Dissertations / Theses on the topic 'GFET'

Les propriétés électriques et mécaniques exceptionnelles du graphène font de ce matériau bidimensionnel à base de carbone, l’un des matériaux phare de la micro-électronique. L’objectif des ces travaux de recherche est de démontrer les possibilités nouvelles offertes par le graphène dans le domaine des transistors ultra-rapides et faible bruit. La fabrication de transistors RF a été réalisée sur des échantillons obtenus par graphitisation de substrat SiC. Ce travail s’est déroulé dans le cadre du projet ANR MIGRAQUEL, en partenariat avec le Laboratoire de Photonique et de Nanostructures (LPN), le Laboratoire Pierre Aigrain (LPA) de l’ENS, et l’Institut d’Electronique Fondamentale (IEF). Les couches de graphène utilisées dans cette thèse ont été synthétisées au LPN. Le développement et l’optimisation des différents procédés technologiques se sont déroulés en salle blanche. Les propriétés du matériau tels que la mobilité, la résistance par carré, ainsi que certaines caractéristiques technologiques comme les résistances de contact sont déduites de structures spécifiques. Ensuite, des caractérisations électriques en régime statique et dynamique effectuées sur des transistors graphène à effet de champ (GFET) ont été effectuées. Les meilleures performances hyperfréquence ont été obtenues sur des transistors à base de nano-rubans de graphène (GNRFET), avec une fréquence de coupure « intrinsèque » du gain en courant ft_intr=50GHz et une fréquence maximale d’oscillation fmax=29GHz; et ce pour une longueur de grille de Lg=75nm à Vds=300mV
Outstanding electrical and mechanical properties of graphene make this two-dimensional carbon-based material, one of the leading microelectronics materials. The aim of this thesis is to demonstrate the new possibilities offered by graphene in the field of high-speed and low-noise transistors. RF transistors have been produced on samples obtained by graphitization of SiC substrates. This was possible through the ANR program MIGRAQUEL in partnership with the Laboratory of Photonics and Nanostructures (LPN), the Pierre Aigrain Laboratory (LPA) of ENS and the Institute of Fundamental Electronics (IEF). Graphene samples used in this thesis were synthesized in LPN. The development and optimization of the different technological steps process took place in clean-rooms. Material properties such as mobility, sheet resistance and some technological parameters such as contact resistance are made using specific samples. Then, each GFET and GNRFET (Graphene Nano-Ribbons FET) transistor were analyzed both in static and high-frequency regime. Finally, the best RF measurement in terms of intrinsisc current gain cut-off frequency and maximum oscillation frequency are respectively fr_intr=50GHz and fmax=29GHz; for a gate length of Lg=75nm at Vds=300mV

Field-effect transistors (FET) based on graphene as channel has extraordinaryproperties in terms of charge mobility, charge carrier density etc. However, there aremany challenges to graphene based FET due to the fact graphene is a monolayer ofatoms in 2-dimentional space that is strongly influenced by the operating conditions.One issue is that the Dirac point, or K-point, shifts to higher gate voltage whengraphene is exposed to atmosphere. In this study graphene field-effect transistors(GFET) based on commercially available CVD graphene are electrically characterizedthrough field effect gated measurements. The Dirac point is initially unobservable andlocated at higher gate voltages (>+42 V), indicating high p-doping in graphene.Different treatments are tried to enhance the properties of GFET devices, such astransconductance, mobility and a decrease of the Dirac point to lower voltages, thatincludes current annealing, vacuum annealing, hot plate annealing, ionized water bathand UV-ozone cleaning. Vacuum annealing and annealing on a hot plate affect thegated response; they might have decreased the overall p-doping, but also introducedDirac points and non-linear features. These are thought to be explained by localp-doping of the graphene under the electrodes. Thus the Dirac point of CVDgraphene is still at higher gate voltages. Finally, the charge carrier mobility decreasedin all treatments except current – and hot plate annealing, and it is also observed that charge carrier mobilities after fabrication are lower than the manufacturer estimatesfor raw graphene on SiO2/Si substrate.

Ce travail a été réalisé dans le cadre du projet GRACY regroupant l’IEMN et d’autres laboratoires de recherche : CALISTO et IMS Bordeaux. Ce manuscrit fait état d’une synthèse exhaustive des études et avancées menées dans le cadre de ce travail de thèse au sein de l’Institut d’Électronique, de Microélectronique et de Nanotechnologie (IEMN) dans le groupe CARBON. Le principal axe de réflexion de ce travail repose sur la conception, la modélisation et la caractérisation des dispositifs actifs et passifs sur substrat souples et rigides en vue du développement de nouveaux composants et de circuits électroniques avec des critères de performances de plus en plus importants. Au cours de ce travail, l’accent a été principalement portée sur les étapes essentielles à la réalisation de circuit intégré en ondes millimétriques utilisant la technologie coplanaire en impression jet d’encre et les transistors à effet de champ à base de graphène (GFETs). Ce mémoire montre en particulier l’intérêt et les potentialités du graphène pour son intégration au sein des circuits électroniques. De plus, une attention particulière a été portée sur la modélisation et les techniques de caractérisations relatives aux dispositifs passifs sur substrat souple. Par conséquent, un banc de caractérisation de ces éléments sur substrat flexibles a été développé au cours de cette thèse afin de vérifier et consolider expérimentalement leurs comportements
This work was carried out under the project involving GRACY IEMN and other research laboratories: CALISTO and IMS Bordeaux. This manuscript reports a comprehensive overview of studies and advanced conducted as part of this thesis in the Institute of Electronics, Microelectronics and Nanotechnology (IEMN) in CARBON group. The main reflection axis of this work is based on the design, modeling and characterization of active and passive devices on flexible and rigid substrates for the development of new components and electronic circuits with increasingly important performance criteria. During this work, the focus was mainly focused on the essential steps to achieving integrated circuit millimeter wave using coplanar technology by inkjet printing and field effect transistors based on graphene (GFETs). This memory in particular shows the importance and potential of graphene for integration into electronic circuits. In addition, special attention was paid on modeling and characterization techniques related to passive devices on flexible substrates. Therefore, a characterization bench of these elements on flexible substrate has been developed during this thesis to verify and consolidate their behavior experimentally

L’électronique flexible est une thématique en plein essor, et impacte de nombreux secteurs applicatifs. L’objectif de cette thèse est de développer des composants sur substrats flexibles, pour des applications dans le domaine des radiofréquences. Elle est constituée de deux grandes parties : (i) la fabrication de composants passifs RF en utilisant la technologie d’impression par jet d’encre ; (ii) la fabrication de transistors graphène sur substrats flexibles. Ces travaux sont partiellement intégrés au projet Européen flagship GRAPHENE, et au projet ANR GRACY. La technique d’impression jet d’encre est particulièrement adaptée à la fabrication de composants sur substrats flexibles. L’un des challenges de cette approche technologique est de pouvoir atteindre une définition et une résolution adaptée au fonctionnement en régime radiofréquence. Le travail mené dans cette thèse a permis de réaliser des lignes homogènes de largeur minimale de 50 µm, et une résolution (distance entre 2 lignes de l’ordre de 15 µm. Différents composants passifs ont été fabriqués et caractérisés avec succès, et ce même en appliquant des contraintes en flexion aux dispositifs.Nous avons également développé et optimiser un procédé technologique, adapté à la fabrication de transistors à effet de champ à base de graphène (GFET), sur substrat flexible. Ce procédé présente un bilan thermique faible, et est basé sur l’utilisation d’une grille arrière à base d’aluminium dont l’oxyde naturel sert d’oxyde de grille. De nombreux transistors ont été fabriqués sur substrat kapton, et avec un bon rendement. Les meilleures performances en termes de fréquence de coupure du gain en courant (ft=39 GHz) et la fréquence maximale d’oscillation (fmax=13GHz) ont été mesurées sur un transistor de longueurs de grille Lg=100 nm et un développement de 12µm. Cette performance est à l’état de l’art de GFET flexibles. Ces performances sont conservées pour des contraintes atteignant 0,5%
Flexible electronic has drawn growing attentions for past several years due to its largely potential applications. The objective of my PhD work is to develop devices based on flexible substrate, for RF applications. There are mainly two parts involved: (i) fabrication of passive devices (transmission lines, antenna, etc) using inkjet printing technology; (ii) fabrication of graphene field effect transistors on flexible substrate using graphene growth by CVD technique. This work is partially involved in the European Flagship program GRAPHENE, and the ANR program GRACY. Inkjet printing is a promising fabrication technology for flexible electronics. The challenge of this technology is the quality and reliability of printed patterns in terms of geometry. Based on optimized printing parameters, the structures of coplanar wave guide (CPW) transmission lines with nice printing quality were realized (definition of 50 µm, resolution down to 20 µm). The RF characterization of these transmission lines combining the considerations of geometric dimensions, sintering temperature, and substrate bending are presented. The outstanding electrical and mechanical properties make graphene suitable for flexible transistors. In this thesis, we have developed and optimized a new low temperature process based on back-gated structure either on rigid substrate than on flexible substrate (here kapton). From flexible transistors, we report as measured current gain cut-off frequency ( ft-DUT ,without any de-embedding) of 39 GHz and maximum oscillation frequency (fmax) of 13 GHz in devices with 100 nm gate length and 12 µm gate width. This result is at the level of the state of art for flexible GFETs

Moore's law has defined the semiconductor industry for the past 50 years. Devices continue to become smaller and increasingly integrated into the world around us. Beginning with personal computers, devices have become integrated into watches, phones, cars, clothing and tablets among other things. These devices have expanded in their functionality as well as their ability to communicate with each other through the internet. Further, devices have increasingly been required to have diverse of functionality. This combination of smaller devices coupled with diversification of device functionality has become known as more than Moore. In this thesis, more than Moore applications of graphene are explored in-depth. Graphene was discovered experimentally in 2004 and since then has fueled tremendous research into its various potential applications. Graphene is a desirable candidate for many applications because of its impressive electronic and mechanical properties. It is stronger than steel, the thinnest known material, and has high electrical conductivity and mobility. In this thesis, the potentials of graphene are examined for pressure sensors, humidity sensors and transistors. Through the course of this work, high sensitivity graphene pressure sensors are developed. These sensors are orders of magnitude more sensitive than competing technologies such as silicon nanowires and carbon nanotubes. Further, these devices are small and can be scaled aggressively. Research into these pressure sensors is then expanded to an exploration of graphene's gas sensing properties -- culminating in a comprehensive investigation of graphene-based humidity sensors. These sensors have rapid response and recovery times over a wide humidity range. Further, these devices can be integrated into CMOS processes back end of the line. In addition to CMOS Integration of these devices, a wafer scale fabrication process flow is established. Both humidity sensors and graphene-based transistors are successfully fabricated on wafer scale in a CMOS compatible process. This is an important step toward both industrialization of graphene as well as heterogeneous integration of graphene devices with diverse functionality. Furthermore, fabrication of graphene transistors on wafer scale provides a framework for the development of statistical analysis software tailored to graphene devices. In summary, graphene-based pressure sensors, humidity sensors, and transistors are developed for potential more than Moore applications. Further, a wafer scale fabrication process flow is established which can incorporate graphene devices into CMOS compatible process flows back end of the line.

