Sviluppo e ottimizzazione di modelli strutturali per ponti ferroviari in soluzione composta acciaio-calcestruzzo nelle nuove linee ad Alta Velocità

La tesi tratta l'analisi delle metodologie per la modellazione delle nuove strutture in soluzione composta acciaio-calcestruzzo impiegate nelle linee ad Alta Velocità, ed i possibili metodi di calibrazione dei modelli utilizzati. Alcune di queste metodologie sono applicate ad un caso studio, costituito dal ponte ferroviario sul fiume Sesia. Il fine ultimo di tale studio è stato quello di riuscire a simulare numericamente il reale comportamento dinamico del ponte in sezione mista

Chapter Biomarkers in Rare Genetic Diseases

Today, as the need of new regenerative solutions is steadily increasing, the demand for new bio-devices with smart functionality is pushing material scientists to develop new synthesis concepts. Indeed, the conventional approaches for biomaterials fail when it comes to generate nano-biocomposites with designed biomimetic composition and hierarchically organized architecture mimicking biologically relevant tissue features. In this respect, an emerging concept in material science is to draw inspiration from natural processes and products, which we may consider as the most advanced examples of smart nanotechnology. Natural processes of supramolecular assembly and mineralization of organic macromolecules, known as biomineralization, generate complex hybrid 3D constructs that are the basis of skeletons, exoskeletons, nacre and shells. On the other hand, natural structures such as woods and plants exhibit multi-scale hierarchic organization that is the source of smart and anisotropic mechanical properties associated with high porosity and lightness. The association of nature-inspired nano-technological products with smart functionalization can provide new advanced solutions to critical and still unmet clinical needs. In this respect, magnetic activation of biomaterials by the use of a recently developed biocompatible, resorbable magnetic apatite promises to represent a new safe and effective switching tool, enabling personalized applications in regenerative medicine and theranostics that so far were not feasible, due to the cytotoxicity of the currently used magnetic materials

Biomarkers in Rare Genetic Diseases

Biomarkers offer a way to speed up medical research by shedding light on the physiopathological mechanisms of disease. Furthermore, biomarkers are considered invaluable tools for monitoring disease progression, prognosis, and response to drugs, especially in clinical trials, where they can be used to assess the efficacy, efficiency, and side effects of novel drugs

The medical genetics of dystrophinopathies: Molecular genetic diagnosis and its impact on clinical practice

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Duchenne muscular dystrophy: From diagnosis to therapy

Duchenne muscular dystrophy (DMD) is an X-linked inherited neuromuscular disorder due to mutations in the dystrophin gene. It is characterized by progressive muscle weakness and wasting due to the absence of dystrophin protein that causes degeneration of skeletal and cardiac muscle. The molecular diagnostic of DMD involves a deletions/duplications analysis performed by quantitative technique such as microarray-based comparative genomic hybridization (array-CGH), Multiple Ligation Probe Assay MLPA. Since traditional methods for detection of point mutations and other sequence variants require high cost and are time consuming, especially for a large gene like dystrophin, the use of next-generation sequencing (NGS) has become a useful tool available for clinical diagnosis. The dystrophin gene is large and finely regulated in terms of tissue expression, and RNA processing and editing includes a variety of fine tuned processes. At present, there are no effective treatments and the steroids are the only fully approved drugs used in DMD therapy able to slow disease progression. In the last years, an increasing variety of strategies have been studied as a possible therapeutic approach aimed to restore dystrophin production and to preserve muscle mass, ameliorating the DMD phenotype. RNA is the most studied target for the development of clinical strategies and Antisense Oligonucleotides (AONs) are the most used molecules for RNA modulation. The identification of delivery system to enhance the efficacy and to reduce the toxicity of AON is the main purpose in this area and nanomaterials are a very promising model as DNA/RNA molecules vectors. Dystrophinopathies therefore represent a pivotal field of investigation, which has opened novel avenues in molecular biology, medical genetics and novel therapeutic options

Methodology to accelerate diagnostic coverage assessment: MADC

Tese (doutorado) - Universidade Federal de Santa Catarina, Centro Tecnológico, Programa de Pós-Graduação em Engenharia Elétrica, Florianópolis, 2016.Os veículos da atualidade vêm integrando um número crescente de eletrônica embarcada, com o objetivo de permitir uma experiência mais segura aos motoristas. Logo, a garantia da segurança física é um requisito que precisa ser observada por completo durante o processo de desenvolvimento. O padrão ISO 26262 provê medidas para garantir que esses requisitos não sejam negligenciados. Injeção de falhas é fortemente recomendada quando da verificação do funcionamento dos mecanismos de segurança implementados, assim como sua capacidade de cobertura associada ao diagnóstico de falhas existentes. A análise exaustiva não é obrigatória, mas evidências de que o máximo esforço foi feito para acurar a cobertura de diagnóstico precisam ser apresentadas, principalmente durante a avalição dos níveis de segurança associados a arquitetura implementada em hardware. Estes níveis dão suporte às alegações de que o projeto obedece às métricas de segurança da integridade física exigida em aplicações automotivas. Os níveis de integridade variam de A à D, sendo este último o mais rigoroso. Essa Tese explora o estado-da-arte em soluções de verificação, e tem por objetivo construir uma metodologia que permita acelerar a verificação da cobertura de diagnóstico alcançado. Diferentemente de outras técnicas voltadas à aceleração de injeção de falhas, a metodologia proposta utiliza uma plataforma de hardware dedicada à verificação, com o intuito de maximizar o desempenho relativo a simulação de falhas. Muitos aspectos relativos a ISO 26262 são observados de forma que a presente contribuição possa ser apreciada no segmento automotivo. Por fim, uma arquitetura OpenRISC é utilizada para confirmar os resultados alcançados com essa solução proposta pertencente ao estado-da-arte.Abstract : Modern vehicles are integrating a growing number of electronics to provide a safer experience for the driver. Therefore, safety is a non-negotiable requirement that must be considered through the vehicle development process. The ISO 26262 standard provides guidance to ensure that such requirements are implemented. Fault injection is highly recommended for the functional verification of safety mechanisms or to evaluate their diagnostic coverage capability. An exhaustive analysis is not required, but evidence of best effort through the diagnostic coverage assessment needs to be provided when performing quantitative evaluation of hardware architectural metrics. These metrics support that the automotive safety integrity level ? ranging from A (lowest) to D (strictest) levels ? was obeyed. This thesis explores the most advanced verification solutions in order to build a methodology to accelerate the diagnostic coverage assessment. Different from similar techniques for fault injection acceleration, the proposed methodology does not require any modification of the design model to enable acceleration. Many functional safety requisites in the ISO 26262 are considered thus allowing the contribution presented to be a suitable solution for the automotive segment. An OpenRISC architecture is used to confirm the results achieved by this state-of-the-art solution

