190 research outputs found

    A Potts Neuron Approach to Communication Routing

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    A feedback neural network approach to communication routing problems is developed with emphasis on Multiple Shortest Path problems, with several requests for transmissions between distinct start- and endnodes. The basic ingredients are a set of Potts neurons for each request, with interactions designed to minimize path lengths and to prevent overloading of network arcs. The topological nature of the problem is conveniently handled using a propagator matrix approach. Although the constraints are global, the algorithmic steps are based entirely on local information, facilitating distributed implementations. In the polynomially solvable single-request case the approach reduces to a fuzzy version of the Bellman-Ford algorithm. The approach is evaluated for synthetic problems of varying sizes and load levels, by comparing with exact solutions from a branch-and-bound method. With very few exceptions, the Potts approach gives legal solutions of very high quality. The computational demand scales merely as the product of the numbers of requests, nodes, and arcs.Comment: 10 pages LaTe

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    Cells move along surfaces both as single cells and multi-cellular units. Recent research points toward pivotal roles for water flux through aquaporins (AQPs) in single cell migration. Their expression is known to facilitate this process by promoting rapid shape changes. However, little is known about the impact on migrating epithelial sheets during wound healing and epithelial renewal. Here, we investigate and compare the effects of AQP9 on single cell and epithelial sheet migration. To achieve this, MDCK-1 cells stably expressing AQP9 were subjected to migration assessment. We found that AQP9 facilitated cell locomotion at both the single and multi-cellular level. Furthermore, we identified major differences in the monolayer integrity and cell size upon expression of AQP9 during epithelial sheet migration, indicating a rapid volume-regulatory mechanism. We suggest a novel mechanism for epithelial wound healing based on AQP-induced swelling and expansion of the monolayer.Funding Agencies|Swedish Research Council for Medicine and Health|2007-34832009-66492010-3045|</p

    Self-consistent theory of reversible ligand binding to a spherical cell

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    In this article, we study the kinetics of reversible ligand binding to receptors on a spherical cell surface using a self-consistent stochastic theory. Binding, dissociation, diffusion and rebinding of ligands are incorporated into the theory in a systematic manner. We derive explicitly the time evolution of the ligand-bound receptor fraction p(t) in various regimes . Contrary to the commonly accepted view, we find that the well-known Berg-Purcell scaling for the association rate is modified as a function of time. Specifically, the effective on-rate changes non-monotonically as a function of time and equals the intrinsic rate at very early as well as late times, while being approximately equal to the Berg-Purcell value at intermediate times. The effective dissociation rate, as it appears in the binding curve or measured in a dissociation experiment, is strongly modified by rebinding events and assumes the Berg-Purcell value except at very late times, where the decay is algebraic and not exponential. In equilibrium, the ligand concentration everywhere in the solution is the same and equals its spatial mean, thus ensuring that there is no depletion in the vicinity of the cell. Implications of our results for binding experiments and numerical simulations of ligand-receptor systems are also discussed.Comment: 23 pages with 4 figure

    On the origin of the Norwegian lemming.

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    The Pleistocene glacial cycles resulted in significant changes in species distributions, and it has been discussed whether this caused increased rates of population divergence and speciation. One species that is likely to have evolved during the Pleistocene is the Norwegian lemming (Lemmus lemmus). However, the origin of this species, both in terms of when and from what ancestral taxon it evolved, has been difficult to ascertain. Here, we use ancient DNA recovered from lemming remains from a series of Late Pleistocene and Holocene sites to explore the species' evolutionary history. The results revealed considerable genetic differentiation between glacial and contemporary samples. Moreover, the analyses provided strong support for a divergence time prior to the Last Glacial Maximum (LGM), therefore likely ruling out a postglacial colonization of Scandinavia. Consequently, it appears that the Norwegian lemming evolved from a small population that survived the LGM in an ice-free Scandinavian refugium