QC 20160610

Mestrado em Engenharia Física
Neste trabalho é descrito o estudo de estruturas híbridas de grafeno e diamante nano-cristalino (GDH) sintetizadas por deposição química em fase vapor por plasma de micro-ondas (MPCVD) em cobre. Foram investigadas técnicas de controlo da nucleação do diamante nano-cristalino, tendo sido encontrados dois processos com sucesso. Procedeu-se ainda à caracterização estrutural, morfológica e ótica das amostras por análise de SEM, TEM, AFM, EFM, medidas de transmitância UV-Vis e espetroscopia de Raman. A avaliação das propriedades de transporte destes materiais foi efetuada pela medição da curva de transferência de transístores de efeito de campo produzidos para o efeito, sendo os GDHs produzidos o material ativo do canal. Foram observadas baixas mobilidades devido à hidrogenação do grafeno. Em linha com resultados teóricos da literatura, foram encontradas evidências de abertura do hiato energético do grafeno, um potencial desenvolvimento para a aplicação em dispositivos de comutação lógica.
In this work, hybrid structures of graphene and nano-crystalline diamond (GDH) produced by microwave plasma chemical vapor deposition (MPCVD) in copper substrates are studied. The control of the diamond clusters nucleation was investigated, having two different approaches been identified as promising. Structural, morphological and optical characterization was carried out by SEM, TEM, AFM, EFM, UV-Vis transmittance, and Raman spectroscopy. The transport properties of this material were analyzed through the transfer curve of field-effect transistors with GDH channels. Low mobilities were found due to graphene hydrogenation. In line with theoretical studies, evidences were found of graphene band gap opening, a potential breakthrough for the development of logical switching devices.

Tato práce se zabývá oblastí dvourozměrných materiálů, jejich přípravou a analýzou. Pravděpodobně nejznámějším zástupcem dvourozměrných materiálů je grafen. Tento 2D allotrop uhlíku, někdy nazývaný „otec 2D materiálů“, v sobě spojuje neobyčejnou kombinaci elektrických, tepelných a mechanických vlastností. Grafen získal mnoho pozornosti a byl také připraven mnoha metodami. Jedna z těchto metod však stále vyniká nad ostatními kvalitou produkovaného grafenu. Mechanická exfoliace je ve srovnání s jinými technikami velmi jednoduchá, takto připravený grafen je však nejkvalitnější. Práce je také zaměřena na optimalizaci procesu tvorby heterostruktur složených z vrstev grafenu a hBN. Dle prezentovaného postupu bylo připraveno několik van der Waalsových heterostruktur, které byly analyzovány Ramanovskou spektroskopií, mikroskopií atomových sil a nízkoenergiovou elektronovou mikroskopií. Měření pohyblivosti nosičů náboje bylo provedeno v GFET uspořádání. Získané hodnoty pohyblivosti prokázaly vynikající transportní vlastnosti exfoliovaného grafenu v porovnání s grafenem připraveným jinými metodami. V práci popsaný proces přípravy je tedy vhodný pro výrobu kvalitních heterostruktur.

Like cell to the human body, transistors are the basic building blocks of any electronics circuits. Silicon has been the industries obvious choice for making transistors. Transistors with large size occupy large chip area, consume lots of power and the number of functionalities will be limited due to area constraints. Thus to make the devices smaller, smarter and faster, the transistors are aggressively scaled down in each generation. Moore's law states that the transistors count in any electronic circuits doubles every 18 months. Following this Moore's law, the transistor has already been scaled down to 14 nm. However there are limitations to how much further these transistors can be scaled down. Particularly below 10 nm, these silicon based transistors hit the fundamental limits like loss of gate control, high leakage and various other short channel effects. Thus it is not possible to favor the silicon transistors for future electronics applications. As a result, the research has shifted to new device concepts and device materials alternative to silicon. Carbon is the next abundant element found in the Earth and one of such carbon based nanomaterial is graphene. Graphene when extracted from Graphite, the same material used as the lid in pencil, have a tremendous potential to take future electronics devices to new heights in terms of size, cost and efficiency. Thus after its first experimental discovery of graphene in 2004, graphene has been the leading research area for both academics as well as industries. This dissertation is focused on the analysis and optimization of graphene based circuits for future electronics. The first part of this dissertation considers graphene based transistors for analog/radio frequency (RF) circuits. In this section, a dual gate Graphene Field Effect Transistor (GFET) is considered to build the case study circuits like voltage controlled oscillator (VCO) and low noise amplifier (LNA). The behavioral model of the transistor is modeled in different tools: well accepted EDA (electronic design automation) and a non-EDA based tool i.e. \simscape. This section of the dissertation addresses the application of non-EDA based concepts for the analysis of new device concepts, taking LC-VCO and LNA as a case study circuits. The non-EDA based approach is very handy for a new device material when the concept is not matured and the model files are not readily available from the fab. The results matches very well with that of the EDA tools. The second part of the section considers application of multiswarm optimization (MSO) in an EDA tool to explore the design space for the design of LC-VCO. The VCO provides an oscillation frequency at 2.85 GHz, with phase noise of less than -80 dBc/Hz and power dissipation less than 16 mW. The second part of this dissertation considers graphene nanotube field effect transistors (GNRFET) for the application of digital domain. As a case study, static random access memory (SRAM) hs been design and the results shows a very promising future for GNRFET based SRAM as compared to silicon based transistor SRAM. The power comparison between the two shows that GNRFET based SRAM are 93% more power efficient than the silicon transistor based SRAM at 45 nm. In summary, the dissertation is to expected to aid the state of the art in following ways: 1) A non-EDA based tool has been used to characterize the device and measure the circuit performance. The results well matches to that obtained from the EDA tools. This tool becomes very handy for new device concepts when the simulation needs to be fast and accuracy can be tradeoff with. 2)Since an analog domain lacks well-design design paradigm, as compared to digital domain, this dissertation considers case study circuits to design the circuits and apply optimization. 3) Performance comparison of GNRFET based SRAM to the conventional silicon based SRAM shows that with maturation of the fabrication technology, graphene can be very useful for digital circuits as well.

Cette thèse présente une étude détaillée de la structure de théories appelées GFT ("Group Field Theory" en anglais),à travers le prisme de la renormalisation. Ce sont des théories des champs issues de divers travaux en gravité quantique, parmi lesquels la gravité quantique à boucles et les modèles de matrices ou de tenseurs. Elles sont interprétées comme desmodèles d'espaces-temps quantiques, dans le sens où elles génèrent des amplitudes de Feynman indexées par des triangulations,qui interpolent les états spatiaux de la gravité quantique à boucles. Afin d'établir ces modèles comme des théories deschamps rigoureusement définies, puis de comprendre leurs conséquences dans l'infrarouge, il est primordial de comprendre leur renormalisation. C'est à cette tâche que cette thèse s'attèle, grâce à des méthodes tensorielles développées récemment,et dans deux directions complémentaires. Premièrement, de nouveaux résultats sur l'expansion asymptotique (en le cut-off) des modèles colorés de Boulatov-Ooguri sont démontrés, donnant accès à un régime non-perturbatif dans lequel une infinité de degrés de liberté contribue. Secondement, un formalisme général pour la renormalisation des GFTs dites tensorielles (TGFTs) et avec invariance de jauge est mis au point. Parmi ces théories, une TGFT en trois dimensions et basée sur le groupe de jauge SU(2) se révèle être juste renormalisable, ce qui ouvre la voie à l'application de ce formalisme à la gravité quantique.

