Dissertations / Theses on the topic 'MSPSHA'

Aujourd’hui, les systèmes MSPSR (Multi-Static Primary Surveillance Radar) passifs se sont installés de manière durable dans le paysage de la surveillance aérienne [1]. L’intérêt que suscitent ces nouveaux systèmes provient du fait qu’en comparaison aux radars mono-statiques utilisés actuellement, les systèmes MSPSR reposent sur une distribution spatiale d’émetteurs et de récepteurs offrant des avantages en termes de fiabilité (redondance), de coûts (absence de joints tournants et émetteurs moins puissants) et de performances (diversité spatiale). Toutefois, le défaut majeur du MSPSR passif réside en l’absence de formes d’ondes dédiées due à l’exploitation d’émetteurs d’opportunités tels que les émetteurs de radio FM (Frequency Modulation) et/ou de DVB-T (Digital Video Broadcasting-Terrestrial) [2]. Afin de pallier à ce défaut, il est envisagé d’utiliser des émetteurs dédiés permettant l’emploi de formes d’ondes optimisées pour une application radar, on parle alors de MSPSR actif. Cette thèse se place dans ce cadre et a pour objectif d’étudier et de définir la ou les formes d’ondes ainsi que les traitements associés permettant d’atteindre de meilleurs performances : une meilleure flexibilité sur la disposition du système (positionnement des émetteurs libres), une continuité de service (non dépendance d’un système tiers) et de meilleurs performances radars (e.g. en terme de précision des mesures, détections, …). Dans ce but, cette thèse étudie : - Les critères de sélection des codes : comportement des fonctions d’ambiguïtés, PAPR (Peak to Average Power Ratio), efficacité spectrale, etc... ; - Les formes d’ondes utilisées en télécommunication (scrambling code, OFDM) afin d’identifier leur possible réemploi pour une application radar ; - L’utilisation d’algorithmes cycliques pour générer des familles de séquences adaptées à notre problème ; - Une approche basée sur une descente de gradient afin de générer des familles de codes de manière plus efficiente ; - Et l’évaluation des performances de ces différents algorithmes à travers l’établissement d’une borne supérieure sur le niveau maximum des lobes secondaires et à travers le dépouillement des données enregistrées suite à des campagnes d’essais
Nowadays, MSPSR (Multi-Static Primary Surveillance Radar) systems are sustainably settled in air surveillance program [1]. Compared to mono-static radar currently in use, an MSPSR system is based on a sparse network of transmitters (Tx) and receivers (Rx) interconnected to a Central Unit and offers advantages in terms of reliability, cost and performance.Two kinds of MSPSR systems exist: the Passive form and the Active one. While the Passive MSPSR uses transmitters of opportunity such as radio Frequency Modulation (FM) transmitters and/or Digital Video Broadcasting-Terrestrial (DVB-T) transmitters [2], the Active MSPSR uses dedicated transmitters, which emit a waveform that is controlled and designed for a radar application. Each receiver processes the signal coming from all transmitters and reflected on the targets; and the Central Unit restores the target location by intersecting “ellipsoids” from all (transmitter, receiver) pairs. Compared to passive MSPSR, the main advantages of the active MSPSR are the use of dedicated waveforms that allow reaching better performances (like a better association of the transmitters’ contributions at the receiver level); more flexibility in the deployment of transmitters and receivers station (in order to meet the requirements in localisation accuracy and in horizontal and altitude coverages); and the guarantee of having a service continuity. On this purpose, this thesis analyses the differents codes criteria such as the ambiguity function behaviour, the PAPR (Peak to Average Power Ratio), the spectrum efficiency, etc... . Then, in order to find dedicated waveforms for MSPSR systems, one solution is to find easily-constructed families of sequences. Thus building on the works carried out by the Telecommunication field for solving multi-user issues, this document investigates the application of spreading codes and OFDM signals in MSPSR concept. Besides, another solution is to directly generate a set of sequences. Based on cyclic algorithms in [3] we derive a new algorithm that allows to optimize sets of sequences. Similarly, using a gradient descent approach, we develop a more efficient algorithm than the cyclic one. Finally, in order to evaluate the performances of the different algorithms, this thesis generalizes the Levenshtein Bound, establishes new lower bounds on the PSLR (Peak Sidelobe Level Ratio) in mismatched filter case, and studies real data recorded during some trials

Anaplasmosis, a persistent intraerythrocytic infection of cattle by Anaplasma marginale, causes severe anemia and a higher rate of abortion, resulting in significant loss to both dairy and beef industries. Clinical diagnosis is based on symptoms and confirmatory laboratory tests are required. Currently, all the diagnostic assays have been developed with whole antigens with indirect ELISA based on multiple epitopes. In a pioneer investigation we demonstrated the use of critical motifs of an epitope as biomarkers for immunosensor applications. Mimotopes of the MSP1a protein functional epitope were obtained through Phage Display after three cycles of selection of a 12-mer random peptide library against the neutralizing monoclonal antibody 15D2. Thirty-nine clones were randomly selected, sequenced, translated and aligned with the native sequence. The consensus sequences SxSSQSEASTSSQLGA was obtained, which is located in C-terminal end of the 28-aa repetitive motif of the MSP1a protein, but the alignment and sequences variation among mimotopes allowed us to map the critical motif STSSxL within the consensus sequence. Based on these results, two peptides were chemically synthesized; one based on the critical motif (STSSQL, Am1) and the other based on the consensus sequence aligned with the native epitope (SEASTSSQLGA, Am2). Sera from 24 infected and 52 healthy animals were tested by ELISA for reactivity against Am1 and Am2, which presented sensitivities of 96% and 100%, respectively. The Am1 peptide was incorporated onto a biolectrode (graphite modified with poly-3-hydroxyphenylacetic acid) and direct serum detection was demonstrated by impedance, differential pulse voltammetry, and atomic force microscopy. The electrochemical sensor system proved to be highly effective in discriminating sera from positive and negative animals. These immunosensors were highly sensitive and selective for positive IgG, contaminants did not affect measurements, and were based on a simple, fast and reproducible electrochemical system.
Anaplasmose, uma infecção intraeritrocitária obrigatória de bovinos, causada pela Anaplasma marginale, causa severa anemia e alta taxa de aborto, resultando em perda significativa para a indústria de laticínios e carne. O diagnóstico clínico é baseado nos sintomas e exames laboratorias confirmatórios são necessários. Atualmente, todos os ensaios de diagnósticos têm sido desenvolvidos com ELISA indireto de antígenos totais baseado em epítopos múltiplos. Em uma investigação pioneira demonstramos o uso de motivos críticos de um epítopo como biomarcador para a aplicação em imunossensores. Mimotopos do epítopo funcional da proteína MSP1a foram obtidos por meio de Phage Display, após três ciclos de seleção, de uma biblioteca randômica de peptídeos 12-mer contra o anticorpo monoclonal 15D2. Trinta e nove clones foram selecionados aleatoriamente, sequenciados, traduzidos e alinhados com a sequência nativa. Foi obtida a sequência consenso SxSSQSEASTSSQLGA, que está localizada na extremidade C-terminal do motivo repetitivo de 28-aa da proteína MSP1a, mas o alinhamento e a variação das sequências entre os mimotopos nos permitiu mapear o motivo crítico STSSxL dentro da sequência consenso. Com base nesses resultados, dois peptídeos foram quimicamente sintetizados; um baseado no motivo crítico (STSSQL, Am1) e o outro baseado na sequência consenso alinhada com o epítopo nativo (SEASTSSQLGA, Am2). Soro de 24 animais infectados e 52 animais saudáveis foram testados por ELISA quanto à reatividade contra Am1 e Am2, que apresentou sensibilidades de 96% e 100%, respectivamente. O peptide Am1 foi incorporado a um bioeletrodo (grafite modificado com ácido poli-3-hidroxyfenilacético) e a detecção direta de soro foi demonstrada por impedância, voltametria de pulso diferencial e microscopia de força atômica. O sistema de sensor eletroquímico provou ser altamente eficaz em soro de animais positivos de negativos. Este imunossensor foi altamente sensível e seletivo para IgG positiva, contaminantes não afetaram as medições, e foram baseados e um sistema simples, rápido e reprodutível.
Doutor em Genética e Bioquímica

