Direct calculation of solid-liquid equilibria from density-of-states Monte Carlo simulations

A density-of-states Monte Carlo method is proposed for simulations of solid-liquid phase equilibria. A modified Wang-Landau density-of-states sampling approach is used to perform a random walk in regions of potential energy and volume relevant to solid-liquid equilibrium. The method provides a direct estimate of the relative density of states [Omega(U,V)] and thus the relative free energy within these regions, which is subsequently used to determine portions of the melting curve over wide ranges of pressure and temperature. The validity and usefulness of the method are demonstrated by performing crystallization simulations for the Lennard-Jones fluid and for NaCl.     

Preparation of protein gradients through the controlled deposition of protein-nanoparticle conjugates onto functionalized surfaces

This paper describes a simple method for the preparation and characterization of protein density gradients on solid supports. The method employs colloidal metal nanoparticles as protein carriers and optical tags and is capable of forming linear, exponential, 1D, 2D, and multiprotein gradients of varying slope without expensive or sophisticated surface patterning techniques. Surfaces patterned with proteins using the procedures described within are shown to support cell growth and are thus suitable for studies of protein-cell interactions.     

Integration of gold nanoparticles in optical resonators

The optical absorption of one-dimensional photonic crystal based resonators containing different types of gold nanoparticles is controllably modified by means of the interplay between planar optical cavity modes and localized surface plasmons. Spin-casting of metal oxide nanoparticle suspensions was used to build multilayered photonic structures that host (silica-coated) gold nanorods and spheres. Strong reinforcement and depletion of the absorptance was observed at designed wavelength ranges, thus proving that our method provides a reliable means to modify the optical absorption originated at plasmonic resonances of particles of arbitrary shape and within a wide range of sizes. These observations are discussed on the basis of calculations of the spatial and spectral dependence of the optical field intensity within the multilayers.     

Effective surface tension for capillary fluctuations at the vapor-liquid interface

Thermal fluctuations of the surface of argon-like cluster are considered. Data obtained by molecular dynamics method are used to find effective surface tension for the capillary component of fluctuations, which characterizes the deviation of Fourier spectrum observed in numerical experiment from the spectrum of macroscopic capillary waves. The variational method was used to solve the problem. It is revealed that effective surface tension is close to constant value within a rather wide wavelength range. At the boundary of this range in the region of large wave numbers, the obtained value quickly tends to infinity, while spectral amplitudes decay thus corresponding to the theory proposed previously. The width of damping region is estimated for different temperatures and cluster sizes.     

An ultramicromethod for the determination of blood glucose using modified o-toluidine reagent

A rapid method for the determination of glucose on ultramicro samples of plasma and serum has been described. Protein precipitation does not seem to be necessary, and thus, has been eliminated from the method. Once the reaction is terminated by placing in cold water, the absorbance of unknown and known may be read at any time within 1 hr. Accurate glucose determinations are obtainable when the reagents are stored at refrigerated temperatures for 6 months. Prepackaging of the reagents in individual test units of the Unopette System streamlines this method by reducing technicians' time and eliminating reagent waste. Ultramicrosampling is easy and accurate with the Unopette System, which makes it possible to use small samples of blood (a desirable quality in pediatrics and when performing glucose tolerance tests).     

Screening of organophosphorus pesticides using liquid chromatography-atmospheric pressure chemical ionization mass spectrometry.

Screening and identification of organophosphorus pesticides in blood from patients suffering from acute agricultural chemical toxicity were established by a liquid chromatography-atmospheric pressure chemical ionization mass spectrometric method. To determine 21 pesticides, it was necessary to monitor both positive and negative ions. This method could easily screen for 21 organophosphorus pesticides in less than 30 min. By comparison with a gas chromatographic-mass spectrometric method, the chemicals indicated a similar extent of specificity and within equivalent detection limits, thus satisfying clinical requirements completely.     

