105 research outputs found

    Numerical validation of a population balance model describing cement paste rheology

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    Rheology control is essential during the period in which cement and concrete pastes are encountered in the fresh state, due to the fact that it directly affects workability, initial placement and the structural performance of the hardened material. Optimizations of clinker formulations and reductions in cement-to-water ratios induced by economic and environmental considerations have a significant effect in rheology, which invokes the need for mechanistic models capable of describing the effect of multiple relevant phenomena on the observed paste flow. In this work, the population balance framework was implemented to develop a model able to relate the transient microstructural evolution of cement pastes under typical experimental conditions with its macroscopic rheological responses. Numerical details and performance are assessed and discussed. It was found that the model is capable of reproducing experimentally observed flow curves by using measured cluster size distribution information. It is also able to predict the complex rheological characteristics typically found in cement pastes. Furthermore, a spatially resolved scheme was proposed to investigate the nature of flow inside a parallel-plates rheometer geometry with the objective of assessing the ability of the model of qualitatively predicting experimentally observed behavior and to gain insight into the effect of possible secondary flows

    Synthesis of 6,8,9 poly-substituted purine analogue libraries as pro-apoptotic inducers of human leukemic lymphocytes and DAPK-1 inhibitors

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    A 18-member library of 6,8,9-poly-substituted purines was prepared from pyrimidines, primary alcohols, and N,N-dimethylamides under basic conditions via a novel one-pot synthetic pathway controlled by amide sizes and the novel analogues were tested against two leukemia cell lines: Jurkat (acute T cell leukemia) and K562 (chronic erythroleukemia) cells. Compounds having a benzoxy group at C6 position of the aromatic ring exhibited antiproliferative activity in Jurkat cells whereas all compounds induced a lower effect on K562 cells. Analysis of cell cycle, Annexin-V staining, and cleavage of initiator caspases assays showed that the active purine analogues induce cell death by apoptosis. Based on these results, a new purine derivative was synthesized, 6-benzyloxy-9-tert-butyl-8-phenyl-9H-purine (6d), which displayed the highest activity of the series against Jurkat cell lines. Finally, 33P-radiolabeled kinase assays using 96 recombinant human kinases known to be involved in apoptotic events were performed. Just one of the kinases tested, DAPK-1, was inhibited 50% or more by the phenotypic hits at 10 őľM, suggesting that the inhibition of this target could be responsible for the induction of cell death by apoptosis. In agreement with the phenotypic results, the most active antiproliferative agent, 6d, displayed also the lowest IC50 value against recombinant DAPK1 (2.5 őľM), further supporting the potential role of this protein on the observed functional response. DAPK-1 inhibition led by 6d together with its pro-apoptotic properties against the Jurkat line makes it an interesting candidate to further investigate the role of DAPK1 kinase in triggering apoptosis in cancer cells, a role which is attracting recent interest.JJDM thanks the Spanish Ministerio de Economia y Competitividad for funding a Ramon y Cajal Fellowship. AUB thanks Medical Research Council UK ‚Äď Institute of Genetics and Molecular Medicine for funding an Academic Fellowship. We acknowledge the generous supply of rIL-2 provided by the National Institutes of Health AIDS Reagent Program. IJM is grateful for the support provided to his laboratory by grant 12UDG01-ATF from Sparks, the children's medical charity, London, UK

    Guías colombianas de cardiología síndrome coronario agudo sin elevación del ST

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    Las enfermedades cardiovasculares constituyen la principal causa de muerte en los pa√≠ses industrializadosy en los pa√≠ses en v√≠a de desarrollo. Dentro de estas patolog√≠as la enfermedad coronaria es la manifes-taci√≥n m√°s prevalente y se asocia con alta mortalidad y morbilidad. Las presentaciones cl√≠nicas de laenfermedad coronaria isqu√©mica incluyen, isquemia silente, angina de pecho estable, falla card√≠aca,angina inestable, infarto agudo del miocardio y muerte s√ļbita. En esta primera entrega se tratar√° els√≠ndrome coronario agudo sin elevaci√≥n del ST que incluye la angina inestable y el infarto agudo delmiocardio sin elevaci√≥n del ST.Q4121-27

    Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

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    The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality

    Impacts of the Tropical Pacific/Indian Oceans on the Seasonal Cycle of the West African Monsoon

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    The current consensus is that drought has developed in the Sahel during the second half of the twentieth century as a result of remote effects of oceanic anomalies amplified by local land‚Äďatmosphere interactions. This paper focuses on the impacts of oceanic anomalies upon West African climate and specifically aims to identify those from SST anomalies in the Pacific/Indian Oceans during spring and summer seasons, when they were significant. Idealized sensitivity experiments are performed with four atmospheric general circulation models (AGCMs). The prescribed SST patterns used in the AGCMs are based on the leading mode of covariability between SST anomalies over the Pacific/Indian Oceans and summer rainfall over West Africa. The results show that such oceanic anomalies in the Pacific/Indian Ocean lead to a northward shift of an anomalous dry belt from the Gulf of Guinea to the Sahel as the season advances. In the Sahel, the magnitude of rainfall anomalies is comparable to that obtained by other authors using SST anomalies confined to the proximity of the Atlantic Ocean. The mechanism connecting the Pacific/Indian SST anomalies with West African rainfall has a strong seasonal cycle. In spring (May and June), anomalous subsidence develops over both the Maritime Continent and the equatorial Atlantic in response to the enhanced equatorial heating. Precipitation increases over continental West Africa in association with stronger zonal convergence of moisture. In addition, precipitation decreases over the Gulf of Guinea. During the monsoon peak (July and August), the SST anomalies move westward over the equatorial Pacific and the two regions where subsidence occurred earlier in the seasons merge over West Africa. The monsoon weakens and rainfall decreases over the Sahel, especially in August.Peer reviewe

    Effects of hospital facilities on patient outcomes after cancer surgery: an international, prospective, observational study