Ces travaux portent sur le développement d’un matériau virtuel pour la simulation et l’optimisation des matériaux à microstructure hétérogène, en particulier des composites à matrice céramique de nouvelle génération. Pour ce faire une modélisation du fil est mise en place, au travers d’une démarche intégrée qui prend en compte la complexité de la microstructure et de sa variabilité issues du procédé de fabrication. La démarche proposée repose sur deux étapes : i) la construction d’une morphologie synthétique du fil, basée sur l’étude de micrographies et ii) une méthode de simulation multiéchelle inspirée de la méthode des éléments finis généralisée. L’originalité de cette dernière provient de l’utilisation de motifs, sorte de situations physiques ou topologiques élémentaires, pour décrire à la fois la microstructure et la cinématique locale. La démarche est validée et appliquée à diverses sections de fil synthétiques 2D, pour lesquelles le choix des motifs est discuté. L’extension au traitement de tronçon 3D du fil, ainsi qu’à la simulation de la fissuration à l’aide d’une méthode discrète est discutée et des premiers éléments de réponse sont apportés
The thesis work focus on the development of a virtual material for heterogeneous materials simulation and optimization, especially in the case of now generation of ceramic-matrix composites. To do that, a model at the scale of the yarn is built up, by using an integrated approach that account for the complexity of the microstructure and its variability arising from the manufacturing process. This approach is made of two steps: i) the construction of a synthetic yarn, using micrographics studies and ii) a multiscale approach based on the generalized finites elements method. The originality of that method come from the use of pattern, sort of typical physical or topological situation, that describe both the local structure and kinematic. The approach is validated and applied to various 2D cross-sections of synthetic yarns, for which the choice of patterns is discussed. Extension to 3D section of the yarn, together with the simulation of the fracture in a discrete manner, is discussed and first elements of answer are proposed

Molecular electronics pursues the use of molecules as fundamental electronic components. The inherent properties of molecules such as nano-size, low cost, scalability, and self-assembly are seen by many as a perfect complement to conventional silicon electronics. Molecule based electronics has captured the attention of a broad cross section of the scientific community. In molecular electronic devices, the possibility of having channels that are just one atomic layer thick, is perhaps the most attractive feature that takes the attention to graphene.The conductivity, stability, uniformity, composition, and 2D nature of graphene make it an excellent material for electronic devices. In this thesis we focused on Zigzag Graphene NanoRibbon(ZGNR) as a transmission channel. Due to the importance of an accurate description of the quantum effects in the operation of graphene devices, a full-quantum transport model has been adopted: the electron dynamics has been described by Density Functional Theory(DFT) and transport has been solved within the formalism of Non-Equilibrium Green’s Functions (NEGF). Using DFT and NEGF methods, the transport properties of ZGNR and ZGNR doped with Si are studied by systematically computing the transmission spectrum. It is observed that Si barrier destroyed the electronic transport properties of ZGNR, an energy gap appeared for ZGNR, and variations from conductor to semiconductor are displayed. Its followed by a ZGNR grown on a SiO2 crystal substrate, while substituting the Graphene electrodes with the Gold ones, and its effect on transmission properties have been studied. Improvement in transmission properties observed due to the formation of C-O bonds between ZGNR and substrate that make the ZGNR corrugated. Finally, we modeled a nano-scale Field Effect Transistor by implementing a gate under SiO2 substrate. A very good I-ON/I-OFF ratio has been observed although the device thickness.

This dissertation describes a new version of the Generalized Finite Element Method (GFEM), which is well suited for problems set in domains with a large number of internal features (e.g. voids, inclusions, etc.), which are practically impossible to solve using the standard FEM. The main idea is to employ the mesh-based handbook functions which are solutions of boundary value problems in domains extracted from vertex patches of the employed mesh and are pasted into the global approximation by the Partition of Unity Method (PUM). It is shown that the p-version of the Generalized FEM using mesh-based handbook functions is capable of achieving very high accuracy. It is also analyzed that the effect of the main factors affecting the accuracy of the method namely: (a) The data and the buffer included in the handbook domains, and (b) The accuracy of the numerical construction of the handbook functions. The robustness of the method is illustrated by several model problems defined in domains with a large number of closely spaced voids and/or inclusions with various shapes, including the heat conduction problem defined on domains with porous media and/or a real composite material.

Chlamydia trachomatis est une bactérie pathogène intracellulaire obligatoire infectant l'Homme causant des infections sexuellement transmissibles et des infections oculaires. Au cours de son cycle infectieux biphasique, elle réside au sein d'un compartiment séparé du cytoplasme par une membrane. Afin d'assurer ses besoins métaboliques, cette bactérie a développé des stratégies variées lui permettant de détourner des fonctions cellulaires. Nous avons étudié l'impact d'une enzyme cellulaire, TG2, sur le développement de C. trachomatis. Cette enzyme possède une activité transamidase consistant en la catalyse d'un lien covalent entre deux protéines ou entre une protéine et une petite amine. Nous avons montré que l'activité de TG2 ainsi que sa quantité augmentent au cours de l'infection par Chlamydia, favorisant la croissance bactérienne. Au niveau cellulaire, nous avons pu mettre en évidence un rôle clé de TG2 dans le contrôle de l'import de glucose dans les cellules infectées. De plus, nous avons identifié GFPT1 comme cible de TG2. GFPT1 est l'enzyme cinétiquement limitante de la voie de biosynthèse des hexosamines, régulant la synthèse d'UDP-GlcNAc. Ce métabolite est utilisé pour la modification de protéines par O-GlcNAcylation. Notre travail a révélé un lien inattendu entre l'activité de TG2 et l'O-GlcNAcylation, interrompu dans les cellules infectées probablement car l'UDP-GlcNAc est utilisé par la bactérie pour sa division. En conclusion, ce travail présente TG2 comme un effecteur clé dans le contrôle de voies métaboliques dérivées du glucose, rôle détourné par C. trachomatis afin de subvenir à ses propres besoins
Chlamydia trachomatis is an obligate intracellular pathogenic bacterium infecting humans, causing sexually transmitted infections or ocular infections. During its biphasic developmental cycle, C. trachomatis remains in a membrane-bound compartment, separated from the cytoplasm. The bacterium has acquired strategies to highjack cellular functions to meet its metabolic needs. Here we focused on the impact of a cellular enzyme called TG2 on C. trachomatis development. The activity of this enzyme is a transamidating activity, i.e. the catalysis of a covalent bound between two proteins or with a small amine present in the cell. We have shown that TG2 expression and transamidating activity increased upon C. trachomatis infection, necessary for optimal bacterial growth. At the cellular level, we focused our work on the impact of TG2 on cellular metabolism modification during infection. We showed that TG2 played a central role in the control of glucose import in infected cells. In addition, we identified GFPT1, as a target of TG2. GFPT1 is the rate-limiting enzyme of the hexosamine biosynthetic pathway, regulating the synthesis of UDP-N-acetylglucosamine. This metabolite is used for post-translational modification of proteins by O-GlcNAcylation. Our work uncovered a link between TG2 transamidating activity and O-GlcNAcylation. This link was disrupted in infected cells likely because UDP-N-acetylglucosamine is consumed by the bacteria to assist division. In conclusion, our work established TG2 as a key player in controlling glucose-derived metabolic pathways in mammalian cells, themselves hijacked by C. trachomatis to sustain its own metabolic needs

Depuis quelques années, nous assistons à l’essor d’une nouvelle filière d’électronique basée sur des supports flexibles. De nombreuses applications difficilement atteignables par l’électronique classique sont visées, c’est notamment le cas des tags RFID, des capteurs mobiles, des écrans flexibles…. Cette électronique est essentiellement basée sur des matériaux organiques pour lesquels la faible mobilité (<1cm2 /V.s) limite considérablement les performances hyperfréquences des composants. Dans ce contexte, l’intégration hétérogène de composants des filières GaN et graphène sur substrat flexible apparait comme une solution prometteuse pour des applications de puissance hyperfréquence où la conformabilité sur surface non plane est souhaitée. Ces travaux présentent d’une part, une méthode de transfert de composants HEMTs AlGaN/GaN sur ruban flexible et d’autre part, une technique de manipulation du substrat souple et de fabrication directe des composants à base de graphène sur celui-ci. Des HEMTs AlGaN/GaN à faible longueur de grille (LG = 100nm) ont été transférés sur ruban flexible et ont permis d’atteindre des résultats à l’état de l’art en termes de puissance hyperfréquence avec un gain de puissance linéaire (Gp) de 15,8 dB, une densité de puissance de sortie (Pout) de 420 mW / mm et une puissance ajoutée (PAE) de 29,6%. Pour les composants à base de graphène, une technique de manipulation du substrat flexible a été développée et a permis de fiabiliser le procédé technologique de fabrication. Une fréquence de coupure ft de 1GHz et une fréquence maximale d’oscillation fmax de 3 GHz ont été obtenues
In recent years, the field of flexible electronics has been expanding. Many applications difficult to achieve by conventional electronics are targeted as RFID tags, mobile sensors, flexible screens… This field is essentially based on organic material for which the poor mobility (<1cm2 /V.s) limits considerably the device performances. In this context, the heterogeneous integration of GaN and graphene devices on a flexible substrate appears to be a promising solution for microwave power applications where conformability on a non-planar surface is needed. This work presents, on the one hand, a method to transfer AlGaN/GaN HEMTs onto flexible tape and, on the other hand, a technique for handling and manufacturing graphene-based components directly on the flexible substrate. HEMTs with short-gate length (LG = 100 nm) have been transferred onto flexible tape and showed state of the art results in terms of microwave power with a linear power gain (Gp) of 15.8 dB, an output power density (Pout) of 420 mW/ mm and an added power efficiency (PAE) of 29.6%. Concerning graphene-based devices, a flexible substrate handling technique has been developed making the manufacturing process more reliable. A cut-off frequency ft of 1 GHz and a maximum oscillation frequency fmax of 3 GHz were obtained

Ces travaux portent sur le développement d'un matériau virtuel pour la simulation et l'optimisation des matériaux à microstructure hétérogène, en particulier des composites à matrice céramique de nouvelle génération. Pour ce faire une modélisation du fil est mise en place, au travers d'une démarche intégrée qui prend en compte la complexité de la microstructure et de sa variabilité issues du procédé de fabrication. La démarche proposée repose sur deux étapes : i) la construction d'une morphologie synthétique du fil, basée sur l'étude de micrographies et ii) une méthode de simulation multiéchelle inspirée de la méthode des éléments finis généralisée. L'originalité de cette dernière provient de l'utilisation de motifs, sorte de situations physiques ou topologiques élémentaires, pour décrire à la fois la microstructure et la cinématique locale. La démarche est validée et appliquée à diverses sections de fil synthétiques 2D, pour lesquelles le choix des motifs est discuté. L'extension au traitement de tronçon 3D du fil, ainsi qu'à la simulation de la fissuration à l'aide d'une méthode discrète est discutée et des premiers éléments de réponse sont apportés.

