Orientador: Newton Cesário Frateschi / Tese (doutorado) - Universidade Estadual de Campinas, Instituto de Física Gleb Wataghin / Made available in DSpace on 2018-08-24T10:26:52Z (GMT). No. of bitstreams: 1 Barea_LuisAlbertoMijam_D.pdf: 8459370 bytes, checksum: 5dd565986711cb06cb24cf63d6d69372 (MD5) Previous issue date: 2014 / Resumo: Sistemas fotônicos baseados em ressonadores na forma de anéis tem uma dependência fundamental dada pela relação estreita entre espaçamento espectral livre (Free Spectral Range, FSR), fator de qualidade total, Q, e o raio dos ressonadores, R. Nesta tese, nós quebramos esta dependência empregando moléculas fotônicas (Photonic Molecules, PMs) baseadas em múltiplos anéis internamente acoplados a um anel externo, que por sua vez está acoplado a um guia de onda. Aplicando o método de matriz de transferência (Transfer-Matrix Method, TMM) e programas robustos de simulação, nós projetamos três tipos de PMs baseada em uma plataforma de Silício-sobre-isolante (Silicon-on-Insulator, SOI). Este projeto mostrou que o acoplamento entre duas ou mais micro-cavidades ópticas, permite separações espectrais e hibridização dos modos quando as frequências ressonantes estão degeneradas nas cavidades, similar ao acoplamento fraco entre átomos. Estas PMs foram fabricadas com um processo convencional e compatível com a tecnologia CMOS, empregando uma Foundry, e suas caracterizações mostraram a emergência de dupletos, tripletos, quadrupletos e sextupletos de ressonâncias degeneradas, com alto Q e espaçamentos curtos, somente possíveis com anéis de algumas ordens de magnitude maiores em área. Estes resultados quebraram o paradigma da interdependência entre Q, FSR e R, evidenciando que é possível ter tempo de vida fotônico, espaçamento espectral e área independentes. As aplicações destas PMs em processamento de sinal óptico também foram demonstrados neste trabalho. Nós apresentamos o uso da molécula com dupleto de ressonâncias para extrair um sinal RF de 34.2 GHz, filtrando as bandas laterais de um sinal modulado. Também foi demonstrado que moduladores ópticos ultracompactos operando à 2.75 vezes acima do limite da largura de linha do ressonador pode ser obtido a partir da PM que apresenta um tripleto de ressonâncias, separadas de ~55 GHz. Finalmente, utilizando a molécula que permite obter um quadrupleto de ressonâncias, foi demonstrado a conversão de comprimento de onda totalmente óptico (multicasting) para quatro canais convertidos e separados de 40-60 GHz, utilizando apenas 1 mW de potência de controle / Abstract: Photonic systems based on microring resonators have a fundamental constraint given by the strict relationship among free spectral range (FSR), total quality factor (Q) and resonator size (R). In this thesis, we break this dependence employing CMOS compatible photonic molecules (PMs) based on multiple inner ring resonators coupled to an outer ring, which is coupled to a straight bus waveguide. Applying the transfer matrix method (TMM) and simulation robust programs, we project three types of PM based on scalable silicon-on-insulator (SOI) platform. This project shows that the coupling between two or more optical micro-cavities, allows spectral splitting and hybridization of the modes when the resonant frequencies are degenerated in the cavities, similar to weak coupling between atoms. These PMs were fabricated in a conventional CMOS Foundry and your characterization shows the emergence of doublet, triplet, quadruplet and sextuplet of degenerated resonances, with high-Q and close-spaced, only achievable with single-ring orders of magnitude larger in footprint. These results break the paradigm of the interdependence between Q, FSR and R, evidencing that is possible to have photonic lifetime, spectral spacing and footprint independents. The applications of these PMs in optical processing signal were also demonstrate in this work. We demonstrate the use of the doublet splitting for 34.2 GHz RF signal extraction by filtering the sidebands of a modulated optical signal. We also demonstrate that very compact optical modulators operating 2.75 times beyond its resonator linewidth limit may be obtained using the PM triplet splitting, with separation of ~ 55 GHz. Finally, using the quadruplet of resonances, we demonstrate four-channel all-optical wavelength multicasting using only 1 mW of control power, with converted channel spacing of 40-60 GHz / Doutorado / Física / Doutor em Ciências

