Nanofabrication, simulation and optical characterization of plasmonic nanostructures

[eng] This thesis is devoted to the nanofabrication, simulation and optical characterization of different plasmonic nanostructures. When an electromagnetic wave reaches a metallic nanostructure, it can give rise to collective oscillations of the free electrons in the metal. These oscillations reach a maximum at the so-called surface plasmon resonance, whose intensity and frequency depend in the material, geometry, embedding medium, interparticle interactions, etc. Based on the tunability of core-shell nanoparticles, hollow cylindrical gold nanostructures (nanocups) have been fabricating using a combination of nanoimprint lithography (NIL) and non-directional metallization. Besides, to overcome the high-aspect ratio limitations of NIL, a trilayer stack (resist-oxide­resist) has been used in such a way that the bottom resist layer, which controls the height of the nanostructure, is not affected by the lithography, which takes place only in the top resist layer. Also, the fabrication method allows for easy changes in the geometry: the height can be changed by changing the thickness of the bottom resist layer, the thickness by modifying the amount of deposited material and the diameter by changing the etching time. By hanging the geometric parameters of the nanostructures, the plasmonic properties can be easily tuned. Besides, for certain dimensions (400 nm in diameter and height and 30 nm of Wall and base thickness), these structures present a peak in the extinction spectra in the visible range that corresponds to a concentration of the electric field within the cavity. This excitation mode has also been reported for other nanostructures with semispherical symmetry. However, the fact of being cylindrical enables a homogeneous enhancement of the electric field along the cavity while in the other case this is not possible due to the lack of symmetry. Also, based on geometrically frustrated magnetic systems, three particular cases of hexagonal lattices of plasmonic nanoelements have been studied. All of them have been designed so that the pitch is of the order of the resonance wavelength and the gaps between elements small enough to enable near-field coupling. Besides, a metal-insulator-metal configuration has been implemented, designed to have constructive interference, which leads to high absorption peaks. The samples have been fabricated by electron beam lithography to be able to change easily the design and study the optical response as a function of the geometries. Both simulation and spectroscopy results show that all these systems present high absorption peaks in the visible and/or near infrared. Also, they present a broad absorption peak in the NIR due to the dipolar excitation of the gaps between neighboring elements and sharper peaks in the visible that are assigned to collective modes. Moreover, these systems present an extended time response where the system fluctuates between collective and localized modes. This behavior, characteristic from magnetic frustrated systems, is induced by the frustration of the dipolar excitation of the gaps due to the geometry of the lattice. Besides, the collective modes give rise to enhancements of the electric field in large areas, making these systems of interest for enhanced spectroscopies.[spa] Esta tesis está dedicada a la nanofabricación, simulación y caracterización de las propiedades ópticas de diferentes nanoestructuras de oro. Por un lado, inspirados por las nanopartículas tipo core-shell, se han fabricado nanoestructuras de oro cilíndricas en forma de taza, combinando litografía por nanoimpresión (NIL) con metalización por pulverización catódica. Para tener la posibilidad de fabricar estructuras de una elevada altura frente a su anchura, se ha utilizado una tricapa de resina-óxido-resina, de manera que la capa inferior de resina controla la altura de las estructuras mientras que la litografía se realiza en la capa superior y por tanto se sobreponen las típicas dificultades que aparecen en NIL para estructuras de elevada relación de aspecto. Estas nanoestructuras, al igual que las nanoparticulas core-shell, presentan tambien gran capacidad de ajuste de sus propiedades como función de su geometria. Por otro lado, basados en los sistemas magnéticos con frustración geometrica, se han estudiado diferentes redes hexagonales de nanoelementos de oro. Todos los sistemas se han diseñado de modo que el periodo es del orden de la longitud de onda de resonancia y los espacios entre estructuras suficientemente pequeños para tener acoplo de campo cercano. Se ha utilizado una configuración metal-aislante­metal para obtener interferencia constructiva y, en consecuencia, picos de alta absorción. Las muestras se han fabricado utilizando litografía por haces de electrones para poder estudiar los cambios en la respuesta óptica en función de la geometría. Estos sistemas presentan un pico de absorción ancho en el infrarrojo ligado a la excitación dipolar de los huecos entre nanoestructuras y picos más estrechos en el visible que corresponden a modos donde predomina el comportamiento colectivo del sistema. Además, el estudio de la evolución temporal del sistema muestra que este tipo de redes presentan una respuesta extendida en el tiempo inducida por la frustración geométrica del sistema, característica de los sistemas magnéticos frustrados, durante la cual el sistema oscila entre modos localizados y modos colectivos. Por todo ello, consideramos que estas estructuras pueden ser de interés para aplicaciones relacionadas con la absorción de luz

