On the track of β-lactam resistance: Studies on the regulation of methicillinresistance in Staphylococcus aureus

Dissertação para obtenção do Grau de Doutor em BiologiaMethicillin-resistant Staphylococcus aureus (MRSA) is an important human pathogen, causing a wide range of infections. MRSA has not only developed an intrinsic resistance to all β-lactams, but has also acquired resistance to virtually all classes of antimicrobial agents. The characteristic MRSA phenotype is conferred by the presence of mecA gene which is regulated by a sensor-inducer (MecR1) and a repressor (MecI). However, mecA induction by its cognate sensor/inducer is very inefficient and, therefore, it is believed that optimal expression of β-lactam resistance in MRSA requires a non-functional MecR1-MecI system. Surprisingly, no correlation was found between the presence of functional MecR1- MecI and the level of β-lactam resistance in a representative collection of epidemic MRSA strains, suggesting the existence of other mecA regulators. In these studies, we show that the mecA regulatory locus is not a two-component system but, actually, it is a three-component system containing besides mecR1-mecI, the previously unidentified antirepressor mecR2. The crystal structure of MecR2 reveals a three-domain architecture, with an N-terminal DNA-binding-like domain, an intermediate scaffold domain, and a C-terminal dimerization domain, important to the functional dimeric oligomerization state. MecR2 disturbs the binding of the repressor MecI to the mecA promoter, which leads to its proteolytic inactivation independently from MecR1, presumably by non-specific cytoplasmatic proteases. Our data also demonstrates that in the presence of functional mecR1-mecI genes, mecR2 is essential for a robust induction of mecA transcription and, consequently, for the optimal expression of resistance phenotype in MRSA. These observations point to a revision of the current model for the transcriptional control of the mecA gene.Fundação para a Ciência e a Tecnologia - Doctoral Project (SFRH/BD/38316/2007

Seismic analysis of a Mexican viaduct with nonlinear modelling of soil-structure interaction

Every day the need to understand earthquakes and how that phenomenon affects construction grows, to make it possible to prevent and minimize inherent risks to their relation. That need increases when projects are located in regions with large seismicity. Therefore, the present paper, which was developed in partnership with GEG - Gabinete de Estruturas e Geotecnia, has, as a final goal, to study and compare the variety of calculation methods available on Eurocode 8 to design and evaluate earthquake resistant structures, using a real case study. The methods approached are linear dynamic analysis, also known as spectral analysis, nonlinear static analysis, also recognized as pushover analysis, and non-linear dynamic analysis, well-known as time-history analysis. Simultaneously to the seismic analyses, it is developed a detailed study of the parameters that affect the damping of soil-structure interaction. Copyright (c) 2019 COMPDYN Proceedings. All rights reserved

Implementation of a structural monitoring network in the new stone masonry bridge in Vila Fria - Portugal

This paper reports on the case of a new stone masonry bridge fully instrumented for structuralmonitoring under service loading. Both the monitoring scope and the instrumentation actuallyinstalled are described for this singular type of new construction. The acquisition systems aswell as remote data transmission and archive are also addressed. Some preliminarymonitoring results are included

Structural design, modelling, material testing and construction of a new stone masonry arch bridge in Vila Fria, Portugal

This paper presents the main activities involved in the construction of a new stonemasonry arch bridge, the Vila Fria Bridge located in the north of Portugal, as part of a widermultidisciplinary project. The paper briefly describes the main aspects related to the design,construction, the characterization of the adopted materials and the numerical simulations tosupport the undertaken choices from the construction to the beginning of the bridge serviceconditions

Aplicações numéricas do modelo de dano a pilares ocos de betão armado

A grande motivação deste trabalho reside na particularidade do comportamento estrutural de pilares de betão armado com secção transversal oca, bastante semelhante aocomportamento de paredes estruturais, e, também, na elevada dificuldade de modelar asua resposta cíclica com ferramentas numéricas simples. De facto, os pilares ocos de pontes têm, normalmente, secções transversais com grandes dimensões e armadura longitudinal distribuída nas duas faces das paredes, assumindo assim o efeito de corte uma importância muito significativa no seu comportamento e justificando-se uma atenção especial a este aspecto quando se analisam pilares de betão armado com secção oca. Neste artigo apresenta-se a modelação numérica de alguns pilares de betão armado com secção oca ensaiados experimentalmente em resposta cíclica. Nas simulações numéricas foi adoptado o Modelo de Dano, desenvolvido na Faculdade de Engenharia da Universidade do Porto e recentemente implementado em CAST3M, envolvendo um modelo constitutivo fundamentado na Mecânica do Dano Contínuo para zonas de betão, discretizadas em elementos finitos 3D, incorporando duas variáveis escalares de dano independentes para a simulação dos mecanismos não lineares de degradação do betão sob condições de tracção e compressão e utilizando o modelo Menegotto-Pinto para a simulação do comportamento cíclico da armadura discretizada com elementos de treliça. As aplicações numéricas envolvem casos de pilares onde a flexão é dominante e outros onde o corte assume um papel principal no seu comportamento cíclico. Adicionalmente, são estudados dois tipos de disposições da armadura transversal, um representativo de pilares de pontes construídos nos anos 70, com estribo único ao longo de cada parede e sem dimensionamento sísmico, e outro seguindo as mais recentes especificações do EC8. A comparação dos resultados numéricos com as respostas experimentais evidenciou a eficiência desta modelação numérica para simular o comportamento cíclico dos pilares, quer com comportamento em flexão, quer em comportamento dominado pelo corte

