion of several transport mechanisms. While diffusion in the extracellular space contributes to transport, recent experiments on the morphogen Decapentaplegic (Dpp) in the fruit fly Drosophila provide evidence for the importance of a cellular transport mechanism that was termed "planar transcytosis". In this mechanism, morphogens are transported through cells by repeated rounds of internalization and externalization. Starting from a microscopic theoretical description of these processes, we derive systems of nonlinear transport equations which describe the interplay of transcytosis and passive diffusion. We compare the results of numerical calculations based on this theoretical description of morphogen transport to recent experimental data on the morphogen Dpp in the Drosophila wing disk. Agreement with the experimental data is only achieved if the parameters entering the theoretical description are chosen such that transcytosis contributes strongly to transport. Analyzing the derived transport equations, we find that transcytosis leads to an increased robustness of the created gradients with respect to morphogen over-expression. Indications for this kind of robustness have been found in experiments. Furthermore, we theoretically investigate morphogen gradient formation in disordered systems. Here, an important question is how the position of concentration thresholds can be defined with high precision in the noisy environment present in typical developing tissues. Among other things, we find that the dimensionality of the system in which the gradient is formed plays an important role for the precision. Comparing gradients formed by transcytosis to those formed by extracellular diffusion, we find substantial differences that may result in a higher precision of gradients formed by transcytosis. Finally, we suggest several experiments to test the theoretical predictions of this work.

The development of a multicellular organism, such as a human or an animal, begins with the fertilization of an egg cell. Thereupon the organism grows by repeated cell divisions until the adult size is reached and growth stops. Although it is known that intrinsic mechanisms determine the final size of developing organs and organisms, the basic principles of growth control are still poorly understood. However, there is strong evidence that certain morphogens, which are a special class of signaling molecules, act as growth factors and play a key role in growth control. In this work, growth control is studied from a mainly theoretical viewpoint. A discrete vertex model describing the organization of cells by a network of polygons is used, including a description of the cell cycle and a description of dynamical morphogen distributions. Self-organized growth is studied by introducing growth rules that govern cell divisions based on the local morphogen level. This discrete description is complemented by a continuum theory to gain further insight into the dynamics of self-organized growth processes. The theoretical description is applied to the developing wing of the fruit fly Drosophila melanogaster. In the developing wing, which is an epithelium consisting of single-layered cell sheets, the morphogen Decapentaplegic (Dpp) acts as a key growth factor. Experimental data shows that the Dpp distribution is dynamic and adapts to the size of the developing wing. Two mechanisms that rely on a regulatory molecule species and lead to such a dynamic behaviour of the Dpp distribution are studied. Several growth rules are tested and the resulting growth behaviour is quantitatively compared to experimental data of the developing wing. A particular growth rule, that triggers a cell division when the local morphogen level has increased by a certain relative amount, is found to be consistent with experimental observations under normal and several perturbed conditions. It is shown that mechanical stresses that arise due to spatial growth inhomogeneities can have a stabilizing effect on the growth process.