This thesis deals with the design of an antenna array for the MSPS Radar L band application. The introduction covers a research for a suitable antenna element which can be used as an element of steerable antenna array. The control of the main beam is enabled in the vertical plane. Based on a presented theory, a slotted waveguide antenna array with an omnidirectional radiation in the vertical plane is designed. The operating frequency is set to 1 367.5 MHz. Slotted array achieves 20° width of the main beam in elevation plane. The achieved gain of the array is 9.15 dBi. Further attention of this work is focused on the beam steering that is allowed by diode switching. The last part of the thesis presents manufacturing process of the designed model. The CST Microwave Studio software was used for the antenna array designing process.

Hirsutism is excessive hair growth in women. The prevalence is estimated at 5%. The aim of this thesis was to describe different aspects of how life is affected for women suffering from hirsutism. Both qualitative and quantitative methods were used. Study I showed that hirsutism deeply affects women’s experiences of their bodies in a negative way and was experienced as a life sorrow. In Study II the patient-physician relationship was described. The patient-physician relationship from the patient’s perspective was suboptimal, as most meetings included feelings of being rejected and even humiliation. In Study III the aim was to translate and psychometrically evaluate an instrument that measures perceived social support, “The Multidimensional Scale of Perceived Social Support” (MSPSS). The translation was performed according to WHO:s official process, and validation was performed in a sample that consisted of 281 participants, 127 women with hirsutism (main sample) and 154 nursing students. MSPSS had good psychometric properties with regard to factor structure, construct validity, internal consistency and reproducibility. Study IV described different aspects of HRQoL in the main sample, the correlation of anxiety, depression, level of hairiness, age and BMI. The F-G scores were dichotomized into minor (F-G ≤14) and major (F-G≥15) hair growth. Higher levels of hair growth were significantly correlated to a lower level of QoL measured by DLQI, EQ-5D and symptoms of both anxiety and depression measured by HADS. Study V investigated if social support was associated with quality of life and outcome of HRQoL compared to a reference group of women (n=1115). SF-36, the MSPSS and the F-G scale were used. Compared to the reference group, women with hirsutism reported lower quality of life in all dimensions of SF-36 (p<0.01) The dimension most affected was vitality (VT=41.2), which had a lower value than has been reported for patients with MS and myasthenia gravis. A Multiple Regression Analysis showed a significant relation between quality of life and social support, indicating its importance for the ability to adapt, in spite of low quality of life.

The Successive Approximation (SAR) Analog-to-Digital converter is one of the most energy-efficient A/D converter. In this thesis, the development of a SAR ADC in a 28-nm CMOS technology based on charge redistribution is presented.The implemented SAR ADC uses a switching procedure based on a modified version of the mono- tonic switching algorithm to reduce the switching energy and area of the DAC. The DAC is a binary- weighted array of unit capacitors. A unit custom capacitor has been designed with a value of 0.8 fF to reduce the DAC energy consumption. Two comparators have been implemented, a dynamic comparator and a static comparator. The dynamic implementation allows to obtain better performance. Therefore, the dynamic comparator is chosen for the SAR ADC. The sampling switches are bootstrapped to reduce the non-linearity introduced when the input signal is sampled. The SAR operations are controlled by an asynchronous logic implemented as a behavioural model in Verilog-A.The effect of the designed circuits on the linearity of the converter is assessed with the integral non- linearity (INL) and differential non-linearity (DNL). Moreover, the performance of the ADC are assessed in terms of signal-to-noise-and-distortion ratio (SNDR). The co-simulation of Verilog-A behavioural models with circuit schematics allowed to evaluate the effect of each block on the overall performance of the ADC. The co-simulations show that the ADC is able to achieve an ENOB of 10.9 at a sampling rate of 200 MSps with a power consumption of 2.83 mW. The resulting FoM is 7.4 fJ/conv-step.
SAR (Analog-Digital-omvandlaren) är en av de mest energieffektiva omvandlare. I den här avhandlingen är utvecklingen av en SAR ADC i en 28-nm CMOS-teknik baserad på laddning omfördelning presen- teras.Den implementerade SAR ADC använder en omkopplingsprocedur baserad på en modifierad version av den monotoniska omkopplingsalgoritm för att reducera omkopplingsenergin och DAC-området. DAC är en binärviktad matris med enhetskondensatorer. En anpassad kondensator för enheten har utformats med ett värde av 0,8 fF för att minska DAC-energiförbrukningen. Två komparatorer har implementerats, en dynamisk komparator och en statisk komparator. Den dynamiska implementering gör det möjligt att få bättre prestanda. Därför väljs den dynamiska komparatorn SAR ADC. Provtagningsomkopplarna startas upp för att minska icke-lineariteten introduceras när insignalen samplas. SAR-operationerna styrs av en asynkron logik implementerad som en beteendemodell i Verilog-A.Effekten av de designade kretsarna på konverterarens linearitet bedöms med integralen icke-linearitet (INL) och differentiell icke-linearitet (DNL). Dessutom är ADC: s prestanda bedömdes i termer av signal-till-brus-och-distorsionsförhållande (SNDR). Samsimulering av Verilog-A beteendemodeller och scheman tillåts utvärdera effekten av varje block på prestandan hos ADC. Omvandlaren kan uppnå en ENOB på 10,9 med en samplingshastighet på 200 MSps, vilket resulterar i en FoM eller 7,4 fJ / konv.- steg.