Temos mostrado que os glicocorticóides endógenos (GE) modulam o rolling e a aderência de neutrófilos in vivo, mediando a expressão de moléculas de adesão no leucócito e no endotélio. Adicionalmente, os GE controlam a maturação neutrofílica na medula e a sua mobilização para o sangue periférico. O presente trabalho visou investigar os mecanismos moleculares e celulares envolvidos na modulação exercida pelos GE neste processo. Utilizando ratos Wistar submetidos à adrenalectomia bilateral, tratados com RU 38486 ou controles (falso-operados, tratados com veículo ou não manipulados), foi demonstrado que: 1) os GE controlam, negativamente, a expressão de L-selectina em neutrófilos circulantes e ICAM-1, VCAM-1, PECAM-1, VAP-1 na célula endotelial e, positivamente, a expressão de L-selectina em granulócitos da medula óssea via seu receptor citosólico (GCR); 2) o mecanismo envolvido no controle dos GE sobre a expressão de L-selectina é independente de ação sobre sua expressão gênica ou da atividade de NFkB, mas dependente da expressão de anexina-A1, como verificado em camundongos knockouts (KO) para esta proteína 3) o controle da expressão de moléculas de adesão endotelial é dependente de ações sobre a expressão gênica, via translocação nuclear do NFkB; 4) a neutrofilia detectada em animais adrenalectomizados (ADR) é mediada pelo GCR, e dependente de anexina- A1; 5) a neutrofilia parece ser dependente da ação da anexina-A1 sobre a secreção de SDF-1 na medula óssea e expressão de CXCR-4 em neutrófilos circulantes e da medula; 6) concentrações circulantes elevadas de GE induzidas pela administração de ACTH confirmaram o controle dos GE, via anexina A-1, sobre o tráfego de neutrófilos da medula óssea para o sangue, mas sugerem um controle diferencial dos GE e anexina A-1 sobre a expressão de L-selectina em células da medula e do sangue circulante. Estes dados mostram mecanismos inéditos do controle dos GE sobre o tráfego de neutrófilos, que diferem em cada microambiente e tipo celular envolvido neste complexo fenômeno. / We have shown that endogenous glucocorticoids (GE) modulate the rolling and adhesion of neutrophils in vivo, mediating the expression of adhesion molecules on leukocytes and the endothelium. Additionally, the GE control neutrophil maturation in bone marrow and mobilization to peripheral blood. This work aimed to investigate the molecular and cellular mechanisms involved in the modulation exerted by GE in this process. Using male Wistar rats, submitted to bilateral adrenalectomy, treatment with RU 38 486 or controls (sham operated, vehicle or non manipulated), it was shown that: 1) GE control, negatively, L-selectin expression on circulating neutrophils and ICAM-1, VCAM-1, PECAM-1, VAP-1 on endothelial cell and, positively, L-selectin expression on bone marrow granulocytes via their cytosolic receptor (GCR); 2) the mechanism involved in the control of GE on the L-selectin expression is independent of its action on gene expression or NFkB activity, but dependent on the expression of anexina-A1, as observed in mice knockouts for this protein; 3) the control of endothelial adhesion molecules is dependent on gene expression, via NFkB translocation; 4) the neutrophilia detected in adrenalectomized animals (ADR) is mediated by GCR, and dependent on anexina-A1; 5) the neutrophilia seems to be dependent on the action of annexin A-1 on SDF-1α secretion in bone marrow and expression of CXCR-4 in peripheral blood and bone marrow; 6) high circulating concentrations of GE induced by administration of ACTH confirmed the control of GE, via the annexin-1, on the traffic of neutrophils from the bone marrow to the blood, but suggest a differential control of GE and annexin A-1 on the L-selectin expression in the bone marrow and circulating blood. These data indicate unpublished mechanisms of control of GE on the traffic of neutrophils, which differ in each microenvironment and cell type involved in this complex phenomenon.

