760 research outputs found

    Theory of commensurable magnetic structures in holmium

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    The tendency for the period of the helically ordered moments in holmium to lock into values which are commensurable with the lattice is studied theoretically as a function of temperature and magnetic field. The commensurable effects are derived in the mean-field approximation from numerical calculations of the free energy of various commensurable structures, and the results are compared with the extensive experimental evidence collected during the last ten years on the magnetic structures in holmium. In general the stability of the different commensurable structures is found to be in accord with the experiments, except for the tau=5/18 structure observed a few degrees below T_N in a b-axis field. The trigonal coupling recently detected in holmium is found to be the interaction required to explain the increased stability of the tau=1/5 structure around 42 K, and of the tau=1/4 structure around 96 K, when a field is applied along the c-axis.Comment: REVTEX, 31 pages, 7 postscript figure

    Interplay between distribution of live cells and growth dynamics of solid tumours

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    Experiments show that simple diffusion of nutrients and waste molecules is not sufficient to explain the typical multilayered structure of solid tumours, where an outer rim of proliferating cells surrounds a layer of quiescent but viable cells and a central necrotic region. These experiments challenge models of tumour growth based exclusively on diffusion. Here we propose a model of tumour growth that incorporates the volume dynamics and the distribution of cells within the viable cell rim. The model is suggested by in silico experiments and is validated using in vitro data. The results correlate with in vivo data as well, and the model can be used to support experimental and clinical oncology

    Adaptive response and enlargement of dynamic range

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    Many membrane channels and receptors exhibit adaptive, or desensitized, response to a strong sustained input stimulus, often supported by protein activity-dependent inactivation. Adaptive response is thought to be related to various cellular functions such as homeostasis and enlargement of dynamic range by background compensation. Here we study the quantitative relation between adaptive response and background compensation within a modeling framework. We show that any particular type of adaptive response is neither sufficient nor necessary for adaptive enlargement of dynamic range. In particular a precise adaptive response, where system activity is maintained at a constant level at steady state, does not ensure a large dynamic range neither in input signal nor in system output. A general mechanism for input dynamic range enlargement can come about from the activity-dependent modulation of protein responsiveness by multiple biochemical modification, regardless of the type of adaptive response it induces. Therefore hierarchical biochemical processes such as methylation and phosphorylation are natural candidates to induce this property in signaling systems.Comment: Corrected typos, minor text revision

    High throughput mutagenesis for identification of residues regulating human prostacyclin (hIP) receptor

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    The human prostacyclin receptor (hIP receptor) is a seven-transmembrane G protein-coupled receptor (GPCR) that plays a critical role in vascular smooth muscle relaxation and platelet aggregation. hIP receptor dysfunction has been implicated in numerous cardiovascular abnormalities, including myocardial infarction, hypertension, thrombosis and atherosclerosis. Genomic sequencing has discovered several genetic variations in the PTGIR gene coding for hIP receptor, however, its structure-function relationship has not been sufficiently explored. Here we set out to investigate the applicability of high throughput random mutagenesis to study the structure-function relationship of hIP receptor. While chemical mutagenesis was not suitable to generate a mutagenesis library with sufficient coverage, our data demonstrate error-prone PCR (epPCR) mediated mutagenesis as a valuable method for the unbiased screening of residues regulating hIP receptor function and expression. Here we describe the generation and functional characterization of an epPCR derived mutagenesis library compromising >4000 mutants of the hIP receptor. We introduce next generation sequencing as a useful tool to validate the quality of mutagenesis libraries by providing information about the coverage, mutation rate and mutational bias. We identified 18 mutants of the hIP receptor that were expressed at the cell surface, but demonstrated impaired receptor function. A total of 38 non-synonymous mutations were identified within the coding region of the hIP receptor, mapping to 36 distinct residues, including several mutations previously reported to affect the signaling of the hIP receptor. Thus, our data demonstrates epPCR mediated random mutagenesis as a valuable and practical method to study the structurefunction relationship of GPCRs. © 2014 Bill et al
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