MathSBML: a package for manipulating SBML-based biological models

Summary: MathSBML is a Mathematica package designed for manipulating Systems Biology Markup Language (SBML) models. It converts SBML models into Mathematica data structures and provides a platform for manipulating and evaluating these models. Once a model is read by MathSBML, it is fully compatible with standard Mathematica functions such as NDSolve (a differential-algebraic equations solver). Math-SBML also provides an application programming interface for viewing, manipulating, running numerical simulations; exporting SBML models; and converting SBML models in to other formats, such as XPP, HTML and FORTRAN. By accessing the full breadth of Mathematica functionality, MathSBML is fully extensible to SBML models of any size or complexity. Availability: Open Source (LGPL) at http://www.sbml.org and http://www.sf.net/projects/sbml. Supplementary information: Extensive online documentation is available at http://www.sbml.org/mathsbml.html. Additional examples are provided at http://www.sbml.org/software/mathsbml/bioinformatics-application-not

An antenna array processing system for multiple source bearing estimation

The principal topic of this dissertation is the application of array signal processing to angle-of-arrival (AOA) estimation of multiple plane waves. Assuming that a passive linear array of uniformly spaced sensors is used to measure the radiation field, a digital signal processing system is proposed which determines the number of narrowband sources and their respective bearings;The proposed direction-finding system integrates several algorithms in a cohesive arrangement to exploit their mutually similar structures. The Modified forward-backward linear prediction (MFBLP) spectral analysis method of Tufts and Kumaresan is used to obtain high spatial resolution, and the eigenanalysis which is central to its operation provides an excellent point of entry for a procedure to estimate the number of plane waves detected by the array. This procedure utilizes the AIC or MDL information theoretic criteria in an ensemble manner to generate a reliable estimate of the rank of the signal subspace of the deterministic correlation matrix of the array snapshot;Two algorithms are presented for determining the spatial frequencies of the incoming plane waves, based on the MFBLP method: one uses an iterative version of Newton\u27s method to locate the spectral peaks, and the other uses an iterative method to locate the equivalent complex poles;Statistical processing of the bearing estimates from a number of array snapshots is then used to maintain accuracy and precision in noisy array environment; two different estimators are proposed for this ensemble averaging, and their performance is characterized when applied to a single-source scenario. This utilizes both analytical and Monte Carlo computer simulation. The distributions are characterized in both wavenumber and bearing domains. Expressions for the bearing CRLB, expected standard deviation, and bearing estimate confidence interval are developed, believed to be the first known formulations of overall DF system performance as a function of array spacing, number of elements, true source bearing, and sensor signal-to-noise ratio. The statistical precision is shown to be related to the effective aperture of the antenna array, revealing the degradation in performance as the angle-of-arrival approaches endfire

Renaissance of Bernal's random close packing and hypercritical line in the theory of liquids

We review the scientific history of random close packing (RCP) of equal spheres, advocated by J D Bernal as a more plausible alternative to the non-ideal gas or imperfect crystal as a structural model of simple liquids. After decades of neglect, computer experiments are revealing a central role for RCP in the theory of liquids. These demonstrate that the RCP amorphous state of hard spheres can be well defined, is reproducible, and has the thermodynamic status of a metastable ground state. Further evidence from simulations of square-well model liquids indicates an extended role of RCP as an amorphous ground state that terminates a supercooled liquid coexistence line, suggesting likewise for real liquids. A phase diagram involving percolation boundaries has been proposed in which there is no merging of liquid and gas phases, and no critical singularity as assumed by van der Waals. Rather, the liquid phase continuously spans all temperatures, but above a critical dividing line on the Gibbs density surface, it is bounded by a percolation transition and separated from the gas phase by a colloidal supercritical mesophase. The colloidal-like inversion in the mesophase as it changes from gas-in-liquid to liquid-in-gas can be identified with the hypercritical line of Bernal. We therefore argue that the statistical theory of simple liquids should start from the RCP reference state rather than the ideal gas. Future experimental priorities are to (i) find evidence for an amorphous ground state in real supercooled liquids, (ii) explore the microscopic structures of the supercritical mesophase, and (iii) determine how these change from gas to liquid, especially across Bernal's hypercritical line. The theoretical priority is a statistical geometrical theory of RCP. Only then might we explain the coincident values of the RCP packing fraction with Buffon's constant, and the RCP residual entropy with Boltzmann's ideal gas constant.info:eu-repo/semantics/publishedVersio

Enzyme activity and dynamics in near-anhydrous conditions

Water is widely assumed to be essential for life 1, although the exact molecular basis of this requirement is unclear 2-4. Water facilitates protein motions 5-9 and although enzyme activity has been demonstrated at low hydrations in organic solvents 10-13, such non-aqueous solvents may allow the necessary motions for catalysis. To examine enzyme function in the absence of solvation and bypass diffusional constraints we have tested the ability of an esterase to catalyse alcoholysis as an anhydrous powder, using a closed reaction system in which the substrates and products of the enzyme reaction are gaseous 14-15, and where the water content can be well defined 16. At hydrations equivalent to 3 (±2) molecules of water per molecule of enzyme, activity is observed that is several orders of magnitude greater than non-enzymatic catalysis. Neutron spectroscopy indicates that the fast (≤nanosecond) global anharmonic dynamics of the anhydrous functional enzyme are heavily suppressed. The results indicate that neither hydration water nor the solvent-activated fast anharmonic dynamics are required for enzyme function. An implication of these results is that one of the essential requirements of water for life may lie with its role as a diffusion medium rather than any of its more specific properties

Enzyme activity below the dynamical transition at 220 K

Enzyme activity requires the activation of anharmonic motions, such as jumps between potential energy wells. However, in general, the forms and time scales of the functionally important anharmonic dynamics coupled to motion along the reaction coordinate remain to be determined. In particular, the question arises whether the temperature-dependent dynamical transition from harmonic to anharmonic motion in proteins, which has been observed experimentally and using molecular dynamics simulation, involves the activation of motions required for enzyme function. Here we present parallel measurements of the activity and dynamics of a cryosolution of glutamate dehydrogenase as a function of temperature. The dynamical atomic fluctuations faster than ~100 ps were determined using neutron scattering. The results show that the enzyme remains active below the dynamical transition observed at ~220 K, i.e., at temperatures where no anharmonic motion is detected. Furthermore, the activity shows no significant deviation from Arrhenius behavior down to 190 K. The results indicate that the observed transition in the enzyme's dynamics is decoupled from the rate-limiting step along the reaction coordinate

Direct determination of vibrational density of states change on ligand binding to a protein

The change in the vibrational density of states of a protein (dihydrofolate reductase) on binding a ligand (methotrexate) is determined using inelastic neutron scattering. The vibrations of the complex soften significantly relative to the unbound protein. The resulting free-energy change, which is directly determined by the density of states change, is found to contribute significantly to the binding equilibrium

Longitudinal Analysis of Technical Debt for Strategic Platform Adoption

Increasingly, software producing organizations utilize a common software platform, joining an ecosystem; however, little expertise exists on selecting which platform to use when presented a number of different platforms. While technical debt can be used to examine the quality of a software platform by the organization that produces the software, a single discrete data point does not provide sufficient context for analysis. In this paper, we seek to resolve this difficulty by applying linear regression analysis to technical debt data collected by the SonarQube static analyzer. We apply this method to a case study on Cytoscape network analysis platform to perform a pedagogical investigation on the longitudinal technical debt found in that platform. We present our case study on the longitudinal technical debt in the form of arguments for and against the adoption of the Cytoscape network analysis platform, utilizing the data and analysis generated from our method