Development of human central nervous system 3D in vitro models for preclinical research

Neurological disorders are a major concern in modern societies, with increasing prevalence mainly related with the higher life expectancy. Most of the current available therapeutic options can only control and ameliorate the patients’ symptoms, often be-coming refractory over time. Therapeutic breakthroughs and advances have been hampered by the lack of accurate central nervous system (CNS) models. The develop-ment of these models allows the study of the disease onset/progression mechanisms and the preclinical evaluation of novel therapeutics. This has traditionally relied on genetically engineered animal models that often diverge considerably from the human phenotype (developmentally, anatomically and physiologically) and 2D in vitro cell models, which fail to recapitulate the characteristics of the target tissue (cell-cell and cell-matrix interactions, cell polarity). The in vitro recapitulation of CNS phenotypic and functional features requires the implementation of advanced culture strategies that enable to mimic the in vivo struc-tural and molecular complexity. Models based on differentiation of human neural stem cells (hNSC) in 3D cultures have great potential as complementary tools in preclinical research, bridging the gap between human clinical studies and animal models. This thesis aimed at the development of novel human 3D in vitro CNS models by integrat-ing agitation-based culture systems and a wide array of characterization tools. Neural differentiation of hNSC as 3D neurospheres was explored in Chapter 2. Here, it was demonstrated that human midbrain-derived neural progenitor cells from fetal origin (hmNPC) can generate complex tissue-like structures containing functional dopaminergic neurons, as well as astrocytes and oligodendrocytes. Chapter 3 focused on the development of cellular characterization assays for cell aggregates based on light-sheet fluorescence imaging systems, which resulted in increased spatial resolu-tion both for fixed samples or live imaging. The applicability of the developed human 3D cell model for preclinical research was explored in Chapter 4, evaluating the poten-tial of a viral vector candidate for gene therapy. The efficacy and safety of helper-dependent CAV-2 (hd-CAV-2) for gene delivery in human neurons was evaluated, demonstrating increased neuronal tropism, efficient transgene expression and minimal toxicity. The potential of human 3D in vitro CNS models to mimic brain functions was further addressed in Chapter 5. Exploring the use of 13C-labeled substrates and Nucle-ar Magnetic Resonance (NMR) spectroscopy tools, neural metabolic signatures were evaluated showing lineage-specific metabolic specialization and establishment of neu-ron-astrocytic shuttles upon differentiation. Chapter 6 focused on transferring the knowledge and strategies described in the previous chapters for the implementation of a scalable and robust process for the 3D differentiation of hNSC derived from human induced pluripotent stem cells (hiPSC). Here, software-controlled perfusion stirred-tank bioreactors were used as technological system to sustain cell aggregation and dif-ferentiation. The work developed in this thesis provides practical and versatile new in vitro ap-proaches to model the human brain. Furthermore, the culture strategies described herein can be further extended to other sources of neural phenotypes, including pa-tient-derived hiPSC. The combination of this 3D culture strategy with the implemented characterization methods represents a powerful complementary tool applicable in the drug discovery, toxicology and disease modeling.

Depois de Orpheu : 1916-1935

O objetivo deste trabalho era verificar como, nos jornais e revistas, o Primeiro Modernismo tinha sido acolhido. Depois do escândalo de Orpheu e da forma agressiva como os seus colaboradores tinham sido recebidos, cabia verificar se tinha havido, ou não, uma evolução na análise da sua obra ao longo dos anos, de 1916 a 1935, tanto mais que as vidas de cada um destes tinha evoluído de forma diferenciada. As mortes prematuras de uns, a subida a postos de influência e poder, ou a longevidade de outros foram fatores que poderiam ter condicionado a evolução da crítica jornalística. Por um lado, os críticos poderiam ter alterado a sua visão face a estes criadores, podendo o tempo ter funcionado a favor destes. O que em 1915 era estranho e bizarro poderia em 1935 ser inédito e original. Por outro lado, a conjuntura política poderia condicionar não só a criação artística, mas também o seu enquadramento social. Em 1915, a guerra entre monárquicos e republicanos foi marcada pelas referências a Orpheu. Mais tarde com a ditadura militar e a ascensão do Estado Novo poderão os nossos artistas voltar a ser alvo de referências políticas. A verdade é que tal não acontece. O poder político menospreza-os, apesar de nalguns casos terem uma participação ativa nas suas fileiras. A verdade é que os autores mais importantes e significativos foram, pouco a pouco, e com o passar dos anos, integrados na sociedade literária e começaram a ser vistos como criadores a ter em conta, senão mesmo de referência. O seu aparecimento em jornais e revistas na qualidade de escritores, jornalistas, artistas plásticos ou mesmo críticos fez com que estivessem sob os holofotes da imprensa e como tal sujeitos a uma análise permanente. E esta foi-se alterando com o passar do tempo e com o reconhecimento dos mesmos. Hoje ninguém duvida do seu valor, mas entre 1915 (data da publicação de Orpheu e 1935 (ano da morte de Pessoa) todos eram vistos como loucos, jovens com alguma habilidade para a escrita, promessas do panorama literário e finalmente, em alguns casos, motivos de orgulho para o nosso património artístico. Só uma leitura dos periódicos mais relevantes permitiria estudar a receção do nosso Primeiro Modernismo. E foi esse o objetivo desta tese.