Neisseria meningitidis, a major cause of bacterial meningitis and septicemia, secretes multiple virulence factors to the extracellular environment, including the adhesion and penetration protein (App) and the meningococcal serine protease A (MspA). Both proteins belong to the serine protease auto transporter family and have the capacity to adhere to host epithelial and endothelial cells. Besides, both proteins have been previously shown to be internalized and translocated to the nuclei of human brain microvascular endothelial cells and dendritic cells (DCs), where they modulate gene expression. However, host cell receptors, endocytic pathways, nuclear translocation mechanisms, and gene expression modulation associated with App or MspA are poorly defined. In an effort to address this knowledge gap, recombinant forms of the passenger domains of both proteins were purified under native conditions using cold shock expression technology. The purified proteins, designated rpdApp and rpdMspA, were used to raise polyclonal, affinity-purified guinea pig antisera. These antibodies facilitated the investigation of interactions between both bacterial proteins and host cell molecules. One of these interactions highlighted in the present study is the entry of rpdApp and rpdMspA into human monocyte-derived immature DCs via receptor-mediated endocytosis. In vitro internalization and blocking assays showed that mannose receptor (MR) and transferrin receptor 1 are involved in the uptake of both proteins into DCs. Besides, two different approaches revealed that the binding of rpdApp and rpdMspA to MR is mediated specifically by the C-type lectin-like carbohydrate recognition domains 4':'7 (CTLD4-7). Additionally, the recognition of both bacterial proteins by these domains was shown to be calcium dependent, in addition to being inhibitable by D-mannose or L- fucose, but not D-galactose. Using gel overlay (Far-Western) analysis, rpdApp and rpdMspA were shown to interact with two nucleocytoplasmic shuttling proteins, namely heat shock protein 70 (Hsp70) and galectin-3 (Gal-3), with some data suggesting that interactions with Gal-3 may be mediated by its carbohydrate-recognition domain. Hsp70, which also interacts with the bacterial proteins, is characterized by possessing lectinic activity towards O-linked ~-N-acetylglucosamine (O-G1cNAc). Given the binding of App and MspA to different lectins, this study sought to examine the glycosylation status of both proteins, with a focus on O-GlcNAc modifications and their possible interplay with phosphorylation. Using in silico prediction methods, multiple sites within each protein were identified as potential sites for phosphorylation, O-GlcNAc modification, and alternative phosphorylation/O-GlcNAc modification. These predictions were supported by a series of Western blot analyses, which reproducibly showed that several meningococcal secreted proteins, including those of the expected size of App or MspA (115-120 kDa), are modified by both O-GlcNAc and tyrosine phosphorylation. The identity of the 115- to 120-kDa proteins was confirmed by stripping and reprobing the blots with antibodies against rpdApp and rpdMspA. However, attempts to detect these post-translational modifications in a sample of meningococcal secreted proteins tagged with TAMRA-alkyne by tandem mass spectrometry were unsuccessful. This may be attributed to the suppressive effect of the attached tag on trypsin cleavage and/or ionization efficiency. Finally, the results of Far-Western and ELISA assays clearly demonstrated the interactions of rpdApp or rpdMspA with various histone subunits. Additionally, both proteins were shown to have trypsin-like serine protease activity and to be capable of cleaving recombinant histone H3.1 in vitro. The proteolytic activity of both proteins on H3.l was shown to be specifically abolished by pre-incubation with serine protease inhibitors. Collectively, these results extend our understanding of the virulence potential of App and MspA beyond the adhesive or invasive functions, and reveal their capacity to participate in multiple interactions with host molecules. Besides, the current findings provide the basis for future studies to explore the epigenetic alterations induced by both proteins. Hopefully, the information gained will provide new insights into meningococcal pathogenesis and will help in the development of improved therapeutic approaches against the disease.

Microtubules are a major constituent of the cytoskeleton in all eukaryotic cells. They are essential for cell morphogenesis and motility. Specifically in the dividing cells, microtubules form the spindle which segregates chromosomes. Microtubule plus ends constantly switch between phases of growth and shrinkage which is necessary for microtubule reorganization and thus their function. Importantly, microtubule dynamics are highly regulated by microtubule-associated proteins (MAPs). EB1 and Mini spindles (Msps) are unique amongst MAPs because they bind and track growing microtubule plus ends autonomously. Although essential for cell division and thus highly expressed in dividing cells, EB1 and Msps are also abundant in differentiated cells. However, to identify post-mitotic roles of proteins essential for cell division, particularly in context of a multicellular organism, is a challenge requiring new tools which I aimed to develop in my project. Since EB1 acts by recruiting MAPs to the microtubule plus ends, I generated short peptides which bind to Drosophila EB1 to block interactions with these MAPs. I showed that an EB1-MAP interaction was disturbed in Drosophila S2 cultured cells and expressing these peptides in developing Drosophila reduced fly viability. Further screening and analysis of peptides interacting with fly EB1 and its human homologues uncovered sequence determinants promoting strong binding and specificity. To uncover Msps function, I generated a msps temperature sensitive mutant and found that Msps is essential for neuromuscular function in developing Drosophila. This study showed that the regulation of microtubule dynamics has crucial functions at the whole organism level. These new tools allow the roles of microtubule regulation to be dissected in developing organisms.

