This dissertation presents a low-power high-resolution delta-sigma ADC. Two new architectural design techniques are proposed to reduce the power dissipation of the ADC. Compared to the conventional active adder, the direct charge transfer (DCT) adder greatly saves power by keeping the feedback factor of the active adder unity. However, the inherent delay originated from the DCT adder will cause instability to the modulator and complex additional branches are usually needed to stabilize the loop. A simple and power-efficient technique is proposed to absorb the delay from the DCT adder and the instability issue is therefore solved. Another proposed low-power design technique is to feed differentiated inverted quantization noise to the input of the last integrator. The modulator noise-shaping order with this proposed technique is effectively increased from two to three without adding additional active elements. The delta-sigma ADC with the proposed architectural design techniques has been implemented in transistor-level and fabricated in 0.18 µm CMOS technology. Measurement results showed a SNDR of 99.3 dB, a DR of 101.3 dB and a SFDR of 112 dB over 20 kHz signal bandwidth, resulting in a very low figure-of-merit (FoM) in its application category. Finally, two new circuit ideas, low-power parasitic-insensitive switched-capacitor integrator for delta-sigma ADCs and switched-resistor tuning technique for highly linear Gm-C filter design are presented. / Graduation date: 2012 / Access restricted to the OSU Community at author's request from June 9, 2012 - June 9, 2014

No description available.

No description available.

Made available in DSpace on 2015-05-14T13:21:25Z (GMT). No. of bitstreams: 1 arquivototal.pdf: 2013817 bytes, checksum: 3393f3576fe03283e4e7fd592df689eb (MD5) Previous issue date: 2013-03-05 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES / This work presents microwave irradiation promoting synthetic studies that producing by the first time indolizine-2-carbonitrile (1) and indolizine-2-carboxylate (2) in good to high yields (70% and 81%, respectively) in one step from Morita-Baylis- Hillman adducts (MBHA) 2-(hydroxy(pyridin-2-yl)methyl)acrylonitrile (10) and methyl 2-(hydroxy(pyridin-2-yl)methyl)acrylate (9) respectively. These compounds were subsequently transformed in excellent yields on three 2-indolizine derivatives know in the literature. they are: indolizin-2-yl methanamine (5), 99%, indolizin-2-ylmethanol (6), 100%, indolizine-2-carboxylic acid (3), 100%, in new more three Indolizine, namely : tert-butyl (indolizin-2-ylmethyl) carbonate (7), 99% new, butyl-indolizine-2- carboxylate(4), 94% new, tert-butyl (indolizin-2-ylmethyl)carbamate (8), 86% new. All of the adducts were characterized by infrared physical methods, Gas Chromatography coupled to Mass Spectrometry and Nuclear Magnetic Resonance (1 H NMR and 13 C NMR).All syntheses were developed in this study appropriate industry standards. The reaction activation by microwave irradiation (MO) has been widely used in most synthetic stages of this work, leading to high chemical yields and reduced reaction times. The eight synthesized compounds were in silico designed aiming to present potential selective activities as modulators of ion channels. These activities were suggested by the high score values obtained by using Molinspiration cheminformatics program. / Este trabalho apresenta um estudo sintético promovido por irradiação de micro-ondas, produzindo pela primeira vez a 2-Indolizina-carbonitrila (1) e a 2- Indolizina-carboxilato de metila (2) em bons a altos rendimentos (70% e 81% de rendimentos respectivamente) em uma única etapa, a partir dos Adutos de Morita- Baylis-Hillman (AMBH) 2 (hidroxi(piridin-2-il)metil)acrilonitrila(10) e metil 2- (hidroxi(piridin-2-il)metil)acrilato(9) respectivamente. Estes compostos foram subseqüentemente transformados em excelentes rendimentos em mais três derivados 2-indolizínicos já conhecidos na literatura, a saber: indolizin-2-il metanamina (5), 99%, indolizin-2-il metanol (6), 100%, acido Indolizina-2- carboxílico(3), 100%, e mais três inéditos , a saber: terc-butil (indolizin-2-il metil) carbonato(7), 99% inédito , butil Indolizina-2-carboxilato (4), 94% inédito, e terc-butil (indolizin-2-il metil)carbamato (8), 86% inédito. Todos os Adutos foram caracterizados através dos métodos físicos de Infravermelho, Cromatografia Gasosa acoplada a Espectrometria de Massas e Ressonância Magnética Nuclear (RMN1H e RMN13C). Todas as sínteses neste trabalho foram desenvolvidas em padrões convenientes a indústria. A ativação reacional por irradiação de microondas (MO) foi amplamente utilizada na maioria das etapas sintéticas deste trabalho, conduzindo aos altos rendimentos químicos e aos tempos reacionais reduzidos. Os oito compostos sintetizados foram idealizados in silico objetivando apresentarem potenciais atividades seletivas como moduladores de canais iônicos. Estas atividades foram sugeridas pelos altos valores obtidos de score usando o programa quimioinformático Molinspiration.

