700 research outputs found

    A safeguard approach to detect stagnation of GMRES(m) with applications in Newton-Krylov methods

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    Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Restarting GMRES, a linear solver frequently used in numerical schemes, is known to suffer from stagnation. In this paper, a simple strategy is proposed to detect and avoid stagnation, without modifying the standard GMRES code. Numerical tests with the proposed modified GMRES(m) procedure for solving linear systems and also as part of an inexact Newton procedure, demonstrate the efficiency of this strategy.272175199Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)PRONEX-OptimizationFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq

    Transcription factor NRF2 protects mice against dietary iron-induced liver injury by preventing hepatocytic cell death

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    BACKGROUND & AIMS: The liver, being the major site of iron storage, is particularly exposed to the toxic effects of iron. Transcription factor NRF2 is critical for protecting the liver against disease by activating the transcription of genes encoding detoxification/antioxidant enzymes. We aimed to determine if the NRF2 pathway plays a significant role in the protection against hepatic iron overload.METHODS: Wild-type and Nrf2(-/-) mouse primary hepatocytes were incubated with ferric ammonium citrate. Wild-type and Nrf2(-/-) mice were fed standard rodent chow or iron-rich diet for 2weeks, with or without daily injection of the antioxidant mito-TEMPOL.RESULTS: In mouse hepatocytes, iron induced the nuclear translocation of NRF2 and the expression of cytoprotective genes in an NRF2-dependent manner. Moreover, Nrf2(-/-) hepatocytes were highly susceptible to iron-induced cell death. Wild-type and Nrf2(-/-) mice fed iron-rich diet accumulated similar amounts of iron in the liver and were equally able to increase the expression of hepatic hepcidin and ferritin. Nevertheless, in Nrf2-null mice the iron loading resulted in progressive liver injury, ranging from mild confluent necrosis to severe necroinflammatory lesions. Hepatocytic cell death was associated with gross ultrastructural damage to the mitochondria. Notably, liver injury was prevented in iron-fed animals that received mito-TEMPOL.CONCLUSIONS: NRF2 protects the mouse liver against the toxicity of dietary iron overload by preventing hepatocytic cell death. We identify NRF2 as a potential modifier of liver disease in iron overload pathology and show the beneficial effect of the antioxidant mito-TEMPOL in a mouse model of dietary iron-induced liver injury.This work is funded by FEDER Funds through the Operational Competitiveness Programme - COMPETE and by National Funds through FCT - Fundacao para a Ciencia e a Tecnologia under the project FCOMP-01-0124-FEDER-011062 (PTDC/SAU-FCF/101177/2008). TLD is supported by "Programa Ciencia - financiado pelo POPH - QREN - Tipologia 4.2 - Promocao do Emprego Cientifico, comparticipado pelo Fundo Social Europeu e por fundos nacionais do MCTES''

    Cell walls of the dimorphic fungal pathogens Sporothrix schenckii and Sporothrix brasiliensis exhibit bilaminate structures and sloughing of extensive and intact layers

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    This work was supported by the Fundação Carlos Chagas de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ), grants E-26/202.974/2015 and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), grants 229755/2013-5, Brazil. LMLB is a senior research fellow of CNPq and Faperj. NG acknowledged support from the Wellcome Trust (Trust (097377, 101873, 200208) and MRC Centre for Medical Mycology (MR/N006364/1). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer reviewedPublisher PD

    Trade-offs during the COVID-19 pandemic: A discrete choice experiment about policy preferences in Portugal

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    The need to control the sanitary situation during the COVID-19 pandemic has led governments to implement several restrictions with substantial social and economic impacts. We explored people’s trade-offs in terms of their income, life restrictions, education, and poverty in the society, compared to their willingness to avoid deaths. We applied a web-based discrete choice experiment to elicit preferences of the Portuguese citizens for these attributes and computed the marginal rate of substitution in terms of avoided deaths. We recorded 2,191 responses that faced the possibility of having 250 COVID-19 related deaths per day as the worst possible outcome from the choice levels presented. Estimates suggested that individuals would be willing to sacrifice 30% instead of 10% of their income to avoid approximately 47 deaths per day during the first six months of 2021. For the same period, they would also accept 30% of the students’ population to become educationally impaired, instead of 10%, to avoid approximately 25 deaths; a strict lockdown, instead of mild life restrictions, to avoid approximately 24 deaths; and 45% of the population to be in risk of poverty, instead of 25%, to avoid approximately 101 deaths. Our paper shows that avoiding deaths was strongly preferred to the remaining societal impacts; and that being a female, as well as working on site, led individuals to be more averse to such health hazards. Furthermore, we show how a DCE can be used to assess the societal support to decision-making during times of crisis