The Marco Polo Programme in the EU was launched in 2003 to stimulate modal shift from trucks to trains or ships. There may be potential for similar programmes in the passenger sector, given the implementation of dynamic Model Shift Policies (MSPs) in the logistics sector. This thesis will focus on the question: ‘What is an effective MSP from the car to public transport in the passenger sector in South Korea?’, ‘What is the best combination of MSPs?’, and ‘What factors influence the transport mode choice of commuters?” The main MSPs considered in this thesis are: 1) the commuting cost subsidy for public transport users, 2) additional parking fees for car users, and 3) the congestion charges for car users. In order to investigate the relative effectiveness of these policies, stated preference data were obtained from 767 respondents, who work in the Gangnam area of Seoul, through an online survey that took place in early 2013. A full factorial design was used for the purpose of the survey to estimate the main effects and interactions without correlation. Various binary standard logit models with alternative-specific, generic and covariate variables were developed to identify the effectiveness of MSP and understand what factors affect people’s mode choice decisions. In order to overcome limitations of standard logit by allowing for random taste variation, mixed logit models are developed. In addition, through various models both without and with interaction terms, the modal shift effects of the combined MSPs, as well as single MSP, are compared. According to the change of allocation ratio of two combined MSPs (e.g. subsidy 0% : parking 100% → subsidy 10% : parking 90%), the market share of travel mode was also evaluated to understand interaction terms. This research offers numerical evidence of negative modal shift synergy effect for three combinations of MSP. With a view to forecasting the modal shift effects of socio-economic groups and a more deep understanding of the characteristics of each group, the segmentation methods were used. An equity impact analysis of MSPs has been conducted to obtain the Compensating Variation Per Person (CVPP). In addition, the ratio of the CVPP to the average income of each income group is calculated to judge whether each MSP is a progressive or regressive policy. The expenditure and revenue of MSPs are calculated. In addition, how revenue from MSPs should be spent in order to achieve a better transport system is considered.

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A anaplasmose é uma importante enfermidade de bovinos de áreas tropicais e subtropicais do mundo, causada pela riquétsia intra-eritrocítica Anaplasma marginale. A vacinação tem sido a forma mais econômica e eficiente de controlar a anaplasmose bovina. No entanto, os métodos de imunização tradicionais, que utilizam organismos provenientes de eritrócitos infectados, apresentam limitações em seu uso, razão pela qual, estudos para o descobrimento de novos imunógenos são necessários. Nos últimos anos, esses estudos têm se concentrado nas proteínas de membrana da riquétsia, sobretudo MSP1a e MSP2, as quais mostraram-se promissoras em ensaios de proteção com as proteínas nativas, utilizadas isoladamente. Este trabalho teve como objetivo geral testar a imunoproteção induzida pelas proteínas de membrana MSP1a e MSP2 recombinantes de A. marginale, associadas com adjuvante CpG ODN 2006, frente a desafio heterólogo e avaliar a resposta imune gerada pela imunização. Para tanto, diversas etapas experimentais foram executadas, desde a clonagem e expressão dos genes que codificam as duas proteínas, padronização dos testes de diagnóstico usados no estudo, imunização e desafio dos animais experimentais e acompanhamento das respostas imunes humoral e celular. Os ELISAS indiretos baseados em MSP1a e MSP2 recombinantes apresentaram sensibilidades de 99,0% e especificidades de 100% (para ambos os testes). A PCR para o gene msp5 da riquétsia detectou infecções ainda no período pré-patente, antes da conversão sorológica. Os bovinos da raça Aberdeen Angus foram imunizados três vezes com 200 μg de MSP2 e/ou MSP1a recombinantes (produzidas a partir do isolado Pernambuco – Zona da Mata), associadas com CpG ODN 2006 e alúmen. Posteriormente, foram desafiados com 3 x 107 eritrócitos infectados do isolado heterólogo de A. marginale (Mossoró - Rio Grande do Norte). Os animais experimentais apresentaram quadro clínico de anaplasmose (redução do volume globular, febre e riquetsemias detectáveis por distensões sangüíneas coradas). Não foram detectadas diferenças significativas entre os grupos imunizados e os controles (que receberam CpG ODN 2006 e alúmen ou alúmen isoladamente) quanto ao percentual de redução do volume globular, riquetsemias máximas e temperaturas retais máximas, indicando que as imunizações não foram protetoras. A despeito da significativa produção de IgG total contra MSP1a e MSP2, detectada no dia do desafio, os animais imunizados apresentaram produção significativa de 14 IgG2 apenas contra MSP1a. Não foi possível detectar resposta proliferativa de células mononucleares de sangue periférico, tanto no momento do desafio quanto após o pico das riquetsemias. Possivelmente, a ausência de proteção deveu-se a uma deficiente ou ausente estimulação de imunidade celular nos bovinos imunizados.

Doctor of Philosophy
Department of Chemistry
Stefan H. Bossmann
This paper describes two methods for utilizing cancer associated proteases for targeting cancer therapy to the tumor. The first method is designing a drug delivery system based on liposomes that are sensitive to cancer associated proteases. Upon contact with the protease, the liposome releases its contents. The second method is designing a prodrug that is based on a porin isolated from Mycobacterium smegmatis. The porin is modified with protease consensus sequences, inhibiting its toxicity. Upon contact with the protease, the drug is activated. Protease sensitive liposomes were synthesized that were sensitive to urokinase plasminogen activator. This was done by synthesizing a cholesterol-anchored, uPA consensus – sequence-containing, acrylic acid block copolymer and using it to form a covalently bound polymer cage around the outside of a hypertonic liposome. Liposomes were synthesized that had a diameter of 136 nm. Upon addition of the polymer the diameter increased by 2.69 nm, indicating it had successfully embedded into the liposome membrane. After crosslinking with either a short peptide containing a lysine (so that it is a diamine) or ethylenediamine, the diameter increased between 5.33 nm and 14.1 nm (depending on the type and amount of the crosslinked). Fluorescence release assays showed that the polymer cage could add in excess of thirty atmospheres of osmotic pressure resistance, and, under isobaric conditions, would prevent release of much of the liposomal contents. Upon treatment with uPA, the polymer caged liposomes released a significantly larger amount of their contents making the liposomes protease sensitive. MspA was shown to be a very stable protein able to be imaged by AFM. AFM imaging demonstrated that MspA is able to form native pore structures in membranes making it a good imitator of the membrane attack complex. MspA was demonstrated to be highly cytotoxic, but poor at distinguishing between cells. Pro-MspA was synthesized by adding a hydrophilic peptide to MspA that prevents insertion. A uPA cleavage sequence embedded causes the MspA to become activated at the cancer site. This was demonstrated in tests against uPA and non-uPA producing cell lines.