División proporcional con múltiples referencias. Aplicación al caso de agregación y actualización de probabilidades

En este trabajo se considera una extensión de los problemas clásicos de reparto en los que las referencias relevantes de cada agente están expresadas por un vector, es decir, problemas de división con múltiples referencias. Nuestro propósito es definir una regla que, permitiendo que se reduzca el número de agentes, se comporte como una regla de división no manipulable y satisfaga algunas propiedades deseables en este tipo de problemas. Como aplicación se analizan los problemas de agregación y actualización de probabilidades.In this paper, we consider an extension of classic division problems in which the relevant references of each agent are represented by a vector, that is, division problems with multiple references. We define a non-manipulable division rule satisfying some desirable properties in the class of multi-issue allocation problems. As an application we analyze the probability aggregation problem and the probability updating problem.Ministerio de Ciencia y Tecnología SEJ2007-62711Consejería de Innovación de la Junta de Andalucía P06-SEJ-0180

Geometric frustration in a hexagonal lattice of plasmonic nanoelements

We introduce the concept of geometric frustration in plasmonic arrays of nanoelements. In particular, we present the case of a hexagonal lattice of Au nanoasterisks arranged so that the gaps between neighboring elements are small and lead to a strong near-field dipolar coupling. Besides, far-field interactions yield higher-order collective modes around the visible region that follow the translational symmetry of the lattice. However, dipolar excitations of the gaps in the hexagonal array are geometrically frustrated for interactions beyond nearest neighbors, yielding the destabilization of the low energy modes in the near infrared. This in turn results in a slow dynamics of the optical response and a complex interplay between localized and collective modes, a behavior that shares features with geometrically frustrated magnetic systems

Geometric frustration in ordered lattices of plasmonic nanoelements

Inspired by geometrically frustrated magnetic systems, we present the optical response of three cases of hexagonal lattices of plasmonic nanoelements. All of them were designed using a metal-insulator-metal configuration to enhance absorption of light, with elements in close proximity to exploit near-field coupling, and with triangular symmetry to induce frustration of the dipolar polarization in the gaps between neighboring structures. Both simulations and experimental results demonstrate that these systems behave as perfect absorbers in the visible and/or the near infrared. Besides, the numerical study of the time evolution shows that they exhibit a relatively extended time response over which the system fluctuates between localized and collective modes. It is of particular interest the echoed excitation of surface lattice resonance modes, which are still present at long times because of the geometric frustration inherent to the triangular lattice. It is worth noting that the excitation of collective modes is also enhanced in other types of arrays where dipolar excitations of the nanoelements are hampered by the symmetry of the array. However, we would like to emphasize that the enhancement in triangular arrays can be significantly larger because of the inherent geometric incompatibility of dipolar excitations and three-fold symmetry axes

Returning to work in cancer survivors: a multi-center cross-sectional study in Spain