Os riscos provocados pela Terapia de Reposição Hormonal, levaram à busca de novas terapias, como os fitoestrógenos. São substâncias com ação estrogênica e propriedades que podem retardar a formação de placas ateroscleróticas. Isoflavonas são os fitoestrógenos mais estudados e são encontradas na soja, no red clover e em outras plantas. Avaliamos os efeitos dos fitoestrógenos extraídos da soja Glycine max: genisteína, formononetina, biocanina A e daidzeína; a mistura entre eles (Mix1); o extrato padronizado de red clover (Menoflavon 40mg) e uma segunda mistura com os fitoestrógenos extraídos da Glycine max nas concentrações encontradas no Menoflavon (Mix2), na expressão de moléculas de adesão de leucócitos, VCAM-1, ICAM-1 e E-selectina, em cultura de células endoteliais de cordão umbilical humano (HUVEC), assim como na linhagem modificada de célula endotelial, ECV304, estimuladas com LPS. Resultados: foram padronizados os tempos e concentrações de exposição ao LPS no cultivo de HUVEC de 1ug durante 12 horas de exposição para as três moléculas de adesão; e no cultivo de ECV304 para a expressão de VCAM-1, de 500ng durante 12 horas, para ICAM-1 de 1ug durante 18 horas, para E-selectina 100ng durante 18 horas na superfície celular e 200ng durante 24 horas no sobrenadante de culturas de ECV304, permitindo que este tipo celular seja utilizado como modelo de inflamação. Os fitoestrógenos reduziram VCAM-1, ICAM-1 e E-selectina na superfície celular assim como as formas solúveis dessas moléculas, tanto em ECV304 como em HUVEC, sendo efetivos como agentes preventivos e também para tratamento da aterosclerose. A mistura entre os fitoestrógenos não apresentou maior eficiência na redução das moléculas de adesão na superfície celular, mas apresentou diferenças significativas na produção das formas solúveis. Tanto em ECV304, quanto em HUVEC os fitoestrógenos extraídos do red clover e os extraídos da soja Glycine max reduziram as moléculas de adesão na superfície celular e no sobrenadante, sendo que o Menoflavon, apresentou maior efetividade na redução das moléculas de adesão que os fitoestrógenos extraídos da soja Glycine max, em HUVEC. Ocorreram interações entre os fitoestrógenos e o 17 estradiol, tanto em ECV304 quanto em HUVEC, principalmente quando este se encontrava em baixas concentrações, sugerindo proteção para mulheres na menopausa. Esses efeitos dos fitoestrógenos ocorreram via receptor de estrógeno, como demonstrado pela inibição de suas ações por ICI. Conclusão: tanto os fitoestrógenos extraídos da soja Glycine max quanto os extraídos do red clover apresentaram efeitos anti-aterogênicos, podendo atuar como cardioprotetores para mulheres pós-menopausa. / The risks of hormone replacement therapy have led to a search for new alternatives such as the use of phytoestrogens, plant compounds with estrogen-like biological activity. Isoflavones are the phytoestrogens most extensively studied and can be found in soy, red clover and other plants. Due this estrogen-like activity phytoestrogens can have some effect on atherosclerosis. We evaluated the effects of the phytoestrogens extracts from Glycine max soy: genistein, formononetin, biocanin A and daidzein; a Mix between them (Mix1); a standardized red clover extracts (Menoflavon 40mg) and a second Mix using phytoestrogens from Glycine max with same Menoflavon concentrations (Mix2) on adhesion molecules expression, VCAM-1, ICAM-1 and E-selectin by endothelial cell HUVEC, and by endothelial cell line ECV304, stimulated with LPS. Results: were standardized time and concentration to LPS exposure, being 1ug during 12 hours for the three adhesion molecules expression on HUVEC, and 500ng during 12 hours for VCAM-1 expression, 1ug during 18 hours for ICAM-1 expression and 100ng during 18 hours for E-selectin expression on cell surface as well as 200ng during 24 hours to E-selectin increase on culture supernadant, on ECV 304 cell line. The phytoestrogens decreased VCAM-1, ICAM-1 and E-selectin levels on cell surface and on culture supernadant in HUVEC and ECV304, being useful as preventive agents as well as treatment agents. Mix1 were not most effective than isolated phytoestrogens on cell surface, but presented decreased results on soluble forms. Menoflavon presented more effectiveness than Glycine max on HUVEC. Phytoestrogens interacted with 17 oestradiol mainly, in low concentrations (10pg), showing protection for post menopausal women. These phytoestrogens effects happened by oestrogen receptor activation, this was demonstrated through phytoestrogens inhibition by ICI. Conclusions: the phytoestrogens from Glycine max as well as phytoestrogens from red clover presented antiatherogenic effects, mainly when 17 estradiol is low, being usefull for postmenopausal women.

