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Orientadores: Konradin Metze, Carlos Lenz Cesar Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas Resumo: A hipertensão arterial sistêmica (HAS) bem como o envelhecimento provoca mudanças na estrutura dos grandes vasos sanguíneos - aorta e seus ramos - propiciando o desenvolvimento de processos degenerativos que são a causa de diversas doenças. O uso de ferramentas fotônicas na aquisição de imagens, associado a recursos matemáticos para a interpretação delas representa um avanço para as análises histopatológicas, pois permitem a visualização e compreensão de pequenas estruturas que antes eram impossíveis de serem observadas. O objetivo desse trabalho foi associar estas duas tecnologias (ferramentas fotônicas e recursos matemáticos) e com isso criar uma metodologia para a análise simultânea de fibras elásticas e colágenas na aorta. Para tanto utilizamos aorta ascendente de 72 pacientes, sendo 22 normotensos, 38 portadores de HAS e 12 aortas de dissecção. As lâminas coradas com hematoxilina eosina foram examinadas no microscópio multifoton, com dois fótons: laser de argônio para fluorescência da eosina, corante de fibras elásticas e Ti:safira para SHG, sinal gerado por moléculas de colágeno. A distribuição e organização das fibras elásticas e colágenas foram analisadas pelas seguintes variáveis: morfometria geométrica, derivadas da matriz de co-ocorrência de Haralick, Transformada de Fourier e fluorescência ótica integrada. Usando estes descritores da textura associados a fractais, observamos que a geração do SHG é dependente não só da presença do colágeno como também do arranjo destas fibras. Observamos ainda que em indivíduos normotensos, quando comparados aos portadores de HAS, ocorre uma diminuição na distribuição do sinal SHG ao longo da espessura da camada média partindo da íntima em sentido à adventícia. Dessa maneira concluímos que os maiores distúrbios das fibras elásticas, nos indivíduos normais ocorrem na transição do terço interno para o médio, enquanto que nos portadores de HAS eles estão distribuídos em toda a espessura da aorta. Além disso, estes estudos nos permitiram verificar que a dissecção da aorta ocorre entre dois reforços de colágeno, uma vez que este fenômeno foi constatado entre dois picos de SHG Abstract: The arterial hypertension as well as aging induces changes in the structure of large blood vessels - aorta and its branches - leading to development of degenerative processes which are the cause of many diseases. The use of photonics tools for image acquisition, associated to mathematical resources for interpretation of them represents an advance in histopathological analysis, because it allows the visualization and understanding of small structures that were impossible to be observed before. The main objective of this study was to associate both technologies (photonics tool and mathematical resources) to create a new methodology to evaluate, simultaneously, elastic and collagen fibers in aorta. For this we've used autopsies of ascending aortas from 72 patients, being 22 samples from normotensives individuals, 38 from HAS patients and 12 aortas from dissection. HE-stained paraffin sections from ascending aortas were analyzed by multifoton microscopy, with 2 types of photons: Two-photon excited fluorescence (TPEF) for elastin and Ti:safira for SHG to analyze collagen fibers. The distribution and organization of elastic and collagen fibers were analyzed by the following variables: geometric morphometric, derived from the co-occurrence matrix of Haralick, Fourier Transform and Fluorescence optics integrated. Using these texture descriptors associated to analysis of fractals, we've observed that SHG generation is not only dependent on the presence of collagen but on the arrangement of these fibers as well. We also observed that in normotensives individuals, if compared to HAS patients, occurs a decrease in the SHG intensity along the medial thickness from intimate in direction to adventitia. Thus we conclude that the major disorders of elastic fibers in normal subjects occur in the transition from the third layer to the middle, while in HAS individuals these disorders are distributed throughout the thickness of the aorta. Furthermore, this study has allowed us to verify that the aortic dissection has occurred between two peaks of SHG, since this phenomenon was observed between two ribs collagen Doutorado Biologia Estrutural, Celular, Molecular e do Desenvolvimento Doutora em Fisiopatologia Médica