Submitted by Renata Lopes (renatasil82@gmail.com) on 2017-01-10T11:15:29Z No. of bitstreams: 1 lilypaolamartinezabad.pdf: 2623487 bytes, checksum: bd4d6d3010f0286720ab5bcfb393b5ea (MD5) / Approved for entry into archive by Diamantino Mayra (mayra.diamantino@ufjf.edu.br) on 2017-01-31T11:20:52Z (GMT) No. of bitstreams: 1 lilypaolamartinezabad.pdf: 2623487 bytes, checksum: bd4d6d3010f0286720ab5bcfb393b5ea (MD5) / Made available in DSpace on 2017-01-31T11:20:52Z (GMT). No. of bitstreams: 1 lilypaolamartinezabad.pdf: 2623487 bytes, checksum: bd4d6d3010f0286720ab5bcfb393b5ea (MD5) Previous issue date: 2016-09-30 / A leishmaniose visceral canina (LVC) representa um grave problema de saúde pública. No Brasil, a prevalência da infecção nos cães é bastante variável, podendo atingir níveis superiores a 60% em alguns surtos. O teste rápido Dual Path Platform (TRDPP®-Bio-Manguinhos), como teste de triagem, seguido por ELISA (EIE-BioManguinhos), como teste confirmatório, tornaram-se parte do protocolo de diagnóstico da LVC, credenciado no Brasil desde 2011. No entanto, o diagnóstico da LVC ainda precisa ser melhorado para alcançar uma taxa de detecção mais precisa. Recentemente, rKLO8, uma nova proteína antigênica de L. donovani do Sudão foi clonada e purificada, e mostrou alta reatividade para diagnosticar leishmaniose visceral em humanos. O presente estudo teve como objetivo avaliar a reatividade de soros de cães frente ao antígeno rKL08 e o antígeno de referência rK26, comparando ambas as proteínas, utilizadas como antígenos em testes de ELISA, com os testes DPP® e EIE, usados como testes de diagnóstico da LVC. Amostras de soros de cães de Governador Valadares, uma área endêmica para leishmaniose em Minas Gerais, Brasil, foram agrupadas da seguinte forma: (I) DPP®/EIE negativo (n = 100), (II) DPP® positivo / EIE negativo e (III) DPP® / EIE positivo (n = 100). Níveis séricos elevados de IgM e IgG para ambos os antígenos, rKLO8 e rK26, foram encontrados no grupo III (p <0,0001). Interessantemente, foram detectados níveis elevados de IgG2 e baixos níveis de IgG1 contra ambos os antígenos no grupo de cães DPP®/EIE positivo, sugerindo a ocorrência de um fenótipo predominantemente do tipo Th1 associado com infecção subclínica. O ELISA-rKLO8 (IgG) e o ELISA-rK26 (IgG) mostraram uma sensibilidade de 68% e 77%, e especificidade de 92% e 91%, respectivamente, determinado através da análise da curva ROC. Além disso, o coeficiente Kappa indicou boa concordância (0,739) entre o ELISA-rKLO8 versus o ELISA-rK26. Ainda, a combinação de antígenos rKLO8 e rK26 (rKLO8+rK26) em um mesmo teste exibiu maior sensibilidade (85%) e especificidade (93%). A análise kappa mostrou que o ELISA-rKLO8 + rK26 (IgG) teve melhor concordância com ambos os testes, DPP® e EIE, com valores de kappa igual a 0,700. Estes dados indicaram que a combinação dos antígenos rKLO8 e rK26 gera uma melhor acurácia no diagnóstico da LVC que os antígenos rKLO8 e rK26 usados em separado na detecção de IgG. Estes resultados demonstraram, pela primeira vez, a utilidade do antígeno rKLO8 no diagnóstico da LVC, e que ELISA-rKLO8, pode representar uma potencial ferramenta adicional para o diagnóstico de LVC. / Canine Visceral Leishmaniasis (CVL) represents a serious public health issue. In Brazil, the prevalence of infection in dogs is quite variable and may reach levels above 60% in some outbreaks. The dual Path Platform (DPP®-Bio-Manguinhos) as quick screening test followed by ELISA (EIE-Bio-Manguinhos) as a confirmatory test became part of the diagnostic protocol of CVL, nationally accreditated in Brazil since 2011. However, CVL diagnosis still needs to be improved to achieve a more accurate detection rate. Recently, rKLO8, a new antigenic protein of Sudanese L. donovani, was cloned and purified and had high reactivity to diagnose human VL. The present study aimed to evaluate serum reactivity to rKL08 and to the reference antigen rK26, and to compare both diagnostic proteins used in ELISA with the combined DPP® and EIE as diagnostic tests of CVL. Dog sera samples from Governador Valadares, an area endemic for leishmaniasis in Minas Gerais, Brazil, were grouped in the following way: (I) DPP®/EIE negative (n = 100), (II) DPP® positive/EIE negative and (III) DPP®/EIE positive dog sera (n = 100). Enhanced serum levels of IgM and IgG to both rKLO8 and rK26 were found in group III (p<0.0001). Interestingly, high IgG2 and low IgG1 levels against both antigens were detected in DPP®/EIE positive dogs, suggesting the occurrence of a predominant Th1 phenotype associated with subclinical infection. The rKLO8-ELISA (IgG) and the rK26-ELISA (IgG) showed a sensitivity of 68% and 77% and specificity of 92% and 91%, respectively, determined by ROC curve analysis. In addition, Kappa coefficient indicated good agreement (0.739) between rKLO8-ELISA and rK26-ELISA. Moreover, the combination of rKLO8 and rK26 antigens (rKLO8+rK26) exhibited higher sensitivity (85%) and specificity (93%). Kappa analysis established that rKLO8+rK26-ELISA (IgG) had better agreement with both DPP® and EIE, with kappa values of 0.700. These data indicate that the combination of rKLO8 and rK26 antigens has better accuracy in the diagnosis of CVL than rKLO8 and rK26 used separately at detecting IgG. These results showed for the first time the usefulness of rKLO8 antigen in the diagnosis of CVL, and that rKLO8-ELISA may represent a potential additional tool for the diagnosis of CVL.