This thesis describes structural studies on the interactions between the fucosylated chondroitin sulfate (fCS) oligosaccharides and human proteins known as selectins. fCS is a carbohydrate obtained from sea cucumbers, that can be classified as a branched glycosaminoglycan (GAG). It has attracted much attention due to its anti-coagulant, anti-inflammatory, antimetastatic and anti-HIV properties and its structure was previously determined by NMR. Selectins constitute a family of proteins involved in cell adhesion processes, such as inflammation, attachment of viral particles and migration of tumour cells. fCS oligosaccharides have been shown to bind to selectins, which is likely a reason behind their biological activity. However, the mechanism of this interaction is currently unknown. The initial part of the thesis describes the experimental work on expression and purification of the recombinant L- and P-selectin constructs in Pichia pastoris, Escherichia coli and HEK 293 cells. The aim of these experiments was to produce two constructs for each selectin, a single domain construct, consisting of the C-type lectin domain only, and a double domain construct, consisting of both the C-type lectin and the EGF-like domains. The intention was that the recombinant proteins would be labelled with 13C and 15N to allow for the in-depth structural NMR studies on the fCS-selectin interaction. Various experimental approaches have been explored, including the use of different cell lines, modifications to construct design, as well as alterations to expression and purification conditions. Although it was not possible to produce soluble selectin constructs in either bacterial or yeast cells, protein expression tests in HEK293 cells, performed in collaboration with the Oxford Protein Production facility (OPPF), led to production of a soluble L-selectin construct, consisting of the L-selectin C-type lectin domain. The produced L-selectin construct, as well as two commercially available constructs of the Land P-selectin extracellular domains, were used in the Saturation Transfer Difference (STD) NMR experiments to provide new information about the nature of the fCS-selectin binding. The STD experiments allowed to identify the regions within the fCS oligosaccharides that are in direct contact with the protein and likely play an important role in this interaction. Experiments on different protein constructs allowed the comparison of fCS binding to P-selectin and to two different recombinant constructs of L-selectin. Results of these studies suggest that the binding occurs via a similar mechanism for both L- and P-selectins and that the fCS oligosaccharides bind to one-domain L-selectin construct with similar affinity as to a larger construct, consisting of the entire extracellular region of the protein. Alongside the experimental work, theoretical in silico studies on the fCS-selectin binding were undertaken as part of this project. The existing X-ray structures of selectin complexes were subjected to Molecular Dynamics (MD) simulations, which allowed to explore the dynamic behaviour of E-selectin upon binding to sialyl Lewis x (sLex). It was found that sLex forms a more favourable interaction with the extended conformation of E-selectin and that the protein in this conformation is characterised by a high degree of interdomain flexibility, with a new type of interdomain movement observed in the MD studies on this complex. In further in silico studies, the fCS oligosaccharides were docked to the existing P-selectin structures. The docking tests were performed on the computationally produced fCS trisaccharides with fucose branches either 2,4 or 3,4-sulfated. Results were evaluated with MD simulations and analysed in the light of current knowledge of selectin-ligand binding and the STD NMR experimental results. The in silico studies allowed to identify a subset of P-selectin residues that are likely involved in the interaction with fCS oligosaccharides in vivo. The conformational behaviour of P-selectin upon binding to fCS was also explored and it was found that the interdomain hinge is flexible during this interaction and allows transition from bent to extended conformational state. Finally, a new NMR method was developed to facilitate the studies of complex carbohydrates, incorporating the concepts of G-matrix Fourier Transform (GFT) NMR into 2D HSQC and 2D HSQC-TOCSY experiments. The method allows to separate peaks in the regions of high spectral overlap, providing information that can simplify the assignment process. The new experiments facilitated the structural evaluation of a sample containing a mixture of oligosaccharides resulting from the depolymerisation of fCS polysaccharide.

O trabalho apresenta uma análise do desempenho de vários métodos de extração de fatores de intensidade de tensão a partir de soluções numéricas obtidas com o método dos elementos finitos generalizados (MEFG). A convergência dos fatores de intensidade de tensão é comparada com a da energia de deformação a fim de investigar a superconvergência dos métodos. Para extração dos fatores de intensidade de tensão e o cálculo da taxa de energia disponibilizada para propagação da fissura, implementam-se os métodos da integral de contorno (MIC), da função cutoff (MFC) e da integral-J no contexto do MEFG. Desenvolve-se a formulação dos métodos de extração de forma a obter uma implementação independente da malha utilizada na modelagem do problema. Aplica-se a extração dos fatores de intensidade de tensão, para modos puros e mistos, em problemas clássicos da mecânica da fratura. Verifica-se a convergência dos fatores de intensidade de tensão e da taxa de energia disponibilizada para a propagação da fissura, obtidos com cada método de extração, com o enriquecimento da ordem polinomial da solução do MEFG. Investiga-se a robustez dos métodos com relação ao tamanho dos domínios de extração
The performance of several techniques to extract stress intensity factors (SIF) from numerical solutions computed with the generalized finite element method (GFEM) is investigated. The convergence of the stress intensity factors is compared with the convergence of strain energy with the aim of investigate the superconvergence of the methods. The contour integral (CIM), the cutoff function (CFM) and the J-integral methods are considered to compute stress intensity factors and energy release rate. The proposed implementation of the extraction techniques is completely independent of the discretization used. Several numerical examples demonstrating the convergence of the computed stress intensity factors and the energy release rate, with the increasing of p order of the GFEM solution, are presented

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Obesity is a chronic disease that has been progressively affecting a growing number of people in the world. Since it is a hard to control pathology that favors the emergence of other health conditions, there is a pressing need to undertake research that might contribute to enhance treatment, as well as improve quality of life and adaptive efficacy. Therefore, this study aims at evaluating obese people s quality of life perception (QL) and adaptive efficacy by relating the results obtained from evaluation of their QL perception with the results from adaptive efficacy, as well as the results from the Global Functioning Evaluation (AGF). For that purpose, the WHOQOL-100 Portuguese-version questionnaire was employed to evaluate their quality of life perception, and a Preventive Diagnosis Interview Functional Adaptive Diagnostic Scale (FADS) was also undertaken as regards adaptive efficacy, to evaluate thirty obese persons (Body Mass Index BMI >=30 kg/m2), with an average age of 52.33, who use the services of anambulatory care center located in the Greater ABC region, in the State of Sao Paulo. The majority of participants have degree I of obesity 46.70%, 33.30% have degree II and 20.00% degree III. The majority started to gain weight at the start of pregnancy (43.30%). The second period during which subjects started to lose control of their body weight occurred between the ages of 40 and 50 (20.00%). In overall evaluation of QL, it has been observed that domain VI Spiritual/Religious/Personal Belief Aspects had the highest average score (16.17 - DP=2.95 [equivalent to 80.83% of the maximum score that could be obtained]), when compared to the remaining evaluated domains. On the other hand, domain I Physical/Fitness provided the owest average score (11.77 - P=2.78 58.83%). All participants are under adaptive nefficacy: Group 2 Light Inefficacy (26.7%), Group 3 oderate Inefficacy (33.3%) and group 4 Severe Inefficacy (30.0%). As regards the global functioning evaluation (GFE),36.67% are observed to fall in the interval between 51-60 points; 23.33% of participants are in the interval between 31-50 points; and only 23.33% obtained a score above 70 points. By correlating the results from the evaluations, strong, positive and significant relations have been found between the evaluation on quality of life perception, adaptive efficacy and global functioning.
A obesidade é uma doença crônica que vem acometendo, progressivamente, cada vez mais pessoas no mundo. Por ser uma patologia de difícil controle que favorece a eclosão de outros agravos à saúde, é premente a necessidade de realização de pesquisas que possam contribuir para o aperfeiçoamento dos tratamentos, bem como para a melhoria da qualidade de vida e eficácia adaptativa. Sendo assim, a presente pesquisa visou avaliar a percepção da qualidade de vida (QV), a eficácia adaptativa (EDAO) e o funcionamento global (AGF) de pessoas com obesidade, relacionando os resultados obtidos na avaliação da percepção da QV com os da eficácia adaptativa, bem como aos do funcionamento global (AGF). Para tanto, utilizou-se o questionário WHOQOL-100 versão em português para avaliação da percepção de qualidade de vida, a Entrevista Diagnóstica Preventiva Escala Diagnóstica Adaptativa Operacionalizada (EDAO) para a eficácia adaptativa e a Escala de Avaliação do Funcionamento Global (AGF) para o funcionamento global. Este estudo contou com a participação de trinta mulheres obesas (Índice de Massa Corporal IMC >=30 kg/m2), com idade média de 52,33 anos, que utilizavam os serviços de um ambulatório situado na região do Grande ABC, estado de SP. A maioria das participantes se encontrava no grau I de obesidade - 46,70%, situava-se no grau II 33,30% e 20,00% no grau III. O aumento de peso da maioria teve início nas gestações (43,30%), o segundo período onde ocorreu o início do descontrole do peso corporal foi entre os 40 aos 50 anos (20,00%). Na avaliação geral da QV, observou-se que no domínio VI Aspectos Espirituais/Religião/Crenças Pessoais foi encontrado o maior escore médio (16,17 - DP=2,95 [equivalente a 80,83% do escore máximo que poderia ser obtido]), comparando-o com os demais domínios avaliados. Em oposição, o domínio I Físico foi o que apresentou o menor escore médio (11,77 - DP=2,78 - 58,83%). Todas as participantes se encontravam em ineficácia adaptativa: Grupo 2 Ineficaz Leve (26,7%), no Grupo 3 Ineficaz Moderada (33,3%) e no Grupo 4 Ineficaz Severa (30,0%). Quanto à avaliação do funcionamento global (AGF), notou-se que 36,67% se situavam no intervalo entre 51-60 pontos. 23,33% das participantes no intervalo entre 31-50 pontos. Apenas 23,33% tiveram pontuação acima de 70 pontos. Relacionando os resultados das avaliações, foram encontradas correlações fortes, positivas e significativas entre a avaliação da percepção de qualidade de vida, da eficácia adaptativa e do funcionamento Global.