Orientador: Flavio Caldas da Cruz Dissertação (mestrado) - Universidade Estadual de Campinas, Instituto de Fisica Gleb Wataghin Resumo: Os relógios atômicos são usados na atualidade em um grande número de aplicações científicas e tecnológicas que vão desde experimentos de relatividade e determinação de constantes fundamentais, até sistema de navegação (GPS) e telecomunicações. A proxima geração de relógios atômicos de alta precisão estará baseada em transições ópticas de átomos frios. Neste trabalho foi desenvolvido um laser de estado sólido de Nd:YLF bombeado por um laser de diodo e duplicado em frequência em 657 nm. Este sistema é proposto como oscilador local em um relógio atômico óptico baseado em átomos de cálcio. Comparado com os lasers de diodo, este apresenta uma potência maior no vermelho, um ruído de frequência e amplitude menores e a possibilidade de transferência remota usando obras ópticas no comprimento de onda fundamental de 1314 nm. Duplicação em frequência intra-cavidade é feita usando um cristal de BiBO, com superfícies anti-refletoras, e com um casamento de fase crítico tipo I à temperatura ambiente. Uma potência de 270 mW na saída do vermelho foi obtida para uma potência de bombeamento de 11.6 W. Abstract: Atomic clocks are used today in a number of scientific and technological applications, ranging from tests of relativity, or variations of fundamental constants, to the use in navigation and telecommunication. The next generation of such high precision devices will be based on optical transitions of suitable laser cooled and trapped atoms. In this work we describe a frequency-doubled, diode-pumped solid-state Nd:YLF ring laser emitting at 657 nm, proposed as a local oscillator in an optical atomic clock based on laser cooled and trapped calcium atoms. Compared to diode lasers, its main advantages include higher power, less intrinsic frequency noise, and the possibility of remote transfer in optical fibers using the fundamental light at 1314 nm. Frequency doubling is performed inside the cavity using a 10 mm long AR-coated BiBO crystal, under type I, critical phase-matching at room temperature. Red output power of 270 mW was achieved for 11.6 W of pumping power. Mestrado Física Atômica e Molecular Mestre em Física

Agradecimentos: The equipment used for the development of this work was purchased with the help of Fapesp (the São Paulo Research Foundation; 08/57906-3) and CNPq (the National Council for Scientific and Technological Development; 573913/2008-0). We reviewed the content of the manuscript, followed by Ms Diane Ellis, B.A. in education. Biostatistician Cleide Aparecida Moreira Silva, Research Committee, Biostatistics Division, Medical Sciences School, Unicamp, provided statistical consultation Abstract: Solid tumors typically contain high levels of fibrillar collagen. The increased stromal collagen deposition usually promotes cancer progression since biochemical and biophysical cues from tumor-associated collagen fibers stimulate neoplastic cells. Few studies have investigated the relationship between Merkel cell carcinoma (MCC) and the extracellular matrix (ECM), but there are no works evaluating collagen. This is an observational, analytical, retrospective study including 11 patients with MCC. Primary tumor-stained sections were evaluated by second harmonic generation microscopy and texture analysis. Peritumoral texture features (area fraction, mean gray value, entropy, and contrast) showed much lower values than normal skin (P < .0001) revealing extensively altered structure of peritumoral collagen fibers. These differences were not significant between tumors with unfavorable and favorable known prognostic factors. Profound changes in collagen fibers present in the stroma accompanying primary MCC may contribute to the aggressive behavior of this tumor. Our results indicate that whatever MCC histological subtype, size or anatomical location, MCC promotes the same type of ECM for its development. As an outlook, therapies using ECM macromolecules or fibroblasts (the architects of ECM remodeling) as target could be useful in the treatment of MCC FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESP CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQ Aberto