Submitted by isabela.moljf@hotmail.com (isabela.moljf@hotmail.com) on 2017-05-18T13:19:42Z No. of bitstreams: 1 josegeraldodecastrojunior.pdf: 7182456 bytes, checksum: 31d33bc1bedcad933b465924da4098e3 (MD5) / Approved for entry into archive by Adriana Oliveira (adriana.oliveira@ufjf.edu.br) on 2017-05-18T13:40:17Z (GMT) No. of bitstreams: 1 josegeraldodecastrojunior.pdf: 7182456 bytes, checksum: 31d33bc1bedcad933b465924da4098e3 (MD5) / Made available in DSpace on 2017-05-18T13:40:17Z (GMT). No. of bitstreams: 1 josegeraldodecastrojunior.pdf: 7182456 bytes, checksum: 31d33bc1bedcad933b465924da4098e3 (MD5) Previous issue date: 2013-12-04 / FAPEMIG - Fundação de Amparo à Pesquisa do Estado de Minas Gerais / No Brasil, a leishmaniose visceral (LV), também conhecida como calazar, é uma zoonose, de transmissão vetorial, causada pelo protozoário Leishmania chagasi. Esta doença, anteriormente descrita como rural vem passando por um processo de urbanização. Em 2008, foram diagnosticados no município de Juiz de Fora, os primeiros casos considerados autóctones de leishmaniose visceral canina (LVC) e estudos sobre epidemias urbanas da LV têm indicado que a LVC vem precedendo a infecção humana, visto que os cães são os principais reservatórios domésticos. Assim, o presente estudo teve como objetivo pesquisar a infecção de LVC no município de Juiz de Fora, bem como avaliar os fatores de risco associados à doença. O trabalho foi realizado com animais do canil municipal e ONGs e a partir do soro destes foram realizadas três técnicas sorológicas: o imunocromatográfico “TR DPP® e ELISA (“EIE-Leishmaniose visceral canina®), ambos fornecidos pela FIOCRUZ/Bio-Manguinhos e ELISA in house. A amostra totalizou 781 animais e a prevalência da LVC variou de acordo com a técnica empregada: o teste DPP apresentou soropositividade de 4,87% (IC 95% de 3,5-6,7%); o ELISA Bio-Manguinhos de 2,18% (IC 95% de 1,3-3,5%) e ELISA in house de 13,73% (IC 10,8-17,3%). Em relação à variabilidade observada entre as técnicas, vale a pena destacar que as mesmas apresentam antígenos diferentes e isto pode refletir nos resultados. A amostra foi composta, em sua maioria por fêmeas adultas, sem raça definida, porte médio e pelo curto. Na análise univariada, utilizando-se o ELISA Bio-Manguinhos como confirmatório para a LVC, foi observada associação estatística (p< 0,05; IC 95%) com sintomatologia clínica segundo Quinnell et al. 2003, origem dos animais (canil municipal) e grupo racial; além disto, houve sugestão de associação com sexo masculino e porte médio/grande dos animais. Na análise multivariada, o fato de ser procedente do canil e sintomatologia clínica mantiveram associadas ao desfecho, sendo também sugestiva o sexo masculino. Este foi o primeiro inquérito da LVC no município de Juiz de Fora e a presença da doença relatada neste trabalho, reforça a idéia de que a leishmaniose está em processo de expansão e urbanização no Brasil, apontando a necessidade de vigilância epidemiológica ativa. / In Brazil, the visceral leishmaniasis (LV), also known as calazar, is a zoonotic disease, with vector transmission caused by the Leishmania chagasi protozoan. This disease, before described as rural is going through a process of urbanization. In 2008, were diagnosed in Juiz de Fora municipality, the first cases considered autochthones of canine visceral leishmaniasis (CVL) and research about urban epidemic of LV has showed that the CVL is preceding the human infection, since that the dogs are the main domestic reservoirs. Then, the present study aimed to investigate the CVL infection in Juiz de Fora, as well as to value the risk factors associated to the disease. This work was done with the animals of the public kennel and ONGs and with the serum were realized three serological techniques: the immunochomatographic “TR DPP® and ELISA (EIE-leishmaniose visceral canine®), both given by FIOCRUZ/BIO-MANGUINHOS and ELISA in house. The samples totalized 781 animals and the prevalence of CVL varied according with the technique used: the test DPP showed soropositivity of 4.87% (IC 95% of 3.5-6.7%); the ELISA Bio-Manguinhos of 2.18% (IC 