Research posters’ eBook: according to 1st WORKSHOP with “Focus on experimental testing of cement based materials”

COST Action TU 1404

Typology based method for choosing old masonry walls inspection procedures

The diagnosis of historic masonry walls is an intricate and complex field and has been an object of research for many years. This paper aims to propose practical methodologies for the diagnosis of historic masonry walls, specifically based on their typological characteristics. In order to develop such procedures, information relating to historic masonry typologies in Portugal, classified as rural, urban and military was gathered and techniques for the assessment of historic masonry were studied. All information was integrated to develop a pattern typology oriented methodology. Developed methodology was tested and validated in a small diagnosis campaign carried out in the Guimarães Castle. Methodology was proven to be advantageous and although the study is limited and focused on the Portuguese architectural specificities, it still holds global classifications, and therefore can be useful for any diagnosis procedure of a historic masonry wall.

Exploring the potentialities of a new type of CFRP laminate for the simultaneous flexural and shear strengthening of RC beams: numerical research

This study aims to develop an innovative carbon fibre reinforced polymer (CFRP) laminate with a U configuration to address strengthening interventions, where the increment of both flexural and shear capacity of reinforced concrete (RC) elements is required. This strengthening solution combines the near surface mounted (NSM) and embedded through section (ETS) techniques in the same application, since these techniques have already evidenced high performance on flexural and shear strengthening of RC beams using FRP systems, respectively. In fact, the proposed hybrid technique aims to mobilize the advantages provided by these two strengthening techniques by using an innovative CFRP laminate. The strengthening efficacy of this new hybrid NSM/ETS technique was numerically assessed and compared to the corresponding efficiency of NSM and ETS techniques applied separately for the flexural and shear strengthening of RC beams, respectively. The numerical models are described and the main relevant results are presented and discussed.

High performance fiber reinforced concrete for the shear reinforcement: experimental and numerical research

High performance fiber reinforced concrete (HPFRC) is developing rapidly to a modern structural material with unique rheological and mechanical characteristics. Despite applying several methodologies to achieve self15 compacting requirements, some doubts still remain regarding the most convenient strategy for developing a HPFRC. In the present study, an innovative mix design method is proposed for the development of high17 performance concrete reinforced with a relatively high dosage of steel fibers. The material properties of the developed concrete are assessed, and the concrete structural behavior is characterized under compressive, flexural and shear loading. This study better clarifies the significant contribution of fibers for shear resistance of concrete elements. This paper further discusses a FEM-based simulation, aiming to address the possibility of calibrating the constitutive model parameters related to fracture modes I and II.

Assessment of the effectiveness of steel fibre reinforcement for the punching resistance of flat slabs by experimental research and design approach

The present paper deals with the experimental assessment of the effectiveness of steel fibre reinforcement in terms of punching resistance of centrically loaded flat slabs, and to the development of an analytical model capable of predicting the punching behaviour of this type of structures. For this purpose, eight slabs of 2550 x 2550 x 150 mm3 dimensions were tested up to failure, by investigating the influence of the content of steel fibres (0, 60, 75 and 90 kg/m3) and concrete strength class (50 and 70 MPa). Two reference slabs without fibre reinforcement, one for each concrete strength class, and one slab for each fibre content and each strength class compose the experimental program. All slabs were flexurally reinforced with a grid of ribbed steel bars in a percentage to assure punching failure mode for the reference slabs. Hooked ends steel fibres provided the unique shear reinforcement. The results have revealed that steel fibres are very effective in converting brittle punching failure into ductile flexural failure, by increasing both the ultimate load and deflection, as long as adequate fibre reinforcement is assured. An analytical model was developed based on the most recent concepts proposed by the fib Mode Code 2010 for predicting the punching resistance of flat slabs and for the characterization of the behaviour of fibre reinforced concrete. The most refined version of this model was capable of predicting the punching resistance of the tested slabs with excellent accuracy and coefficient of variation of about 5%.

