Functional models for large-scale gene regulation networks: realism and fiction

High-throughput experiments are shedding light on the topology of large regulatory networks and at the same time their functional states, namely the states of activation of the nodes (for example transcript or protein levels) in different conditions, times, environments. We now possess a certain amount of information about these two levels of description, stored in libraries, databases and ontologies. A current challenge is to bridge the gap between topology and function, i.e. developing quantitative models aimed at characterizing the expression patterns of large sets of genes. However, approaches that work well for small networks become impossible to master at large scales, mainly because parameters proliferate. In this review we discuss the state of the art of large-scale functional network models, addressing the issue of what can be considered as realistic and what the main limitations may be. We also show some directions for future work, trying to set the goals that future models should try to achieve. Finally, we will emphasize the possible benefits in the understanding of biological mechanisms underlying complex multifactorial diseases, and in the development of novel strategies for the description and the treatment of such pathologies.Comment: to appear on Mol. BioSyst. 200

Hydrodynamic induced deformation and orientation of a microscopic elastic filament

We describe simulations of a microscopic elastic filament immersed in a fluid and subject to a uniform external force. Our method accounts for the hydrodynamic coupling between the flow generated by the filament and the friction force it experiences. While models that neglect this coupling predict a drift in a straight configuration, our findings are very different. Notably, a force with a component perpendicular to the filament axis induces bending and perpendicular alignment. Moreover, with increasing force we observe four shape regimes, ranging from slight distortion to a state of tumbling motion that lacks a steady state. We also identify the appearance of marginally stable structures. Both the instability of these shapes and the observed alignment can be explained by the combined action of induced bending and non-local hydrodynamic interactions. Most of these effects should be experimentally relevant for stiff micro-filaments, such as microtubules.Comment: three figures. To appear in Phys Rev Let

Fragility Functions for Tall URM Buildings around Early 20th Century in Lisbon, Part 2: Application to Different Classes of Buildings

This article describes the application of the procedure for the derivation of fragility functions presented in the companion article entitled Fragility functions for tall URM buildings around early 20th century in Lisbon. Part 1: methodology and application at building level. The procedure, based on the execution of non-linear analyses, was developed to be applied to unreinforced masonry buildings considering both the in-plane and out-of-plane response. Different sources of uncertainty, both epistemic and aleatory, affecting the behaviour of these unreinforced masonry buildings are discussed and treated with a probabilistic procedure. The fragility curves determined for the different classes of buildings are compared and then combined to define the final fragility curves for these unreinforced masonry buildings. The results put in evidence the high seismic vulnerability of these buildings and the urgent need for the structural intervention and for the design of retrofitting measures in order to reduce potential losses due to future earthquakes

Mean-field methods in evolutionary duplication-innovation-loss models for the genome-level repertoire of protein domains

We present a combined mean-field and simulation approach to different models describing the dynamics of classes formed by elements that can appear, disappear or copy themselves. These models, related to a paradigm duplication-innovation model known as Chinese Restaurant Process, are devised to reproduce the scaling behavior observed in the genome-wide repertoire of protein domains of all known species. In view of these data, we discuss the qualitative and quantitative differences of the alternative model formulations, focusing in particular on the roles of element loss and of the specificity of empirical domain classes.Comment: 10 Figures, 2 Table

Statistical Mechanics of the Chinese Restaurant Process: lack of self-averaging, anomalous finite-size effects and condensation

The Pitman-Yor, or Chinese Restaurant Process, is a stochastic process that generates distributions following a power-law with exponents lower than two, as found in a numerous physical, biological, technological and social systems. We discuss its rich behavior with the tools and viewpoint of statistical mechanics. We show that this process invariably gives rise to a condensation, i.e. a distribution dominated by a finite number of classes. We also evaluate thoroughly the finite-size effects, finding that the lack of stationary state and self-averaging of the process creates realization-dependent cutoffs and behavior of the distributions with no equivalent in other statistical mechanical models.Comment: (5pages, 1 figure

