Look before you leap : a confidence-based method for selecting species criticality while avoiding negative populations in τ-leaping

The stochastic simulation algorithm was introduced by Gillespie and in a different form by Kurtz. There have been many attempts at accelerating the algorithm without deviating from the behavior of the simulated system. The crux of the explicit τ-leaping procedure is the use of Poisson random variables to approximate the number of occurrences of each type of reaction event during a carefully selected time period, τ. This method is acceptable providing the leap condition, that no propensity function changes “significantly” during any time-step, is met. Using this method there is a possibility that species numbers can, artificially, become negative. Several recent papers have demonstrated methods that avoid this situation. One such method classifies, as critical, those reactions in danger of sending species populations negative. At most, one of these critical reactions is allowed to occur in the next time-step. We argue that the criticality of a reactant species and its dependent reaction channels should be related to the probability of the species number becoming negative. This way only reactions that, if fired, produce a high probability of driving a reactant population negative are labeled critical. The number of firings of more reaction channels can be approximated using Poisson random variables thus speeding up the simulation while maintaining the accuracy. In implementing this revised method of criticality selection we make use of the probability distribution from which the random variable describing the change in species number is drawn. We give several numerical examples to demonstrate the effectiveness of our new method.

Modeling intrinsic noise and delays in chemical kinetics of coupled autoregulated oscillating cells

Delays are an important feature in temporal models of genetic regulation due to slow biochemical processes, such as transcription and translation. In this paper, we show how to model intrinsic noise effects in a delayed setting by either using a delay stochastic simulation algorithm (DSSA) or, for larger and more complex systems, a generalized Binomial τ-leap method (Bτ-DSSA). As a particular application, we apply these ideas to modeling somite segmentation in zebra fish across a number of cells in which two linked oscillatory genes (her1 and her7) are synchronized via Notch signaling between the cells.

A Krylov-based finite state projection algorithm for solving the chemical master equation arising in the discrete modelling of biological systems

Biochemical reactions underlying genetic regulation are often modelled as a continuous-time, discrete-state, Markov process, and the evolution of the associated probability density is described by the so-called chemical master equation (CME). However the CME is typically difficult to solve, since the state-space involved can be very large or even countably infinite. Recently a finite state projection method (FSP) that truncates the state-space was suggested and shown to be effective in an example of a model of the Pap-pili epigenetic switch. However in this example, both the model and the final time at which the solution was computed, were relatively small. Presented here is a Krylov FSP algorithm based on a combination of state-space truncation and inexact matrix-vector product routines. This allows larger-scale models to be studied and solutions for larger final times to be computed in a realistic execution time. Additionally the new method computes the solution at intermediate times at virtually no extra cost, since it is derived from Krylov-type methods for computing matrix exponentials. For the purpose of comparison the new algorithm is applied to the model of the Pap-pili epigenetic switch, where the original FSP was first demonstrated. Also the method is applied to a more sophisticated model of regulated transcription. Numerical results indicate that the new approach is significantly faster and extendable to larger biological models.

A novel method for the synthesis of monodisperse gold-coated silica nanoparticles

Monodisperse silica nanoparticles were synthesised by the well-known Stober protocol, then dispersed in acetonitrile (ACN) and subsequently added to a bisacetonitrile gold(I) coordination complex ([Au(MeCN)2]?) in ACN. The silica hydroxyl groups were deprotonated in the presence of ACN, generating a formal negative charge on the siloxy groups. This allowed the [Au(MeCN)2]? complex to undergo ligand exchange with the silica nanoparticles and form a surface coordination complex with reduction to metallic gold (Au0) proceeding by an inner sphere mechanism. The residual [Au(MeCN)2]? complex was allowed to react with water, disproportionating into Au0 and Au(III), respectively, with the Au0 adding to the reduced gold already bound on the silica surface. The so-formed metallic gold seed surface was found to be suitable for the conventional reduction of Au(III) to Au0 by ascorbic acid (ASC). This process generated a thin and uniform gold coating on the silica nanoparticles. The silica NPs batches synthesised were in a size range from 45 to 460 nm. Of these silica NP batches, the size range from 400 to 480 nm were used for the gold-coating experiments.