Objetivo: Analizar la situación laboral, así como variables sociodemográficas (edad, sexo, estado civil y titulación) relacionadas con el cáncer (tipo de cáncer, estrategia de tratamiento primario y fase de supervivencia) en supervivientes españoles de cáncer. Método y procedimiento: Estudio transversal sobre una muestra heterogénea de 772 supervivientes de cáncer de inicio en la edad adulta en edad laboral. Se realizaron análisis correlacionales y de regresión logística para estudiar la capacidad predictiva de las variables sociodemográficas y relacionadas con el cáncer sobre la situación laboral y la posible modulación de los resultados por la CVRS evaluada mediante el QLACS. Resultados: Sólo el 55% de los supervivientes de cáncer estaban empleados. La edad, la cualificación y el tipo de cáncer fueron predictores independientes de la situación laboral, así como de la fase de supervivencia en los supervivientes con una CVRS baja. Conclusiones: Un alto porcentaje de supervivientes en edad laboral no vuelve a trabajar tras la experiencia oncológica. Algunas variables sociodemográficas y relacionadas con la enfermedad pueden ayudar a la identificación precoz de la población de riesgo en la que centrar la atención. Objective: To analyze the employment status as well as sociodemographic (age, gender, marital status, and qualification) and cancer-related variables (cancer type, primary treatment strategy, and survival phase) in Spanish cancer survivors. Method and procedure: Cross-sectional study on a heterogeneous sample of 772 working-age survivors of adult-onset cancer. Correlational and logistic regression analyses were performed to study the predictive ability of sociodemographic and cancer-related variables on employment status and the possible modulation of results by HRQOL assessed by the QLACS. Results: Only 55% of cancer survivors were employed. Age, qualification, and type of cancer were independent predictors of employment status as well as the survival phase in survivors with a low HRQOL. Conclusions: A high percentage of working-age survivors do not return to work after the cancer experience. Some sociodemographic and disease-related variables can help in the early identification of the risk population on which to focus attention

Metal Node Control of Brønsted Acidity in Heterobimetallic Titanium–Organic Frameworks

Compared to indirect framework modification, synthetic control of cluster composition can be used to gain direct access to catalytic activities exclusive of specific metal combinations. We demonstrate this concept by testing the aminolysis of epoxides with a family of isostructural mesoporous frameworks featuring five combinations of homometallic and heterobimetallic metal-oxo trimers (Fe3, Ti3, TiFe2, TiCo2, and TiNi2). Only TiFe2 nodes display activities comparable to benchmark catalysts based on grafting of strong acids, which here originate from the combination of Lewis Ti4+ and Brønsted Fe3+–OH acid sites. The applicability of MUV-101(Fe) to the synthesis of β-amino alcohols is demonstrated with a scope that also includes the gram scale synthesis of propranolol, a natural β-blocker listed as an essential medicine by the World Health Organization, with excellent yield and selectivity

Geometric frustration in ordered lattices of plasmonic nanoelements

Inspired by geometrically frustrated magnetic systems, we present the optical response of three cases of hexagonal lattices of plasmonic nanoelements. All of them were designed using a metal-insulator-metal configuration to enhance absorption of light, with elements in close proximity to exploit near-field coupling, and with triangular symmetry to induce frustration of the dipolar polarization in the gaps between neighboring structures. Both simulations and experimental results demonstrate that these systems behave as perfect absorbers in the visible and/or the near infrared. Besides, the numerical study of the time evolution shows that they exhibit a relatively extended time response over which the system fluctuates between localized and collective modes. It is of particular interest the echoed excitation of surface lattice resonance modes, which are still present at long times because of the geometric frustration inherent to the triangular lattice. It is worth noting that the excitation of collective modes is also enhanced in other types of arrays where dipolar excitations of the nanoelements are hampered by the symmetry of the array. However, we would like to emphasize that the enhancement in triangular arrays can be significantly larger because of the inherent geometric incompatibility of dipolar excitations and three-fold symmetry axes

Cuprizone-Induced Neurotoxicity in Human Neural Cell Lines Is Mediated by a Reversible Mitochondrial Dysfunction: Relevance for Demyelination Models

