Mechanical response of low density expanded polypropylene foams in compression and tension at different loading rates and temperatures

Polymer foams are often used for impact mitigation and protection due to low weight and excellent energy absorbing capability. Depending on the application, different loading rates and environmental conditions can be expected, including various operating temperatures. In this paper, experimental results from mechanical testing of expanded polypropylene (EPP) are presented, focusing on temperature and rate dependence. The compressive and tensile responses of two EPP foams of similar nominal density (30 kg/m3) but different morphology are compared. Both foams were tested in compression at low to intermediate strain rates (10 3 to 100s 1) to determine the strain rate dependence. The temperature dependence of one foam type was quantified in both compression and tension for temperatures between 30°C and 60°C in order to highlight the importance of operating temperature. It was found that both strain rate and temperature have a definitive effect on the mechanical properties. The morphology of the two EPP foams also seems to affect the response.The present work has been carried out with financial support from Centre of Advanced Structural Analysis (CASA), Centre for Research-based Innovation, at the Norwegian University of Science and Technology (NTNU) and the Research Council of Norway through project no. 237885 (CASA).publishedVersio

Os custos da aterosclerose em Portugal

Copyright © 2020 Sociedade Portuguesa de Cardiologia. Published by Elsevier España, S.L.U. All rights reserved.© 2020 Sociedade Portuguesa de Cardiologia. Published by Elsevier Espa ̃na, S.L.U. This is an open access article under the CC-BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).Introduction and objectives: Cardiovascular disease is the leading cause of death in Portugal and atherosclerosis is the most common underlying pathophysiological process. The aim of this study was to quantify the economic impact of atherosclerosis in Portugal by estimating disease-related costs. Methods: Costs were estimated based on a prevalence approach and following a societal perspective. Three national epidemiological sources were used to estimate the prevalence of the main clinical manifestations of atherosclerosis. The annual costs of atherosclerosis included both direct costs (resource consumption) and indirect costs (impact on population productivity). These costs were estimated for 2016, based on data from the Hospital Morbidity Database, the health care database (SIARS) of the Regional Health Administration of Lisbon and Tagus Valley including real-world data from primary care, the 2014 National Health Interview Survey, and expert opinion. Results: The total cost of atherosclerosis in 2016 reached 1.9 billion euros (58% and 42% of which was direct and indirect costs, respectively). Most of the direct costs were associated with primary care (55%), followed by hospital outpatient care (27%) and hospitalizations (18%). Indirect costs were mainly driven by early exit from the labor force (91%). Conclusions: Atherosclerosis has a major economic impact, being responsible for health expenditure equivalent to 1% of Portuguese gross domestic product and 11% of current health expenditure in 2016.info:eu-repo/semantics/publishedVersio

Activation of PKA via asymmetric allosteric coupling of structurally conserved cyclic nucleotide binding domains

Cyclic nucleotide-binding (CNB) domains allosterically regulate the activity of proteins with diverse functions, but the mechanisms that enable the cyclic nucleotide-binding signal to regulate distant domains are not well understood. Here we use optical tweezers and molecular dynamics to dissect changes in folding energy landscape associated with cAMP-binding signals transduced between the two CNB domains of protein kinase A (PKA). We find that the response of the energy landscape upon cAMP binding is domain specific, resulting in unique but mutually coordinated tasks: one CNB domain initiates cAMP binding and cooperativity, whereas the other triggers inter-domain interactions that promote the active conformation. Inter-domain interactions occur in a stepwise manner, beginning in intermediate-liganded states between apo and cAMP-bound domains. Moreover, we identify a cAMP-responsive switch, the N3A motif, whose conformation and stability depend on cAMP occupancy. This switch serves as a signaling hub, amplifying cAMP-binding signals during PKA activation

Uma subtilase serina protease adaptada ao frio: produção, purificação e aplicação