Thesis (MScEng)--Stellenbosch University, 2012
ENGLISH ABSTRACT: Through many years of research, a number of production schemes have been developed for converting lignocellulosic biomass into transport fuels. These technologies have been assessed through a number of techno-economic studies for application in a particular context in terms of the technical and economic feasibility. However, previous studies using these methods have tended to lack vigour in various aspects. Either the energy efficiency of the processes were not maximised through adequate heat integration, or a competing technology which existed was not considered. From an economic perspective, the financial models would often lack the vigour to account for the risk and uncertainty that is inherent in the market prices of the commodities. This phenomenon is especially relevant for the biofuel industry that faces the full fledge of uncertainties experienced by the agricultural sector and the energy sector. Furthermore, from an environmental perspective, the techno-economic studies had often ignored the environmental impacts that are associated with biofuel production. Thus, a comparative study could have favoured an option due to its economic feasibility, while it could have had serious environmental consequences. The aim of this study was to address these issues in a South African context, where biofuels could be produced from sugarcane bagasse. The first step would be to modify an existing simulation model for a bioethanol scenario that operates with a Separate Hydrolysis and Fermentation (SHF process) configuration into a second processing scenario that operates with a Simultaneous Saccharification and Fermentation (SSF process) configuration using reliable experimental data. The second step was to ensure that the maximum energy efficiency of each scenario was realised by carrying out pinch point analysis as a heat integration step. In contrast to these biological models is the thermochemical model that converts bagasse to gasoline and diesel via gasification, Fischer-Tropsch synthesis and refining (GFT process). While there were no significant advances in technology concerning this type of process, the energy efficiency was to be maximised with pinch point analysis. The GFT process obtained the highest energy efficiency of 50.6%. Without the affects of pinch point technology, the efficiency dropped to 46%, which thus emphasises the importance of heat integration. The SSF had an efficiency of 42.8%, which was superior to that of the SHF at 39.3%. This resulted from a higher conversion of biomass to ethanol in the SSF scenario. Comparing the SHF model to an identical model found in literature that did not have pinch point retrofits, this study showed lower efficiency. This arose because the previous study did not account for the energy demands of the cold utility systems such as the cooling tower operation, which has been shown in this study to account for 40% of the electrical energy needs. The economic viability of all three processes was assessed with Monte Carlo Simulations to account for the risks that the fluctuations in commodity prices and financial indices pose. This was accomplished by projecting the fluctuations of these parameters from samples of a historical database that has been transformed into a probability distribution function. The consequences were measured in terms of the Net Present Value (NPV) and Internal Rate of Return (IRR) for a large number of simulations. The results of these variables were aggregated and were then assessed by testing the probability that the NPV<0, and that the IRR recedes below the interest rate of 12.64%. The investment was thus deemed unfeasible if these probabilities were greater than 20%. Both biological models were deemed profitable in terms of this standard. The probabilities were 13% for the SSF and 14% for the SHF. The GFT process however was deemed completely unfeasible because the probability that the NPV<0 was 78%. Given that the GFT process had the highest energy efficiency, this result arises mainly because the capital investment of 140,000USD/MWHHV of biomass energy input is to enormous for any payback to be expected. The environmental footprint of each process was measured using Life Cycle Assessments (LCAs). LCAs are a scientifically intricate way of quantifying and qualifying the effects of a product or process within a specified boundary. The impacts are assessed on a range of environmental issues, such as Global Warming, Acidification, Eutrophication and Human toxicity. Furthermore, if the project under concern has multiple output products, then the impacts are distributed between the output products in proportion to the revenue that each generates. The impacts were either relative to the flow of feedstock, which was 600MW of bagasse, or to the functional unit, which was the amount of fuel required to power a standard vehicle for a distance of 1 kilometre. In either case, the GFT scenario was the least burdening on the environmental. This was expected because the GFT process had the highest energy efficiency and the process itself lacked the use of processing chemicals. Relative to the feedstock flow, the SSF was the most environmentally burdening scenario due to the intensive use of processing chemicals. Relative to the functional unit, the SHF was the most severe due to its low energy efficiency. Thus, the following conclusions were drawn from the study:  The GFT is the most energy and environmentally efficient process, but it showed no sign of economic feasibility. iv  There is no significant difference in the economic and environmental evaluation of the SSF and SHF process, even though the SSF is considered to be a newer and more efficient process. The major cause of this is because the setup of the SSF model was not optimised.
AFRIKAANSE OPSOMMING: Deur baie jare van navorsing is ‘n aantal produksie-skemas vir die omskakeling van lignosellulose biomassa na vloeibarebrandstof ontwikkel. Hierdie tegnologië is geassesseer ten opsigte van die tegniese en ekonomiese haalbaarheid deur middel van tegno-ekonomiese studies in bepaalde tekste. Tog het hierdie vorige studies besliste beperkings gehad. Of die energie-doeltreffendheid van die proses is nie gemaksimeer deur voldoende hitte-integrasie nie, of 'n mededingende tegnologie wat bestaan is nie oorweeg nie. Vanuit 'n ekonomiese perspektief, was die finansiële modelle dikwels nie die omvattend genoeg om rekening te hou met die risiko en onsekerheid wat inherent is in die markpryse van die kommoditeite nie. Hierdie verskynsel is veral relevant vir die biobrandstof bedryf wat die volle omvang van onsekerhede ervaar waaraan die landbousektor en die energiesektoronderhewig is. Verder het die tegno-ekonomiese studies dikwels die omgewingsimpakte wat verband hou met biobrandstofproduksie geïgnoreer. Dus kon ‘n opsie deur die ekonomiese haalbaarheid bevoordeel word, ten spyte van die ernstige omgewingsimpakte wat dit kon inhou. Die doel van hierdie studie was om hierdie kwessies aan te spreek in 'n Suid-Afrikaanse konteks, waar biobrandstof uit suikerriet bagasse geproduseer kan word. Die eerste stap was om 'n bestaande simulasiemodel vir 'n bio-scenario wat met Afsonderlike Hidroliese en Fermentasie (SHF proses) stappe werk, te modifiseer vir 'n tweede verwerking scenario wat met 'n gelyktydige Versuikering en Fermentasie (SSF proses) konfigurasie werk. Die verandering is gedoen deur die gebruik van betroubare eksperimentele data. Die tweede stap was om te verseker dat elke scenario die maksimum energie-doeltreffendheid het, deur 'n hitte-integrasie stap, wat gebruik maak van “pinch-point” analise. In teenstelling met hierdie biologiese modelle, is daar die thermochemiese roete waar petrol en diesel van bagasse vervaardig word via vergassing, Fischer-Tropsch-sintese en rafinering (GFT proses). Daar was geen betekenisvolle vooruitgang in tegnologie vir hierdie proses nie, maar die energie-doeltreffendheid is gemaksimeer word deur energie-integrasie. Die GFT proses toon die hoogste energie-doeltreffendheid van 50,6%. Sonder die invloed van energie-integrasie het die doeltreffendheid gedaal tot 46%, wat dus die belangrikheid van hitte-integrasie beklemtoon. Die SSF het 'n effektiwiteit van 42,8% gehad, wat beter was as dié 39,3% van die SHF opsie. Hierdie hoër effektiwiteit wasas gevolg van die hoër omskakeling van biomassa na etanol in die SSF scenario. Die energie doeltreffendheid vir die SHF-model was laer as met 'n identiese model (sonder energie-integrasie) wat in die literatuur gevind wat is. Dit het ontstaan omdat die vorige studie nie 'n volledig voorsiening gemaak het met die energie-eise van die verkillingstelselsnie, wat tot 40% van die elektriese energie behoeftes kan uitmaak. Die ekonomiese lewensvatbaarheid van al drie prosesse is bepaal met Monte Carlo simulasies om die risiko's wat die fluktuasies in kommoditeitspryse en finansiële indekse inhou, in berekening te bring. Hierdie is bereik deur die projeksie van die fluktuasies van hierdie parameters aan die hand van 'n historiese databasis wat omskep is in 'n waarskynlikheid verspreiding funksie. Die gevolge is gemeet in terme van die netto huidige waarde (NHW) en Interne Opbrengskoers (IOK) vir 'n groot aantal simulasies. Die resultate van hierdie veranderlikes is saamgevoeg en daarna, deur die toets van die waarskynlikheid dat die NPV <0, en dat die IRR laer as die rentekoers van 12,64% daal, beoordeel. Die belegging is dus nie realiseerbaar geag as die waarskynlikhede meer as 20% was nie. Beide biologieseprosesse kan as winsgewend beskou word in terme van bostaande norme. Die waarskynlikhede was 13% vir die SSF en 14% vir die SHF. Aangesien die NHW van die GFT-proses onder 0 met ‘n waarskynlikheid van 78% is, is die opsie as nie-winsgewend beskou. Gegewe dat die GFT-proses die hoogste energie-doeltreffendheid het, is die resultaat hoofsaaklik omdat die kapitale belegging van 140,000 USD / MWHHV-biomassa energie-inset te groot is, om enige terugbetaling te verwag. Die omgewingsvoetspoor van elke proses is bepaal deur die gebruik van Lewens Siklus Analises (“Life Cycle Assessments”) (LCAS). LCAS is 'n wetenskaplike metodeom die effek van ‘n produk of proses binne bepaalde grense beide kwalitatief en kwantitatief te bepaal. Die impakte word beoordeel vir 'n verskeidenheid van omgewingskwessies, soos aardverwarming, versuring, eutrofikasie en menslike toksisiteit. Voorts, indien die projek onder die saak verskeie afvoer produkte het, word die impakte tussen die afvoer produkte verdeel, in verhouding tot die inkomste wat elkeen genereer. Die impak was met of relatief tot die vloei van roumateriaal (600MW van bagasse), of tot die funksionele eenheid, wat die hoeveelheid van brandstof is om 'n standaard voertuig aan te dryf oor 'n afstand van 1 kilometer. In al die gevalle het die GFT scenario die laagste belading op die omgewing geplaas. Hierdie is te verwagte omdat die GFT proses die hoogste energie-doeltreffendheid het en die proses self nie enige addisionele chemikalieë vereis nie. Relatief tot die roumateriaal vloei, het die SSF die grootse belading op die omgewing geplaas as gevolg van die intensiewe gebruik van verwerkte chemikalieë. Relatief tot die funksionele eenheid, was die SHF die swakste as gevolg van sy lae energie-doeltreffendheid.