O glioblastoma multiforme (GBM) é uma neoplasia do sistema nervoso central (SNC), caracterizada por uma elevada capacidade proliferativa e migratória. O desenvolvimento do tumor provoca uma remodelação da matriz extracelular (MEC) que facilita a migração tumoral. Eicosanóides são moléculas lipídicas importantes na carcinogênese e a sua síntese está correlacionada com o grau de desenvolvimento do tumor. As prostaglandinas são eicosanóides envolvidas na estimulação da angiogênese, na adesão celular e proliferação celular. Este estudo tem por objetivo avaliar in vitro o efeito da PGE2 na expressão moléculas da MEC e das moléculas de adesão envolvidas na migração, em células U87MG e U251MG. As células U251MG e U87MG foram tratadas com PGE2 (10µM) e Ibuprofeno (25µM), por um período 48hs. As proteínas da MEC foram analisadas por RT-qPCR após o tratamento. Foram realizadas reações de imunohistoquímica para as moléculas da MEC. As alterações foram encontradas na expressão de laminina, fibronectina, colágeno tipo IV e as integrinas αv , α3 e α5 para células U87MG . Observamos imunomarcação nas linhas celulares para colágeno tipo IV, laminina e fibronectina. Concluímos que o tratamento com IBU e PGE2, afeta a expressão gênica de moléculas de MEC. / Glioblastoma Multiforme (GBM) is a neoplasm of the central nervous system (CNS), characterized by a high proliferative and migratory capacity. Tumor development leads to extracellular matrix (ECM) remodeling and facilitating the migration of these cells. Eicosanoids are important lipid molecules in carcinogenesis, and their synthesis often correlates with the degree of tumor development. Prostaglandins are eicosanoids involved in the stimulation of angiogenesis, cell adhesion and cell proliferation. This study is aimed to evaluate the expression of several ECM molecules involved in migration after altering the concentration of prostaglandins, using human glioma cell lines as an in vitro model. The cell lines U87MG and U251MG were treated with PGE2 (10µM) and Ibuprofen (25µM), for a predetermined period of 48hs. Proteins involved in extracellular matrix were analyzed by RT-qPCR after treatment in vitro. Immunohistochemical reactions were also performed for the ECM molecules. Changes were found in the expression of laminin, fibronectin, type IV collagen and αv, α3 and α5 integrins in cells U87MG. We observed immunostaining in cell lines to type IV collagen, laminin and fibronectin. In conclusion, Ibuprofen and PGE2, affects gene expression of ECM molecules.

Les bandes interstellaires diffuses (DIBs) représentent un mystère centenaire : aucune des centaines de bandes n'a pu être identifiée avec certitude avec un porteur spécifique, à l'exception très probable du cation buckminsterfullerène C60+. Il est obligatoire d'identifier et de quantifier la quantité de grosses molécules carbonées interstellaires qui sont très probablement responsables des DIBs : Les porteurs de DIB représentent probablement le plus grand réservoir de matière organique dans le Milieu interstellaire (MIS) et constituent un élément important de la chaîne des processus qui régissent le cycle interstellaire/stellaire. Jusqu'à récemment, la plupart des études liées aux DIBs avaient pour objectif unique l'identification des porteurs et, pour ce faire, se concentraient sur un nombre limité d'étoiles chaudes, distantes et rougies. Mon travail de recherche en thèse marque un tournant dans les méthodes et les objectifs associés aux DIBs, une évolution permise et motivée par le nombre croissant de relevés stellaires avec des instruments de plus en plus puissants à haute résolution spectrale. En effet, il est aujourd'hui possible de recueillir des quantités massives de données, tant du point de vue du nombre d'étoiles cibles que du point de vue du nombre de DIBs observées simultanément. Cela a ouvert la voie à de nouveaux types d'études, à des objectifs plus ambitieux et, surtout, à de nouvelles comparaisons potentielles avec les données de laboratoire. Ma thèse présente un grand nombre d'extractions de DIBs et quatre de ces nouvelles analyses :- Méthodes d'extraction et recherche de nouvelles DIBs.- Lien avec les propriétés physiques des nuages.- Constitution de bases de données pour la cartographie du MIS.- Tomographie des structures individuelles.