700 research outputs found

    Fluid-structure interaction with flexible multibody dynamics and smoothed particle hydrodynamics

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    In this work, we present a versatile and eïŹƒcient computational approach to ïŹ‚uid-structure interaction based on the coupling of ïŹ‚exible multibody systems with ïŹ‚uids analyzed by means of the meshfree particle-based method smoothed particle hydrodynamics. Regarding numerical examples, rigid or ïŹ‚exible cells, and ïŹbers in microchannel ïŹ‚ows are investigated. As a main feature of this paper, our results are validated with reference simulations obtained from fundamentally diïŹ€erent approaches

    Die filling process simulation using discrete element method (DEM)

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    Powder compaction and sintering are important techniques for the mass production of geometrically complex parts. Powder is poured from a reservoir into the feeding shoe, which then passes the cavity one or more times thereby delivering powder into it. The powder is then compressed to create a relatively brittle green body. Finally, the green body is ejected from the cavity and sintered in a furnace where thermal activation below the melting point produces a fully dense structure. Necks form and grow between adjacent grains thereby eliminating the porosity of the part. In general, a consistent and uniform die filling process is always desirable. Heterogeneity during die filling can propagate through the subsequent processes and finally lead to serious product defects, such as cracking, low strength, distortion and shrinkage [1]. Capillary cohesion is known to influence strongly the strength and flow properties of granular materials. At low levels of water content, the water forms a discontinuous phase composed of interparticle bridges that are unevenly distributed in the bulk (the pendular state) [2]. For powder filling process these capillary forces may have strong influence in the particle dynamics and subsequent packing. An approach using discrete element method (DEM) simulation is proposed to reproduce die filling process and investigate process characteristics that affect final sand cake shape and may lead to in-homogeneities in powder during the filling process. Also an experimental apparatus able to reproduce the die filling process was built to validate numerical model. A coarse grain model is also necessary to reduce the model size (reduce the number of particles)

    Shifting patterns of oil palm driven deforestation in Indonesia and implications for zero-deforestation commitments

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    Oil palm plantations in Indonesia have been linked to substantial deforestation in the 1990s and 2000s, though recent studies suggest that new plantations are increasingly developed on non-forest land. Without nationwide data to establish recent baseline trends, the impact of commitments to eliminate deforestation from palm oil supply chains could therefore be overestimated. We examine the area and proportion of plantations replacing forests across Sumatra, Kalimantan, and Papua up to 2015, and map biophysically suitable areas for future deforestation-free expansion. We created new maps of oil palm plantations for the years 1995, 2000, 2005, 2010 and 2015, and examined land cover replaced in each period. Nationwide, oil palm plantation expansion occurred at an average rate of 450,000 ha yr−1, and resulted in an average of 117,000 ha yr−1 of deforestation, during 1995–2015. Our analysis of the most recent five-year period (2010–2015) shows that the rate of deforestation due to new plantations has remained relatively stable since 2005, despite large increases in the extent of plantations. As a result, the proportion of plantations replacing forests decreased from 54% during 1995–2000, to 18% during 2010–2015. In addition, we estimate there are 30.2 million hectares of non-forest land nationwide which meet biophysical suitability criteria for oil palm cultivation. Our findings suggest that recent zero-deforestation commitments may not have a large impact on deforestation in Sumatra, where plantations have increasingly expanded onto non-forest land over the past twenty years, and which hosts large potentially suitable areas for future deforestation-free expansion. On the other hand, these pledges could have more influence in Kalimantan, where oil palm driven deforestation increased over our study period, and in Papua, a new frontier of expansion with substantial remaining forest cover

    Aggressiveness of human melanoma xenograft models is promoted by aneuploidy-driven gene expression deregulation.

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    Melanoma is a devastating skin cancer characterized by distinct biological subtypes. Besides frequent mutations in growth- and survival-promoting genes like BRAF and NRAS, melanomas additionally harbor complex non-random genomic alterations. Using an integrative approach, we have analysed genomic and gene expression changes in human melanoma cell lines (N=32) derived from primary tumors and various metastatic sites and investigated the relation to local growth aggressiveness as xenografts in immuno-compromised mice (N=22). Although the vast majority >90% of melanoma models harbored mutations in either BRAF or NRAS, significant differences in subcutaneous growth aggressiveness became obvious. Unsupervised clustering revealed that genomic alterations rather than gene expression data reflected this aggressive phenotype, while no association with histology, stage or metastatic site of the original melanoma was found. Genomic clustering allowed separation of melanoma models into two subgroups with differing local growth aggressiveness in vivo. Regarding genes expressed at significantly altered levels between these subgroups, a surprising correlation with the respective gene doses (>85% accordance) was found. Genes deregulated at the DNA and mRNA level included well-known cancer genes partly already linked to melanoma (RAS genes, PTEN, AURKA, MAPK inhibitors Sprouty/Spred), but also novel candidates like SIPA1 (a Rap1GAP). Pathway mining further supported deregulation of Rap1 signaling in the aggressive subgroup e.g. by additional repression of two Rap1GEFs. Accordingly, siRNA-mediated down-regulation of SIPA1 exerted significant effects on clonogenicity, adherence and migration in aggressive melanoma models. Together our data suggest that an aneuploidy-driven gene expression deregulation drives local aggressiveness in human melanoma

    Deletion of the gabra2 gene results in hypersensitivity to the acute effects of ethanol but does not alter ethanol self administration

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    Human genetic studies have suggested that polymorphisms of the GABRA2 gene encoding the GABA(A) α2-subunit are associated with ethanol dependence. Variations in this gene also convey sensitivity to the subjective effects of ethanol, indicating a role in mediating ethanol-related behaviours. We therefore investigated the consequences of deleting the α2-subunit on the ataxic and rewarding properties of ethanol in mice. Ataxic and sedative effects of ethanol were explored in GABA(A) α2-subunit wildtype (WT) and knockout (KO) mice using a Rotarod apparatus, wire hang and the duration of loss of righting reflex. Following training, KO mice showed shorter latencies to fall than WT littermates under ethanol (2 g/kg i.p.) in both Rotarod and wire hang tests. After administration of ethanol (3.5 g/kg i.p.), KO mice took longer to regain the righting reflex than WT mice. To ensure the acute effects are not due to the gabra2 deletion affecting pharmacokinetics, blood ethanol concentrations were measured at 20 minute intervals after acute administration (2 g/kg i.p.), and did not differ between genotypes. To investigate ethanol's rewarding properties, WT and KO mice were trained to lever press to receive increasing concentrations of ethanol on an FR4 schedule of reinforcement. Both WT and KO mice self-administered ethanol at similar rates, with no differences in the numbers of reinforcers earned. These data indicate a protective role for α2-subunits, against the acute sedative and ataxic effects of ethanol. However, no change was observed in ethanol self administration, suggesting the rewarding effects of ethanol remain unchange
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