Suitable in vivo and in vitro models are instrumental for the development of new drugs aimed at improving symptoms or progression of multiple sclerosis (MS). The cuprizone (CPZ)-induced murine model has gained momentum in recent decades, aiming to address the demyelination component of the disease. This work aims at assessing the differential cytotoxicity of CPZ in cells of different types and from different species: human oligodendroglial (HOG), human neuroblastoma (SH-SY5Y), human glioblastoma (T-98), and mouse microglial (N-9) cell lines. Moreover, the effect of CPZ was investigated in primary rat brain cells. Cell viability was assayed by oxygen rate consumption and by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide-based (MTT) method. Our results demonstrated that CPZ did not cause death in any of the assayed cell models but affected mitochondrial function and aerobic cell respiration, thus compromising cell metabolism in neural cells and neuron-glia co-cultures. In this sense, we found differential vulnerability between glial cells and neurons as is the case of the CPZ-induced mouse model of MS. In addition, our findings demonstrated that reduced viability was spontaneous reverted in a time-dependent manner by treatment discontinuation. This reversible cell-based model may help to further investigate the role of mitochondria in the disease, and study the molecular intricacies underlying the pathophysiology of the MS and other demyelinating diseases. Keywords: neurodegenerative diseases, copper chelator, pathophysiology, cell metabolism, gli

The Use of P63 Immunohistochemistry for the Identification of Squamous Cell Carcinoma of the Lung

6 páginas, 2 figuras, 3 tablas.Introduction While some targeted agents should not be used in squamous cell carcinomas (SCCs), other agents might preferably target SCCs. In a previous microarray study, one of the top differentially expressed genes between adenocarcinomas (ACs) and SCCs is P63. It is a well-known marker of squamous differentiation, but surprisingly, its expression is not widely used for this purpose. Our goals in this study were (1) to further confirm our microarray data, (2) to analize the value of P63 immunohistochemistry (IHC) in reducing the number of large cell carcinoma (LCC) diagnoses in surgical specimens, and (3) to investigate the potential of P63 IHC to minimize the proportion of “carcinoma NOS (not otherwise specified)” in a prospective series of small tumor samples. Methods With these goals in mind, we studied (1) a tissue-microarray comprising 33 ACs and 99 SCCs on which we performed P63 IHC, (2) a series of 20 surgically resected LCCs studied for P63 and TTF-1 IHC, and (3) a prospective cohort of 66 small thoracic samples, including 32 carcinoma NOS, that were further classified by the result of P63 and TTF-1 IHC. Results The results in the three independent cohorts were as follows: (1) P63 IHC was differentially expressed in SCCs when compared to ACs (p<0.0001); (2) half of the 20 (50%) LCCs were positive for P63 and were reclassified as SCCs; and (3) all P63 positive cases (34%) were diagnosed as SCCs. Conclusions P63 IHC is useful for the identification of lung SCCs.This work was partially funded by grants from Fundacion Mutua Madrileña to EC, FLR, and LPA; CIBER Respiratory Disease to ALE (ISCIII-CB06/06); and Red Temática de Investigacion Cooperativa en Cancer (RTICC) to MSC (RD06/0020/0062). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer reviewe

Cuprizone-Induced Neurotoxicity in Human Neural Cell Lines Is Mediated by a Reversible Mitochondrial Dysfunction: Relevance for Demyelination Models

