Meta-Analysis of High-Throughput Datasets Reveals Cellular Responses Following Hemorrhagic Fever Virus Infection

The continuing use of high-throughput assays to investigate cellular responses to infection is providing a large repository of information. Due to the large number of differentially expressed transcripts, often running into the thousands, the majority of these data have not been thoroughly investigated. Advances in techniques for the downstream analysis of high-throughput datasets are providing additional methods for the generation of additional hypotheses for further investigation. The large number of experimental observations, combined with databases that correlate particular genes and proteins with canonical pathways, functions and diseases, allows for the bioinformatic exploration of functional networks that may be implicated in replication or pathogenesis. Herein, we provide an example of how analysis of published high-throughput datasets of cellular responses to hemorrhagic fever virus infection can generate additional functional data. We describe enrichment of genes involved in metabolism, post-translational modification and cardiac damage; potential roles for specific transcription factors and a conserved involvement of a pathway based around cyclooxygenase-2. We believe that these types of analyses can provide virologists with additional hypotheses for continued investigation

Crystalline Order On Riemannian Manifolds With Variable Gaussian Curvature And Boundary

We investigate the zero temperature structure of a crystalline monolayer constrained to lie on a two-dimensional Riemannian manifold with variable Gaussian curvature and boundary. A full analytical treatment is presented for the case of a paraboloid of revolution. Using the geometrical theory of topological defects in a continuum elastic background we find that the presence of a variable Gaussian curvature, combined with the additional constraint of a boundary, gives rise to a rich variety of phenomena beyond that known for spherical crystals. We also provide a numerical analysis of a system of classical particles interacting via a Coulomb potential on the surface of a paraboloid.Comment: 12 pages, 8 figure

Comparative Pathogenesis and Systems Biology for Biodefense Virus Vaccine Development

Developing vaccines to biothreat agents presents a number of challenges for discovery, preclinical development, and licensure. The need for high containment to work with live agents limits the amount and types of research that can be done using complete pathogens, and small markets reduce potential returns for industry. However, a number of tools, from comparative pathogenesis of viral strains at the molecular level to novel computational approaches, are being used to understand the basis of viral attenuation and characterize protective immune responses. As the amount of basic molecular knowledge grows, we will be able to take advantage of these tools not only to rationally attenuate virus strains for candidate vaccines, but also to assess immunogenicity and safety in silico. This review discusses how a basic understanding of pathogenesis, allied with systems biology and machine learning methods, can impact biodefense vaccinology

Dynamical Decompactification and Three Large Dimensions

We study string gas dynamics in the early universe and seek to realize the Brandenberger - Vafa mechanism - a goal that has eluded earlier works - that singles out three or fewer spatial dimensions as the number which grow large cosmologically. Considering wound string interactions in an impact parameter picture, we show that a strong exponential suppression in the interaction rates for d > 3 spatial dimensions reflects the classical argument that string worldsheets generically intersect in at most four spacetime dimensions. This description is appropriate in the early universe if wound strings are heavy - wrapping long cycles - and diluted. We consider the dynamics of a string gas coupled to dilaton-gravity and find that a) for any number of dimensions the universe generically stays trapped in the Hagedorn regime and b) if the universe fluctuates to a radiation regime any residual winding modes are diluted enough so that they freeze-out in d > 3 large dimensions while they generically annihilate for d = 3. In this sense the Brandenberger-Vafa mechanism is operative.Comment: 20 pages, 2 figures, minor changes, updated figures, as will appear in Phys.Rev.

Dynamics of quantum phase transition: exact solution in quantum Ising model

Quantum Ising model is an exactly solvable model of quantum phase transition. This paper gives an exact solution when the system is driven through the critical point at finite rate. The evolution goes through a series of Landau-Zener level anticrossings when pairs of quasiparticles with opposite pseudomomenta get excited with probability depending on the transition rate. Average density of defects excited in this way scales like a square root of the transition rate. This scaling is the same as the scaling obtained when the standard Kibble-Zurek mechanism of thermodynamic second order phase transitions is applied to the quantum phase transition in the Ising model.Comment: misprints corrected; version to appear in Phys.Rev.Let

Curvature-Induced Defect Unbinding in Toroidal Geometries

Toroidal templates such as vesicles with hexatic bond orientational order are discussed. The total energy including disclination charges is explicitly computed for hexatic order embedded in a toroidal geometry. Related results apply for tilt or nematic order on the torus in the one Frank constant approximation. Although there is no topological necessity for defects in the ground state, we find that excess disclination defects are nevertheless energetically favored for fat torii or moderate vesicle sizes. Some experimental consequences are discussed.Comment: 12 pages, 15 eps figure

Folding of the Triangular Lattice in the FCC Lattice with Quenched Random Spontaneous Curvature

We study the folding of the regular two-dimensional triangular lattice embedded in the regular three-dimensional Face Centered Cubic lattice, in the presence of quenched random spontaneous curvature. We consider two types of quenched randomness: (1) a ``physical'' randomness arising from a prior random folding of the lattice, creating a prefered spontaneous curvature on the bonds; (2) a simple randomness where the spontaneous curvature is chosen at random independently on each bond. We study the folding transitions of the two models within the hexagon approximation of the Cluster Variation Method. Depending on the type of randomness, the system shows different behaviors. We finally discuss a Hopfield-like model as an extension of the physical randomness problem to account for the case where several different configurations are stored in the prior pre-folding process.Comment: 12 pages, Tex (harvmac.tex), 4 figures. J.Phys.A (in press

Bubble Raft Model for a Paraboloidal Crystal

We investigate crystalline order on a two-dimensional paraboloid of revolution by assembling a single layer of millimeter-sized soap bubbles on the surface of a rotating liquid, thus extending the classic work of Bragg and Nye on planar soap bubble rafts. Topological constraints require crystalline configurations to contain a certain minimum number of topological defects such as disclinations or grain boundary scars whose structure is analyzed as a function of the aspect ratio of the paraboloid. We find the defect structure to agree with theoretical predictions and propose a mechanism for scar nucleation in the presence of large Gaussian curvature.Comment: 4 pages, 4 figure

Universality in the Screening Cloud of Dislocations Surrounding a Disclination

A detailed analytical and numerical analysis for the dislocation cloud surrounding a disclination is presented. The analytical results show that the combined system behaves as a single disclination with an effective fractional charge which can be computed from the properties of the grain boundaries forming the dislocation cloud. Expressions are also given when the crystal is subjected to an external two-dimensional pressure. The analytical results are generalized to a scaling form for the energy which up to core energies is given by the Young modulus of the crystal times a universal function. The accuracy of the universality hypothesis is numerically checked to high accuracy. The numerical approach, based on a generalization from previous work by S. Seung and D.R. Nelson ({\em Phys. Rev A 38:1005 (1988)}), is interesting on its own and allows to compute the energy for an {\em arbitrary} distribution of defects, on an {\em arbitrary geometry} with an arbitrary elastic {\em energy} with very minor additional computational effort. Some implications for recent experimental, computational and theoretical work are also discussed.Comment: 35 pages, 21 eps file