Doctor of Philosophy
Department of Chemistry
Stefan H. Bossmann
Porin A from Mycobacterial smegmatis (MspA) is an octameric trans-membrane channel protein and is one of the most stable porins known to date. MspA has been successfully isolated and purified to obtain liquid extracts and crystals using a modified extraction procedure. A full analytical assessment has been carried out to authenticate its’ structure, including gel electrophoresis, spectroscopy (fluorescence, UV, FTIR, NMR), HPLC, Bradford protein assay, dynamic light scattering and X-ray crystallography. Nanoscopic vesicle formation of MspA molecules in aqueous media has been thoughroughly investigated. Temperature dependent dynamic light scattering experiments reveal that size of such vesicles is dependent on temperature but is independent of ionic strength of the medium. Zeta potential measurements reveal a steady build up of positive charge on the vesicle surface with increasing temperature. For the first time, wild type (WT) MspA has been utilized as a channel forming agent. This phenomenon has future potential in DNA sequencing and the development of antimycobacterial drugs. Channel activity of WT MspA and mutant A96C MspA has been investigated and has shown to form stable channels across DPhPC lipid bilayers. Blocking of the channel current via external molecules (i.e. channel blocking) is an extremely important process, which helps to evaluate the biosensor ability of the pore. In this regard, two Ruthenium based compounds, Ru(QP-C2)38+ (i.e. RuC2) and Ru(bpy)32+have been successfully employed as channel blocking agents. Both compounds show evidence for channel blocking of WT MspA. However, these results are not reproducible. Three dimensional aggregation behavior of RuC2-MspA vesicles have been thoughroughly investigated. It is evident that addition of RuC2 significantly increases vesicle size and polydispersity of MspA aggregates in solution. The results provide explanations onto the lack of channel blocking ability of MspA by RuC2. Development of a ‘greener’ dye sensitized solar cell with the use of MspA as an electron carrier is investigated for the first time. A series of Ru(II)-phenanthroline-based dyes have been synthesized as non-toxic dyes in this regard. Chemical binding between the dyes and MspA has been achieved successfully. Two types of solar cell prototypes, i.e. TiO2-based (Grätzel type) and FTO-based have been developed and tested. Significant current generation and conversion efficiencies have been achieved for both cell types. This marks the first development of a protein-based photovoltaic device, which has the potential to be developed as a new class of “hybrid soft solar cells”.

Doctor of Philosophy
Department of Chemistry
Stefan H. Bossmann
The photochromic spirodihydroindolizine/betaine (DHI/B) system has been reinvestigated applying picosecond, microsecond, stationary absorption measurements, and NMR-kinetics. The first surprise was that the electronic structure of the betaines is quite different than commonly assumed. The photochemical ring-opening of DHIs to betaines is a conrotatory 1,5 electrocyclic reaction, as picosecond absorption spectroscopy confirms. The (disrotatory) thermal ring-closing occurs from the cisoid betaine. The lifetime of the transoid betaine is 60 s at 300 K, whereas the lifetime of the cisoid isomer is of the order of 250 microseconds. According to these results, the electrocyclic back reaction of the betaines to the DHI is NOT rate determining, as previously thought, but the cisoid-transoid-isomerization of the betaine. Although the presence of a second nitrogen atom increases the photostability of the spirodihydroindolizine-pyridazine/betaine-system remarkably, the photochemical reaction mechanism appears to be exactly the same for spirodihydroindolizine-pyridazine/betaine-system. A nondestructive photoswitch or an information recording systems has been explored using styryl-quinolyldihydroindolizines. Both isomers DHI and betaine are fluorescent. When the blue betaine is stabilized in a thin polymethyl methacrylate (PMMA) matrix, it is stable for several hours even in room temperature and very stable at 77K. Although irradiation of visible light = 532 nm allows the photo-induced reaction of the Betaine back to the DHI, a nondestructive read-out can be performed at λ = 645 nm upon excitation with λ = 580 nm. Image recording (write) and read-out, as well as information storage (at 77K) have been demonstrated. Charged and maleimide-functionalized DHI/B systems have beed synthesized for use as photochemical gates of the mycobacterial channel porin MspA. Positively charged and maleimide functionalized DHI groups that were attached to the DHI/B-system permit the binding of the photoswitch to selective positions in the channel proteins due to the presence of a cysteine moiety. An inexpensive new method for the large scale synthesis of coelenterazine is developed. A modified Negishi coupling reaction is used to make pyrazine intermediates from aminopyrazine as an economical starting material. This method permits the use of up to 1g coelenterazine per kg body weight and day, which turns the renilla transfected stem cells into powerful light sources.