Moduler l’agrégation de protéines amyloïdes est thérapeutiquement pertinent (p. ex. la polyneuropathie amyloïde familiale traitée avec le Tafamidis). Cependant, pour de nombreuses amyloïdoses, il n’existe pas encore de modulateur d'agrégation efficace pour thérapie. Il a été récemment montré que combiner des composés qui modulent l’agrégation d’amyloïdes peut résulter en des effets synergiques. Une stratégie de criblage combinatoire, pour identifier des cocktails synergiques de composés, pourrait donc conduire à une percée thérapeutique pour de nombreuses amyloïdoses. Cependant, les technologies à haut débit existantes ne sont pas adaptées pour le criblage combinatoire.J’ai développé SynAggreg – une technologie in vitro à haut débit très sensible, précise, reproductible, peu coûteuse et flexible - qui permet d'identifier à la fois des inhibiteurs et des accélérateurs d'agrégation, de caractériser leur mécanisme d'action sur la cinétique d'agrégation et de les classer par leur efficacité. SynAggreg est également la première technologie adaptée au criblage combinatoire et pour l’étude d’effets synergiques de manière fiable. Enfin, cette nouvelle technologie peut être facilement adaptée à plusieurs amyloïdoses en remplaçant la partie amyloïde de la protéine de fusion par des techniques de biologie moléculaire. Ainsi, SynAggreg apparaît comme une boîte à outils pour la recherche fondamentale et appliquée et possède un fort potentiel de valorisation. / Modulating amyloid proteins aggregation is therapeutically relevant (e.g. the familial amyloid polyneuropathy treated with Tafamidis). However, for many amyloidoses, there is yet no efficient aggregation modulator for therapy. It was recently shown that combining compounds that modulate the aggregation of amyloids can result in synergistic effects. A combinatorial screening strategy to identify synergistic cocktails of compounds could thus lead to a therapeutic break through for many amyloidoses. However, existing high-throughput technologies are not adapted for combinatorial screening.I developed SynAggreg - a very sensitive, accurate, reproducible, cost effective, flexible and high-throughput in vitro technology - which allows identifying both aggregation inhibitors and accelerators, characterizing their mechanism of action on aggregation kinetics and ranking them by their efficiency. SynAggreg is also the first technology suitable for combinatorial screening and for studying reliably synergistic effects of combinations of compounds. Finally, this new technology can be easily adapted to several amyloidoses by replacing the amyloid part of the fusion protein with molecular biology techniques. Thus, SynAggreg appears as a toolbox for fundamental and applied research, and has a high potential for valorization.