- Des extractions de profils de DIBs basées sur des lignes de visée soigneusement sélectionnées, des études de leurs sous-structures et de leur variabilité spatiale et des contraintes subséquentes sur leurs porteurs moléculaires potentiels. / Diffuse interstellar bands (DIBs) represent a century-old mystery: none of the hundreds of bands could be identified with certainty with a specific carrier, at the very likely exception of the buckminsterfullerene cation C60+. Identifying and quantifying the amount of the large interstellar carbonaceous molecules that are very likely responsible for the DIBs is mandatory: DIB carriers likely represent the largest amount of organic matter in the Universe and are an important piece of the chain of processes that govern the interstellar/stellar cycle.Up to recently, most of the DIB studies have had as a unique goal the identification of the carriers, and to do so have been focusing on a limited number of hot, distant and reddened stars, using increasingly powerful instruments. This thesis marks a turning point in the methods and goals associated with the DIBs, an evolution allowed and motivated by the increasing number of stellar surveys with high multiplex instruments. As a matter of fact, it is possible today to gather massive amounts of data, both from the point of view of the number of target stars and from the point of view of the number of DIBs simultaneously observed. This has opened the way to new types of studies, more ambitious goals, and, importantly, new potential comparisons with laboratory data. This thesis presents a large number of DIB extractions and four of these novel analyses :- Methods of extraction and search for new DIBs.- Statistical studies of the link between DIB strengths and the physical properties of their hosting clouds.- Tomographic studies of the carriers on large and small spatial scales.- Line profile extractions based on carefully selected sightlines, studies of their substructures and spatial variability and subsequent constraints on their potential molecular carriers.

Carbon nanotubes have unique electronic, optical, mechanical, and transport properties which make them an important element of nanoscience and nanotechnology. However, successful application and integration of carbon nanotubes into new nanodevices requires fundamental understanding of their property changes under the influence of many external factors. This dissertation presents qualitative and quantitative theoretical understanding of property changes, while carbon nanotubes are exposed to the deformations, defects, external electric fields, and adsorption. Adsorption mechanisms due to Van der Waals dispersion forces are analyzed first for the interactions of graphitic materials and biological molecules with carbon nanotubes. In particular, the calculations are performed for the carbon nanotubes and graphene nanoribbons, DNA bases, and their radicals on the surface of carbon nanotubes in terms of binding energies, structural changes, and electronic properties alterations. The results have shown the importance of many-body effects and discrete nature of system, which are commonly neglected in many calculations for Van der Waals forces in the nanotube interactions with other materials at nanoscale. Then, the effect of the simultaneous application of two external factors, such as radial deformation and different defects (a Stone Wales, nitrogen impurity, and mono-vacancy) on properties of carbon nanotubes is studied. The results reveal significant changes in mechanical, electrical, and magnetic characteristics of nanotubes. The complicated interplay between radial deformation and different kinds of defects leads to the appearance of magnetism in carbon nanotubes which does not exist in perfect ones. Moreover, the combined effect of radial deformation and external electric fields on their electronic properties is shown for the first time. As a result, metal-semiconductor or semiconductor-metal transitions occur and are strongly correlated with the strength and direction of external electric field and the degree of radial deformations.

The initial step in odor recognition by the nose is the binding of odorant molecules to receptor sites embedded in the dendritic membranes of olfactory receptor cells. Despite considerable interest and experimentation into the nature of these receptor sites, little is known of their specificity to different types of odorant molecules. This lack of knowledge partially stems from the fact that the nature of receptor proteins is most effectively studied when specific and irreversible inhibitors are available for use as chemical probes, yet no such agents have been discovered for use in the olfactory system. A series of alkylating agents and other chemically active odorants were tested to determine whether they might react with specific odorant receptors and modify olfactory responses. Electroolfactogram (EOG) recordings were obtained before, during, and after treatment of the olfactory mucosae of grass frogs (Rana pipiens) with a chemically active odorant.