O Anaplasma marginale é um importante patógeno riquetsial de bovinos transmitido por carrapato que invade e se multiplica dentro de eritrócitos, causando anemia hemolítica durante a infecção aguda. A imunização com proteínas de membrana externa (OMP) purificadas induz proteção contra doença aguda. Das 21 OMPs descritas, seis MSPs (1a, 1b, 2-5) já foram bem caracterizadas. O complexo MSP1 (MSP1a e 1b) é adesinas de eritrócitos de bovinos. A MSP1a varia em tamanho pelo número de repetições in tandem de 28-29 aminoácidos. Vacina de DNA contra a anaplasmose tem sido investigada usando os genes msp1? e msp1?, e os resultados evidenciaram resposta celular e humoral em camundongos e bovinos. A imunização com DNA plasmidial que codifica genes de interesse é uma tecnologia nova e promissora no desenvolvimento de vacinas. Vacinas de DNA que visam múltiplos epitopos têm se mostrado mais eficientes aumentando a imunogenicidade e a proteção de animais vacinados quando comparadas com as de epitopo único. Os objetivos deste trabalho foram analisar a variabilidade do gene msp1a de amostras paranaenses de A. marginale, testar a capacidade dos plasmídios recombinantes expressarem MSP1a, MSP1b e MSP5 em células eucarióticas e avaliar a imunogenicidade destas vacinas administradas individualmente ou em associação, em camundongos BALB/c. A análise da região repetitiva do gene msp1a identificou a presença de seis, cinco e três repetições nas amostras PR1, PR2 e PR3, respectivamente, e seis padrões de repetições inéditas. Contudo, a região da MSP1a responsável pela imunogenicidade foi conservada. Os plasmídios pcDNA/ msp1a, pcDNA/ msp1 ? e pcDNA/ msp5, os quais codificam os genes das MSPs sob o controle do promotor do citomegalovirus e intron A, foram construídos, multiplicados em E. coli TOPO10 e purificados. A expressão das proteínas MSP1a, MSP1b e MSP5 in vitro foi realizada em células Vero usando lipofectamina 2000 e Imunofluorescência Indireta (IFA), utilizando anticorpos monoclonais. Sete grupos de camundongos foram imunizados para avaliar a produção de IgG total e determinar os isotipos IgG1 e IgG2a: G1-100 mL PBS; G2-100 mg de vetor; G3- 100 mg de corpúsculos iniciais de A. marginale + adjuvante de Freund; G4- 100 mg pcDNA-msp1a; G5-100 mg pcDNA-msp1b; G6-100 mg of pcDNA-msp5 e G7- pool de plasmídios (33 mg de cada plasmídio). Três semanas após a última imunização, os camundongos foram sacrificados para avaliar a proliferação dos esplenócitos. As células Vero transfectadas com plasmídios recombinantes reagiram com anticorpos monoclonais específicos, demonstrando a expressão dos genes msp. IgG específica para a MSP1a e MSP5 foram detectadas tanto por ELISA quanto por Western blot. Os grupos que receberam pcDNA-msp1a and pcDNA-msp5 mostraram predomínio do isotipo IgG2a, e proliferação de esplenócitos, sugerindo que estes plasmídios são bons candidatos para estimular reposta imune Th1. A associação dos três plasmídios recombinantes (pcDNA-msp1a, pcDNA-msp1b and pcDNA-msp5) empregados na imunização de camundongos induziram altos títulos de anticorpos por ELISA e reagiram com todas proteínas recombinantes (rMSP1a, rMSP1b e rMSP5) de A. marginale por Western blot. Adicionalmente, a combinação dos plasmídios levou a uma forte proliferação de linfócitos (SI = 12, 2), enquanto o gene msp1a determinou significante proliferação significativa (SI = 2,6) e os genes msp1b e msp5 não promoveram proliferação (SI<2). Os resultados demonstraram que a associação dos plasmídios induziu a expressão das MSPs e estimulou significante produção de linfócitos T, podendo ser uma estratégia eficiente para a imunoprofilaxia da anaplasmose.
Anaplasma marginale is an important tick-transmitted rickettsial pathogen of cattle that invades and multiplies within erythrocytes, causing severe hemolytic anemia during acute infection. Immunization with purified outer membrane proteins (OMP) induces protection against acute A. marginale disease. Of 21 OMP described six major surface proteins (MSPs 1a, 1b, 2-5) have been well-characterized. The complex MSP1 (MSP1a and 1b) is an adhesin for bovine erythrocyte, and MSP1a vary in size and sequence due to the number of tandem 28-29-amino acid repeats. DNA vaccine against anaplasmosis has been investigated using the msp1a and msp1? genes, and the results related cellular and humoral response in mice and cattle. Immunization with DNA plasmids encoding antigens of interest represents a novel and promising method in vaccine research and development. Multiepitope DNA vaccine is a new experience to increase immunogenicity and protection for vaccinated animal as compared in single epitope. The objectives of this study were to analyze the variability of the msp1a gene of A. marginale strains from Parana State, evaluate the capacity of the recombinant plasmids to express MSP1a, MSP1b, and MSP5 in eukaryotic cells, and evaluate the immunogenicity of BALB/c mice immunized with these DNA vaccines encoding MSPs of A. marginale PR1 strain individually or in association. The analysis of the msp1a gene identified the presence of six, five and three tandem repeats in PR1, PR2 PR3, respectively; however, the region of MSP1a responsible for immunogenicity was conserved. The plasmids pcDNA-msp1?, pcDNA-msp1? and pcDNA-msp5, which encode the MSPs genes under the control of cytomegalovirus enhancer/promoter and intron A, were constructed, multiplied in TOP10 E. coli and purified. Expression of MSP1a, MSP1b, and MSP5 in vitro was performed into Vero cells using lipofectamine 2000, following Indirect Immunofluorescen Assay (IFA) using monoclonal antibodies. Seven experimental groups of mice were immunized to evaluate the production of whole IgG and to determinate IgG1 and IgG2a isotype: G1-100 ml PBS; G2-100 mg empty vector; G3-100 mg A. marginale initial bodies + Freund´s adjuvant; G4-100 mg pcDNA-msp1a; G5-100 mg pcDNA-msp1b; G6-100 mg pcDNA-msp5; and G7-pool of recombinant plasmids (33 mg for each). Three weeks after the last immunization, mice were sacrified to evaluate spleen cells proliferation. Vero cells transfected with recombinants plasmids reacted with specific monoclonal antibodies, demonstrating the expression of msp genes. Specific IgG against MSP1a and MSP5 were detected in either by ELISA and Western blot. The groups that received pcDNA-msp1a and pcDNA-msp5 exhibited predominance for IgG2a production and splenocytes proliferation, suggesting that these recombinant plasmids are good candidates for elicited T helper 1 immune response. The association of three recombinant plasmids (pcDNA-msp1a, pcDNA-msp1b and pcDNA-msp5) used in the immunization of mice induced high antibodies response by ELISA and reacted with all recombinant proteins (rMSP1a, rMSP1b, and rMSP5) of A. marginale by Western blot. Also, the combination of plasmids provide strong lymphoproliferation (SI = 12,2), whereas the genes to MSP1a provide significant splenocytes (SI = 2,6) and the genes to MSP1b and MSP5 did not provide significant proliferation (SI<2). The results showed no suppression when the recombinant plasmids were taken in association, and demonstrated that they can generate significant T-cell lymphocyte. Thus, the immunization in association of recombinant plasmids encoding MSPs can be an effective strategy for immunoprofilaxy of anaplasmosis.

The project is dedicated to the identification of the problems found while building RT operating systems for use in embedded devices. The project's main topic is the possibility of using RT system in the FITkit platform and it also discusses individual problems and their possible solutions. One of the problems is the way of acquiring the timing information for tasks to ensure their RT properties. We have extended existing simulator for given microcontroller that is also part of the FITkit. The simulator can be used for detailed monitoring of the execution of individual tasks in the system based on dynamic analysis, collecting timing statistics for given blocks of the program or it can be extended by new modules. The RM scheduling mechanism has been integrated into the FreeRTOS system as an example by considering the knowledge of the concrete operating system and acquired timing information.

