Tunable Silicon integrated photonics based on functional materials

This thesis is concerned with the design, fabrication, testing and development of tunable silicon photonic integrated circuits based on functional materials. This tunability is achieved by integrating liquid crystals, 2D materials and chalcogenide phase-change materials with silicon and silicon nitride integrated circuits. Switching the functional materials between their various states results in dramatic changes in the optical properties, with consequent changes in the optical response of the individual devices. Furthermore, such changes are volatile or non-volatile depending on the materials.Engineering and Physical Sciences Research Council (EPSRC

Tiny hearts, great solutions: a Literature Review about the surgical therapeutic approaches for Hypoplastic Left Heart Syndrome

Hypoplastic left heart syndrome (HLHS) is a complex congenital malformation characterized by underdevelopment of the left heart with significant left ventricle hypoplasia, including atresia, stenosis, or hypoplasia of the aortic and mitral valves. It is one of the most severe forms of congenital heart disease and, without surgical treatment, the mortality rate for infants with HLHS exceeds 90% in the first year of life. About five decades ago, comfort care was the only therapeutic option available, resulting in premature death of infants with this syndrome. Nowadays, there are two recognized surgical modalities, palliative staged reconstruction, and cardiac transplantation. Conventional surgical therapy involves recruiting the right ventricle to the systemic circulation and separating the pulmonary and systemic circulations, in three stages. It consists of an initial Norwood operation during the neonatal period, followed by a bidirectional Glenn or a Hemi-Fontan procedure performed at 4 to 6 months of age, and a Fontan operation between 18 and 48 months of age. Changes in patient selection, pre- and postoperative management, and improved surgical techniques, have contributed to minimize perioperative mortality to 10%. However, the surviving cohort presents with multiple early and late complications, with some patients evolving to the “failing” Fontan. Cardiac transplantation has been established as a primary treatment option in infants with HLHS. The main advantage is the replacement of a functionally univentricular heart with a normal heart in a single surgery. Although survival is excellent, the multistage palliation has been favored due to limited number of available donors. With prenatal diagnosis advancements in the second decade of the 21st century, in-utero procedures were proposed to change the rules of the game. The rationale for in-utero interventions is restoration of onward flow and reduction of intraventricular pressure, hence promoting left ventricle growth and function. Fetal aortic valvuloplasty requires numerous resources and expertise in fetal diagnosis, obstetric and cardiovascular imaging, catheter techniques, and maternal care. Few centers have the capacity to do so successfully, nevertheless its results are more and more encouraging. This literature review aims to assess the role of different surgical therapeutic options for HLHS, procedures, optimizations, survival, and improvement in quality of life, adverse effects, long-term outcomes, and burden of disease in these patients. It also wants to shed light and explore future perspectives regarding the best approach to these patients.A síndrome do coração esquerdo hipoplásico (SCEH) é uma malformação congénita complexa, caracterizada pelo subdesenvolvimento do lado esquerdo do coração na presença de um ventrículo esquerdo hipoplásico, normalmente com hipoplasia ou atresia da aorta e/ou das válvulas aórtica e mitral. A SCEH é umas das cardiopatias congénitas mais severas e, na ausência de tratamento, apresenta uma mortalidade superior a 90% no primeiro ano de vida. Há cerca de cinco décadas o tratamento convencional incluía apenas medidas de conforto e o curso natural da doença culminava na morte precoce destas crianças. Atualmente, há duas modalidades cirúrgicas reconhecidas, a reconstrução paliativa e a transplantação cardíaca. A terapêutica convencional envolve o recrutamento do ventrículo direito para a circulação sistémica e a separação da circulação pulmonar da sistémica, em três fases. Consiste na cirurgia de Norwood durante o período neonatal, seguido do procedimento bilateral de Glenn ou um Hemi-Fontan entre os 4 e os 6 meses, terminando com a cirurgia de Fontan entre os 18 e os 48 meses de idade. Mudanças na seleção dos doentes, gestão pré- e pós-operatória, e melhoria das técnicas cirúrgicas contribuíram para a diminuição da mortalidade peri-operatória para 10%. Contudo, os sobreviventes apresentam várias complicações e alguns doentes evoluem para falência circulatória. A transplantação cardíaca foi estabelecida com uma opção terapêutica primária para crianças com SCEH, sendo que a principal vantagem é a substituição de um coração univentricular por um coração normal, numa única cirurgia. Apesar da sobrevivência ser excelente, a reconstrução paliativa tem sido favorecida face à limitada disponibilidade de órgãos. Com os avanços do diagnóstico pré-natal, na segunda metade do século XXI, procedimentos in útero foram propostos para alterar curso natural da doença. O racional por detrás destas intervenções é o restabelecimento do fluxo e a redução da pressão intraventricular, promovendo o crescimento e a função do ventrículo esquerdo. A valvuloplastia aórtica fetal requere numerosos recursos e experiência nas áreas do diagnóstico fetal, obstétrica e imagem cardiovascular, bem como técnicas percutâneas avançadas. Poucos centros o detêm para o fazer com sucesso, sendo os resultados cada vez mais encorajadores. A presente revisão da literatura tem como objetivo avaliar o papel das diferentes opções cirúrgicas existentes para a SCEH, procedimentos, otimizações, sobrevivência e melhoria da qualidade de vida, bem como efeitos adversos, outcomes a longo prazo e morbilidade. Pretende ainda explorar algumas perspetivas de futuro quantos à gestão destes doentes