95% of 1.3-3.5%) and ELISA in house of 13.73% (IC 10.8-17.3%). In relation to variability observed among the techniques, as worth pointing out that same showed different antigens and this can reflect in the results. The sampIes were compound in majority by adult females, without definite race, medium-sized and short hair. In the univarious analysis using the ELISA Bio-Manguinhos as confirmatory for the CVL, was observed statistic association (p<0.05; IC 95%) with clinic sintomatology according by Quinnell et al. (2003), origin of animals (public kennel) and racial group; and also, there was suggestion of the association with masculine sex and medium/big port animals. In the multivarious analysis, the fact of being precedent from the kennell and clinic sintomatology kept associated to the result, being suggestive the masculine sex. This was the first enquiry of CVL in Juiz de Fora municipality and presence of the disease showed in this research, reinforce the idea that the leishmaniasis is in the process of expansion and urbanization in Brazil, pointing out necessity of an active epidemiologic vigilance.

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / Diabetes mellitus is a metabolic disease characterized by hyperglycemia due defective or deficient response to insulin secretion. Type 2 diabetes mellitus (Type 2 DM) is therefore associated with a general activation of the innate immune system, in which there is a chronic, cytokine-mediated state of low-grade inflammation. Dipeptidyl peptidase IV (DPP-IV) is a cell-surface protease that bind with Adenosine deaminase (ADA) and both enzymes act in the lymphocytes proliferation and citokyne production. Vitis vinifera is a plant that has been studied due its pharmacology effects including the hypoglycemic properties. Thus, the aim of this study is to evaluate some inflammatory biomarkers, the ADA and DPP-IV activities in type 2 DM and investigate the effects of aqueous grape seed extract from Vitis vinifera (cv. Merlot) (GSE) in the ADA and DPP-IV activities in lymphocytes submitted to different glucose concentrations, in vitro. In the manuscript I, in lymphocytes, we observed a decrease in CD26 expression, an increase in ADA and n-acetil-β-d-glucosaminidase (NAG) activities in type 2 DM patients when compared to controls, while the gamma-glutamyl tranferase (GGT) and DPP-IV activities did not show differences between the groups. Moreover, the NAG activity demonstrated a positive correlation with ADA activity and a negative, with CD26 expression. GGT activity was positively correlated with waist circumference and body mass index (BMI), in type 2 DM. In the manuscript II, we observed we observed an increase in ADA activity when lymphocytes were exposure to the high concentration (100mM) of glucose and GSE prevented this increase in ADA activity. In serum, in the manuscript I, we showed an increase in ADA activity and in C reactive protein (CRP) levels in type 2 DM. Furthermore, the levels of CRP in diabetics were positively correlated with waist circumference and BMI. The GGT and DPP-IV activities did not show alterations between the groups, but in type 2 DM the DPP-IV activity was positively correlated with glicated hemoglobin. We concluded that, glucose might stimulated the ADA activity in the same time that it cause decrease in CD26 expression, in lymphocytes. Moreover, GSE prevents the ADA activation in presence of glucose possible due its hypoglycemic properties. / O diabetes melito (DM) é uma desordem metabólica caracterizada por hiperglicemia em virtude de resposta defeituosa ou deficiente à secreção de insulina. O DM tipo 2 (DM 2) está associado com a ativação do sistema imune, no qual há uma inflamação de baixo grau mediada por citocinas. A dipeptidil peptidase IV (DPP-IV, CD26) é uma protease multifuncional e na superfície celular ela encontra-se ligada a adenosina deaminase (ADA). Ambas estão envolvidas na proliferação de linfócitos e na produção de citocinas inflamatórias. A Vitis vinifera é uma planta que tem sido estudada devido suas propriedades farmacológicas, dentre essas, por apresentar efeitos hipoglicêmiantes. Desta