234 research outputs found

    Immunization strategies for funding multiple inflation-linked retirement income benefits

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    Simões, C., Oliveira, L., & Bravo, J. M. (2021). Immunization strategies for funding multiple inflation-linked retirement income benefits. Risks, 9(4), [60]. https://doi.org/10.3390/risks9040060Protecting against unexpected yield curve, inflation, and longevity shifts are some of the most critical issues institutional and private investors must solve when managing post-retirement income benefits. This paper empirically investigates the performance of alternative immunization strategies for funding targeted multiple liabilities that are fixed in timing but random in size (inflation-linked), i.e., that change stochastically according to consumer price or wage level indexes. The immunization procedure is based on a targeted minimax strategy considering the M-Absolute as the interest rate risk measure. We investigate to what extent the inflation-hedging properties of ILBs in asset liability management strategies targeted to immunize multiple liabilities of random size are superior to that of nominal bonds. We use two alternative datasets comprising daily closing prices for U.S. Treasuries and U.S. inflation-linked bonds from 2000 to 2018. The immunization performance is tested over 3-year and 5-year investment horizons, uses real and not simulated bond data and takes into consideration the impact of transaction costs in the performance of immunization strategies and in the selection of optimal investment strategies. The results show that the multiple liability immunization strategy using inflation-linked bonds outperforms the equivalent strategy using nominal bonds and is robust even in a nearly zero interest rate scenario. These results have important implications in the design and structuring of ALM liability-driven investment strategies, particularly for retirement income providers such as pension schemes or life insurance companies.publishersversionpublishe

    Purification and characterization of a thrombolytic enzyme produced by a new strain of Bacillus subtilis

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    Fibrinolytic enzymes with a direct mechanism of action and safer properties are currently requested for thrombolytic therapy. This paper reports on a new enzyme capable of degrading blood clots directly without impairing blood coagulation. This enzyme is also non-cytotoxic and constitutes an alternative to other thrombolytic enzymes known to cause undesired side effects. Twenty-four Bacillus isolates were screened for production of fibrinolytic enzymes using a fibrin agar plate. Based on produced activity, isolate S127e was selected and identified as B. subtilis using the 16S rDNA gene sequence. This strain is of biotechnological interest for producing high fibrinolytic yield and consequently has potential in the industrial field. The purified fibrinolytic enzyme has a molecular mass of 27.3 kDa, a predicted pI of 6.6, and a maximal affinity for Ala-Ala-Pro-Phe. This enzyme was almost completely inhibited by chymostatin with optimal activity at 48°C and pH 7. Specific subtilisin features were found in the gene sequence, indicating that this enzyme belongs to the BPN group of the S8 subtilisin family and was assigned as AprE127. This subtilisin increased thromboplastin time by 3.7% (37.6 to 39 s) and prothrombin time by 3.2% (12.6 to 13 s), both within normal ranges. In a whole blood euglobulin assay, this enzyme did not impair coagulation but reduced lysis time significantly. Moreover, in an in vitro assay, AprE127 completely dissolved a thrombus of about 1 cc within 50 min and, in vivo, reduced a thrombus prompted in a rat tail by 11.4% in 24 h compared to non-treated animals.This work was supported by Direcao Regional da Ciencia e Tecnologia - DRCT-Acores (Medida 2.2.2/I/025/2008) . Duarte Toubarro received a post-doctoral grant (SFRH/BPD/77483/2011; M3.1.a/F/050/2016) from FundacAo para a Ciencia e Tecnologia, Portugal; Jorge Frias received a doctoral grant (SFRH/BD/131698/2017) . The authors are grateful to Dr. Teresa Sampaio and Nelia Arruda, from Dr. Forjaz Sampaio Medical Center, for helping with the plasma anticoagulation assays. Duarte Toubarro and Nelson Simoes designed the study and helped with the paper's redaction. Jorge Frias performed the experiments, analyzed the data and wrote the paper. Alexandra Fraga and Jorge Pedrosa performed thrombolytic assays in a rat model. Claudia Botelho and Jose Teixeira participated in the discussion and redaction of the paper.info:eu-repo/semantics/publishedVersio

    Selective activation of protein kinase C-δ and -ɛ by 6,11,12,14-tetrahydroxy-abieta-5,8,11,13-tetraene-7-one (coleon U)