Les Formes réactives de l’oxygène (FRO) ont un rôle bien établi dans l’oncogénèse en augmentant les capacités de prolifération et d’invasion des cellules tumorales. Mais les FRO exercent aussi un effet important sur le microenvironnement tumoral, en particulier en participant à l’échappement des tumeurs au système immunitaire. Une modulation pharmacologique de l’équilibre oxydo-réductif tumoral est donc susceptible d’influencer la progression tumorale. Il a été montré que l’induction pharmacologique d’un stress oxydant dans les cellules tumorales peut induire un effet cytotoxique mais ses effets sur le microenvironnement sont moins bien connus. L’objectif de nos travaux était d’étudier l’effet d’une modulation du stress oxydant sur les cellules immunitaires du microenvironnement tumoral et in fine de préciser les conséquences potentielles sur la progression tumorale. L’arsenic trioxyde (As2O3), inducteur de FRO, présentait à faible dose, dénuée d’effet cytotoxique direct sur les cellules malignes, un effet antitumoral dans un modèle de cancer colique murin. Cet effet était lié à une déplétion sélective en lymphocytes T régulateurs (Tregs) et était médié par la génération d’anions superoxyde (O2°-) et de monoxyde d’azote (NO), eux même responsables de la formation de peroxynitrite. Les Tregs présentaient un niveau basal de FRO plus élevé que les autres populations lymphocytaires, qui pourrait expliquer leur plus grande sensibilité à un surcroît de stress oxydant induit par l’As2O3. Un cytotoxique antitumoral, la vinorelbine, s’est également montré capable d’exercer un effet sur le microenvironnement tumoral. Par co-cultures, nous avons montré que la vinorelbine induisait un effet bystander toxique sur les cellules immunitaires effectrices voisines des cellules tumorales. In vivo, le prétraitement par vinorelbine de cellules malignes implantées à la souris était responsable d’une perte de la réactivité anti-tumorale des cellules mono-nuclées. Cet effet était dépendant de la production d’O2°- et de NO par les cellules malignes. Un modulateur du stress oxydant, le mangafodipir, inhibait cet effet, permettant ainsi de restaurer la réponse immunitaire antitumorale locale. Notre travail a donc permis de mettre en évidence que des modulateurs du stress oxydant peuvent agir sur le microenvironnement, et spécialement sur les cellules immunitaires. Ils pourraient être utilisés en clinique pour restaurer la réponse immunitaire antitumorale. Une meilleure compréhension du rôle du stress oxydant dans la défaillance de l’immunité antitumorale est nécessaire. / Several reports have demonstrated the involvement of reactive oxygen species (ROS) in carcinogenesis, through promotion of cancer cell proliferation and invasion. But ROS could also have consequences on non cancerous cells which are part of the tumor microenvironment, such as immune cells. Therefore, a pharmacological modulation of oxidative stress can induce a cytotoxic effect on tumor cells but its consequences on microenvironment are unknown. The aim of our studies was to evaluate the effects of a pharmacological modulation of oxidative stress on immune cells from the tumor microenvironment. At low dose, Arsenic trioxide (As203), an oxidative stress modulator, was shown to exert antitumor effects in colon tumor-bearing mice. We observed that this effect was related to As203-induced regulatory T cells (Tregs) -selective depletion in vitro and in vivo and was mediated by oxidative and nitrosative bursts. The differential effect of As203 on Tregs versus other CD4 cells was related to difference in the cells’redox status. We also observed that vinorelbine, an anticancer agent, could interfere with the antitumor immune response. We showed that vinorelbine could alter the function of immune cells surrounding tumor cells by a bystander toxic effect against tumor effector cells. In vivo experiment in A549 tumor bearing nude mice showed that adoptive transfer of A549 immune splenocytes was not able to delay tumor growth when vinorelbine-pretreated A549 cells were used for immunization. This effect was mediated by ROS and was inhibited by an oxidative stress modulator, mangafodipir, which restored antitumor immune function. Therefore, our work showed that oxidative stress modulators can influence tumor microenvironment and more specifically, immune cells. They could be used to restore antitumor immune response.

No description available.

No description available.