Dissertação de mestrado em Genética MolecularVPRp é uma subtilase serina protease isolada da bactéria gram-negativa psicrofílica Vibrio sp. PA-44. Devido a partilhar homologia com proteinase K, possui o potencial para uma ampla especificidade de substratos. Tais características sugerem um elevado potencial para uso em várias aplicações, entre as quais a decomposição eficiente de biomassa rica em proteínas. Atualmente, esta protease é produzida em E. coli por produção batch e o presente estudo objetivou otimizar o processo de produção batch e avaliar o papel das principais variáveis do processo na produtividade de VPRp. Além disso, a proteína foi purificada e investigada para uso na quebra de um substrato de proteína insolúvel. Estudos preliminares de vários meios e seus componentes sugeriam 2xYT como o meio de escolha devido à compatibilidade com cálcio, conforme necessário para a estabilidade de VPRp e altos níveis de produção. Para otimização do processo de produção, uma técnica estatística multivariada, nomeadamente, metodologia de superfície de resposta (MSR) com um projeto composto central (PCC), foi aplicada para desenho experimental, modelagem estatística, avaliação do modelo aplicado, avaliação de variáveis de processo e identificação das condições do processo para produção máxima de VPRp. Os efeitos das variáveis de processo: concentração de IPTG, tempo de indução e período de indução foram estudados e um modelo quadrático com um valor de p <0,01 foi aplicado para descrever o conjunto de dados e prever a variável de resposta. O tempo de indução e o período de indução mostraram-se críticos para a produção de VPRp. Utilizando o modelo quadrático, as condições ótimas das variáveis do processo foram identificadas como indução com 1,35 mM de IPTG a 15,2 h de incubação durante um período de indução de 34,4 h. Um protocolo de purificação de três etapas foi desenvolvido para purificar VPRp produzido intracelularmente e possibilitou a obtenção de 217 mg de protease pura por litro de cultura de produção. Uma investigação comparativa da atividade de VPRp na solubilização de substrato de proteína insolúvel indicou maior atividade com esta enzima em comparação com três proteases comerciais. Foi 1,7 vezes mais ativa que a sua homóloga mesofílica proteinase K sob as condições de temperatura moderada (25 °C) utilizadas, enquanto as outras proteases demonstraram apenas atividade residual ou nenhuma atividade. Tais observações são promissoras para estudos futuros.VPRp is a subtilisin-like serine protease isolated from the psychrophilic gram-negative bacterium Vibrio sp. PA-44 and characterised by a high activity at low to moderate temperatures and, due to homology to proteinase K, potentially a broad substrate specificity. Such attributes indicate its potential for use in various applications, among which is the efficient breakdown of protein rich biomass. Presently, this protease is produced in E. coli by batch production and the current study aimed to optimise the batch production process and evaluate the role of key process variables in VPRp productivity. In addition, the protein was to be purified and investigated for use in the breakdown of an insoluble protein substrate. Preliminary investigations of various media and media components suggested 2xYT as the medium of choice due to compatibility with calcium, as required for VPRp stability, and high VPRp production levels. For optimisation of the production process, a multivariate statistical technique, namely, response surface methodology (RSM) with a central composite design (CCD), was employed for experimental design, statistical modelling, evaluation of the applied model, evaluation of process variables and identification of process conditions for maximum VPRp production. The effects of the process variables: IPTG concentration, time of induction and induction period were studied and a quadratic model with a p-value of < 0.01 applied to describe the dataset and predict the response variable. The time of induction and induction period were shown to be critical for VPRp production. Using the quadratic model, the optimum process variable conditions were identified as induction with 1.35 mM IPTG at 15.2 h incubation for a 34.4 h induction period. An abridged three-step purification protocol was developed to purify intracellularly produced VPRp and enabled the obtention of 217 mg of pure protease per litre of production culture. A comparative investigation of VPRp activity in solubilising an insoluble protein substrate indicated highest activity with this enzyme as compared to three commercial protease preparations. It was 1.7-fold more active than its mesophilic homolog proteinase K under the moderate temperature (25 °C) conditions used, while the other proteases only demonstrated residual or no activity. Such observations show promise for future studies and may be resultant of the high activity cold adapted characteristics of VPRp combined with a broad substrate specificity

Electronic health records-based research in Cardiology: The time has come for pragmatic trials