Risk assessment in a research laboratory during sol–gel synthesis of nano-TiO2

The occupational risks in the nanotechnology research laboratories are an important topic since a great number of researchers are involved in this area. The risk assessment performed by both qualitative and quantitative methods is a necessary step for the management of the occupational risks. Risk assessment could be performed by qualitative methods that gather consensus in the scientific community. It is also possible to use quantitative methods, based in different technics and metrics, as indicative exposure limits are been settled by several institutions. While performing the risk assessment, the information on the materials used is very important and, if it is not updated, it could create a bias in the assessment results. The exposure to TiO2 nanoparticles risk was assessed in a research laboratory using a quantitative exposure method and qualitative risk assessment methods. It was found the results from direct-reading Condensation Particle Counter (CPC) equipment and the CB Nanotool seem to be related and aligned, while the results obtained from the use of the Stoffenmanager Nano seem to indicate a higher risk level.

Design of a case-based reasoner for information security in military organizations

Information security is concerned with the protection of information, which can be stored, processed or transmitted within critical information systems of the organizations, against loss of confidentiality, integrity or availability. Protection measures to prevent these problems result through the implementation of controls at several dimensions: technical, administrative or physical. A vital objective for military organizations is to ensure superiority in contexts of information warfare and competitive intelligence. Therefore, the problem of information security in military organizations has been a topic of intensive work at both national and transnational levels, and extensive conceptual and standardization work is being produced. A current effort is therefore to develop automated decision support systems to assist military decision makers, at different levels in the command chain, to provide suitable control measures that can effectively deal with potential attacks and, at the same time, prevent, detect and contain vulnerabilities targeted at their information systems. The concept and processes of the Case-Based Reasoning (CBR) methodology outstandingly resembles classical military processes and doctrine, in particular the analysis of “lessons learned” and definition of “modes of action”. Therefore, the present paper addresses the modeling and design of a CBR system with two key objectives: to support an effective response in context of information security for military organizations; to allow for scenario planning and analysis for training and auditing processes.

Validação de design de armazém automatizado com uso de simulação discreta

Dissertação de mestrado em Engenharia de Sistemas

Development of computational tools for the integrated analysis of DNA microarray data with applications in cancer research

The MAP-i Doctoral Program of the Universities of Minho, Aveiro and Porto

FOSTER: facilitate open science training for european research

FOSTER aims to support different stakeholders, especially young researchers, in adopting open access in the context of the European Research Area (ERA) and in complying with the open access policies and rules of participation set out for Horizon 2020 (H2020). FOSTER establish a European-wide training programme on open access and open data, consolidating training activities at downstream level and reaching diverse disciplinary communities and countries in the ERA. The training programme includes different approaches and delivery options: elearning, blearning, self-learning, dissemination of training materials/contents, helpdesk, face-to-face training, especially training-the-trainers, summer schools, seminars, etc.

Introduction to special Issue: future priorities in European media and communication research

(Excerto) The European Journal of Communication seeks to present the best in current research in the broad field of media and communication research. Irregularly, we seek to take stock by inviting a small group of leading scholars to present their work at a symposium on a common theme, which then forms the basis for a Special Issue of the Journal. In 2014, the European Science Foundation (ESF) published one of their ‘Forward Looks’ entitled Media in Europe: New Questions for Research and Policy. We subsequently invited several of the Forward Look’s authors to meet and discuss their work with us at a symposium hosted by the European University Cyprus, and the discussion and revised papers that resulted are published here.

Climate change research and policy in Portugal

This article offers a review of research and policy on climate change in Portugal and is organized into three main themes: scientific knowledge and assessment of climate change; policy analysis and evaluation; and public engagement. Modern scientific research on meteorology and climatology started in Portugal in the 1950s and a strong community of researchers in climate science, vulnerabilities, impacts, and adaptation has since developed, particularly in the last decade. Nevertheless, there are still many gaps in research, especially regarding the economic costs of climate change in Portugal and costs and benefits of adaptation. Governmental policies with a strong emphasis on mitigation were introduced at the end of the 1990s. As greenhouse gas emissions continued to rise beyond its Kyoto target for 2012, the country had to resort to the Kyoto Flexibility Mechanisms in order to comply. Climate change adaptation policies were introduced in 2010 but are far from being fully implemented. Regarding public engagement with climate change, high levels of concern contrast with limited understanding and rather weak behavioral dispositions to address climate change. Citizens display a heavy reliance on the media as sources of information, which are dominated by a techno-managerial discourse mainly focused on the global level. The final part of the article identifies research gaps and outlines a research agenda. Connections between policy and research are also discussed