Monitorização do comportamento estrutural de uma ponte nova em arcos de alvenaria de pedra

Apresenta-se o caso de uma nova ponte em alvenaria de pedra, construída de raiz, que está a ser instrumentada para monitorização do seu comportamento estrutural sob a acção de cargas de serviço. Abordam-se os objectivos da monitorização da ponte e descreve-se a instrumentação efectivamente adoptada nesta obra nova de características singulares. Refere-se os aspectos básicos do sistema de aquisição de dados. Não são apresentados resultados de registos, por não estar ainda concluída a instalação de todos os sensores

Monitoring and testing of a new stone masonry arch bridge in Vila Fria, Portugal

This paper reports on the monitoring and load testing of a new stone masonryarch bridge recently built over the river Vizela in Vila Fria, Felgueiras, located about 60 kmfrom Porto, Portugal. Besides highlighting the scientific purposes subjacent to this bridgeconstruction initiative, the paper addresses basic aspects on the installed instrumentation andprovides a general overview of sensor types, location and measured signals, as well as dataacquisition and transmission systems. Some of the most relevant result measurements obtainedfrom the load test and their comparison with available numerical analyses are also presented

Grillage Modeling Approach Applied to Simple-span Slab-girder Skewed Bridges for Dynamic Analysis

This study involves the applicability of a simplified modeling technique to simple-span slab-girder skewed bridges for dynamic analysis, based on grillage modeling strategies. To evaluate the applicability of this technique, skew angles ranging from 0° to 60° are studied. The ability to capture vibration modes of grillage models is compared with three-dimensional (3-D) finite element (FE) models, using shell and frame elements. The effect of the skew angle in the grillage modeling technique of the bridge's deck and the grillage model accuracy associated with the orientation of the transverse grillage members (TGMs) are studied. The grillage modeling technique eliminates shell elements to model the slab, reducing the number of degrees of freedom and the computational time in the bridge model, but, although its simplicity, demonstrates good ability to capture the vibration modes

Seismic Retrofit of RC Hollow-Section Piers with Shear Failure

The objective of this paper is to perform an experimental evaluation of seismic retrofit of reinforced concrete hollow piers with CFRP to prevent shear failure. The experimental campaign was carried out regarding the evaluation of: i) shear retrofit strategy efficiency and ii) the influence of different transverse reinforcement details on the shear capacity and concrete confinement. The experimental campaign has been carried out at LESE FEUP (Laboratory of Earthquake and Structural Engineering of the Faculty of Engineering of University of Porto), on a set of four RC piers with hollow section. Within the scope of this work it is also the study of design procedures for CFRP shear retrofitting and the evaluation of the associated ductility capacity improvement. Efficiency assessment is pursued for different scenarios of shear failure prevention, and the corresponding seismic response enhancement is evaluated. The most relevant experimental information is presented in the paper, as for instance the evolution of shear cracks and the illustration of the outside and inside damage pattern

Simulação numérica de ensaios cíclicos de pilares ocos com rotura por corte

Este trabalho baseia-se na simulação numérica de ensaios experimentais realizados sobrepilares de secção quadrada e rectangular oca, sendo a sua modelação numérica realizada através demodelos constitutivos refinados. O Modelo de Dano, baseado na Mecânica do Dano Contínuo,permite reproduzir o comportamento não-linear do betão armado, e o modelo Giuffré-Menegotto-Pinto simula o comportamento cíclico do aço.Os referidos pilares apresentam particular vulnerabilidade aos efeitos do corte cuja tradução pormetodologias numéricas simplificadas não encontra actualmente respostas adequadas, sendo comosabemos estes efeitos de corte muito sensível aos parâmetros associados ao comportamento emtracção do betão, nomeadamente a tensão de rotura do betão à tracção e energia de fractura. Aestratégia de modelação utilizada, recorrendo a modelos constitutivos refinados em associação a umadiscretização baseada em elementos finitos, revela-se particularmente atractiva, em especial quandoa modelação numérica se enquadra numa perspectiva de apoio à componente experimental dolaboratório, isto é, quando se pretende obter uma previsão numérica dos ensaios experimentais ecomplementarmente um apoio à interpretação dos resultados experimentais