Dissertação de mestrado em Biofísica e Bionanossistemas
Ischemic stroke is the most common type of stroke and is one of the leading causes of death and permanent brain damage in the world. The only treatment tested and aproved by the FDA (Food and Drug Administration) is the thrombolytic therapy which, although being efficient, has a reduced therapeutic window (< 4.5 hours). Moreover, it can cause some severe side effects, as the hemorrhagic transformation (HT). Some scientists have identified a set of protein biomarkers that can be used to stratify patients at high-risk of developing a HT. Stroke is a complex and heterogeneous disease, which a single biomarker is not sufficient for a diagnostic. As such, a panel of biomarkers composed of: Matrix Mettaloproteinase-9 (MMP-9), Cellular fibronectin (c-Fn), Platelet-Derived Growth Factor-CC (PDGF-CC), Angiopoietin-1 (Ang1), Neuroserpin and Calcium-binding protein S100-β were selected to observe the risk associated to HT in each patient. In this work, proteins MMP-9 and c-Fn were studied for the electrical detection of their concentration using electrolyte-gated graphene field-effect transistors (EG-GFET) and external gold gates connected to commercial transistors as biosensors. The graphene and gold surfaces were modified/functionalized immobilizing probes (antibodies) on that are highly specific for particular proteins. In this way, the proteins can be detected with high specificity, sensitivity, and speed, within the dynamic range that matches the relevant clinical range for the disease under study. Graphene is a monolayer material that presents unique electrical properties compatible with detecting with high sensitivity, changes of the electrolyte composition. Those changes were directly observed and measured on the graphene transistors' transfer curve, monitoring its Dirac point. In order to have a term of comparison, the same study was observed on gold external gates, observing the changes in the electrolyte composition through the electrical characteristics of commercial MOSFETs.
O acidente vascular cerebral (AVC) isquémico é o tipo de AVC mais frequente e é umas das principais causas de morte e de danos cerebrais permanentes no mundo. O único tratamento testado e aprovado pela FDA (Food and Drug Administration) atualmente, é a terapia trombolitica, que apesar de ser eficiente, tem uma janela terapêutica reduzida (<4.5h). Além disso, pode causar alguns efeitos secundários graves, como a transformação hemorrágica (TH). Alguns cientistas identificaram um conjunto de biomarcadores proteicos que podem ser usados para estratificar os pacientes com risco de desenvolverem uma TH. O AVC é uma doença complexa e heterogênia, pelo que só um biomarcador não é suficiente para um diagnóstico. Como tal, um painel de biomarcadores composto por: metaloproteinase da matriz 9 (MMP- 9), fibronectina celular (c-Fn), fator de crescimento derivado de plaquetas-CC (PDGF-CC), Angiopoietina- 1 (Ang1), Neuroserpina e proteína de ligação ao cálcio S100-β foram selecionados para observar o risco associado a uma TH para cada paciente. Neste trabalho foram estudadas as proteínas MMP-9 e c-Fn para deteção elétrica das suas concentrações utilizando transistores de efeito de campo de grafeno com porta liquida (EG-GFETs) e portas externas de ouro conectadas a transistores comerciais como biossensores. As superfícies de ouro e de grafeno foram modificadas/funcionalizadas imobilizando sondas moleculares (anticorpos) que são altamente especificas para as proteinas em estudo. Desta forma as proteinas podem ser detetadas com uma elevada especificidade, sensibilidade e rapidez, dentro da gama dinâmica coincidente com a relevância clinica do caso em estudo. O grafeno é um material em monocamada que apresenta propriedades elétricas únicas compativeis com a deteção de alterações na composição do eletrólito que se encontra em contacto com o canal de grafeno. Essas alterações foram diretamente observadas e medidas na curva de transferência dos transistores de grafeno, monitorizando o seu ponto de Dirac. De modo a haver um meio de comparação, o mesmo estudo foi observado em gates externas de ouro, observando as mudanças na composição do eletrólito através das caracteristicas elétricas de MOSFETs comerciais.

A atmosfera é uma camada constituída por vários gases que envolvem o planeta. Os principais são o Nitrogénio (N2) e o Oxigénio (O2) que, juntos, compõem cerca de 99% da atmosfera. Alguns outros gases encontram-se presentes em pequenas quantidades, entre eles os gases com efeito de estufa (GEE) que têm a capacidade de reter a radiação infravermelha emitida pela Terra, impedindo-a de escapar para o espaço causando o fenómeno denominado Efeito de Estufa (Ambiente, 2017). A tendência de aquecimento está em grande parte relacionada ao aumento crescente das emissões de dióxido de carbono e de outros gases com efeito de estufa libertados na atmosfera, preponderantemente, por atividades humanas. A União Europeia (UE), no âmbito da sua estratégia de redução de emissões de GEE e como forma de garantir o cumprimento dos compromissos assumidos no contexto internacional, tem vindo a criar mecanismos de controlo e de regulação das emissões de GEE. O inventário nacional de emissões de GEE (elaborado pela Agência Portuguesa do Ambiente – APA) é o instrumento que permite monitorizar e verificar o cumprimento nacional face às metas assumidas. São contabilizados os GEE cujas emissões devem ser reduzidas, onde estão incluídos os hidrofluorcarbonetos (HFC´s) - gases fluorados com efeito de estufa (GFEE) - utilizados durante a instalação, a manutenção e a assistência técnica de equipamentos fixos de refrigeração, de ar condicionado e em bombas de calor. Deve referir-se que embora os gases fluorados contribuam intensamente para o aquecimento globala sua libertação ocorre em pequenas quantidades e a sua utilização tem vindo a ser gradualmente reduzida ao abrigo da regulamentação da União Europeia. Neste contexto, este estudo incide sobre o estado de conformidade da empresa objeto de estudo e dos seus operadores com a regulamentação em vigor sobre emissão de GFEE. São estudados os vários meios de operação, tanto no armazenamento como na manipulação destes gases, e apresenta-se a preparação e o acompanhamento de uma auditoria de certificação deste serviço da empresa.

Since its discovery in 2004, graphene has been widely touted as a potential replacement for silicon in the next generation of electronic circuits owing to its exceptionally high carrier mobilities and its ultra-thin body. Graphene field effect transistors (GFETs) show promising potential for use in analog and radio frequency (RF) applications, with theoretically predicted THz frequencies only being limited by fabrication challenges. High series resistance of the source/drain access regions in a GFET is one such major factor responsible for performance degradation. In this thesis, a simple and straightforward scheme of reducing this resistance by self-aligned spin-on-doping of graphene using surface transfer dopants is presented. Back-gated GFETs were fabricated on Si/SiO2 and doped using various surface transfer dopants. A novel method of spin-on-doping graphene using poly(ethyleneimine) (PEI) was developed. Top-gated GFETs with mobilities up to 6,900 cm2/Vs were fabricated and their access regions were spin-on-doped in a self-aligned manner offering a 3X reduction in the series resistance. GFET drive currents improved by up to 4X and transconductances up to 3X after self-aligned doping. GFETs were also fabricated on insulating quartz substrates with mobilities up to 5,600 cm2/Vs and showed performance enhancements up to 2X after self-aligned doping.
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Thesis (Ph.D.)--State University of New York at Buffalo, 2006.
Title from PDF title page (viewed on July. 18, 2006) Available through UMI ProQuest Digital Dissertations. Thesis adviser: Atwood, Jim D., Szyperski, Thomas. Includes bibliographical references.

Hematopoiesis is the process in which billions of blood cells are produced on a daily basis, and is vital for sustaining life. This process is tightly regulated by a dynamic balance between hematopoietic stem cell (HSC) self-renewal and differentiation, and maintenance of this balance is of critical importance as dysregulation of HSCs can lead to hematopoietic deficiencies or malignancies such as leukemogenesis. While the signaling mechanisms that regulate HSC homeostasis and function are not well understood, our previous studies have identified a calcium/calmodulin (CaM)-dependent protein kinase, CaMKIV, that is intrinsically required for regulating normal proliferation and survival in HSCs. These findings suggest not only the importance of calcium-initiated pathways including CaMKIV-dependent signaling in hematopoietic cells, but also the potential for other calcium/CaM-dependent effector proteins such as other CaM-kinases to be involved in regulating HSCs and hematopoiesis.

The first major section of this dissertation work presented herein was based on the usage of RNA interference (RNAi) technology to specifically deplete HSCs of growth factor erv1-like (Gfer), a gene whose expression appeared to be absent in CaMKIV null HSCs based on comparative microarray analysis with wild-type HSCs, and seemed a potential target of CaMKIV. We showed that depletion of Gfer in HSCs compromised their in vivo engraftment potential and triggered a hyper-proliferative response that led to their exhaustion. We further assessed Gfer-depleted HSCs by using microscopy techniques and found that these cells possessed significantly reduced levels of the cyclin-dependent kinase inhibitor (CDKI) p27^kip1. In contrast, ectopic over-expression of Gfer in HSCs resulted in significantly elevated total and nuclear p27^kip1. We next performed immunoprecipitation-immunoblot analyses to determine whether alteration of Gfer levels would affect p27^kip1's binding with its inhibitor, the COP9 signalosome subunit jun activation-domain binding protein 1 (Jab1), that would subsequently lead to its ubiquitination, and determined that depletion of Gfer resulted in enhanced binding of p27^kip1 to Jab1. Conversely, over-expression of Gfer resulted in its enhanced binding to Jab1 and inhibition of the Jab1-p27^kip1 interaction. Furthermore, normalization of p27^kip1 in Gfer-KD HSCs rescued their in vitro proliferation deficits. These results provide evidence for a novel Gfer-Jab1-p27^kip1 pathway present in HSCs that functions to restrict abnormal proliferation.