An empirical study of business method patent applications filed in Australia 2000-2009

This article sets out the results of an empirical research study into the uses to which the Australian patent system is being put in the early 21st century. The focus of the study is business method patents, which are of interest because they are a controversial class of patent that are thought to differ significantly from the mechanical, chemical and industrial inventions that have traditionally been the mainstay of the patent system. The purpose of the study is to understand what sort of business method patent applications have been lodged in Australia in the first decade of this century and how the patent office is responding to those applications.

A multi-scaled approach for simulating chemical reaction systems

In this paper we give an overview of some very recent work, as well as presenting a new approach, on the stochastic simulation of multi-scaled systems involving chemical reactions. In many biological systems (such as genetic regulation and cellular dynamics) there is a mix between small numbers of key regulatory proteins, and medium and large numbers of molecules. In addition, it is important to be able to follow the trajectories of individual molecules by taking proper account of the randomness inherent in such a system. We describe different types of simulation techniques (including the stochastic simulation algorithm, Poisson Runge-Kutta methods and the balanced Euler method) for treating simulations in the three different reaction regimes: slow, medium and fast. We then review some recent techniques on the treatment of coupled slow and fast reactions for stochastic chemical kinetics and present a new approach which couples the three regimes mentioned above. We then apply this approach to a biologically inspired problem involving the expression and activity of LacZ and LacY proteins in E coli, and conclude with a discussion on the significance of this work. (C) 2004 Elsevier Ltd. All rights reserved.

Predicting the localized surface plasmon resonances of spherical nanoparticles on substrate : electrostatic eigenmode method

We present experimental results that demonstrate that the wavelength of the fundamental localised surface plasmon resonance for spherical gold nanoparticles on glass can be predicted using a simple, one line analytical formula derived from the electrostatic eigenmode method. This allows the role of the substrate in lifting mode degeneracies to be determined, and the role of local environment refractive indices on the plasmon resonance to be investigated. The effect of adding silica to the casting solution in minimizing nanopaticle agglomeration is also discussed.

Effect of preparation method of palygorskite-supported Fe and Ni catalysts on catalytic cracking of biomass tar

In this study, the effect of catalyst preparation and additive precursors on the catalytic decomposition of biomass using palygorskite-supported Fe and Ni catalysts was investigated. The catalysts were characterized by X-ray diffraction (XRD) and transmission electron microscopy (TEM). It is concluded that the most active additive precursor was Fe(NO3)3·9H2O. As for the catalyst preparation method, co-precipitation had superiority over incipient wetness impregnation at low Fe loadings.

A hydrogen/methane sensor based on niobium tungsten oxide nanorods synthesised by hydrothermal method

An investigation on hydrogen and methane sensing performance of hydrothermally formed niobium tungsten oxide nanorods employed in a Schottky diode structure is presented herein. By implementing tungsten into the surface of the niobium lattice, we create Nb5+ and W5+ oxide states and an abundant number of surface traps, which can collect and hold the adsorbate charge to reinforce a greater bending of the energy bands at the metal/oxide interface. We show experimentally, that extremely large voltage shifts can be achieved by these nanorods under exposure to gas at both room and high temperatures and attribute this to the strong accumulation of the dipolar charges at the interface via the surface traps. Thus, our results demonstrate that niobium tungsten oxide nanorods can be implemented for gas sensing applications, showing ultra-high sensitivities.

Development of a rapid and validated method for investigating the metabolism of scoparone in rat using ultra-performance liquid chromatography/electrospray ionization quadruple time-of-flight mass spectrometry

Scoparone (6,7-dimethoxycoumarin) is known to have a wide range of pharmacological properties. In this study, a rapid and validated ultra-performance liquid chromatography/electrospray ionization quadruple time-of-flight mass spectrometry (UPLC/ESI-QTof-MS) method was developed to investigate the metabolism of scoparone in rat for the first time. The new method reduced the sample handling and analytical time by three- to six-fold, and the detection limit by five- to 1000-fold, compared to published methods. Far more metabolites were detected and identified compared to published data, which were preliminarily identified as scopoletin, isoscopoletin, isofraxidin, and fraxidin, respectively, when subjected to tandem mass spectrometry analyses. It is found that the metabolic trajectory of scoparone in rat focused on phase I metabolism which is obviously different from published results, and revealed a wide range of pharmacological properties of scoparone partly attributed to the bioactivities of its metabolites.