forma, o objetivo deste estudo foi avaliar biomarcadores inflamatórios, a atividade da ADA e da DPP-IV em pacientes com DM 2, e verificar o efeito do extrato aquoso de sementes de Vitis vinifera (cv. Merlot) sobre a atividade da ADA e da DPP-IV em linfócitos expostos a diferentes concentrações de glicose, in vitro. Em linfócitos, no manuscrito I observamos uma diminuição na expressão do CD26, um aumento na atividade da ADA e da n-acetil-β-d-glicosaminidase (NAG) em pacientes com DM 2 em relação aos controles, enquanto que a atividade da gamaglutamil transferase (GGT) e da DPP-IV não se alterou. Também, a atividade da NAG linfocitária em pacientes com DM 2 mostrou-se positivamente relacionada com a atividade da ADA e negativamente com a expressão do CD26 e a atividade da GGT mostrou-se positivamente relacionada à circunferência abdominal e ao IMC. Já no manuscrito II, observamos um aumento na atividade da ADA quando os linfócitos forma expostos a 100mM de glicose e este aumento foi atenuado quando, expostos a glicose e extrato aquoso de sementes de Vitis vinifera. Em soro, no manuscrito I, observamos um aumento na atividade da ADA e também nos níveis de proteína C reativa (PCR) em pacientes com DM 2. Além disso, os níveis de PCR em diabéticos mostraram-se positivamente correlacionados com a circunferência abdominal e o índice de massa corporal (IMC) desses pacientes. A atividade da GGT e da DPP-IV não mostraram diferenças entre os grupos. No entanto, a atividade da DPP-IV sérica mostrou-se correlacionada com os níveis de hemoglobina glicada nos pacientes com DM 2. Conclui-se que, a glicose possa estimular a atividade da ADA ao mesmo tempo em que provoca uma redução da expressão do CD26 em linfócitos. Além disso, o extrato aquoso de sementes de Vitis vinifera é capaz de impedir a ativação da atividade da ADA em presença de glicose possivelmente devido suas propriedades hipoglicemiantes.

Le travail présenté dans ce mémoire de thèse avait pour but de synthétiser de nouveaux composés pour des applications en imagerie médicale. La première partie porte sur la synthèse de ligands hétéroleptiques pour la chélation de deux métaux différents en vue d’une utilisation dans deux types d’imagerie. Pour cela, nous avons d’abord synthétisé des porphyrines. Ces molécules sont connues pour la chélation de nombreux métaux de transition et notamment le cuivre, dont l’isotope cuivre-64 est un radioémetteur β+ utilisable en Tomographie par Émission de Positron (TEP). Ces porphyrines ont été couplées à un dérivé du DOTA, molécule connue pour son application, après métallation avec du gadolinium, en Imagerie par Résonance Magnétique (IRM). Ces composés possèdent des valeurs de relaxivité encourageantes pour une application en IRM. Enfin, des biomolécules ont été modifiées afin de vectoriser nos composés. La seconde partie porte sur la synthèse de composés pour l’imagerie médicale par optique non-linéaire. Nous avons dans un premier temps synthétisé des porphyrines amphiphiles et zwiterrioniques pour la Génération de Second Harmonique (GSH). Leur efficacité a été mesurée et celle-ci est suffisante pour pouvoir envisager l’obtention d’images. Dans un second temps, nous avons travaillé sur la synthèse d’un composé pour une application en imagerie biphotonique et en IRM. Pour cela, nous avons relié un dérivé du DOTA avec un fluorophore de type DPP. Le composé final a été métallé avec du gadolinium et sa relaxivité est supérieure à celle du DOTA(Gd). / The goal of my PhD studies was to synthesize new compounds for possible medical imaging applications. The first part of my thesis focused on the synthesis of heteroleptic ligands to achieve the chelation of two different metals aimed at addressing two types of medical imaging. We first synthesized porphyrins, which are well-known for the chelation of numerous transition metals. We focused on copper, whose copper-64 isotope is a β+ emitter usable in Positron Emission Tomography (PET). These porphyrins have been coupled with a DOTA derivative. This molecule, metallated with gadolinium, is well-known in Magnetic Resonance Imaging (MRI). Our compounds