Combined use of x-ray fluorescence microscopy, phase contrast imaging for high resolution quantitative iron mapping in inflamed cells

X-ray fluorescence microscopy (XRFM) is a powerful technique to detect and localize elements in cells. To derive information useful for biology and medicine, it is essential not only to localize, but also to map quantitatively the element concentration. Here we applied quantitative XRFM to iron in phagocytic cells. Iron, a primary component of living cells, can become toxic when present in excess. In human fluids, free iron is maintained at 10-18 M concentration thanks to iron binding proteins as lactoferrin (Lf). The iron homeostasis, involving the physiological ratio of iron between tissues/secretions and blood, is strictly regulated by ferroportin, the sole protein able to export iron from cells to blood. Inflammatory processes induced by lipopolysaccharide (LPS) or bacterial pathoge inhibit ferroportin synthesis in epithelial and phagocytic cells thus hindering iron export, increasing intracellular iron and bacterial multiplication. In this respect, Lf is emerging as an important regulator of both iron and inflammatory homeostasis. Here we studied phagocytic cells inflamed by bacterial LPS and untreated or treated with milk derived bovine Lf. Quantitative mapping of iron concentration and mass fraction at high spatial resolution is obtained combining X-ray fluorescence microscopy, atomic force microscopy and synchrotron phase contrast imaging

Hydrodynamic Synchronisation of Model Microswimmers

We define a model microswimmer with a variable cycle time, thus allowing the possibility of phase locking driven by hydrodynamic interactions between swimmers. We find that, for extensile or contractile swimmers, phase locking does occur, with the relative phase of the two swimmers being, in general, close to 0 or pi, depending on their relative position and orientation. We show that, as expected on grounds of symmetry, self T-dual swimmers, which are time-reversal covariant, do not phase-lock. We also discuss the phase behaviour of a line of tethered swimmers, or pumps. These show oscillations in their relative phases reminiscent of the metachronal waves of cilia.Comment: 17 pages, 8 figure

Carbon nanotube - Based cold cathodes: Field emission angular properties and temporal stability

The field emission (FE) properties of carbon nanotube (CNT)-based cathodes have been investigated on nanostructured surfaces grown by plasma enhanced chemical vapor deposition. The FE angular properties and temporal stability of the emergent electron beam have been determined using a dedicated apparatus for cathodes of various architectures and geometries, characterized by scanning electron microscopy and I-V measurements. The angular electron beam divergence and time instability at the extraction stage, which are crucial parameters in order to obtain high brilliance of FE-based-cathode electron sources, have been measured for electrons emitted by several regular architectures of vertically aligned arrays and critically compared to conventional disordered cathodes. The measured divergences strongly depend on the grid mesh. For regular arrays of individual CNT, divergences from 2° to 5° have been obtained; in this specific case, measurements together with ray-tracing simulations suggest that the maximum emission angle is of the order of ±30° about the tube main axis. Larger divergences have been measured for electron beams emitted from honeycomb-structured cathodes (6°) and significantly broader angle distributions (10°) from disordered CNT surfaces. Emission current instabilities of the order of 1% for temporal stability studies conducted across a medium time scale (hours) have been noted for all cathodes consisting of a high number (10$^{4}$ and larger) of aligned CNTs, with the degree of stability being largely independent of the architecture.The European AXIS project (FP7-SME-1-2007) is acknowledged for financial support

Micro-beam and pulsed laser beam techniques for the micro-fabrication of diamond surface and bulk structures

Micro-fabrication in diamond is involved in a wide set of emerging technologies, exploiting the exceptional characteristics of diamond for application in bio-physics, photonics, radiation detection. Micro ion-beam irradiation and pulsed laser irradiation are complementary techniques, which permit the implementation of complex geometries, by modification and functionalization of surface and/or bulk material, modifying the optical, electrical and mechanical characteristics of the material. In this article we summarize the work done in Florence (Italy) concerning ion beam and pulsed laser beam micro-fabrication in diamond.Comment: 14 pages, 5 figure

Electrical and Raman-imaging characterization of laser-made electrodes for 3D diamond detectors

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