<p>Cyclobutane pyrimidine dimers (CPD) are the predominant DNA lesions formed upon exposure of this biopolymer to sunlight. Given the potentially dire biological consequences of DNA lesions, there is a need to fully characterize their behaviour, with an eye towards understanding their complete reactivity and as a possible means to detect and quantify their presence in the genome. The work described in this dissertation describes studies of the alkaline reactivity of CPD lesions generated within dinucleotide & polynucleotide strands. It was found that CPD-TpT is generally inert under alkaline conditions at room temperature, which is in agreement with earlier studies on alkaline hydrolysis of CPD-thymine and CPD-thymidine. However, a re-evaluation of the same reaction in the presence of ¹⁸O labelled water demonstrated that, similar to other UV-induced DNA lesions containing a saturated pyrimidine ring, CPD undergoes a water addition at the C4=O group of the nucleobase leading to the formation of a hemiaminal intermediate. This intermediate, however, does not lead to hydrolysis products and completely reverts to starting material under those same conditions. Moreover, the two C4=O groups present on 3′ and 5′-thymines in a CPD molecule show different chemical reactivities, with the 3′ C4=O group having greater affinity towards water addition as compared to the one on 5′ end, a fact reflected in different rates of exchange with the incoming nucleophile leading to the hemiaminal intermediate. The ¹⁸O labelling reaction was also investigated in CPD lesions generated within oligonucleotides to probe the cause of asymmetry between the 3′ <i>vs</i> 5′ C4=O groups; ultimately, it was determined that the asymmetric reactivity observed to occur between the two C4=O groups was an intrinsic property of the CPD molecule and did not arise as a result of asymmetry in a dinucleotide setting.</p><p><br></p> <p>In addition to the above studies, during the course of the investigation of the nucleophilic reactivity of CPD, a chemical reaction was observed leading to what appeared to be the rapid and total chemical reversal of CPD lesions to the original TpT (thymine-thymine dinucleotide)! This “repair” reaction occurred when CPD reacted with hydrazine, and appears facilitated by an inert atmosphere under which it rapidly proceeds to completion at room temperature.</p><br>

京都大学 / 0048 / 新制・論文博士 / 博士(医科学) / 乙第12872号 / 論医科博第1号 / 新制||医科||4(附属図書館) / 31590 / (主査)教授 野田 亮, 教授 楠見 明弘, 教授 瀬原 淳子 / 学位規則第4条第2項該当 / Doctor of Medical Science / Kyoto University / DFAM

In organic photovoltaics (OPVs) the key processes relevant to device operation such as exciton dissociation and free carriers recombination occur at the donor-acceptor (D-A) interface. OPV devices require the bulk heterojunction (BHJ) architecture to function efficiently. In these BHJs, D-A interfaces are arranged in three dimensions, which makes molecular arrangements at these interfaces ill defined and hard to characterize. In addition, molecular materials used in OPVs are inherently disordered and may exhibit variable degrees of structural order in the same BHJ. Yet, D-A molecular arrangements and structure are crucial because they shape the energy landscape and photovoltaic (PV) performance in OPVs. Studies that use well-defined model systems to look in details at the interfacial molecular structure in OPVs and link it to interfacial energy landscape and device operation are critically lacking. We have used in situ photoelectron spectroscopy and ex situ x-ray scattering to study D-A interfaces in tailored bilayers and BHJs based on small molecule donors. We show preferential miscibility at the D-A interface depending on molecular conformation in zinc phthalocyanine (ZnPc)/ C60 bilayers and we derive implications for exciton dissociation. Using sexithiophene (6T), a crystalline donor, we show that the energy landscape at the D-A interface varies markedly depending on the molecular composition of the BHJ. Both the ionization energies of sexithiophene and C60 shift by over ~0.4 eV while the energy of the charge transfer state shifts by ~0.5 eV depending on composition. Such shifts create a downward energy landscape that helps interfacial excitons to overcome their binding energies. Finally, we demonstrate that when both disordered and ordered phases of D coexist at the interface, low-lying energy states form in ordered phases and significantly limit the Voc in devices. Overall our work underlines the importance of the aggregation and conformation states of molecular materials at and near the D-A interface in determining the operation and performance of OPV devices. This work shows that the role of D-A interfaces in complex BHJ devices can be unraveled through careful experimental design and by in depth characterization of planar heterojunction bilayer devices recreating model interfaces.