Les mycobactéries sont classées parmi les bactéries contenant des acides mycoliques dans leur paroi et un haut GC% dans leur génome. Elles peuvent être isolées à partir du sol ou d'environnement d'eau douce où vivent aussi les protozoaires libres. Plusieurs études ont montré une possibilité de co-isolement des mycobactéries et des amibes à partir de ces sources environnementales. Il a été montré également que la plupart des mycobactéries de l'environnement ont la capacité à survivre dans les trophozoites et les kystes d'amibes et dans certaines cellules eucaryotes, y compris les macrophages. Les manipulations génétiques des mycobactéries en général et des mycobactéries du complexe Mycobacterium tuberculosis en particulier sont compliquées et aucune étude de modification génétique des mycobactéries (pathogènes ou non pathogènes) n'avait été réalisée dans notre laboratoire avant notre travail de thèse. Dans notre travail de thèse, nous avons montré que les amibes ou d'autres organismes phagocytaires peuvent servir comme sources et lieu de transfert des gènes chez les mycobactéries. Ce transfert des gènes peut avoir contribué à l'adaptation des mycobactéries à un mode de vie intracellulaire. Nous avons développé ensuite deux systèmes de coculture: Mycobacterium smegmatis-Acanthamoeba polyphaga et Mycobacterium gilvum-A. polyphaga et nous avons clarifié le spectre des interactions des mycobactéries à croissance rapide avec les amibes. Ce modèle d'interaction mycobactéries-amibes a été utilisé pour tester l'hypothèse contraire au paradigme dominant que l'addition des gènes réduit la virulence des bactéries
Mycobacteria are mycolic-acid containing, high GC% bacterial organisms which can be recovered from soil and fresh water environments where free-living protozoa also live. Co-isolation of mycobacteria and amoeba collected from such environmental sources has been reported. Several experiments further demonstrated the ability of most environmental mycobacteria to survive in the amoebal trophozoites and cysts and in some eukaryotic cells including macrophages. Genetic modification of mycobacteria in general and mycobacteria belonging to Mycobacterium tuberculosis complex in particular are complicated and no studies using genetic modification of mycobacteria (pathogenic or non-pathogenic) had been performed in our laboratory prior to our work. In our thesis work, we showed that amoebae or other phagocytic organisms can serve as sources and places for gene transfers in mycobacteria. Gene transfers may have contributed to the adaptation of mycobacteria to an intracellular lifestyle. In addition, we developed two co-culture systems: Mycobacterium smegmatis-Acanthamoeba polyphaga and Mycobacterium gilvum-A. polyphaga and we clarified the spectrum of rapid-growing mycobacteria and amoeba interactions. This model of mycobacteria-amoeba interactions was then used to test another hypothesis according to which unlike the prevailing paradigm, the addition of genes does not reduce the virulence of bacteria. For the first time in our laboratory we modified two species of the M. tuberculosis complex, M. tuberculosis H37Rv and Mycobacterium bovis BCG to observe the effect of these changes on their pathogenicity and survival

Doctor of Philosophy
Department of Chemistry
Stefan Bossmann
Tris-homoleptic ruthenium(II)-quaterpyridyl and quaterpyridinium complexes, with +8 and +14 charge were synthesized by utilizing high pressure reaction pathway. These complexes have diameters ranging from 1.82 to 4.55 nm according to the molecular modeling calculations. These ruthenium complexes are highly luminescent and contain long excited state life times. The novel ruthenium(II)-quaterpyridinium complexes exhibit superior reactivity as sensitizer-relay-assemblies (SRA‟s) in sacrificial systems for water and carbon dioxide reductions, while harvesting the ultraviolet- and most of the visible fraction of the incident solar spectrum. Ru(II)-quaterpyridinium complexes and Pd/TiO2 catalysts were successfully used as the catalytic system for the photo catalytic reduction of water and carbon dioxide to hydrogen and methane respectively. Phosphonate-tethered Ru(II)-quaterpyridinium complexes were synthesized from Ru(II)-tris-quaterpyridyl complexes. These complexes form stable adhesive layers on indium tin oxide (ITO) electrodes. A series of differential pulse voltammetry experiments were carried out to measure the ground state and excited state redox potentials of all the Ru(II)quaterpyridinium complexes. The reductive potentials obtained were compared with the reductive potentials of CO2 to CH4 and H2O to H2 reductions. The measurements obtained from the experiments confirmed that it is possible to thermodynamically oxidize water and reduce CO2 by using phosphonate-tethered Ru(II)-quaterpyridinium complexes. These complexes are successfully utilized as prototypes for mycobacterial channel blockers. The Ru(II) complexes show distinct changes in their luminescence spectra when bound to the porin MspA from M. smegmatis, which is a non-pathogenic relative of M. tuberculosis. By using HPLC, we have determined binding constants of the Ru(II)-complexes to MspA in phosphate buffer (0.05 M, pH = 6.8) ranging from 5.2 x 109 M-1 (Ru-C2) to 1.8 x 109 M-1 (Ru-C4). Our findings indicate that channel blocking is a promising treatment strategy for mycobacterial infections. Poly-N-isopropyl-acrylamide/acetic acid copolymers were synthesized and characterized by elemental analysis and gel permeation chromatography. The average composition of the copolymers determined from CHN analysis is in excellent correlation with the feed composition indicating that the radical polymerization process is indeed statistical. Crosslinking of individual polymer chains permitted the generation of ultraflat layers on Mica surfaces by a simple spin-casting procedure, which are able to host the mycobacterial channel protein MspA, while retaining its channel function.

Mixed-signal processing systems especially data converters can be reliably tested at high frequencies using on-chip testing schemes based on memory. In this thesis, an on-chip testing strategy based on shift registers/memory (2 k bits) has been proposed for digital-to-analog converters (DACs) operating at 5 GHz. The proposed design uses word length of 8 bits in order to test DAC at high speed of 5 GHz. The proposed testing strategy has been designed in standard 65 nm CMOS technology with additional requirement of 1-V supply. This design has been implemented using Cadence IC design environment. The additional advantage of the proposed testing strategy is that it requires lower number of I/O pins and avoids the large number of high speed I/O pads. It therefore also solves the problem of the bandwidth limitation that is associated with I/O transmission paths. The design of the on-chip tester based on memory contains no analog block and is implemented entirely in digital domain. In the proposed design, low frequency of 1 MHz has been used outside the chip to load the data into the memory during the write mode. During the read mode, the frequency of 625 MHz is used to read the data from the memory. A multiplexing system is used to reuse the stored data during read mode to test the intended functionality and performance. In order to convert the parallel data into serial data at high frequency at the memory output, serializer has been used. By using the frequencies of 1.25 GHz and 2.5 GHz, the serializer speeds up the data from the lower frequency of 625 MHz to the highest frequency of 5 GHz in order to test DAC at 5 GHz.

