453 research outputs found

    Flexible and scalable digital library search

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    In this report the development of a specialised search engine for a digital library is described. The proposed system architecture consists of three levels: the conceptual, the logical and the physical level. The conceptual level schema enables by its exposure of a domain specific schema semantically rich conceptual search. The logical level provides a description language to achieve a high degree of flexibility for multimedia retrieval. The physical level takes care of scalable and efficient persistent data storage. The role, played by each level, changes during the various stages of a search engine's lifecycle: (1) modeling the index, (2) populating and maintaining the index and (3) querying the index. The integration of all this functionality allows the combination of both conceptual and content-based querying in the query stage. A search engine for the Australian Open tennis tournament website is used as a running example, which shows the power of the complete architecture and its various component

    The integrin expression profile modulates orientation and dynamics of force transmission at cell–matrix adhesions

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    Integrin adhesion receptors connect the extracellular matrix (ECM) to the cytoskeleton and serve as bidirectional mechanotransducers. During development, angiogenesis, wound healing and cancer progression, the relative abundance of fibronectin receptors, including integrins α5β1 and αvβ3, changes, thus altering the integrin composition of cell-matrix adhesions. Here, we show that enhanced αvβ3 expression can fully compensate for loss of α5β1 and other β1 integrins to support outside-in and inside-out force transmission. α5β1 and αvβ3 each mediate actin cytoskeletal remodeling in response to stiffening or cyclic stretching of the ECM. Likewise, α5β1 and αvβ3 support cellular traction forces of comparable magnitudes and similarly increase these forces in response to ECM stiffening. However, cells using αvβ3 respond to lower stiffness ranges, reorganize their actin cytoskeleton more substantially in response to stretch, and show more randomly oriented traction forces. Centripetal traction force orientation requires long stress fibers that are formed through the action of Rho kinase (ROCK) and myosin II, and that are supported by α5β1. Thus, altering the relative abundance of fibronectin-binding integrins in cell-matrix adhesions affects the spatiotemporal organization of force transmission.Toxicolog

    Mesoscopic interplay of superconductivity and ferromagnetism in ultra-small metallic grains

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    We review the effects of electron-electron interactions on the ground-state spin and the transport properties of ultra-small chaotic metallic grains. Our studies are based on an effective Hamiltonian that combines a superconducting BCS-like term and a ferromagnetic Stoner-like term. Such terms originate in pairing and spin exchange correlations, respectively. This description is valid in the limit of a large dimensionless Thouless conductance. We present the ground-state phase diagram in the fluctuation-dominated regime where the single-particle mean level spacing is comparable to the bulk BCS pairing gap. This phase diagram contains a regime in which pairing and spin exchange correlations coexist in the ground-state wave function. We discuss the calculation of the tunneling conductance for an almost-isolated grain in the Coulomb-blockade regime, and present measurable signatures of the competition between superconductivity and ferromagnetism in the mesoscopic fluctuations of the conductance.Comment: 6 pages, 3 figures, To be published in the proceedings of the NATO Advance Research Workshop "Recent Advances in Nonlinear Dynamics and Complex System Physics.

    A Current Induced Transition in atomic-sized contacts of metallic Alloys

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    We have measured conductance histograms of atomic point contacts made from the noble-transition metal alloys CuNi, AgPd, and AuPt for a concentration ratio of 1:1. For all alloys these histograms at low bias voltage (below 300 mV) resemble those of the noble metals whereas at high bias (above 300 mV) they resemble those of the transition metals. We interpret this effect as a change in the composition of the point contact with bias voltage. We discuss possible explanations in terms of electromigration and differential diffusion induced by current heating.Comment: 5 pages, 6 figure

    Balance of Isotropic and Directed Forces Determines Cell Shape

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    The shape of a cell membrane is largely defined by the underlying actin cytoskeleton and membrane mechanics. The actin cytoskeleton asserts contractile forces on the membrane that can be divided in isotropic and directed forces. We present a theory which is an extension of the Young-Laplace equation. It models cell edges as parts of one uniform ellipse, which changes from cell to cell. The ellipse parameters are characterized by the ratio of isotropic to directed contractility of the cell. We demonstrate the capabilities of this model using fibroblasts seeded on an elastic micro-pillar array. In this way adhesion forces exerted by the cell at single adhesion sites are measured. We show that isotropic and directed forces balance the line tension in cortical actin. Furthermore, for cells with homogeneous contractile forces and a single orientation of stress-fibers any part of the cell edge follows a universal ellipse, enabling us to calculate the magnitude of isotropic and directed contractility in a single cell. We show that in 3T3 fibroblasts the directed contractility is about three times as strong as the isotropic contractility. If myosin motors are inhibited, however, directed contractility decreases, effectively disabling forces generated by stress-fibers, and the elliptical cell cortex turns into a circular shape predicted for an isotropic contractile cytoskeleton. Our analysis shows that a simple two-parameter model explains polarity, shape of the cell cortex and cellular forces as experimentally observed. Potentially this model can be used to predict stresses and forces on the extracellular matrix and tissue.  Biological and Soft Matter Physic

    Chromosome-free bacterial cells are safe and programmable platforms for synthetic biology

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    A type of chromosome-free cell called SimCells (simple cells) has been generated from Escherichia coli, Pseudomonas putida, and Ralstonia eutropha. The removal of the native chromosomes of these bacteria was achieved by double-stranded breaks made by heterologous I-CeuI endonuclease and the degradation activity of endogenous nucleases. We have shown that the cellular machinery remained functional in these chromosome-free SimCells and was able to process various genetic circuits. This includes the glycolysis pathway (composed of 10 genes) and inducible genetic circuits. It was found that the glycolysis pathway significantly extended longevity of SimCells due to its ability to regenerate ATP and NADH/NADPH. The SimCells were able to continuously express synthetic genetic circuits for 10 d after chromosome removal. As a proof of principle, we demonstrated that SimCells can be used as a safe agent (as they cannot replicate) for bacterial therapy. SimCells were used to synthesize catechol (a potent anticancer drug) from salicylic acid to inhibit lung, brain, and soft-tissue cancer cells. SimCells represent a simplified synthetic biology chassis that can be programmed to manufacture and deliver products safely without interference from the host genome
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