121 research outputs found

    Preliminary results on confidence intervals for open bonus malus

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    This work was partially supported by Financiamento Base 2009 ISFL-1-297 from FCT/MCTES/PT.Considering open portfolios, we analyze bonus–malus systems (BMS) under a realistic approach, as we already did in Guerreiro and Mexia (Discuss. Math. Probab. Stat. 24(2):197–213, 2004). Using stochastic vortices model we are now able to predict long-run distribution through confidence intervals.authorsversionpublishe

    Experimental study on the seismic behavior of masonry wall-to-floor connections

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    The global structural performance of masonry buildings, under earthquake loading, is affected by the efficiency of wall-to-floor connections, since they assure the continuity of the energy path and prevent the occurrence of most of the local collapse mechanisms. In fact, out-of-plane behaviour of masonry walls observed in recent seismic events showed the critical importance of proper connections in historical buildings. A review of current literature yields little in terms of experimental and numerical data on the subject. Thus, there is an urgent need to study the behaviour of these connections. The present paper presents a series of tests carried out to characterize the wall-to-floor connections. Different specimens were constructed in laboratory to represent connections found in ‘Gaioleiro’ and Late ‘Pombalino’ buildings in downtown Lisbon. Pull-out tests of wall-to-floor connections were carried out on unstrengthened and strengthened specimens in order to study failure modes, maximum pullout forces, and corresponding displacements. These parameters allow better understanding of this type of connection and also the development of design recommendations for the strengthening

    Cure and discontinuation of treatment in a tuberculosis control state programme in Brazil: insights from dispensing data

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    Poster presented at the 45th ESCP Symposium on Clinical Pharmacy. 4-6 October 2016, Oslo, NorwayN/

    Multiple Sclerosis Patient Management During the COVID-19 Pandemic: Practical Recommendations From the Portuguese Multiple Sclerosis Study Group (GEEM)

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    The spread of the COVID-19 pandemic has imposed significant challenges on healthcare provision, requiring changes in the conventional patient management, particularly in chronic diseases like multiple sclerosis (MS). To increase patient safety and reduce the risk of infection, while ensuring an appropriate and regular follow-up, tele-medicine gained prominence as a valid alternative to face-to-face appointments. However, the urgency of the implementation and the lack of experience in most MS centers led to "ad hoc" and extremely diverse approaches, which now merit to be standardized and refined. Indeed, while tele-consultation cannot fully replace face-to-face visits, it certainly can, and will, be incorporated as part of the routine care of MS patients in the near future. Bearing this in mind, the Portuguese Multiple Sclerosis Study Group (GEEM) has developed a set of recommendations for the usage of tele-medicine in the management of MS patients, both during the pandemic and in the future. The consensus was obtained through a two-step modified Delphi methodology, resulting in 15 recommendations, which are detailed in the manuscript.The consensus and the publication of this manuscript were supported by an educational grant from Novartis Portugal to the Grupo de Estudos de Esclerose Múltipla. These funds were used to pay the work of the consultancy MOAI, which set up the online questionnaire and helped with writing the summary of the meeting and the first draft of the consensus, and the publishing fee (article processing charge). The funding source had no role in the process and did not influence, by any means, the content of the consensus or the present manuscriptinfo:eu-repo/semantics/publishedVersio

    MPV17 Mutations Are Associated With a Quiescent Energetic Metabolic Profile

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    Funding: SJ was funded by Fundação Calouste Gulbenkian. TO was supported by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany’s Excellence Strategy - EXC 2067/1- 390729940). AR and TC-O were funded by Fundação para a Ciência e a Tecnologia and European Regional Development Fund (CENTRO-01-0145-FEDER000012- HealthyAging2020), (POCI-010145-FEDER-007440), and (POCI-01-145-FEDER-29297). MS and MG were funded by UID/NEU/04539/2019 (Strategic Plan CNC.IBILI).Mutations in the MPV17 gene are associated with hepatocerebral form of mitochondrial depletion syndrome. The mechanisms through which MPV17 mutations cause respiratory chain dysfunction and mtDNA depletion is still unclear. The MPV17 gene encodes an inner membrane mitochondrial protein that was recently described to function as a non-selective channel. Although its exact function is unknown, it is thought to be important in the maintenance of mitochondrial membrane potential (ΔΨm). To obtain more information about the role of MPV17 in human disease, we investigated the effect of MPV17 knockdown and of selected known MPV17 mutations associated with MPV17 disease in vitro. We used different approaches in order to evaluate the cellular consequences of MPV17 deficiency. We found that lower levels of MPV17 were associated with impaired mitochondrial respiration and with a quiescent energetic metabolic profile. All the mutations studied destabilized the protein, resulting in reduced protein levels. We also demonstrated that different mutations caused different cellular abnormalities, including increased ROS production, decreased oxygen consumption, loss of ΔΨm, and mislocalization of MPV17 protein. Our study provides novel insight into the molecular effects of MPV17 mutations and opens novel possibilities for testing therapeutic strategies for a devastating group of disorders.publishersversionpublishe

    The fate of acetic acid during glucose co-metabolism by the spoilage yeast Zygosaccharomyces bailii

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    Zygosaccharomyces bailii is one of the most widely represented spoilage yeast species, being able to metabolise acetic acid in the presence of glucose. To clarify whether simultaneous utilisation of the two substrates affects growth efficiency, we examined growth in single- and mixed-substrate cultures with glucose and acetic acid. Our findings indicate that the biomass yield in the first phase of growth is the result of the weighted sum of the respective biomass yields on single-substrate medium, supporting the conclusion that biomass yield on each substrate is not affected by the presence of the other at pH 3.0 and 5.0, at least for the substrate concentrations examined. In vivo(13)C-NMR spectroscopy studies showed that the gluconeogenic pathway is not operational and that [2-(13)C]acetate is metabolised via the Krebs cycle leading to the production of glutamate labelled on C(2), C(3) and C(4). The incorporation of [U-(14)C]acetate in the cellular constituents resulted mainly in the labelling of the protein and lipid pools 51.5% and 31.5%, respectively. Overall, our data establish that glucose is metabolised primarily through the glycolytic pathway, and acetic acid is used as an additional source of acetyl-CoA both for lipid synthesis and the Krebs cycle. This study provides useful clues for the design of new strategies aimed at overcoming yeast spoilage in acidic, sugar-containing food environments. Moreover, the elucidation of the molecular basis underlying the resistance phenotype of Z. bailii to acetic acid will have a potential impact on the improvement of the performance of S. cerevisiae industrial strains often exposed to acetic acid stress conditions, such as in wine and bioethanol production.This work was supported by Fundacao para a Ciencia e Tecnologia (FCT), Portugal Grant PTDC/AGR-ALI/102608/2008 and by project FCOMP-01-0124-FEDER- 007047 and by FEDER through POFC - COMPETE and national funds from FCT - project PEst-C/BIA/UI4050/2011. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript
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