Agradecimentos: This study was supported by the São Paulo Research Foundation—FAPESP (Grant Nos. 2016/22927-7, 2017/17149-8, and 11/51959-0) and by Coordination of Superior Level Staff Improvement (CAPES) (Grant No. 01-P-3368/2017). We would like to express our thanks for the access to equipment and assistance provided by the National Institute of Science and Technology on Photonics Applied to Cell Biology (INFABIC), which is cofounded by FAPESP (Grant No. 2014/50938-8) and by National Council for Scientific and Technological Development (CNPq) (Grant Nos. 465699/2014-6 and 312049/2014-5). We are also grateful to Adilson A. Piaza and Mercedes F. Santos for assistance in photographic documentation, Ana C. Piaza and Luzia A. Magalhães for technical assistance, and Cleide A.M. Silva and Juliana L.P. Argenton for statistical assistance Abstract: Sarcoidosis and tuberculoid leprosy (TL) are prototypes of granulomatous inflammation in dermatology, which embody one of the histopathology limitations in distinguishing some diseases. Recent advances in the use of nonlinear optical microscopy in skin have enabled techniques, such as second-harmonic generation (SHG), to become powerful tools to study the physical and biochemical properties of skin. We use SHG images to analyze the collagen network, to distinguish differences between sarcoidosis and TL granulomas. SHG images obtained from skin biopsies of 33 patients with TL and 24 with sarcoidosis retrospectively were analyzed using first-order statistics (FOS) and second-order statistics, such as gray-level co-occurrence matrix (GLCM). Among the four parameters evaluated (optical density, entropy, contrast, and second angular moment), only contrast demonstrated statistical significance, being higher in sarcoidosis (p = 0.02||4908.31 versus 2822.17). The results may indicate insufficient differentiating power for most tested FOS and GLCM parameters in classifying sarcoidosis and TL granulomas, when used individually. But in combination with histopathology (H&E and complementary stains, such as silver and fast acid stains), SHG analysis, like contrast, can contribute to distinguishing between these diseases. This study can provide a way to evaluate collagen distribution in granulomatous diseases FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESP COORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL DE NÍVEL SUPERIOR - CAPES CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQ Aberto

Orientadores: Maria Letícia Cintra, Gislaine Vieira Damiani Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas Resumo: Introdução: Mais de 200.000 casos novos de hanseníase são detectados anualmente em todo o mundo. O Brasil é o segundo país com maior incidência, perdendo apenas para a Índia. Mesmo em locais endêmicos como o Brasil, o diagnóstico da hanseníase pode ser deveras desafiador, haja vista algumas regiões apresentarem um atraso médio de dois anos para que ele seja definido. Com o aumento progressivo dos fluxos migratórios, países não endêmicos também poderão enfretar esse desafio. Outrossim, os médicos comumente têm dificuldade em diferenciar a forma tuberculoide da hanseníase (HT) da manifestação cutânea da sarcoidose, doença esta multissistêmica e também de padrão inflamatório crônico granulomatoso. Classicamente, a histopatologia da HT é caracterizada por granulomas envoltos por rica orla linfocitária, enquanto a da sarcoidose por granulomas nus, ou seja, envoltos por raros linfócitos. Todavia, fato é que tais achados não estão sempre presentes na prática diária, o que torna essas duas doenças, muitas vezes, clínica- e histopatologicamente semelhantes. Neste trabalho, foram pesquisados critérios adicionais de auxílio à distinção destas doenças, seja por meio da microscopia óptica de luz, seja por ferramentas mais novas, como a geração de segundo harmônico - SHG (microscopia óptica não linear). Material e Métodos: Biopsias de pele de 33 pacientes com HT e 24 com sarcoidose foram revisadas, retrospectivamente, sob colorações de rotina - hematoxilina e eosina (H&E) e pela prata (técnica Gomori). Foram avaliados, de forma cega, 24 achados histomorfológicos (dentre eles, o tipo de granuloma, tipo de distribuição granulomatosa; presença de estruturas como Corpos de Schaumann, corpos asteroides, corpos de Hamazaki Wesenberg, células gigantes de Langhans, plasmócitos; presença de fibrose, necrose fibrinoide, necrose caseosa) à coloração pela H&E, por dois observadores distintos, com o intuito de verificar se algum desses achados mostraria valor diagnóstico preditivo significante para HT ou sarcoidose. Os espécimes corados pela prata foram fotografados e avaliados pela morfometria dos cicloides virtuais, com o objetivo de estimar o valor preditivo diagnóstico da densidade média das fibras reticulínicas nos granulomas. A partir das lâminas coradas pela H&E, as imagens do SHG foram obtidas e os dados da avaliação da densidade e textura do colágeno foram analisados. Resultados: Nove das 24 características histomorfológicas analisadas