Suitable in vivo and in vitro models are instrumental for the development of new drugs aimed at improving symptoms or progression of multiple sclerosis (MS). The cuprizone (CPZ)-induced murine model has gained momentum in recent decades, aiming to address the demyelination component of the disease. This work aims at assessing the differential cytotoxicity of CPZ in cells of different types and from different species: human oligodendroglial (HOG), human neuroblastoma (SH-SY5Y), human glioblastoma (T-98), and mouse microglial (N-9) cell lines. Moreover, the effect of CPZ was investigated in primary rat brain cells. Cell viability was assayed by oxygen rate consumption and by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide-based (MTT) method. Our results demonstrated that CPZ did not cause death in any of the assayed cell models but affected mitochondrial function and aerobic cell respiration, thus compromising cell metabolism in neural cells and neuron-glia co-cultures. In this sense, we found differential vulnerability between glial cells and neurons as is the case of the CPZ-induced mouse model of MS. In addition, our findings demonstrated that reduced viability was spontaneous reverted in a time-dependent manner by treatment discontinuation. This reversible cell-based model may help to further investigate the role of mitochondria in the disease, and study the molecular intricacies underlying the pathophysiology of the MS and other demyelinating diseases.Los modelos in vivo e in vitro adecuados son fundamentales para el desarrollo de nuevos fármacos destinados a mejorar los síntomas o la progresión de la esclerosis múltiple (EM). El modelo murino inducido por cuprizona (CPZ) ha ganado impulso en las últimas décadas, con el objetivo de abordar el componente de desmielinización de la enfermedad. Este trabajo tiene como objetivo evaluar la citotoxicidad diferencial de CPZ en células de diferentes tipos y de diferentes especies: oligodendroglial humano (HOG), neuroblastoma humano (SH-SY5Y), glioblastoma humano (T-98) y microglial de ratón (N-9). líneas celulares. Además, se investigó el efecto de CPZ en células cerebrales primarias de rata. La viabilidad celular se ensayó mediante el consumo de oxígeno y mediante el método basado en bromuro de 3-(4,5-dimetiltiazol-2-il)-2,5-difeniltetrazolio (MTT). Nuestros resultados demostraron que CPZ no causó la muerte en ninguno de los modelos celulares ensayados, pero afectó la función mitocondrial y la respiración celular aeróbica, comprometiendo así el metabolismo celular en las células neurales y los cocultivos de neuronas y glías. En este sentido, encontramos una vulnerabilidad diferencial entre las células gliales y las neuronas, como es el caso del modelo de EM en ratón inducido por CPZ. Además, nuestros hallazgos demostraron que la reducción de la viabilidad se revirtió espontáneamente de manera dependiente del tiempo al suspender el tratamiento. Este modelo reversible basado en células puede ayudar a investigar más a fondo el papel de las mitocondrias en la enfermedad y estudiar las complejidades moleculares que subyacen a la fisiopatología de la EM y otras enfermedades desmielinizantes. comprometiendo así el metabolismo celular en las células neurales y los cocultivos de neurona y glía. En este sentido, encontramos una vulnerabilidad diferencial entre las células gliales y las neuronas, como es el caso del modelo de EM en ratón inducido por CPZ. Además, nuestros hallazgos demostraron que la reducción de la viabilidad se revirtió espontáneamente de manera dependiente del tiempo al suspender el tratamiento. Este modelo reversible basado en células puede ayudar a investigar más a fondo el papel de las mitocondrias en la enfermedad y estudiar las complejidades moleculares que subyacen a la fisiopatología de la EM y otras enfermedades desmielinizantes. comprometiendo así el metabolismo celular en las células neurales y los cocultivos de neurona y glía. En este sentido, encontramos una vulnerabilidad diferencial entre las células gliales y las neuronas, como es el caso del modelo de EM en ratón inducido por CPZ. Además, nuestros hallazgos demostraron que la reducción de la viabilidad se revirtió espontáneamente de manera dependiente del tiempo al suspender el tratamiento. Este modelo reversible basado en células puede ayudar a investigar más a fondo el papel de las mitocondrias en la enfermedad y estudiar las complejidades moleculares que subyacen a la fisiopatología de la EM y otras enfermedades desmielinizantes. nuestros hallazgos demostraron que la viabilidad reducida se revirtió espontáneamente de manera dependiente del tiempo al suspender el tratamiento. Este modelo reversible basado en células puede ayudar a investigar más a fondo el papel de las mitocondrias en la enfermedad y estudiar las complejidades moleculares que subyacen a la fisiopatología de la EM y otras enfermedades desmielinizantes. nuestros hallazgos demostraron que la viabilidad reducida se revirtió espontáneamente de manera dependiente del tiempo al suspender el tratamiento. Este modelo reversible basado en células puede ayudar a investigar más a fondo el papel de las mitocondrias en la enfermedad y estudiar las complejidades moleculares que subyacen a la fisiopatología de la EM y otras enfermedades desmielinizantes