Disease-specific, neurosphere-derived cells as models for brain disorders

There is a pressing need for patient-derived cell models of brain diseases that are relevant and robust enough to produce the large quantities of cells required for molecular and functional analyses. We describe here a new cell model based on patient-derived cells from the human olfactory mucosa, the organ of smell, which regenerates throughout life from neural stem cells. Olfactory mucosa biopsies were obtained from healthy controls and patients with either schizophrenia, a neurodevelopmental psychiatric disorder, or Parkinson's disease, a neurodegenerative disease. Biopsies were dissociated and grown as neurospheres in defined medium. Neurosphere-derived cell lines were grown in serum-containing medium as adherent monolayers and stored frozen. By comparing 42 patient and control cell lines we demonstrated significant disease-specific alterations in gene expression, protein expression and cell function, including dysregulated neurodevelopmental pathways in schizophrenia and dysregulated mitochondrial function, oxidative stress and xenobiotic metabolism in Parkinson's disease. The study has identified new candidate genes and cell pathways for future investigation. Fibroblasts from schizophrenia patients did not show these differences. Olfactory neurosphere-derived cells have many advantages over embryonic stem cells and induced pluripotent stem cells as models for brain diseases. They do not require genetic reprogramming and they can be obtained from adults with complex genetic diseases. They will be useful for understanding disease aetiology, for diagnostics and for drug discovery

Mode-Locking in Driven Disordered Systems as a Boundary-Value Problem

We study mode-locking in disordered media as a boundary-value problem. Focusing on the simplest class of mode-locking models which consists of a single driven overdamped degree-of-freedom, we develop an analytical method to obtain the shape of the Arnol'd tongues in the regime of low ac-driving amplitude or high ac-driving frequency. The method is exact for a scalloped pinning potential and easily adapted to other pinning potentials. It is complementary to the analysis based on the well-known Shapiro's argument that holds in the perturbative regime of large driving amplitudes or low driving frequency, where the effect of pinning is weak.Comment: 6 pages, 7 figures, RevTeX, Submitte

Novel Respiratory Virus Infections in Children, Brazil

Recently discovered respiratory viruses were detected in 19 (9.2%) of 205 nasal swab specimens from children in Brazil with respiratory illnesses. Five each were positive for human metapneumovirus (HMPV) alone and human bocavirus (HBoV) alone, 3 for human coronaviruses (HCoV-HKU1 or -NL63) alone, and 6 for more than 1 recently discovered virus

Chaotic Diffusion on Periodic Orbits: The Perturbed Arnol'd Cat Map

Chaotic diffusion on periodic orbits (POs) is studied for the perturbed Arnol'd cat map on a cylinder, in a range of perturbation parameters corresponding to an extended structural-stability regime of the system on the torus. The diffusion coefficient is calculated using the following PO formulas: (a) The curvature expansion of the Ruelle zeta function. (b) The average of the PO winding-number squared, $w^{2}$, weighted by a stability factor. (c) The uniform (nonweighted) average of $w^{2}$. The results from formulas (a) and (b) agree very well with those obtained by standard methods, for all the perturbation parameters considered. Formula (c) gives reasonably accurate results for sufficiently small parameters corresponding also to cases of a considerably nonuniform hyperbolicity. This is due to {\em uniformity sum rules} satisfied by the PO Lyapunov eigenvalues at {\em fixed} $w$. These sum rules follow from general arguments and are supported by much numerical evidence.Comment: 6 Tables, 2 Figures (postscript); To appear in Physical Review

Foreground removal from CMB temperature maps using an MLP neural network

One of the main obstacles in extracting the Cosmic Microwave Background (CMB) signal from observations in the mm-submm range is the foreground contamination by emission from galactic components: mainly synchrotron, free-free and thermal dust emission. Due to the statistical nature of the intrinsic CMB signal it is essential to minimize the systematic errors in the CMB temperature determinations. Following the available knowledge of the spectral behavior of the galactic foregrounds simple, power law-like spectra have been assumed. The feasibility of using a simple neural network for extracting the CMB temperature signal from the combined CMB and foreground signals has been investigated. As a specific example, we have analysed simulated data, like that expected from the ESA Planck Surveyor mission. A simple multilayer perceptron neural network with 2 hidden layers can provide temperature estimates, over more than 80 percent of the sky, that are to a high degree uncorrelated with the foreground signals. A single network will be able to cover the dynamic range of the Planck noise level over the entire sky.Comment: Accepted for publication in Astrophysics and Space Scienc