Relatório de estágio curricular na Novartis Farma Portugal

Included in this report are accounts of an internship undertaken at Novartis Pharma Portugal in the fulfilment of the Master of Clinical Research Management degree. During the training period, the intern performed multidisciplinary tasks covering the different functions performed by the members of the trial monitoring team. Additionally, the intern selected performance and risk indicators to not only reflect but also assess the operational quality of national sites through the creation of a site card. In face of the current state of clinical research in Portugal, the site card supported by the commitment of all stakeholders could contribute to further clinical trial development in Portugal.O presente relatório destina-se a reportar as atividades realizadas durante o estágio curricular na Novartis Farma Portugal, no âmbito do Mestrado de Gestão em Investigação Clínica, realizado entre outubro de 2020 e maio de 2021. Durante o período de formação, a estagiária desempenhou funções multidisciplinares inerentes às diferentes funções da equipa de monitorização de estudos clínicos. Para além disso, a estagiária elaborou um site card com base na seleção de indicadores de risco e desempenho, visando não só avaliar, mas também traduzir a qualidade operacional dos centros. Face ao atual estado da investigação clínica em Portugal, este documento aliado ao empenho e compromisso de todos os intervenientes poderá contribuir para o desenvolvimento da investigação clínica em Portugal.Mestrado em Gestão da Investigação Clínic