apresentaram valor preditivo significativo para o diagnóstico da HT (granuloma tuberculoide, distribuição peri-neural e peri-anexial, granulomas nos limites do glomérulo sudoríparo substituindo o nervo da região) ou sarcoidose (fibrose, distribuição dos granulomas de modo consecutivo, plasmócitos, elevado número de células gigantes de Langhans convencionais, elevado número de células gigantes bizarras, granulomas junto a resto de nervo). A média da densidade das fibras retinulínicas foi significativamente maior na sarcoidose do que na HT pelo teste de Mann-Whitney. No entanto, ao utilizarmos o método estatístico da regressão logística, essa variável não discriminou as duas doenças. Entre os quatro parâmetros avaliados nas imagens de SHG (densidade óptica, entropia, contraste e segundo momento angular), apenas o contraste demonstrou significância estatística, sendo maior na sarcoidose. Conclusões: as características hitomorfológicas, histomorfométricas, ou a análise de imagem pelo SHG podem ser insuficientes para diferenciar a HT da sarcoidose, se avaliadas isoladamente. Mas, quando combinadas, podem se tornar ferramentas muito úteis nesse intento. Os resultados desse trabalho reforçam a importância da morfometria para uma análise histológica mais objetiva das doenças, e abrem as portas para o estudo do colágeno cutâneo nas afecções granulomatosas Abstract: Background: More than 200,000 new cases of leprosy are detected, annually, around the world. Brazil is the second country in highest incidence, behind only India. Even in endemic places like Brazil, the diagnosis of leprosy can be very challenging, since in some regions there is an average delay of two years for it. With the progressive increase in migratory flows, non-endemic countries may also meet this challenge. Besides, not uncommonly, physicians have difficulty distinguishing tuberculoid form of leprosy (TL) from sarcoidosis' cutaneous manifestation. The latter is multisystemic and also manifests as a chronic granulomatous inflammation. Classically, the histopathology of TL is characterized by granulomas surrounded by evident lymphocytic rim, whereas that of sarcoidosis by naked granulomas, i.e., surrounded by rare lymphocytes. However, such findings are not always present in daily practice, which makes these two diseases often clinically and histopathologically similar. The present work aimed, therefore, investigate criteria that aid in their distinction, either through standard optical microscopy or through newer tools such as second harmonic generation - SHG (non-linear optical microscopy). Material and Methods: Skin biopsies from 33 patients with TL and 24 with sarcoidosis were reviewed in hematoxylin and eosin (H&E) and silver (Gomori technique) staining. Two distinct observers blindly evaluated twenty-four histomorphological findings on H&E staining, in order to verify if any of them had significant predictive diagnosis value to TL or sarcoidosis. The specimens stained by silver were photographed and evaluated through the morphometry of the virtual cycloids in order to estimate the predictive diagnosis value of the mean density of the reticulin fibers. From the H&E stained specimens, the SHG images were obtained and collagen features of density and texture were analyzed. Results: Nine of the 24 histomorphological characteristics analyzed presented significant predictive value for the diagnosis of HT or sarcoidosis. The mean density of reticulin fibers was significantly higher in sarcoidosis than in HT. However, using logistic regression, this variable did not discriminate the two diseases. Among the four characteristics evaluated in SHG images (optical density, entropy, contrast and second angular momentum), only contrast was useful, revealing significant predictive diagnosis value, being higher in sarcoidosis. Conclusions: Histomorphologic, histomorphometric, or SHG imaging may be insufficient to differentiate HT from sarcoidosis, if evaluated alone. However, when combined, they can become very useful tools in this endeavor. Our results reinforce the importance of morphometry for a more objective histological analysis of the diseases, and open the doors for the study of cutaneous collagen in the granulomatous disorders Doutorado Anatomia Patologica Doutora em Ciências FAPESP 2016/22927-7 CAPES 01-P-3368/2017