Physics of Solar Prominences: II - Magnetic Structure and Dynamics

Observations and models of solar prominences are reviewed. We focus on non-eruptive prominences, and describe recent progress in four areas of prominence research: (1) magnetic structure deduced from observations and models, (2) the dynamics of prominence plasmas (formation and flows), (3) Magneto-hydrodynamic (MHD) waves in prominences and (4) the formation and large-scale patterns of the filament channels in which prominences are located. Finally, several outstanding issues in prominence research are discussed, along with observations and models required to resolve them.Comment: 75 pages, 31 pictures, review pape

Quantum walks: a comprehensive review

Quantum walks, the quantum mechanical counterpart of classical random walks, is an advanced tool for building quantum algorithms that has been recently shown to constitute a universal model of quantum computation. Quantum walks is now a solid field of research of quantum computation full of exciting open problems for physicists, computer scientists, mathematicians and engineers. In this paper we review theoretical advances on the foundations of both discrete- and continuous-time quantum walks, together with the role that randomness plays in quantum walks, the connections between the mathematical models of coined discrete quantum walks and continuous quantum walks, the quantumness of quantum walks, a summary of papers published on discrete quantum walks and entanglement as well as a succinct review of experimental proposals and realizations of discrete-time quantum walks. Furthermore, we have reviewed several algorithms based on both discrete- and continuous-time quantum walks as well as a most important result: the computational universality of both continuous- and discrete- time quantum walks.Comment: Paper accepted for publication in Quantum Information Processing Journa

Flux-rope twist in eruptive flares and CMEs : due to zipper and main-phase reconnection

Funding: UK Science and Technology Facilities CouncilThe nature of three-dimensional reconnection when a twisted flux tube erupts during an eruptive flare or coronal mass ejection is considered. The reconnection has two phases: first of all, 3D “zipper reconnection” propagates along the initial coronal arcade, parallel to the polarity inversion line (PIL); then subsequent quasi-2D “main phase reconnection” in the low corona around a flux rope during its eruption produces coronal loops and chromospheric ribbons that propagate away from the PIL in a direction normal to it. One scenario starts with a sheared arcade: the zipper reconnection creates a twisted flux rope of roughly one turn (2π radians of twist), and then main phase reconnection builds up the bulk of the erupting flux rope with a relatively uniform twist of a few turns. A second scenario starts with a pre-existing flux rope under the arcade. Here the zipper phase can create a core with many turns that depend on the ratio of the magnetic fluxes in the newly formed flare ribbons and the new flux rope. Main phase reconnection then adds a layer of roughly uniform twist to the twisted central core. Both phases and scenarios are modeled in a simple way that assumes the initial magnetic flux is fragmented along the PIL. The model uses conservation of magnetic helicity and flux, together with equipartition of magnetic helicity, to deduce the twist of the erupting flux rope in terms the geometry of the initial configuration. Interplanetary observations show some flux ropes have a fairly uniform twist, which could be produced when the zipper phase and any pre-existing flux rope possess small or moderate twist (up to one or two turns). Other interplanetary flux ropes have highly twisted cores (up to five turns), which could be produced when there is a pre-existing flux rope and an active zipper phase that creates substantial extra twist.PostprintPublisher PDFPeer reviewe

Rho GTPase function in flies: insights from a developmental and organismal perspective.

Morphogenesis is a key event in the development of a multicellular organism and is reliant on coordinated transcriptional and signal transduction events. To establish the segmented body plan that underlies much of metazoan development, individual cells and groups of cells must respond to exogenous signals with complex movements and shape changes. One class of proteins that plays a pivotal role in the interpretation of extracellular cues into cellular behavior is the Rho family of small GTPases. These molecular switches are essential components of a growing number of signaling pathways, many of which regulate actin cytoskeletal remodeling. Much of our understanding of Rho biology has come from work done in cell culture. More recently, the fruit fly Drosophila melanogaster has emerged as an excellent genetic system for the study of these proteins in a developmental and organismal context. Studies in flies have greatly enhanced our understanding of pathways involving Rho GTPases and their roles in development