Pharmacokinetics of isofraxidin in rat plasma after oral administration of the extract of acanthopanax senticosus using HPLC with solid phase extraction method

High-performance liquid chromatography coupled with solid phase extraction method was developed for determination of isofraxidin in rat plasma after oral administration of Acanthopanax senticosus extract (ASE), and pharmacokinetic parameters of isofraxidin either in ASE or pure compound were measured. The HPLC analysis was performed on a Dikma Diamonsil RP(18) column (4.6 mm x 150 mm, 5 microm) with the isocratic elution of solvent A (acetonitrile) and solvent B (0.1% aqueous phosphoric acid, v/v) (A : B = 22 : 78) and the detection wavelength was set at 343 nm. The calibration curve was linear over the range of 0.156-15.625 microg/ml. The limit of detection was 60 ng/ml. The intra-day precision was 5.8%, and the inter-day precision was 6.0%. The recovery was 87.30+/-1.73%. When the dosage of ASE is equal to pure compound caculated by the amount of isofraxidin, it has been found to have two maximum concentrations in plasma while the pure compound only showed one peak in the plasma concentration-time curve. The determined content of isofraxidin in plasma after oral administration of ASE is the total contents of free isofraxidin and its precursors in ASE in vitro. The pharmacokinetic characteristics of ASE showed the priority of the extract and the properities of traditional Chinese medicine.

Rapid synthesis of porous honeycomb Cu/Pd through a hydrogen-bubble templating method

A rapid electrochemical method based on using a clean hydrogen-bubble template to form a bimetallic porous honeycomb Cu/Pd structure has been investigated. The addition of palladium salt to a copper-plating bath under conditions of vigorous hydrogen evolution was found to influence the pore size and bulk concentration of copper and palladium in the honeycomb bimetallic structure. The surface was characterised by X-ray photoelectron spectroscopy, which revealed that the surface of honeycomb Cu/Pd was found to be rich with a Cu/Pd alloy. The inclusion of palladium in the bimetallic structure not only influenced the pore size, but also modified the dendritic nature of the internal wall structure of the parent copper material into small nanometre-sized crystallites. The chemical composition of the bimetallic structure and substantial morphology changes were found to significantly influence the surface-enhanced Raman spectroscopic response for immobilised rhodamine B and the hydrogen-evolution reaction. The ability to create free-standing films of this honeycomb material may also have many advantages in the areas of gas- and liquid-phase heterogeneous catalysis.

Method of making metal oxides

A method for producing particles having at least regions of at least one metal oxide having nano-sized grains comprises providing particles of material having an initial, non-equiaxed particle shape, making a mixture of the particles of material and one or more precursors of the metal oxide, and treating the mixture such that the one or more precursors of the metal oxide react with the particles of material to thereby form at least regions of metal oxide on or within the particles, wherein atoms from the particles of material form part of a matrix of the at least one metal oxide and the at least one metal oxide has nano-sized grains and wherein at least some of the regions of metal oxide on or within the particles have a non-equiaxed grain shape.

Method for the production of porous complex metal oxides using a porogen

A method of producing porous complex oxides includes the steps of providing a mixt. of (a) precursor elements suitable to produce the complex oxide, or (b) one or more precursor elements suitable to produce particles of the complex oxide and one or more metal oxide particles; and (c) a particulate carbon-contg. pore-forming material selected to provide pore sizes in the range of 7-250 nm, and treating the mixt. to (i) form the porous complex oxide in which two or more of the precursor elements from (a) above or one or more of the precursor elements and one or more of the metals in the metal oxide particles from (b) above are incorporated into a phase of the complex metal oxide and the complex metal oxide has grain sizes in the range of 1-150 nm, and (ii) removing the pore-forming material under conditions such that the porous structure and compn. of the complex oxide is substantially preserved. The method may be used to produce nonrefractory metal oxides as well. The mixt. further includes a surfactant, or a polymer. [on SciFinder(R)]