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    6,11,12,14-tetrahydroxy-abieta-5,8,11,13-tetraene-7-one (coleon U) is a diterpene compound isolated from Plectranthus grandidentatus with an antiproliferative effect on several human cancer cell lines. Herein, we studied the modulatory activity of coleon U on individual isoforms of the three protein kinase C (PKC) subfamilies, classical (cPKC-α and -βI), novel (nPKC-δ and -ɛ) and atypical (aPKC-ζ), using a yeast PKC assay. The results showed that, whereas the PKC activator phorbol-12-myristate-13-acetate (PMA) activated every PKC tested except aPKC, coleon U had no effect on aPKC and cPKCs. Besides, the effect of coleon U on nPKCs was higher than that of PMA. This revealed that coleon U was a potent and selective activator of nPKCs. The isoform-selectivity of coleon U for nPKC-δ and -ɛ was confirmed using an in vitro PKC assay. Most importantly, while PMA activated nPKCs inducing an isoform translocation from the cytosol to the plasma membrane and a G2/M cell cycle arrest, coleon U induced nPKCs translocation to the nucleus and a metacaspase- and mitochondrial-dependent apoptosis. This work therefore reconstitutes in yeast distinct subcellular translocations of a PKC isoform and the subsequent distinct cellular responses reported for mammalian cells. Together, our study identifies a new isoform-selective PKC activator with promising pharmacological applications. Indeed, since coleon U has no effect on cPKCs and aPKC, recognised as anti-apoptotic proteins, and selectively induces an apoptotic pathway dependent on nPKC-δ and -ɛ activation, it represents a promising compound for evaluation as an anti-cancer drug.We are grateful to Dr. Nigel Goode for providing YEplac181-PKC-α, PKC-βI, PKC-δ, -PKC-ɛ and -PKC-ζ; to Dr. Heimo Riedel for providing YEp52-PKC-α and Yep51-PKC-βI; to Dr. Charles Rudin for providing pOW4-Bcl-xL; to Dr. Stéphen Manon for providing pCLbGFP-mt-GFP; to Joana Tavares for her help and technical advice in some experiments; to Cristina G-Marques for the previous isolation of coleon U; to Helena Vasconcelos for critical reading of the manuscript. We thank REQUIMTE/CEQUP and FCT (I&D No 8/94), POCTI (QCA III) and FEDER for financial support. I. Coutinho is recipient of a PhD fellowship from FCT (SFRH/BD/36066/2007).info:eu-repo/semantics/publishedVersio

    Disease mapping models for data with weak spatial dependence or spatial discontinuities

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    Recent advances in the spatial epidemiology literature have extended traditional approaches by including determinant disease factors that allow for non-local smoothing and/or non-spatial smoothing. In this article, two of those approaches are compared and are further extended to areas of high interest from the public health perspective. These are a conditionally specified Gaussian random field model, using a similaritybased non-spatial weight matrix to facilitate non-spatial smoothing in Bayesian disease mapping; and a spatially adaptive conditional autoregressive prior model.info:eu-repo/semantics/publishedVersio

    Probable Person-to-Person Transmission of Legionnaires’ Disease

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    Correspondence to the Editor.Legionnaires’ disease is an often severe form of pneumonia that is typically acquired by susceptible persons (e.g., elderly persons and smokers) through inhalation of aerosols that contain legionella species.1-4 A cluster of cases of this disease occurred in Vila Franca de Xira, Portugal, in 2014

    Supercritical CO2 extraction of V. vinifera leaves: influence of cosolvents and particle size on removal kinetics and selectivity to target compounds

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    Leaves from Vitis vinifera L. contain potential bioactive compounds, namely: long chain aliphatic alcohols (e.g., 1-hexacosanol, 1-octacosanol and 1-triacontanol), α-tocopherol, β-sitosterol, and the triterpenes β-amyrin and lupeol. Supercritical fluid extraction (SFE) runs were measured at lab scale using: crushed and ground biomass; pure CO2 at 300 bar and 40−80 °C; and CO2 modified with 5 and 10 wt.% of ethanol or ethyl acetate. Total SFE yields ranged from 1.86 to 7.52 wt.%. The broken plus intact cells model (BICM), provided a good fitting of the SFE curves with 4.06 % error for total yield and 1.98–5.49 % for the individual yields of the said compounds. The BICM results revealed that the SFE is limited by intraparticle diffusion. Remarkable experimental and calculated selectivities were obtained for triterpenes (lupeol and β-amyrin), starting with a score of 1.7 and increasing along time to 10−100.publishe

    Influence of soil placement on decomposition of leaves and stems of Cistus salviifolius L.