Agradecimentos: This study was funded by the São Paulo Research Foundation (08/57906–3), the National Council for Scientific and Technological Development (573913/2008–0), and the Biologia das Doenças Neoplásicas da Medula Óssea (FAPESP grant 11/51959-0) project with fellowship support from CNPq (310518/2015-6) Abstract: Background: The diagnosis of idiopathic atrophoderma of Pasini and Pierini (IAPP) relies on typical clinical features, particularly distinctive pigmented ovular/round depressed plaques. Histologic examination often reveals no obvious changes, but patterns of collagen distribution, using multiphoton imaging and second harmonic generation can help track hidden details of tissue organization contributing to atrophy. Objective: To identify histologic features that distinguish IAPP from unaffected skin. Methods: Eleven patients were included for conventional analyses. Masson trichromee and Unna-Tanzer orcein-stained sections were evaluated using automated morphometry. Hematoxylin-eosinestained sections were analyzed by multiphoton imaging using 2-photon excited fluorescence and second harmonic generation. Results: No abnormalities were found under light microscopy or by automated quantification. Multiphoton imaging revealed no difference in optical density of either collagen or elastic fibers in lesioned and unaffected skin; however, horizontal collagen fiber organization in lesion specimens increased toward the lower dermis, whereas elastic fibers featured greater disorganization within the upper dermis. Limitations: The low number of patients evaluated. Conclusion: The atrophic appearance of IAPP lesions reflects changes in organization, but not in collagen and elastic tissue content. Minute organizational differences that are imperceptible to the experienced pathologist and undetectable by automated analyses were revealed by multiphoton analyses, particularly second harmonic generation, in association with texture analyses FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESP CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQ Fechado

Agradecimentos: We would like to thank Aaron C. Hryciw and J. P. Hadden for their assistance with this project. This work was supported by NRC, CFI, iCORE/AITF, NSERC, and CNPq Abstract: Resonant second harmonic generation between 1550 nm and 775 nm with normalized outside efficiency > 3.8 × 10 - 4 mW - 1 is demonstrated in a gallium phosphide microdisk supporting high-Q modes at visible (Q ~ 10 4) and infrared (Q ~ 10 5) wavelengths. The double resonance condition is satisfied for a specific pump power through intracavity photothermal temperature tuning using ~ 360 µ W of 1550 nm light input to a fiber taper and coupled to a microdisk resonance. Power dependent efficiency consistent with a simple model for thermal tuning of the double resonance condition is observed CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQ Aberto

Orientador: Carlos Lenz César Tese (doutorado) - Universidade Estadual de Campinas, Instituto de Física Gleb Wataghin Resumo: Técnicas de microscopias ópticas são as principais ferramentas capazes de observar células e tecidos biológicos em tempo real e com mínimo dano. Essa área foi revolucionada recentemente através das microscopias confocais de varredura a laser e as microscopias de óptica não linear, naturalmente confocais. Entre os processos não lineares temos, a fluorescência excitada por dois ou mais fótons, geração de segundo harmônico [Second Harmonic Generation - SHG] e terceiro harmônico [Third Harmonic Generation - THG]. SHG e THG são técnicas de óptica não linear coerentes, não necessitam de marcadores exógenos e permitem reconstrução de imagens em três dimensões com resolução espacial subcelular. As técnicas de fluorescência permitem visualizar estruturas específicas no espaço, mas não permitem discriminar as substâncias químicas nas estruturas celulares, e as técnicas de SHG e THG não possuem especificidade química. Espectroscopia Raman possui especificidade química através das propriedades vibracionais das moléculas e pode ser usada como mecanismo de contraste na aquisição de imagens. Comparada com a espectroscopia/microscopia infravermelho, a microscopia Raman traz a informação das vibrações moleculares do infravermelho para o visível, eliminando os problemas da baixa resolução espacial e opacidade das amostras. Entretanto a baixa sensibilidade dessa técnica implica em tempos de aquisição de imagens muito longos, da ordem de horas, inviabilizando acompanhar a dinâmica de processos celulares em tempo real. Como solução para essa baixa sensibilidade do espalhamento Raman espontâneo, surgiu a microscopia por espalhamento Raman Coerente anti-Stokes [Coherent Anti-Stokes Raman Scattering - CARS]. Comparado com Raman espontâneo, a microscopia CARS representa aumento de 4 a 5 ordens de grandeza na sensitividade da técnica, diminuindo os