    High photon count rates improve the quality of super-resolution fluorescence fluctuation spectroscopy

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    Probing the diffusion of molecules has become a routine measurement across the life sciences, chemistry and physics. It provides valuable insights into reaction dynamics, oligomerisation, molecular (re-)organisation or cellular heterogeneities. Fluorescence correlation spectroscopy (FCS) is one of the widely applied techniques to determine diffusion dynamics in two and three dimensions. This technique relies on the temporal autocorrelation of intensity fluctuations but recording these fluctuations has thus far been limited by the detection electronics, which could not efficiently and accurately time-tag photons at high count rates. This has until now restricted the range of measurable dye concentrations, as well as the data quality of the FCS recordings, especially in combination with super-resolution stimulated emission depletion (STED) nanoscopy. Here, we investigate the applicability and reliability of (STED-)FCS at high photon count rates (average intensities of more than 1 MHz) using novel detection equipment, namely hybrid detectors and real-time gigahertz sampling of the photon streams implemented on a commercial microscope. By measuring the diffusion of fluorophores in solution and cytoplasm of live cells, as well as in model and cellular membranes, we show that accurate diffusion and concentration measurements are possible in these previously inaccessible high photon count regimes. Specifically, it offers much greater flexibility of experiments with biological samples with highly variable intensity, e.g. due to a wide range of expression levels of fluorescent proteins. In this context, we highlight the independence of diffusion properties of cytosolic GFP in a concentration range of approx. 0.01-1 µm. We further show that higher photon count rates also allow for much shorter acquisition times, and improved data quality. Finally, this approach also pronouncedly increases the robustness of challenging live cell STED-FCS measurements of nanoscale diffusion dynamics, which we testify by confirming a free diffusion pattern for a fluorescent lipid analogue on the apical membrane of adherent cells. © The Author(s). Published by IOP Publishing Ltd

    Towards Truly “Global” Near Infrared Calibrations for Protein and Neutral Detergent Fibre in Dried Ground Forages

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    Over the past five years, Foss and DeLaval have sponsored the activities of a group of forage analysts with the aim of developing global Near Infrared (NIR) calibrations for parameters that are important in ruminant nutrition. The approach adopted has been based on the amalgamation of historical databases from centres worldwide and calibrations for protein and neutral detergent fibre (NDF) in dried ground forages have been developed based on databases that currently comprise approximately 30,000 records. Protein and NDF, while not the most important parameters in ruminant nutrition, were chosen for the initial calibration development exercise because of the amount of data available and because the methodologies adopted by different laboratories worldwide were relatively uniform. The aim was to create calibrations that would work for any forage type in any area of the world. Over the past two years, several trials have been carried out worldwide comparing the performance of global calibrations with the performance of locally developed calibrations for indigenous forages and based on reference values from local laboratories

    On-microscope staging of live cells reveals changes in the dynamics of transcriptional bursting during differentiation

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    Determining the mechanisms by which genes are switched on and off during development is a key aim of current biomedical research. Gene transcription has been widely observed to occur in a discontinuous fashion, with short bursts of activity interspersed with periods of inactivity. It is currently not known if or how this dynamic behaviour changes as mammalian cells differentiate. To investigate this, using an on-microscope analysis, we monitored mouse α-globin transcription in live cells throughout erythropoiesis. We find that changes in the overall levels of α-globin transcription are most closely associated with changes in the fraction of time a gene spends in the active transcriptional state. We identify differences in the patterns of transcriptional bursting throughout differentiation, with maximal transcriptional activity occurring in the mid-phase of differentiation. Early in differentiation, we observe increased fluctuation in transcriptional activity whereas at the peak of gene expression, in early erythroblasts, transcription is relatively stable. Later during differentiation as α-globin expression declines, we again observe more variability in transcription within individual cells. We propose that the observed changes in transcriptional behaviour may reflect changes in the stability of active transcriptional compartments as gene expression is regulated during differentiation
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