The second major section of this dissertation work describes our studies of a CaMKIV kinase, CaMKK2, and its role in HSCs and hematopoietic development. These studies were largely based on the usage of mice genetically ablated for the Camkk2 gene in the germline. Herein, we identified a role for CaMKK2 in the restriction of granulocytic fate commitment and differentiation of myeloid progenitor cells. We performed bone marrow transplantation studies and discovered that engraftment by Camkk2^-/- donor cells resulted in the increased production of mature granulocytes in the bone marrow and peripheral blood. Similarly, we used fluorescence activated cell sorting (FACS) to determine that Camkk2^-/- mice possessed elevated numbers of common myeloid progenitor cells, and exhibited an accelerated granulopoietic phenotype in the bone marrow. Expression of ectopic CaMKK2 in Camkk2^-/- common myeloid progenitors was sufficient to rescue aberrant granulocyte differentiation, and when over-expressed in 32Dcl3 cells was also sufficient to impede granulocyte differentiation in a kinase activity-dependent manner. Collectively, our results reveal a novel role for CaMKK2 as an inhibitor of granulocytic fate commitment and differentiation in early myeloid progenitors.

While our original intent was to identify and link a downstream target and upstream kinase to CaMKIV in HSCs, our results ultimately did not suggest that Gfer or CaMKK2 function in the same pathway in HSCs as discussed in the following chapters. Nonetheless, our findings represent a considerable advance in identifying and characterizing the functions of two novel regulators, Gfer and CaMKK2, that are important for HSC proliferation and the commitment and early differentiation steps of granulopoiesis, respectively.

Dissertation

博士
國立臺灣科技大學
企業管理系
96
This paper studies cost of living standards and variations in growth trends for consumers in Taiwan between 1951 and 2001 by considering consumer’s preference to be or not to be a variable. The comparison and analysis are made by using the two Konyus TCLIs with constant preferences and variable preferences constructed on the basis of the Generalized Fechner-Thurstone (GFT) direct utility function -- GFT(Pk0) and GFT(Pk1), as well as the Laspeyres and Paasche price indexes. This study shows that ignoring changes in preference structure frequently leads to the underestimation of the consumer’s true cost of living standards and growth scales in Taiwan. When changes in preference structure are taken into consideration, as was done in studies by Phlips and Sanz-Ferrer (1975) and Heien and Dunn (1985) in the U.S., the Laspeyres price index may underestimate, not overestimate, the true cost of living standards and the growth scale in Taiwan for the 1980s and 1990s. Based on the above findings, when it is necessary to apply the cost of living adjustment clause to all relevant programs, an alternative index such as the nonparametric TCLI – GFT(Pk1) studied in this paper may be more appropriate than the usual Laspeyres CPI. Therefore, it would be suggested that the statistical authorities in Taiwan should also consider routinely compiling and publishing the nonparametric TCLI – GFT(Pk1), together with the Laspeyres CPI.

O estudo apresentado relacionou o reconhecimento de faces, que permite distinguir conhecidos e desconhecidos e aceder a informações sobre rostos familiares, o qual é imprescindível no quotidiano, e alexitimia, que se carateriza pela dificuldade do indivíduo em descrever as emoções em si próprio ou nos outros. Ainda que diversos estudos se tenham debruçado sobre o estudo da alexitimia, são poucos os que se relacionam com o reconhecimento de faces neutras. Para o protocolo de investigação deste projeto foram aplicadas as escalas Toronto Alexithymia Scale 20-item e a The Glasgow Face Matching Test modificada, a uma amostra de conveniência de 75 alunos do Ensino Secundário, com idades compreendidas entre 15 e os 20 anos, com 61.3% do género feminino. Este projeto focou-se na manipulação do intervalo de tempo interestímulos, de modo a reduzir as expetativas dos sujeitos. Os resultados mostraram que quando maior o intervalo de tempo entre os estímulos, maior o tempo de resposta; contudo não se tiram conclusões relativamente à taxa de acerto.
The presented study related facial recognition, which allows distinguishing known and unknown and accessing information about familiar faces, and is essential in everyday life, and alexithymia, which is characterized by the individual's difficulty in describing emotions in himself or in others. Although several studies have focused on the study of alexithymia, few related to facial recognition using neutral faces. The Toronto Alexithymia Scale 20-item and the modified The Glasgow Face Matching Test were applied to the research protocol for this project, to a convenience sample of 75 High School students, aged between 15 and 20, 61.3 % female. This project focused on manipulating the interstimulus interval, in order to reduce the subjects' expectations. The results showed that the longer the interval between stimuli, the longer the response time; however, no conclusions are drawn regarding the accuracy rate.

My research work for PhD has focused on: (i) the development and application of new NMR methodologies to solve challenging problems in structural biology and (ii) studying important biological systems to correlate their structural and functional aspects. I have worked on diverse research projects ranging from NMR methodology development to the study of structure and dynamics of protein-based nanotubes. Chapter 1 of my thesis gives brief introduction to bio-molecular NMR spectroscopy and the different biological systems that I have studied. In recent years, several new methods have emerged for rapid NMR data collection. One class of methods is G-matrix Fourier transform (GFT) projection NMR spectroscopy. GFT NMR spectroscopy involves phase sensitive joint sampling of two or more chemical shifts in an indirect dimension of a multidimensional NMR experiment. Chapter 2 describes a new method based on the principle of GFT NMR for increasing further the speed of data collection. In the current implementations of the GFT method, cosine/sine modulation of all chemical shifts involved in the joint sampling are collected and stored as separate FIDs. A post-acquisition data processing step (application of G-matrix) then separates the different inter-modulations of chemical shifts. Thus, joint sampling of K+1 spins results in 2K combination of chemical shifts (also representing 2K projection angles). One limitation of this approach is that even if only a few of the 2K components of the multiplet (or projection angles) is desired, an entire data set containing information for all 2K shift combinations is collected. We have proposed a simple method which releases this restriction and allows one to selectively detect only the desired linear combination of chemical shifts/projection angles out of 2K combinations in a phase sensitive manner. The method involves selecting the appropriate cosine/sine modulations of chemical shifts and forming the desired linear combination by phase cycling of the radiofrequency pulses and receiver. This will benefit applications where only certain linear combination of shifts are desired or/and are sufficient. Further, G-matrix transformation required for forming the linear combination is performed within the pulse sequence. This avoids the need for any post-acquisition data processing. Taken together, this mode of data acquisition will foster new applications in projection NMR spectroscopy for rapid resonance assignment and structure determination. Chapter 3 describes another GFT NMR-based method for rapid estimation of secondary structure in proteins. This involves the detection of specific linear combination of backbone chemical shifts and facilitates a clear separation and estimation of residues in different secondary structures of a given protein. This methodology named as CSSI-PRO (Combination of Shifts for Secondary structure Identification in PROteins), involves detection of specific linear combination of backbone 1Hα and 13C’ chemical shifts in a two dimensional (2D) NMR experiment. Such linear combination of shifts facilitates editing of residue belonging to α-helical/ β-strand regions into distinct spectral regions nearly independent of the amino acid type. This helps in the estimation of overall secondary structure content of the protein. Comparison of the estimated secondary structure content with those obtained from the respective 3D structures and/or the method of Chemical Shift Index (CSI) was carried out for 254 proteins and gives a correlation of more than 90% and an overall RMSD of 6.5%. The method has high sensitivity and data can be acquired in a few minutes. This methodology has several applications such as for high-throughput screening of proteins in structural proteomics and for monitoring conformational changes during protein folding and/or ligand-binding events. Chapter 4 (Part-A and Part-B) describes an area of my research which involves the study of structure and function in the Insulin-like Growth Factor Binding Protein (IGFBP) family. IGFBPs (six in number; IGFBP1-6) belong to the IGF-system, which plays an important role in growth and development of the human body. This system is comprised of the following components: (i) Two peptide hormones, IGF-1 and -2, (ii) type 1 and type 2 IGF receptors, (iii) six IGF-binding proteins (IGFBP; numbered 1-6) and (iv) IGFBP proteases. IGF-1 and -2 are small signalling peptides (~7.5 kDa) that stimulate action by binding to specific cell surface receptors (IGF-1R) evoking subsequent response inside the cell. Six soluble IGF binding proteins, the IGFBPs, which range in 22-31 kDa in size and share overall sequence and structural homology with each other, regulate the activity of the IGFs. IGFBPs bind strongly to IGFs (KD ~ 300-700 pM) to ensure that all the circulating IGF in the blood stream is sequestered and inhibit the action of IGFs by blocking their access to the receptors. Proteolysis of the IGFBPs dissociates IGFs from the complex, enabling them to bind and activate the cell surface receptors. IGFBPs have been recently implicated in different cancers and HIV/AIDS. However, the nature of their interaction with the ligand: IGF-1 or IGF-2 at a molecular level poorly understood. This is due to the difficulty in over-expressing these proteins in large scale and in soluble amounts which is required for structural studies. We have for the first time developed an efficient method for bacterial expression of full-length human IGFBP-2, a 33 kDa system, in soluble (upto 30 mg/ml) and folded form. Using a single step purification protocol, hIGFBP-2 was obtained with >95% purity and structurally characterized using NMR spectroscopy. The protein was found to exist as a monomer at the high concentrations required for structural studies and to exist in a single conformation exhibiting a unique intra-molecular disulfide-bonding pattern. The protein retained full biologic activity as evident from its strong binding to IGF-1 and IGF-2 detected using surface plasmon resonance (SPR). This study represents the first high-yield expression of wild-type recombinant human IGFBP-2 in E. coli and first structural characterization by NMR. Using different NMR methods, we are now in the process of elucidating the 3D structure of this molecule. Chapter 5 (Part-A and Part-B) describes our discovery of nanotubular structures formed by spontaneous self-assembly of a small fragment from the C-terminal domain of hIGFBP-2. The nanotubular structures are several micrometers long and have a uniform outer diameter of ~35 nm. These structures were studied extensively by NMR and other techniques such as TEM, fluorescence and circular dichroism (CD). The water soluble nanotubes form through intermolecular disulphide bonds due to the presence of three cysteines in the polypeptide chain and exhibit enhanced tyrosine fluorescence. Based on different experimental evidences we have proposed a mechanism for the formation of the nanotubes. This was considered as a breakthrough by the journal ChemComm and featured on the cover-page of the journal. An article highlighting the discovery was also published in RSC news. In recent years, a number of novel polypeptide and DNA based nanotubes have been reported. Our study reveals intrinsically fluorescent self-assembling nanotubes made up of disulphide bonds having the following novel properties: (i) their formation/dissociation can be controlled by tuning the redox conditions, (ii) they do not require the support of any additional chemical agent for self-assembly, (iii) they have high stability due to the involvement of covalent interactions, (iv) the monomer is a small polypeptide chain which can be chemically synthesized or produced using simple recombinant methods and (v) they possess high inherent fluorescence and can thus be easily detected against a background of other proteins. In addition, the presence of an RGD motif in this polypeptide fragment offers avenues for novel biomedical applications. The RGD motif is known to be recognized by integrins. The design of such self-assembling polypeptide fragments containing an RGD motif can be utilized to enhance the efficacy of cancer therapeutics. Towards this end, we have investigated the structural basis of formation of these nanotubular structures by NMR spectroscopy and proposed its application for cancer cell imaging.