tempos de aquisição ao ponto de viabilizar a aquisição em taxas de vídeos (mais rápido do que 30 quadros por segundo) e estudos em tempo real. Essa tese é dedicada ao estudo experimental e teórico, assim como de algumas aplicações, das técnicas de óptica não linear, com destaque para processos de óptica não linear coerentes. Apresentamos de forma detalhada três sistemas experimentais para a aquisição de imagens de Raman coerente e um sistema integrado com várias técnicas de óptica não linear. Mostramos as primeiras imagens de CARS realizadas no Brasil. Além do CARS convencional, trabalhamos com outra técnica de CARS de ordem mais alta, o CARS cascata [cascade CARS - CCARS], e, no melhor do nosso conhecimento, apresentamos as primeiras imagens internacionais obtidas com essa metodologia. CCARS aumenta o contraste da técnica CARS, diminuindo o fundo não ressonante, um problema que aflige a comunidade científica dedicada ao uso dessa técnica. Além da diminuição do fundo não ressonante, a emissão do CCARS acontece em um comprimento de onda diferente de qualquer outro efeito não linear coerente, significando um acréscimo de complexidade mínimo para sua detecção quando comparado com o CARS. Por último mostramos algumas aplicações realizadas com o sistema experimental desenvolvido para integrar diversas modalidades ópticas em paralelo, especialmente da geração de harmônicos com a fluorescência excitada por dois fótons e suas variantes, como microscopia de tempo de vida de fluorescência (Fluorescence Lifetime Imaging ¿ FLIM) Abstract: Optical microscopies techniques are the main tools capable of observing cell and biological tissues in real time and with minimum damage. This area have recently been revolutionized by confocal laser scanning microscopies and non-linear microscopies, naturally confocal. Among the non-linear process we have, the two or more photons excited fluorescence, second harmonic generation [SHG] and third harmonic generation [THG]. SHG and THG are coherent nonlinear techniques, they do not require exogenous markers and allow three dimension imaging reconstruction with subcellular resolution. The fluorescence techniques allow visualizing specific structures in space, but do not allow discriminating the chemical substances in cellular structures, SHG and THG techniques do not have chemical specificity. Raman spectroscopy has chemical specificity through the vibrational properties of the molecules and can be used as a contrast mechanism for imaging acquisition. Compared to infrared spectroscopy/microscopy, Raman microscopy brings information about molecular vibration from infrared to visible, eliminating the low resolution and sample opacity problems. However, this technique low sensibility implies in very long imaging acquisition times, order of hours, making it not viable for following cellular process dynamics in real time. As an answer for the spontaneous Raman scattering low sensibility, the coherent anti-Stokes Raman scattering [CARS] emerged. Compared to spontaneous Raman, CARS microscopy presents an increase of 4 to 5 orders of magnitude in the sensitivity of the technique, lowering the acquisition times to the point of making video acquisition (faster than 30 frames per second) and real time studies possible. This thesis is dedicated to the experimental and theoretical study, as well as some applications, of the non-linear techniques, with emphasis on coherent non-linear optical processes. We present in detailed form three experimental systems for the acquisition of coherent Raman images, and a system with the integration of various non-linear techniques. We show the first CARS images acquired in Brazil. In addition to conventional CARS, we worked with other higher order CARS technique, the cascade CARS [CCARS], and, in the best of our knowledge, we present the first international image acquired with this methodology. CCARS increases the contrast from CARS technique, decreasing the non-resonant background, a problem that afflicts the scientific community dedicated to the use of this technique. Besides the decrease of the non-resonant background, the CCARS emission occurs in a different wavelength from any other non-linear coherent effect, meaning a minimum complexity increase for its detection when compared with CARS. Finally we show some applications performed with the experimental system developed to integrate several optical modalities in parallel, especially the generation of harmonics with two photons excitation fluorescence and their variants such as Fluorescence Lifetime Imaging [FLIM] Doutorado Física Doutor em Ciências CAPES 830406/2010

