758 research outputs found

    Immune Selection and Within-Host Competition Can Structure the Repertoire of Variant Surface Antigens in Plasmodium falciparum - A Mathematical Model

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    , the best-studied VSA family is erythrocyte membrane protein 1 (PfEMP1). Each parasite genome encodes about 60 PfEMP1 variants, which are important virulence factors and major targets of host antibody responses. Transcriptional switching is the basis of clonal PfEMP1 variation and immune evasion. A relatively conserved subset of PfEMP1 variants tends to dominate in non-immune patients and in patients with severe malaria, while more diverse subsets relate to uncomplicated infection and higher levels of pre-existing protective immunity.Here, we use the available molecular and serological evidence regarding VSAs, in particular PfEMP1, to formulate a mathematical model of the evolutionary mechanisms shaping VSA organization and expression patterns. The model integrates the transmission dynamics between hosts and the competitive interactions within hosts, based on the hypothesis that the VSAs can be organized into so-called dominance blocks, which characterize their competitive potential. The model reproduces immunological trends observed in field data, and predicts an evolutionary stable balance between inter-clonally conserved dominance blocks that are highly competitive within-host and diverse blocks that are favoured by immune selection at the population level.The application of a monotonic dominance profile to VSAs encoded by a gene family generates two opposing selective forces and, consequently, two distinct clusters of genes emerge in adaptation to naĂŻve and partially immune hosts, respectively

    Shape modeling technique KOALA validated by ESA Rosetta at (21) Lutetia

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    We present a comparison of our results from ground-based observations of asteroid (21) Lutetia with imaging data acquired during the flyby of the asteroid by the ESA Rosetta mission. This flyby provided a unique opportunity to evaluate and calibrate our method of determination of size, 3-D shape, and spin of an asteroid from ground-based observations. We present our 3-D shape-modeling technique KOALA which is based on multi-dataset inversion. We compare the results we obtained with KOALA, prior to the flyby, on asteroid (21) Lutetia with the high-spatial resolution images of the asteroid taken with the OSIRIS camera on-board the ESA Rosetta spacecraft, during its encounter with Lutetia. The spin axis determined with KOALA was found to be accurate to within two degrees, while the KOALA diameter determinations were within 2% of the Rosetta-derived values. The 3-D shape of the KOALA model is also confirmed by the spectacular visual agreement between both 3-D shape models (KOALA pre- and OSIRIS post-flyby). We found a typical deviation of only 2 km at local scales between the profiles from KOALA predictions and OSIRIS images, resulting in a volume uncertainty provided by KOALA better than 10%. Radiometric techniques for the interpretation of thermal infrared data also benefit greatly from the KOALA shape model: the absolute size and geometric albedo can be derived with high accuracy, and thermal properties, for example the thermal inertia, can be determined unambiguously. We consider this to be a validation of the KOALA method. Because space exploration will remain limited to only a few objects, KOALA stands as a powerful technique to study a much larger set of small bodies using Earth-based observations.Comment: 15 pages, 8 figures, 2 tables, accepted for publication in P&S

    Microscopic Views of Martian Soils and Evidence for Incipient Diagenesis

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    Mars landed missions returned im-ages at increasingly higher spatial resolution (Table 1). These images help to constrain the microstructure of Martian soils, i.e. the grain-by-grain association of chemistry and mineralogy with secondary properties, such as albedo, color, magnetic properties, and mor-phology (size, shape, texture). The secondary charac-teristics are controlled by mineralogical composition as well as the geo-setting (transport and weathering modes, e.g. water supply, pH, atmospheric properties, exposure to radiation, etc.). As of today this association is poorly constrained. However, it is important to un-derstand soil-forming processes on the surface of Mars. Here we analyze high-resolution images of soils re-turned by different landed missions. Eventually these images must be combined with other types of data (chemistry and mineralogy at small spatial scale) to nail down the microstructure of Martian soils

    Raising rivals’ fixed costs

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    This article demonstrates that raising fixed costs can serve as a credible mechanism for a well placed firm to exclude its rivals. We identify a number of credible avenues, such as increased regulation, vexatious litigation and increased prices for essential inputs, through which such a firm can raise fixed costs. We show that for a wide range of oligopoly models this may be a profitable strategy, even if the firm’s own fixed costs are affected as much (or even more) than its rivals and even if it is less efficient. The resulting reduction in the number of firms in the market is detrimental to consumer welfare and hence worthy of scrutiny by competition and regulatory authorities
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