Randomized clinical trials (RCTs) are the cornerstone of evidence-based medicine, as they minimize bias in the allocation of interventions. However, RCTs performed in a very selective population and overcontrolled conditions may impair the generalizability of results. Moreover, increasing running costs and regulatory complexity compromise the conduct of these studies. The need for pragmatic trial designs, with streamlined procedures and low running costs, will shape the short-term future of research in RCTs.Electronic health records (EHR) are routinely collected as part of the treatment of patients. These provide large amounts of data at no significant cost. The so-called “real-world data” are often used in observational studies with unavoidable bias. However, by combining the randomization of large numbers of patients with the data collected in EHRs, it is possible to answer very relevant clinical questions at a relatively low cost.In this review, we describe how the integration of EHR and randomization is fostering innovative approaches to the conduct of RCTs in Cardiology. Resumo: Os ensaios clínicos randomizados (ECR) são o fundamento da medicina baseada na evidência, garantindo que o efeito observado de uma determinada intervenção depende apenas da alocação das intervenções. Contudo, os ECR são geralmente conduzidos em populações muito selecionadas e em condições extremamente controladas, o que pode limitar a generalização dos seus resultados. Além disso, os elevados custos e a complexidade regulamentar associada aos ECR representam barreiras significativas à sua execução. A necessidade de ensaios pragmáticos, com procedimentos simplificados e custos operacionais reduzidos, está a moldar o futuro da investigação em ECR.Os registos de saúde eletrónicos (RSE), realizados por motivos clínicos ou administrativos, oferecem uma vasta quantidade de dados sem custos adicionais significativos. Os «dados do mundo real» são frequentemente utilizados em estudos observacionais, mas estes, embora revelando associações e levantando hipótese de estudo, têm como maior limitação a existência de fatores confundidores desconhecidos, para os quais não é possível fazer ajustamento. A combinação da randomização de um grande número de doentes com os dados recolhidos através dos RSE permite responder a questões clínicas pertinentes a um custo significativamente mais baixo e com menor sobrecarga das equipas de investigação e dos participantes.Esta revisão descreve como a integração dos RSE e da randomização está a promover abordagens inovadoras na realização de ECR pragmáticos em Cardiologia, potencialmente revolucionando a forma como esses estudos são conduzidos e melhorando a sua aplicabilidade clínica

Mechanical response of low density expanded polypropylene foams in compression and tension at different loading rates and temperatures

Polymer foams are often used for impact mitigation and protection due to low weight and excellent energy absorbing capability. Depending on the application, different loading rates and environmental conditions can be expected, including various operating temperatures. In this paper, experimental results from mechanical testing of expanded polypropylene (EPP) are presented, focusing on temperature and rate dependence. The compressive and tensile responses of two EPP foams of similar nominal density (30 kg/m3) but different morphology are compared. Both foams were tested in compression at low to intermediate strain rates (10 3 to 100s 1) to determine the strain rate dependence. The temperature dependence of one foam type was quantified in both compression and tension for temperatures between 30°C and 60°C in order to highlight the importance of operating temperature. It was found that both strain rate and temperature have a definitive effect on the mechanical properties. The morphology of the two EPP foams also seems to affect the response

Mechanical response of low density expanded polypropylene foams in compression and tension at different loading rates and temperatures

Polymer foams are often used for impact mitigation and protection due to low weight and excellent energy absorbing capability. Depending on the application, different loading rates and environmental conditions can be expected, including various operating temperatures. In this paper, experimental results from mechanical testing of expanded polypropylene (EPP) are presented, focusing on temperature and rate dependence. The compressive and tensile responses of two EPP foams of similar nominal density (30 kg/m3) but different morphology are compared. Both foams were tested in compression at low to intermediate strain rates (10 3 to 100s 1) to determine the strain rate dependence. The temperature dependence of one foam type was quantified in both compression and tension for temperatures between 30°C and 60°C in order to highlight the importance of operating temperature. It was found that both strain rate and temperature have a definitive effect on the mechanical properties. The morphology of the two EPP foams also seems to affect the response

Recent Strategies in the Nucleophilic Dearomatization of Pyridines, Quinolines, and Isoquinolines

Dearomatization reactions have become fundamental chemical transformations in organic synthesis since they allow for the generation of three-dimensional complexity from two-dimensional precursors, bridging arene feedstocks with alicyclic structures. When those processes are applied to pyridines, quinolines, and isoquinolines, partially or fully saturated nitrogen heterocycles are formed, which are among the most significant structural components of pharmaceuticals and natural products. The inherent challenge of those transformations lies in the low reactivity of heteroaromatic substrates, which makes the dearomatization process thermodynamically unfavorable. Usually, connecting the dearomatization event to the irreversible formation of a strong C-C, C-H, or C-heteroatom bond compensates the energy required to disrupt the aromaticity. This aromaticity breakup normally results in a 1,2- or 1,4-functionalization of the heterocycle. Moreover, the combination of these dearomatization processes with subsequent transformations in tandem or stepwise protocols allows for multiple heterocycle functionalizations, giving access to complex molecular skeletons. The aim of this review, which covers the period from 2016 to 2022, is to update the state of the art of nucleophilic dearomatizations of pyridines, quinolines, and isoquinolines, showing the extraordinary ability of the dearomative methodology in organic synthesis and indicating their limitations and future trends