Agradecimentos: Financial support from FAPESP, CEPOF, and CNPq is gratefully acknowledged. Flavio C. Cruz benefited from stimulating discussions and suggestions from Prof. Marcos Dantus, from Michigan State University Abstract: We demonstrate broadband second harmonic generation of low-energy pulses produced by injecting two single-frequency lasers into a highly nonlinear fiber. Full nonlinear conversion of the corresponding spectra, consisting of broadband (similar to 200 nm) optical frequency combs at similar to 1580 nm, were obtained by using conventional birefringence phase-matching in two BIBO crystals (2-mm and 100-mu m long) with a normal incidence configuration. The crystals were not tilted and the pulses were not compressed. This broadband conversion results from the large phase-matching bandwidth of the nonlinear BIBO crystals at similar to 1550 nm, but also seems to be a consequence of a fundamental comb with small spectral phase variation FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESP CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQ Fechado

Agradecimentos: The authors thank Joao Batista Rodrigues, from the Quantum Electronics Department machine shop, for his support and excellent work, and Luis E. E. de Araujo for discussions. L. S. Cruz acknowledges a post doctoral fellowship from FAPESP. F. C. Cruz (flavio@ifi.unicamp.br) acknowledges the financial support of FAPESP, CEPOF, CNPq, and AFOSR Abstract: We report on continuous-wave second harmonic generation of near infrared Ti: sapphire lasers using room temperature critically phasematched, angle-tuned BIBO ( bismuth triborate, BiB3O6) crystals, placed both in an external power enhancement cavity and inside the laser resonator. In the first case we generate 70 mW of single-frequency radiation at 423 nm for 330 mW of input power at 846 nm. For intracavity frequency doubling we achieve 690 mW at 423 nm for 7.3 Watts of the Ti: sapphire laser pump power at 532 nm, representing a conversion efficiency of 9.5% from 532 to 423 nm. These tunable blue-violet systems are particularly attractive for laser cooling and trapping of alkaline-Earth atoms FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESP CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQ Aberto

Agradecimentos: This work was supported by FAPESP, CNPq, and CAPES, Brazilian government agencies. We would like to thank Jim Bergquist for many of the design concepts used by us and for the continuing assistance and support; V.S. Bagnato, L.G. Marcassa, and S.C. Zilio for supplying Ti:Al2O3, a TGG crystal, and the mirrors from the University of São Carlos Optics Workshop (Brazil); Nelson B. Sales, Jorge L. Pires, Antônio J. Polaquini, and João B. Rodrigues for the mechanical parts Autor: We describe in detail the design, construction, and characterization of an efficient frequency doubled and stabilized all-solid-state Ti:sapphire laser. The laser frequency has been locked to the resonance of a Fabry-Perot cavity, and doubled in a Brewster-cut potassium niobate crystal placed inside a power enhancement cavity. Up to 200 mW of single frequency blue light with fast frequency instabilities of 40-kHz rms and a drift of 10 MHz/hour has been generated. The spectral distributions of amplitude and frequency noise for the free-running laser have been measured and compared with the case of pumping from an argon ion laser. Our laser is well suited in atomic physics for high resolution spectroscopy and for laser cooling and trapping using transitions in the blue-violet region, as we demonstrate with the calcium resonant transition, at 423 nm FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESP CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQ COORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL DE NÍVEL SUPERIOR - CAPES Fechado

Agradecimentos: We thank Professor R. K. Chang for providing information about electrolytic cycling on Au and Cu. This work was supported by the Division of Materials Sciences, Office of Basic Energy Sciences, U. S. Department of Energy under Contract No. W-7405-ENG-48. One of us (A.R.B.d.C.) acknowledges support from Universidade Estadual de Campinas and Conselho Nacicnal de Pesquisas, Brazil Abstract: Second-harmonic generation at a silver-air interface was enhanced by a factor of 104 by surface roughness. The local-field enhancement is believed to be responsible for the effect. An unusually broad luminescence background extending far beyond the anti-Stokes side of the second harmonic was also observed CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQ Aberto