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    Estudou-se a influência do posicionamento no solo na dinâmica da decomposição de resíduos de arbustos mediterrânicos, numa comunidade característica de montados do Alentejo, durante um período de cerca de 2 anos. Para o efeito, monitorizaram- se as variações de matéria orgânica e de nutrientes em folhas e raminhos de Cistus salviifolius L. colocados na superfície do solo e incorporados a 10 cm de profundidade, através da técnica dos “sacos de decomposição” A taxa anual decomposição das folhas na superfície do solo (-0,71) foi mais rápida do que a dos raminhos em posição homóloga (-0,17). Esta diferenciação foi também observada para as folhas e raminhos incorporados a 10 cm de profundidade, tendo a taxa sido bastante mais elevada (respectivamente -0,98 e -0,43). A diminuição da matéria orgânica ocorreu em duas fases: uma fase inicial de decréscimo bastante rápido, influenciado principalmente pela natureza do substrato, à qual se seguiu uma fase de decréscimo muito lento, no qual se fez sentir tanto o efeito do substrato como o da sua localização. A libertação dos nutrientes foi mais influenciada pela composição inicial dos resíduos do que pela localização destes no solo, tendo a libertação sido mais rápida nas folhas do que nos raminhos. As relações lineares inversas observadas entre a MO remanescente e a concentração de N no material residual indicam maiores períodos de imobilização de N nas folhas colocadas na superfície do que nas incorporadas no solo

    Effects of agricultural tillage practices on decomposition and nutrient dynamics of Cistus salviifolius L. leaves

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    Estudou-se o efeito das alterações na estrutura do sistema solo-folhada na dinâmica da decomposição, através da simulação de duas técnicas de maneio do solo, numa comunidade arbustiva característica de montados do Alentejo. Para o efeito, monitorizou-se, durante cerca de 2 anos, a dinâmica da perda de MO e da libertação de N, P, K Ca e Mg de folhas de Cistus salviifolius L., através da técnica dos “litter bags”, colocados à superfície do solo e enterrados a 10 cm de profundidade. A decomposição das folhas enterradas foi bastante mais rápida do que a das colocadas à superfície do solo. As proporções de MO remanescente foram, respectivamente, de 13 e 26%, após 2 anos e as taxas anuais de decomposição, k, de 0,99 e de 0,70. A libertação de N foi igualmente mais rápida nas folhas enterradas do que nas colocadas à superfície, tendo as proporções remanescentes, ao fim de 289 dias, sido respectivamente de 60 e 98% (22 e 47% no final). A libertação de P seguiu a mesma tendência que a do N, tendo a proporção residual, após 289 dias, sido de 48% nas folhas enterradas (16% no final) e de 70% à superfície (32% no final). Os padrões de libertação de K, Ca e Mg foram idênticos nas duas situações, tendo as proporções remanescentes, no final do período de estudo, sido de 3 e 6%, 28 e 32% e 20 e 29%, respectivamente para as folhas enterradas e para as colocadas à superfície. A localização das folhas influenciou o processo de decomposição. A mais lenta decomposição à superfície do solo pode contribuir para a redução das perdas de MO e nutrientes nos solos não mobilizados, relativamente aos mobilizados segundo as técnicas agrícolas tradicionais

    CavBench: a benchmark for protein cavity detection methods

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    Extensive research has been applied to discover new techniques and methods to model protein-ligand interactions. In particular, considerable efforts focused on identifying candidate binding sites, which quite often are active sites that correspond to protein pockets or cavities. Thus, these cavities play an important role in molecular docking. However, there is no established benchmark to assess the accuracy of new cavity detection methods. In practice, each new technique is evaluated using a small set of proteins with known binding sites as ground-truth. However, studies supported by large datasets of known cavities and/or binding sites and statistical classification (i.e., false positives, false negatives, true positives, and true negatives) would yield much stronger and reliable assessments. To this end, we propose CavBench, a generic and extensible benchmark to compare different cavity detection methods relative to diverse ground truth datasets (e.g., PDBsum) using statistical classification methods.info:eu-repo/semantics/publishedVersio
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