L'objectif de cette thèse est de proposer une analyse multidimensionnelle de la pauvreté au Sénégal, et de montrer l'intérêt d'intégrer l'approche par les capabilités dans l'analyse de la pauvreté. Cette thèse vise à faire valoir que l'approche par les capabilités est un cadre adéquat et pertinent pour l'identification des pauvres et présente un grand intérêt pour l'élaboration de meilleures politiques publiques de lutte contre la pauvreté en rapport avec les OMD.Pour mener à bien ce travail, la thèse s'organise en deux temps. Dans un premier, il est question de traiter du concept de pauvreté en confrontant l'approche monétaire traditionnelle et l'approche par les capabilités, et de montrer l'intérêt de l'économie du bonheur dans l'analyse de la pauvreté et du bien-être. Dans un second temps, il s'agit d'éclairer les options méthodologiques pour traiter empiriquement la mesure de la pauvreté et d'apporter les arguments en faveur de l'approche par les capabilités.Les traits essentiels de cette thèse s'organisent autour de trois apports principaux. Le premier est d'ordre théorique. Il propose une analyse de la pauvreté au Sénégal en termes de capabilités. Le second est d'ordre empirique et fournit une mesure multidimensionnelle basée sur la théorie des ensembles flous à partir de l'enquête de suivi de la pauvreté au Sénégal (ESPS 2). Le troisième est méthodologique et propose une démarche originale qui consiste à construire un noyau dur de la pauvreté utilitariste (en confrontant les pauvretés monétaire et subjective), puis d'analyser l'évolution de ce noyau dur selon la distribution des degrés de pauvreté des capabilités
The aim of this thesis is to propose a multidimensional analysis of poverty in Senegal, and to show the importance of integrating the capability approach in the analysis of poverty. This thesis aims at showing that the capability approach is an adequate and appropriate framework for identifying the poor and proves to be of real interest in setting up better public policies in order to fight against poverty relating to the MDGs.This study is divided in two parts. The first part deals with the concept of poverty confronting the traditional monetary approach with the capability approach, and shows the interest of the economics of happiness in the analysis of poverty and well being. In a second phase, the objective is to illuminate methodological options in order to treat the extent of poverty empirically and bring the arguments in favor of the capability approach.The essential features of this thesis revolve around three main contributions. The first one is theoretical. It offers an analysis of poverty in Senegal in terms of capabilities. The second is empirical and provides a multidimensional measure based on the theory of fuzzy sets from the monitoring survey of poverty in Senegal (MSPS 2). The third one is methodological and proposes an original approach consisting of building a core of utilitarian poverty (by comparing the monetary and subjective poverty) and then analyzing the evolution of the core according to the distribution of the degrees of poverty capabilities

The market for battery powered communications devices has grown significantly in recent years. These devices require a large number of analog to digital converters (ADCs) to transform wireless and other physical data into the digital signals required for digital signal processing elements and micro-processors. For these applications, power efficiency and accuracy are of the utmost importance. Successive approximation register (SAR) ADCs are frequently used in power constrained applications, but their main limitation is their low sampling rate. In this work, a two stage pipelined ADC is presented that attempts to mitigate some of the sampling rate limitations of a SAR while maintaining its power and resolution advantages. Special techniques are used to reduce the overall sampling capacitance required in both SAR stages and to increase the linearity of the multiplying digital to analog converter (MDAC) output. The SAR sampling network, control logic, and MDAC blocks are completely implemented. Ideal components were used for the clocking, comparators, and switches. At the end of this design, a figure of merit of 51 fJ/conversion-step was achieved.
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碩士
中華大學
電機工程學系(所)
94
This thesis presents a 10-bit 250-MSPS 1.8-V digital to analog converter (DAC) and is implemented in TSMC 0.18μm CMOS technology. A segmented current steering architecture is used with optimized performance for speed, resolution, power consumption and area. The DAC can be operated up to 250MHz sampling frequency and the settling time is less than 3.5 ns. The differential nonlinearity (DNL) and integral nonlinearity (INL) are ±0.15 and ±0.13 least significant bits (LSBs), respectively. The spurious free dynamic range (SFDR) at 250-MSPS remains above 63.6 dB for input frequency up to 120 MHz. Total power dissipation is 30.6 mW with 1.8-V power supply. The chip size is 1.258 mm × 1.485 mm.

碩士
國立臺灣大學
電機工程學研究所
89
The goal of this thesis is to understand the calibration in capacitor’s mismatch error for pipelined ADC, one precision multiply-by-2 circuit is made from Switch-Capacitor, the capacitor’s mismatch error will reduce the Differential Nonlinearity(DNL), for increasing the pipelined ADC’s Signal-to-Noise ratio, we first have to understand the calibration algorithm in capacitor’s mismatch. This thesis is divided six chapters, chapter 1 and chapter 2 is the introduction and the classification in ADC. In chapter 5 is the layout and test , chapter 6 is the conclusion. The followings are chapter 3 and 4’s brief description: In chapter 3, the calibration method is divided two domain, analog-domain and digital-domain. The analog-domain used in calibration for pipelined ADC are larger in area and complex in design. If we use the digital-domain, the area will be smaller and the design is simpler. In this thesis, the improvement in SNR is about 1.5~2 bit under 1% capacitor error mismatch. In chapter 4, we described the detailed circuit buliding block in pipelined ADC, containing operational amplifier, multipling DAC, fully differential comparator, and sample and hold circuit. The operation speed in pipelined ADC is the design in opamp. and MDAC, we described some design issues in the operational amplifier.

碩士
國立成功大學
電機工程研究所
84
In this thesis, a differential low power, 10-bit, 20 MSample/ sec (MSPS) pipeline A/D converter for vedio- rate applications is designed. The 1.5b/stage pipeline architecture with digital correction is adopted in the framework. The whole-chip simulation shows 52 dB signal-to-(noise+distortion) ratio (SNDR) for 1.25MHz input sampled at 20 MSPS. The prototype A/D converter has been fabricated in a double-poly-double-metal 0.6-um CMOS technology.