Fosforilação da TAU Thr231 como potencial biomarcador da doença de Alzheimer

Mestrado em Biomedicina MolecularAlzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by the presence of extracellular amyloid plaques (senile plaques) and intracellular neurofibrillary tangles formed by hyperphosphorylated TAU protein. TAU protein when hyperphosphorylated loses the ability to bind to microtubules and can be released into peripheral fluids. This process leads to neuronal degradation and neuronal death. Phosphorylation at threonine 231 has been shown to be specific for AD and to precede assembly of paired helical filaments in the human brain. In order to understand more about this residue we analysed SH-SY5Y cells undifferentiated and in differentiated cells induced by retinoic acid (RA). Treatment with RA increased expression of TAU phosphorylated at Thr231 (TAUpThr231) as determined by Western blot analysis. We further explored TAU phosphorylation by immunocytochemistry and noticed that in undifferentiated SH-SY5Y cells, TAUpThr231 was located mainly in the nucleus. In contrast, TAU and TAUpThr231 was redistributed to the neurites and in the soma of SH-SY5Y cells, which were induced to differentiate by retinoic acid (RA). In order to evaluate the potential of TAUpThr231 as a biomarker, we measured TAUpThr231 in CSF by a sandwich enzyme immunoassay and observed that the ratio of TAUpThr231/TAU levels discriminated significantly the AD group for the non-AD group. These findings indicate that TAUpThr231/t-TAU ratio levels may be a valuable marker for the clinical diagnosis of AD, irrespective of age and gender.A doença de Alzheimer (AD) é uma doença neurodegenerativa progressiva caracterizada pela presença de placas de amilóide extracelulares (placas senis) e tranças neurofibrilhares intracelulares formadas pela proteína TAU hiperfosforilada. A proteína TAU quando hiperfosforilada perde a capacidade de se ligar a microtúbulos e pode ser libertada para fluidos periféricos. Este processo leva à degradação neuronal e à morte neuronal. A fosforilação na treonina 231 tem-se demonstrado ser específica para a AD e preceder a formação de filamentos helicoidais emparelhados no cérebro humano. Para melhor perceber a função deste resíduo e a contribuição para a localização da TAU, analisámos células SH-SY5Y indiferenciadas e células diferenciadas, pela adição de ácido retinoico (RA). O tratamento com RA aumentou a expressão de TAU fosforilada na Thr231 (TAUpThr231) conforme determinado por Western blot. Explorámos ainda a fosforilação da TAU por imunocitoquímica e percebemos que em células SH-SY5Y indiferenciadas, a phosphoTAU231 estava localizada principalmente no núcleo. Em contraste, TAU e phosphoTAU231 foram redistribuídas para as dendrites e citosol das células SH-SY5Y diferenciadas pelo ácido retinoico (RA). Para avaliar o potencial deste resíduo como biomarcador; medimos TAUpThr231 em CSF por meio de um imunoensaio enzimático em sanduíche e observámos que a proporção de níveis de TAUpThr231 / TAU discriminou de forma significativa o grupo AD do grupo não-AD. Essas descobertas podem indicar que os níveis da relação TAUpThr231 / t-TAU podem ser um marcador valioso para o diagnóstico clínico de AD, independentemente da idade e do género

Authenticated file broadcast protocol

The File Broadcast Protocol (FBP) was developed as a part of the DETIboot system. DETIboot allows a host to broadcast an operating system image through an 802.11 wireless network to an arbitrary number of receivers. Receivers can load the image and immediately boot a Linux live session. The initial version of FBP had no security mechanisms. In this paper we present an authentication protocol developed for FBP that ensures a correct file distribution from the intended source to the receivers. The performance valuations have shown that, with the best operational configuration tested, the file download time is increased by less than 5%

Caracterización mecánica y a fractura de películas de LDPE y LDPE/PS

El objetivo del siguiente estudio es la realización de un análisis sobre la influencia que tienen ciertas condiciones de procesamiento, como la relación de estirado y la altura de la línea de enfriamiento, sobre las propiedades mecánicas finales de películas de LDPE (Polietileno de Baja Densidad) y LDPE/PS (Polietileno de Baja Densidad/Poliestireno) obtenidas por extrusión por soplado. Para llevar a cabo el estudio se desarrollaron las siguientes tareas: - Preparación de una mezcla LDPE/PS con un contenido de 2.5% de PS a través de extrusión. - Se procesaron tres tipos de película con LDPE variando únicamente la velocidad de estirado de los rodillos colapsadores para una relación de soplado constante, y manteniendo fija la posición del anillo de enfriamiento. Posteriormente se soplaron otras tres películas con la mezcla LDPE/PS aplicando unas condiciones de procesamiento idénticas a las anteriores. - La caracterización de las películas obtenidas se realizó mediante los siguientes ensayos: Espectroscopia Infrarroja por Transformada de Fourier (FTIR) Dicroico, Calorimetría Diferencial de Barrido (DSC), Tracción, Desgarro, Trabajo Esencial de Fractura (EWF), y ensayos de fluidez. La adición de PS, si bien se tradujo en una mayor facilidad de montaje y estabilización de la burbuja, produjo también una reducción del caudal másico a la salida de la extrusora. Por otro lado, se observó que las condiciones de procesamiento afectaron en gran medida a la morfología, la orientación y la cristalinidad desarrollada por las películas, y estas, a su vez, provocaron diferencias importantes en las propiedades mecánicas finales obtenidas. Para las películas de LDPE/PS, puesto que presentaron líneas de enfriamiento bastante bajas y prácticamente constantes, el aumento de la relación de estirado se tradujo en una mayor anisotropía de las propiedades mecánicas a tracción y desgarro. Las películas de LDPE por otro lado, por presentar diferencias significativas en la línea de enfriamiento, la variación de los niveles de cristalinidad y el aumento de la relación de estirado, produjeron una mayor anisotropía de las propiedades mecánicas a tracción y desgarro para las condiciones de procesamiento intermedias