    A canonical correlation analysis of the association between carcass and ham traits in pigs used to produce dry-cured ham

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    The association between carcass and ham traits in a pig population used to produce dry-cured ham was studied using canonical correlation analysis. The carcass traits examined were hot carcass weight (HCW), backfat thickness (BT) and loin depth (LD), and the ham traits studied were gross ham weight (GHW), trimmed ham weight (THW), ham inner layer fat thickness (HIFT), ham outer layer fat thickness (HOFT), pH (pH) and the Göfo value. Carcass and ham traits are not independent. The canonical correlations (r) between the carcass and ham traits at 130 kg were 0.77, 0.24 and 0.20 for the first, second and third canonical pair, respectively, and were all significant (p < 0.01) by the Wilks test. The corresponding canonical correlations between the three canonical variate pairs for the carcass and ham traits at 160 kg were 0.88, 0.42 and 0.14, respectively (p < 0.05 for all, except the third). The correlations between the traits and their canonical variate showed an association among HCW, GHW and THW, and between BT and HOFT. These results indicate that carcass traits should be used to cull pigs that are not suitable for dry-cured ham production

    Effects of bromopride on the healing of left colon anastomoses of rats

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    Objetivo: Avaliar os efeitos da bromoprida sobre a formação de aderências e a cicatrização de anastomoses de cólon esquerdo de ratos. Métodos: Foram incluídos 40 ratos, divididos em dois grupos contendo 20 animais, para administração de bromoprida (grupo de estudo- E) ou solução fisiológica (grupo controle- C). Cada grupo foi dividido em subgrupos contendo 10 animais cada, para eutanásia no terceiro (E3 e C3) ou no sétimo dia (E7 e C7) de pós-operatório. Os ratos foram submetidos à secção do cólon esquerdo e anastomose término-terminal. No dia da relaparotomia, foi avaliada a quantidade total de aderências e removido um segmento colônico contendo a anastomose para análise histopatológica, da força de ruptura e da concentração de hidroxiprolina. Resultados: Não houve diferença entre os grupos em relação à evolução clínica. Dois animais do grupo de estudo apresentaram deiscência de anastomose bloqueada. Os animais que receberam bromoprida apresentaram número de aderências intracavitárias e aderências à anastomose semelhantes ao grupo controle. As anastomoses dos animais do grupo E3 apresentaram menor resistência de ruptura do que as do grupo C3 (p=0,04). Este efeito não ocorreu no sétimo dia de pós-operatório (p=0,37). Não houve diferença significativa entre os grupos em relação à histopatologia ou concentração de hidroxiprolina das anastomoses. Conclusão: O uso da bromoprida está associado à diminuição da resistência tênsil de anastomoses do cólon esquerdo de ratos no terceiro dia de pós-operatório.Objective: To evaluate the effects of bromopride on the formation of adhesions and anastomotic healing in the left colon of rats. Methods: We divided 40 rats into two groups of 20 animals, administration of bromopride (study group-E) or saline (control group- C). Each group was divided into subgroups containing 10 animals each for euthanasia in the third (C3 and E3) or the seventh (E7 and C7) postoperative days. The rats were submitted to section of the left colon and end-to-end anastomosis. On the day of reoperation, we evaluated the total amount of adhesions and removed a colonic segment containing the anastomosis for histopathological analysis, assessment of rupture strength and hydroxyproline concentration. Results: There was no difference between groups in relation to clinical outcome. Two animals in the study group had blocked anastomotic leakage. The animals that received bromopride had the number of intracavitary adhesions and adhesions to the anastomosis similar to the control group. The anastomoses from the group E3 animals showed lower resistance to rupture the one from the C3 group (p = 0.04). This effect did not occur on the seventh postoperative day (p = 0.37). There was no significant difference between groups in relation to histopathology and hydroxyproline concentration in the anastomoses. Conclusion: The use of bromopride was associated with decreased tensile strength of left colon anastomosis in rats in the third postoperative day
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