931 research outputs found

    An efficient numerical method for shakedown analysis

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    The algorithm proposed in [9] for incremental elastoplasticity is extended and applied to shakedown analysis. Using the three field mixed finite element proposed in [22] a series of mathematical programming problems or steps, obtained from the application of the proximal point algorithm to the static shakedown theorem, are obtained. Each step is solved by an Equality Constrained Sequential Quadratic Programming (EC-SQP) tech- nique that allows a consistent linearization of the equations improving the computational efficiency

    Humans and Water in Desert “Refugium” Areas: Palynological Evidence of Climate Oscillations and Cultural Developments in Early and Mid-Holocene Saharan Edges

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    Saharan anthropic deposits from archaeological sites, located along wadis or close to lakes, and sedimentary sequences from permanent and dried basins demonstrate that water has always been an attractive environmental feature, especially during periods of drought. This paper reports on two very different examples of Holocene sites where “humans and water” coexisted during dry periods, as observed by stratigraphic, archaeological and palynological evidence. Independent research was carried out on the Jefara Plain (Libya, 32°N) and the Gobero area (Niger, 17°N), at the extreme northern and southern limits of the Sahara, respectively. The histories of the Jefara and Gobero areas, as revealed by the archaeological and palaeoenvironmental reconstructions, suggest that these areas were likely to have been visited and exploited for a long time, acting as anthropic refugia, and therefore they have been profoundly transformed. Human presence and actions have conditioned the local growing of plants and selected a more or less synanthropic flora. Today, modern conservation strategies should take into consideration that water reservoirs, which are crucial for the long-term conservation of biodiversity, have provided refugia in the past just as they presently do under global warming conditions

    A mixed algorithm for incremental elastoplastic analysis

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    A new method for the incremental analysis of elastoplastic associated materials is presented. The method fully retains all the equations and variables of the problems at the same level and uses a sequential quadratic programming with equality constraints to solve in an efficient and robust fashion the elastoplastic step equations derived by means of a suitable mathematical programming formulation of the problem. The new proposal is compared with standard strain driven formulations which use a return mapping by closest point projection schemes. The numerical tests performed show a good performance and a great robustness of the proposed formulation also in the case of multi–surface elastoplasticity

    MicroRNAs targeting oncogenes are down-regulated in pancreatic malignant transformation from benign tumors

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    BACKGROUND MicroRNA (miRNA) expression profiles have been described in pancreatic ductal adenocarcinoma (PDAC), but these have not been compared with pre-malignant pancreatic tumors. We wished to compare the miRNA expression signatures in pancreatic benign cystic tumors (BCT) of low and high malignant potential with PDAC, in order to identify miRNAs deregulated during PDAC development. The mechanistic consequences of miRNA dysregulation were further evaluated. METHODS Tissue samples were obtained at a tertiary pancreatic unit from individuals with BCT and PDAC. MiRNA profiling was performed using a custom microarray and results were validated using RT-qPCR prior to evaluation of miRNA targets. RESULTS Widespread miRNA down-regulation was observed in PDAC compared to low malignant potential BCT. We show that amongst those miRNAs down-regulated, miR-16, miR-126 and let-7d regulate known PDAC oncogenes (targeting BCL2, CRK and KRAS respectively). Notably, miR-126 also directly targets the KRAS transcript at a "seedless" binding site within its 3'UTR. In clinical specimens, miR-126 was strongly down-regulated in PDAC tissues, with an associated elevation in KRAS and CRK proteins. Furthermore, miR-21, a known oncogenic miRNA in pancreatic and other cancers, was not elevated in PDAC compared to serous microcystic adenoma (SMCA), but in both groups it was up-regulated compared to normal pancreas, implicating early up-regulation during malignant change. CONCLUSIONS Expression profiling revealed 21 miRNAs down-regulated in PDAC compared to SMCA, the most benign lesion that rarely progresses to invasive carcinoma. It appears that miR-21 up-regulation is an early event in the transformation from normal pancreatic tissue. MiRNA expression has the potential to distinguish PDAC from normal pancreas and BCT. Mechanistically the down-regulation of miR-16, miR-126 and let-7d promotes PDAC transformation by post-transcriptional up-regulation of crucial PDAC oncogenes. We show that miR-126 is able to directly target KRAS; re-expression has the potential as a therapeutic strategy against PDAC and other KRAS-driven cancers

    Corpus approaches to news translation: We can do better than comparable!

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    This contribution addresses the challenging issue of building corpus resources for the study of news translation, a domain in which the coexistence of radical rewriting and close translation makes the use of established corpus-assisted analytical techniques problematic. In an attempt to address these challenges, we illustrate and test two related methods for identifying translated segments within trilingual (Spanish, French and English) sets of dispatches issued by the global news agency Agence France-Press. One relies on machine translation and semantic similarity scores, the other on multilingual sentence embeddings. To evaluate these methods, we apply them to a benchmark dataset of translations from the same domain and perform manual evaluation of the dataset under study. We finally leverage the cross-linguistic equivalences thus identified to build a 'comparallel' corpus, which combines the parallel and comparable corpus architectures, highlighting its affordances and limitations for the study of news translation. We conclude by discussing the theoretical and methodological implications of our findings both for the study of news translation and more generally for the study of contemporary, novel forms of translation

    Mucin Biopolymers As Broad-Spectrum Antiviral Agents

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    Mucus is a porous biopolymer matrix that coats all wet epithelia in the human body and serves as the first line of defense against many pathogenic bacteria and viruses. However, under certain conditions viruses are able to penetrate this infection barrier, which compromises the protective function of native mucus. Here, we find that isolated porcine gastric mucin polymers, key structural components of native mucus, can protect an underlying cell layer from infection by small viruses such as human papillomavirus (HPV), Merkel cell polyomavirus (MCV), or a strain of influenza A virus. Single particle analysis of virus mobility inside the mucin barrier reveals that this shielding effect is in part based on a retardation of virus diffusion inside the biopolymer matrix. Our findings suggest that purified mucins may be used as a broad-range antiviral supplement to personal hygiene products, baby formula or lubricants to support our immune system.National Institutes of Health (U.S.) (grant P30-ES002109)National Institutes of Health (U.S.) (grant P50-GM068763)German Academic Exchange Service (Postdoctoral fellowship
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