Delta-Sigma (ΔΣ) analog-to-digital converters (ADCs) are traditionally used in high quality audio systems, instrumentation and measurement (I&M) and biomedical devices. With the continued downscaling of CMOS technology, they are becoming popular in wideband applications such as wireless and wired communication systems,high-definition television and radar systems. There are two general realizations of a ΔΣ modulator. One is based on the discrete-time (DT) switched-capacitor (SC) circuitry and the other employs continuous-time (CT) circuitry. Compared to a CT structure, the DT ΔΣ ADC is easier to analyze and design, is more robust to process variations and jitter noise, and is more flexible in the multi-mode applications. On the other hand, the CT ΔΣ ADC does not suffer from the strict settling accuracy requirement for the loop filter and thus can achieve lower power dissipation and higher sampling frequency than its DT counterpart. In this thesis, both DT and CT ΔΣ ADCs are investigated. Several design innovations, in both system-level and circuit-level, are proposed to achieve lower power consumption and wider signal bandwidth. For DT ΔΣ ADCs, a new dynamic-biasing scheme is proposed to reduce opamp bias current and the associated signal-dependent harmonic distortion is minimized by using the low-distortion architecture. The technique was verified in a 2.5MHz BW and 13bit dynamic range DT ΔΣ ADC. In addition, a second-order noise coupling technique is presented to save two integrators for the loop filter, and to achieve low power dissipation. Also, a direct-charge-transfer (DCT) technique is suggested to reduce the speed requirements of the adder, which is also preferable in wideband low-power applications. For CT ΔΣ ADCs, a wideband low power CT 2-2 MASH has been designed. High linearity performance was achieved by using a modified low-distortion technique, and the modulator achieves higher noise-shaping ability than the single stage structure due to the inter-stage gain. Also, the quantization noise leakage due to analog circuit non-idealities can be adaptively compensated by a designed digital calibration filter. Using a 90nm process, simulation of the modulator predicts a 12bit resolution within 20MHz BW and consumes only 25mW for analog circuitry. In addition, the noise-coupling technique is investigated and proposed for the design of CT ΔΣ ADCs and it is promising to achieve low power dissipation for wideband applications. Finally, the application of noise-coupling technique is extended and introduced to high-accuracy incremental data converters. Low power dissipation can be expected. / Graduation date: 2010

O trabalho tem por objetivo o estudo e o desenvolvimento de interferômetros recuperadores com baixa tensão de meia onda utilizando moduladores eletro-ópticos para serem aplicados em sistemas Interferométricos de luz branca. Ele dá continuidade às pesquisas do autor em seu mestrado, em que foi desenvolvido e testado um sistema de sensoriamento eletro-óptico capaz de medir diretamente tensões de até 69,4 kVRMS. Desta forma aperfeiçoa-se o sistema de processamento de sinais ópticos desenvolvendo um novo interferômetro recuperador, baseado em óptica integrada. Para o desenvolvimento do tema proposto, inicialmente foi feito uma revisão da literatura/bibliografia, baseada em livros, artigos e teses, visando identificar o \"estado da arte\" relacionado aos moduladores eletro-ópticos para definir o tipo de modulador mais adequado à aplicação em vista. O estudo resultou na escolha de um componente em óptica integrada que foi aplicado numa configuração inédita em um protótipo de transformador de potencial óptico para medição de elevados níveis de tensão elétrica. As características de desempenho deste protótipo foram comparadas com as do protótipo previamente construído. Como resultado deste trabalho, amplia-se o conhecimento e fixa-se em âmbito nacional o domínio sobre as técnicas de construção de interferômetros recuperadores baseados em óptica integrada aplicáveis à recuperação de sinais ópticos em sistemas interferométricos para medição de altas tensões. / This work has as objective the study and development of low half-wave voltage recovery interferometers using electro-optical modulators to be applied to white light interferometric systems. This work is a continuation in the research carried out by the author to obtain his master degree, in which it was developed and tested an electro- optic sensing system capable to measure direct voltage to 69.4 kVrms. In the present work the optical signals processing system is improved by developing a new recovery interferometer based on integrated optics. To develop the proposed subject, initially a review of the literature, based on books, articles and thesis, has been done aiming to identify the State of the Art related to electro-optic modulators and helping to define the most suitable type of modulator for the desired application. The study resulted in the selection of an integrated optical device arranged in an unpublished configuration that was applied to a prototype of optical voltage transformer, intended to measure high voltage levels. The performance of this prototype was compared with a previous version. The results of this work increase the knowledge of the construction techniques of recovery interferometers based on integrated optic devices applicable to the recovering of optical signals in interferometric systems for high voltage measurement.