Novel fluid materials for CMOS photonic WDM systems

We propose a simple and low-cost WDM (Wavelength division multiplexing) system (Fig 1a) based on novel fluid materials using micro-ring multichannel filter design with in-situ, electrically and magnetically tunable, integrated 2D liquid crystal nanocomposite materials. We achieved a quality factor on the order of 10# − 10% and fine tuning within the entire C-band range.Engineering and Physical Sciences Research Council (EPSRC

Desarrollo de hormigones conductores con adición de fibras de carbono recicladas

Pla de Doctorat industrial de la Generalitat de Catalunya. Tesi en modalitat de compendi de publicacionsInside the studies of intelligent materials and considering concrete as one of the most building material used, getting new functionalities to him, would provide new uses and applications to the usual structural or facing purposes. Factor that would allow the material to evolve while maintaining its validity in new challenges that arise in infrastructure areas, such as the smart city, mobility, self-sensing of structures and other possible applications still to be developed. With this objective marked and introducing factors such as sustainability and medium-term industrialization, this thesis focuses on the use of recycled carbon fibers from products or processes, added to concrete, in order to modify its electrical properties and transform it, from one insulating material, to another with conductive properties. Therefore, based on previous studies, two concrete matrix are characterized with particular differences in the size of their aggregates. Both two matrix receive the addition of different types of carbon fiber recycled in different percentages. In a first phase, the study focuses on the characterization of the different basic properties of concrete, such as structural capacity and workability in fresh condition. The determination of electrical properties is added and established specific test typologies to evaluate, compare and analyze the effect of the different phases present in the material, on the electrical conductivity of all combinations of proposed mixes. Subsequently, focusing on the combinations of matrix, type and quantity of fiber with better conductive properties, deeper electrical characterization is done, contrasting it with associated functionalities such as the piezoelectric effect and the Joule effect. Functionalities that govern the self-sensing and self-heating of concrete applications such as the control of deformations of structures or pavements with de-icing effect. Finally, the material developed in a full-scale pilot test is applied, in which the functionality of self-heating is tested in an element of urban furniture by the company ESCOFET 1886 S.A., which has participated in the realization of this doctoral thesis inside the framework of the Industrial Doctoral Program of the Generalitat de Catalunya.Dentro del ámbito de los materiales inteligentes y considerando el hormigón como uno de los principales materiales de la construcción, conseguir dotarle de nuevas funcionalidades le proporcionaría nuevos usos y aplicaciones a las meramente estructurales o de revestimiento habituales. Factor que permitiría evolucionar el material manteniendo su vigencia ante nuevos retos que se plantean en ámbitos de las infraestructuras, como la ciudad inteligente, movilidad, sensorización de estructuras y otras aplicaciones posibles todavía por desarrollar. Con este objetivo marcado e introduciendo factores como la sostenibilidad y una industrialización a medio plazo, esta tesis se centra en la utilización de fibras de carbono recicladas de productos o procesos, adicionadas al hormigón, con el fin de modificar sus propiedades eléctricas y transformarlo de un material aislante a otro con propiedades conductivas. Por ello y basándose en estudios previos, se caracterizan dos matrices de hormigón con marcadas diferencias en lo que refiere al tamaño de sus agregados, que reciben la adición de diferentes tipos de fibra de carbono recicladas en distintos porcentajes. En una primera fase, el estudio se centra en la caracterización de las diferentes propiedades básicas del hormigón, como la capacidad estructural o trabajabilidad en estado fresco, a la que se añade la determinación de las propiedades eléctricas a la vez que se establecen tipologías de ensayo específicos con los que poder evaluar, comparar y analizar el efecto de las diferentes fases presentes en el material en la conductividad eléctrica de todas las combinaciones de dosificaciones propuestas. Posteriormente, focalizándose en las combinaciones de matriz, tipo y cantidad de fibra con mejores propiedades conductivas, se profundiza en la caracterización eléctrica, contrastándola con funcionalidades asociadas como el efecto piezoeléctrico y el efecto Joule, funcionalidades que gobiernan la sensorización del hormigón y autocalentamiento en aplicaciones como el control de deformaciones de estructuras o pavimentos con efecto deshielo respectivamente. Finalmente se aplica el material desarrollado en una prueba piloto a escala real, en la que se testean la funcionalidad de autocalentamiento en un elemento de mobiliario urbano de la empresa ESCOFET 1886 S.A., que ha participado en la realización de esta tesis doctoral en el marco del Programa de Doctorado Industrial de la Generalitat de CatalunyaPostprint (published version