display encouraging relaxivities for MRI applications. At last, these molecular probes have been conjugated to a few biomolecules in order to vectorize our compounds. The second part of this work is related to the synthesis of fluorophores for nonlinear optical imaging. We first synthesized amphiphilic zwitterionic porphyrins for Second Harmonic Generation (SHG). The efficiency of these compounds has been measured and was satisying enough to consider the possibility to perform imaging studies. We also worked on the synthesis of compounds for Two Photon Emission Fluorescence (TPEF) imaging and MRI. We have linked a DOTA derivative with a diketopyrrolopyrrole (DPP). This conjugate has been metallated with gadolinium and its relaxivity has been measured. Interestingly, this value is superior to that of DOTA(Gd).

Dans l'instrumentation nucléaire, les architectures de traitement numérique du signal doivent faire face à la nature poissonienne du signal, composée d'impulsions d'arrivées aléatoires qui imposent aux architectures actuelles de travailler en flux de données. En effet, si le débit d'impulsion est trop élevé, les besoins en temps réel impliquent de paralyser l'acquisition du signal durant le traitement d'une impulsion. Durant ce délai, appelé temps mort, des impulsions peuvent être perdues. Cette contrainte conduit les architectures actuelles à utiliser des solutions dédiées à base de FPGA. Les utilisateurs finaux doivent cependant pouvoir mettre en oeuvre un large éventail d'applications sur un nombre de canaux d'acquisition qui varie. Ce besoin en flexibilité conduit à proposer une architecture programmable (C, C ++). Cette thèse présente une architecture numérique « dirigée par les impulsions » qui répond à ces contraintes. En premier lieu, cette architecture se compose d'extracteurs d'impulsions capables d'extraire de façon dynamique les impulsions en fonction de leur taille pour n'importe quel type de détecteur délivrant des impulsions. Ces impulsions sont ensuite distribuées sur des unités fonctionnelles programmables (FU) indépendante. Ces FUs gèrent l'arrivée d'événements aléatoires et des durées d'exécution de programme non-déterministes. Le simulateur de l'architecture est développé en SystemC au cycle d'horloge près. Il montre des résultats prometteurs en termes de passage à l'échelle, tout en maintenant le zéro-temps mort. Cette architecture permet d'embarquer de nouveaux algorithmes de traitement des impulsions traditionnellement utilisés hors ligne. / In the field of nuclear instrumentation, digital signal processing architectures have to deal with the poissonian characteristic of the signal, composed of random arrival pulses which requires current architectures to work in dataflow. Thus, the real-time needs implies losing pulses when the pulse rate is too high. Current architectures paralyze the acquisition of the signal during the pulse processing inducing a time during no signal can be processed, this is called the dead time. These issue have led current architectures to use dedicated solutions based on reconfigurable components such as FPGAs. The requirement of end users to implement a wide range of applications on a large number of channels leads to propose an easily programmable architecture platform (C, C++). This thesis present presents a digital “pulse-driven” architecture that meets these constraints. This architecture is first composed of pulse extractors. They are capable of dynamically extracting the pulses according to their size for any type of detector that delivering pulses. These pulses are then distributed on a set of programmable and independent Functional Units (FU) which are "pulses driven". These FUs are able to handle the arrival of non-deterministic events and variable program execution times and indeterminate in advance. The virtual prototype of the architecture is developed in cycle accurate SystemC and shows promising results in terms of scalability while maintaining zero dead time. This architecture paves the way for novel real time pulse processing by reducing the gap between embedded real time processing and offline processing.