Innovative Therapeutic Approaches for Duchenne Muscular Dystrophy

Duchenne muscular dystrophy (DMD) is the most common childhood muscular dystrophy affecting ~1:5000 live male births. Following the identification of pathogenic variations in the dystrophin gene in 1986, the underlining genotype/phenotype correlations emerged and the role of the dystrophin protein was elucidated in skeletal, smooth, and cardiac muscles, as well as in the brain. When the dystrophin protein is absent or quantitatively or qualitatively modified, the muscle cannot sustain the stress of repeated contractions. Dystrophin acts as a bridging and anchoring protein between the sarcomere and the sarcolemma, and its absence or reduction leads to severe muscle damage that eventually cannot be repaired, with its ultimate substitution by connective tissue and fat. The advances of an understanding of the molecular pathways affected in DMD have led to the development of many therapeutic strategies that tackle different aspects of disease etiopathogenesis, which have recently led to the first successful approved orphan drugs for this condition. The therapeutic advances in this field have progressed exponentially, with second-generation drugs now entering in clinical trials as gene therapy, potentially providing a further effective approach to the condition

Plaeser - plataforma de emulação de soft errors visando a análise experimental de técnicas de tolerância a falhas: uma prototipação rápida utilizando FPGAs

Dissertação (mestrado) - Universidade Federal de Santa Catarina, Centro Tecnológico. Programa de Pós-Graduação em Engenharia ElétricaO constante avanço na fabricação de circuitos integrados com a miniaturização da tecnologia, o aumento da frequência de operação e a diminuição da tensão de alimentação fazem deles cada vez mais sensíveis à radiação. A preocupação com a sensibilidade de circuitos integrados não é mais restrita a projetos de aplicações espaciais onde o ambiente é mais hostil quanto à radiação. Circuitos fabricados com tecnologias em escala nanométrica são potencialmente sensíveis a partículas que se encontram na atmosfera terrestre e até no nível do mar. A importância da tolerância a falhas em semicondutores existe desde quando anomalias foram observadas no comportamento de dispositivos operando no espaço. A larga presença de circuitos integrados em diversas áreas do nosso cotidiano faz com que técnicas de tolerância a falhas ganhem importância também para aplicações terrestres. Desse modo, formas eficientes de avaliação dessas técnicas de tolerância a falhas são essenciais para lidar com essa demanda. É importante que essa avaliação possa ser realizada em etapas iniciais do projeto de circuitos integrados tolerantes à radiação de forma a reduzir o custo com locação de instalações que utilizam equipamentos de radiação induzida para verificação. Nesse contexto, o trabalho de dissertação apresenta um estudo sobre diferentes técnicas de injeção de falhas. Além do estudo, foi desenvolvida uma plataforma de emulação de soft errors (PLAESER) visando a análise experimental de técnicas de tolerância a falhas. A plataforma PLAESER provê suporte ao fluxo proposto para avaliação de técnicas de tolerância a falhas em fase inicial do projeto de circuitos robustos através da prototipação rápida em FPGAs. Os resultados obtidos com os casos de teste utilizados procuram mostrar o emprego do fluxo proposto para análise de técnicas de tolerância a falhas.The continuous improvements in the integrated circuits manufacture process considering the miniaturization of technology, increase of clock frequencies and limitation of power supply, make them more susceptible to radiation. The concern with circuit sensitivity is no longer restricted to space applications, in harsh environment. Integrated circuits manufactured with nanometric technologies are potentially sensitive to particles present in the atmosphere and also at the sea level. Fault tolerance strategies applied to semiconductors have been around since upsets were first experienced in space applications. The large usage of integrated circuits in several areas of everyday life makes fault tolerance techniques important also for terrestrial applications. Therefore, efficient hardness evaluation solutions are essential to deal with this demand. Such evaluation is important and should be performed earlier in hardened integrated circuit designs in order to reduce costs with rental of radiation facilities. In this context, this work presents a evaluation of different fault injection techniques. Moreover, a soft error emulation platform (PLAESER) has been developed in order to analyze fault tolerance techniques experimentally. PLEASER gives support to the flow proposed to evaluate fault tolerance techniques earlier in hardened circuit designs through rapid prototyping. The results obtained with the selected test cases show the employment of the proposed flow to analyze fault tolerance techniques