Electromagnetic flow meters are simple, rugged, non-invasive flow measuring instruments, which are extensively employed in many applications. In particular, they are ideally suited for the flow rate measurement of liquid metals, which serve as coolants in fast breeder reactors. In such applications, theoretical evaluation of the sensitivity turns out to be the best possible choice. Invariably, an evaluation of the associated electromagnetic fields forms the first step. However, due to the complexity of the problem, only numerical field computational approach would be feasible. In the pertinent literature, couple of e orts could be found which employ the well-known Galerkin Finite Element Method (GFEM) for the required task. However, GFEM is known to suffer from the numerical stability problem even at moderate flow rates. This problem is quite common in fluid dynamics area and several stabilization schemes have been suggested as a remedial measure. Among such schemes, the Streamline Upwinding Petrov Galerkin (SU/PG) method is a simple and widely employed approach. The same has been adopted in some of the moving conductor literatures for obtaining a stable solution. Nevertheless, in fluid dynamics literature, it has been shown that the SU/PG solution can suffer from distortion/peaking at the boundary. The remedial measures proposed are nonlinear in nature and hence are computationally demanding. Also, even the SU/PG scheme by itself requires significant additional computation for quadratic and higher order elements. Further, the value of stabilization parameter is not accurately known for 2D and 3D problems. The present work is basically an attempt to address the above problem for flow meter and other rectilinearly moving conductor problems. More specifically, but for the requirement of (graded) structured mesh along the flow direction, it basically aims to address a more general class of problems not just limited to the flow meter. Following the classical approach employed in fluid dynamics literature, first the problem is studied in its 1D form. It was observed that a relatively better performance of GFEM over FDM scheme is basically due to the difference in their Right Hand Side (RHS) terms, which represents the applied magnetic field. Taking clue from this, it was envisaged that a better insight to the numerical problem can be obtained by using the control system theory's transfer function approach. An application of FDM or GFEM to the 1D form of the governing equation, leads to flalge-braic equations with space variable in discrete form. Hence, a Z-transform based approach is employed to relate the applied magnetic field to the vector potential of the resulting reaction magnetic field. It is then shown that the presence of a pole at Z = -1 is basically responsible for the oscillations in the numerical solution. It is then proposed that by using the control systems pole-zero cancellation principle, stability can be brought into the numerical solution. This requires suitable modification of RHS terms in the discretised equations and accordingly, two novel schemes have been proposed which works within the framework of GFEM. In author's considered opinion, the use of Z-transform for analysing the stability of the numerical schemes and the idea of employing pole-zero cancellation to bring in stability, are first of its kind. In the first of the proposed schemes, the pole-zero cancellation is achieved by simply restating the input magnetic field in terms its vector potential. Solving the difference equations given by the application of FDM or GFEM to 1D version of the governing equation, it is analytically shown that the proposed scheme is absolutely stable at high flow rates. However, at midrange of flow rates there is a small error, which is analytically quantified. Then the scheme is applied to the original flow meter problem which has only axially varying applied field and the stability is demonstrated for an extensive range of flow rates. Note that the discretisation along the flow direction was restricted in the above exercise to graded regular mesh, which can readily be realised for problems involving rectilinearly moving conductors. In order to cater for more general cases in which the applied field varies in both axial and transverse directions, a second scheme is developed. Here the RHS term representing the input magnetic field is considered in a generic weighted average form. The required weights are evaluated by imposing apart from the need for an essential zero yielding term, the flux preservation and other symmetry conditions. The stability of this scheme is proven analytically for both 1D and 2D version of the problem using respectively, the 1D and 2D Z-transform based approaches. The analytical inferences are adequately validated with numerical exercises. Also, the small error present for the midrange of flow rates is analytically quantified. Then the second scheme is applied to the actual flow meter with a general magnetic field pro le. The proposed scheme is shown to be very stable and accurate even at very high flow rates. As before, the discretisation was restricted to graded regular mesh along the flow direction. By solving for the standard TEAM No. 9 benchmark problem, applicability of the second scheme for other rectilinearly moving conductor problem has been adequately demonstrated. Even though the problems considered in this work readily permits the use of a graded regular mesh along the flow direction, for the sake of completeness, discretisation with arbitrary quadrilateral and triangular mesh is also considered. The performance of the proposed schemes for such cases even though found to deteriorate, is still shown to be considerably better than the GFEM. In summary, this work has successfully proposed two novel, computationally effcient and stable GFEM schemes for the simulation of electromagnetic flow meters and other rectilin early moving conductor problems.

Synopsis My research work is focused on: (i) development of novel Fast NMR methods in solution state and their application to metabolomics and small molecules. (ii) NMR based metabolic study of human IVF to assess embryo viability for implantation. The major components of the embryo growth media were identified for evaluating the embryo quality. Described below are the projects carried out towards the dissertation of my PhD. Chapter 1 describes NMR methods which are the foundation stones for new Fast NMR methods developed. Typical 1D and 2D NMR experiments used in metabolomics and statistical methods for analysis are described. A few applications of metabolomics are also covered in the chapter. Chapter 2 describes a new Fast NMR method based on polarization sharing and parallel acquisition using the dual receiver system. The method developed helps in acquiring simultaneously three 2D NMR spectra: 2D [13C-1H] HETCOR, 2D [1H-1H] TOCSY and 2D [13C-1H] HSQC-TOCSY in a single data set. This method achieves a time saving of about two fold. All the experiments are acquired on molecules with natural abundance of 13C. The method was used to assign the side chain atoms (1H and 13C) of two important peptides. i) 12 amino acid residue peptide, which is a part of central linker domain of Human Insulin like Growth Factor Binding Protein-2 known to play a vital role in the IGF system and ii) a 18 amino acid residue peptide which acts as an antimicrobial agent. Chapter 3 describes extension of the Fast NMR method described in chapter 2. The method is combined with G-matrix Fourier Transform NMR spectroscopy. In this method we have acquire simultaneously two 2D NMR experiments and one reduced dimensional 3D experiment. The three experiments are 2D [13C-1H] HETCOR, 2D [1H-1H] TOCSY and GFT (3,2)D [13C-1H] HSQC-TOCSY, which provide complementary information for rapid assignments. GFT (3,2)D [13C-1H] HSQC-TOCSY gives 3D correlations in a 2D manner facilitating high resolution and unambiguous assignments. The experiments were applied for complete assignment of 21 unlabeled metabolite mixtures corresponding to the Innovative Sequential medium (ISM1) used for culturing human embryos for IVF. Further, a 13C multiplicity edition block is added to the method to simplify the resonances assignment in GFT (3,2)D [13C-1H] HSQC-TOCSY. Taken together, experiments provide time gain of order of magnitudes compared to conventional data acquisition. Chapter 4 of the thesis describes a metabolomics study of Human in-vitro fertilization to assess viable embryos of implantation potential using NMR as non-invasive tool. NMR study included the analysis of 127 embryo culture media (Innovative Sequential Media-1) and 29 controls (culture media without embryo) of both day-2 and day-3 transferred. The embryos were divided into 3 categories 1) implanted (successful) 2) transferred not-implanted (unsuccessful) 3) not transferred based on morphological studies. All NMR experiments were acquired with CPMG (T2 filter) incorporated in 1D 1H presaturation pulse scheme. The study was based on estimation of lactate, pyruvate and alanine levels in the embryo culture media (ISM1). The study reveals higher uptake of pyruvate and high pyruvate/alanine ratios in case of implanted embryos compared to one which failed to implant. Present study provides pyruvate/alanine ratio as a biomarker to select the embryos with high implantation potential. The method combined with morphology based assessment or with other biomarkers can be serve as a powerful tool to assess the embryo quality. Chapter 5 describes a novel NMR method for rapid characterization of translation diffusion of molecules in solution either in mixture or pure form. Unlike acquisition of several 2D [13C-1H] HSQC experiments with varying gradients to get diffusion measurement, a single 2D [13C-1H] HSQC is sufficient to measure the diffusion coefficients which is in the linewidths of peaks. The method uses the idea of accordion NMR spectroscopy, wherein gradients are linearly co-incremented with 13C chemical shift evolution period during t1. The methodology speeds up the acquisition by replacing series of 2D [13C-1H] HSQC with single 2D constant time [13C-1H] HSQC. The method was used to monitor the diffusion of metabolites in a time-resolved manner during polymerization of SDS-PAGE gel. Using this method, it was possible to detect the presence of oligomers of diphenylalanine (FF) during its self assembly to form nanotubular structures.