Italian translator formative itinerary and its didactic implications: the case of Italian as C Language within the Translation and Interpreting Degree in Spain

El presente trabajo se centra en el estudio del currículo formativo del traductor de italiano, contextualizado a través de la descripción y análisis de los planes de estudios de las universidades que ofrecen el italiano como lengua de trabajo dentro del Grado en Traducción e Interpretación. Se trata de una investigación descriptiva, de tipo censal y de carácter exploratorio cuyo objetivo principal es el de indagar acerca de las diferencias existentes, entre universidades, para la formación respecto a una misma lengua. Esta irregularidad se hace patente, sobre todo, en el carácter del itinerario en sí (Lengua C, Lengua D o equivalente, con asignaturas de traducción), los tipos de asignaturas que se ofertan y los créditos de lengua que el estudiante recibe.The present work focuses on the study of the Italian translator curriculum within the Translation and Interpreting degree, contextualized through the description and analysis of the study plans of the Spanish universities offering this language. This is a descriptive, exploratory and census research whose main aim is to examine the existing differences, among universities, when it comes to train translators whose working language is the same. This irregularity is clearly visible, particularly, in the nature of the language itinerary itseld (C Language, D Language or equivalent, with translation subjects), the type of subjects offered and the language credits that the students receives

Association of albumin or protamine to lipoplexes: enhancement of transfection and resistance to serum

The successful application of gene therapy depends on the availability of carriers to efficiently deliver genetic material into target cells. Such efficacy is strongly related to key parameters including serum resistance and protection of DNA.The complexes were tested in terms of their biological activity, in the absence or presence of serum, by following transfection activity. Interaction with plasma proteins was evaluated by immunoblotting, while cytotoxicity was assessed by the Alamar Blue assay. Extent of DNA protection was determined both by using ethidium bromide intercalation and DNase I digestion assays.Our results show that, depending on the charge ratio and on the lipid composition, albumin and protamine can be used (either individually or co-associated) to generate cationic liposome/DNA complexes fulfilling in vivo requirements, while exhibiting high levels of transfection activity. In the present work a novel cationic lipid was tested. It was demonstrated that 1-palmitoyl-2-oleoyl-sn-glycero-3-ethylphosphocholine (EPOPC):cholesterol (Chol) liposomes constitute a very promising carrier for gene delivery as illustrated by their enhancing effect on transfection, as compared with DOTAP-containing liposomes. Moreover, the biological activity of EPOPC-containing complexes is significantly improved upon association of albumin, even in the presence of 60% serum (namely for the 4/1 lipid/DNA charge ratio). Nevertheless, our studies also show that transfection activity mediated by DOTAP-containing complexes can be significantly enhanced upon pre-condensation of DNA with protamine.Co-association of HSA and protamine to lipoplexes ensures a high degree of DNA protection and results in high levels of transfection activity even in the presence of serum. Copyright © 2004 John Wiley & Sons, Ltd