Vanadium-containing mesoporous silica of high photocatalytic activity and stability even in water

Vanadium-containing mesoporous silica molecular sieve (V proportional HMS) with tetrahedrally coordinated V-oxide species (VVO4) has been prepared by a modified surfactant-templating method, consisting of an addition of surfactant to a mixture of water, alcohol, and Si and V precursors followed by calcination. The V proportional HMS demonstrates high photocatalytic activity even in the presence of water, while other V proportional HMS's prepared by conventional templating methods and V/HMS prepared by an impregnation method show almost no activity owing to hydrolysis of the VVO4 species. ESR and photoluminescence measurements reveal that the modified templating method creates VVO4 species confined within a silica layer, while other methods create VVO4 species exposed on silica surface. The former VVO4 species are highly stabilized by the confinement within the silica, thus suppressing the hydrolysis. Another notable property of the confined VVO4 species is the higher photocatalytic activity even without water, despite their confined structure. This is explained by higher electrophilicity and longer lifetime of the excited-state VVO4 species (VIVO4*) derived from their distorted structure. The obtained findings suggest potential use of the modified surfactant-templating method for synthesis of stable and recyclable V-containing mesoporous silica with high photocatalytic activity.     

Molecular orbital calculations based on linear combinations of fragment orbitals

A semiempirical MO method based on localized fragment orbitals has been developed, which is particularly suited for the construction of orbital correlation diagrams for the discussion of the electronic structure of complex molecules in terms of fragments and their interactions. The method allows for the inclusion of experimental ionization potentials and electron affinities of the fragments within the calculation of the Fock matrix elements and may thus form the basis of an interpretation of photoelectron spectra, comparable to the interpretation of UV spectra by means of the MIM method of Longuet-Higgins and Murrell. Several levels of approximation are discussed using the acrolein molecule as an example.     

Detection of chemical alterations at internal walls of microchannel flow cells by nondestructive fluorescence depolarization

A recent trend is the production of workable microchannel flow cells (MF cells). The nondestructive methods used to assess their reliability are based mainly on output monitoring and do not evaluate internal chemical interactions. We investigate a nondestructive method for evaluating changes in the chemical composition of the inner walls based on evaluation of the extent of alignment of a fluorescent probe in a liquid flowing within MF cells. Two MF cells were built with a 10-microm inner spacing. Their inner walls had four parallel SnO(2) strips, 2.00 mm wide, separated by 0.50-mm-wide glass strips. One cell had strips parallel to the flow and the other perpendicular. Flow-induced intermolecular alignment of rhodamine B in monoethylene glycol was scanned with 28-microm precision by fluorescence depolarization, using polarized-laser-induced fluorescence within induced flows (PLF-FI). No changes of polarization were seen when the flow was stopped. Under flowing conditions, polarization was always 4% lower in the glass region as compared to SnO(2). Glass had a higher solid-liquid interfacial tension (determined by contact angle measurements), thus being more wettable and increasing the drag, which propagates into the liquid flow, decreasing polarization. PLF-FI can thus identify regions with different chemical constitutions.     

Constant pH Molecular Dynamics in Explicit Solvent with λ-Dynamics

pH is an important parameter in condensed-phase systems, because it determines the protonation state of titratable groups and thus influences the structure, dynamics, and function of molecules in solution. In most force field simulation protocols, however, the protonation state of a system (rather than its pH) is kept fixed and cannot adapt to changes of the local environment. Here, we present a method, implemented within the MD package GROMACS, for constant pH molecular dynamics simulations in explicit solvent that is based on the λ-dynamics approach. In the latter, the dynamics of the titration coordinate λ, which interpolates between the protonated and deprotonated states, is driven by generalized forces between the protonated and deprotonated states. The hydration free energy, as a function of pH, is included to facilitate constant pH simulations. The protonation states of titratable groups are allowed to change dynamically during a simulation, thus reproducing average protonation probabilities at a certain pH. The accuracy of the method is tested against titration curves of single amino acids and a dipeptide in explicit solvent.     

Where are the GaPs? A rational approach to monomer acquisition and selection

Gridding and partitioning (GaP) is a computational method for the classification and selection of monomers for combinatorial libraries. The molecules are described in terms of the pharmacophoric groups they contain and where those pharmacophoric groups can be located in three-dimensional space. The approach involves a detailed conformational analysis of each molecule. This conformational analysis is done within a common coordinate frame, thus enabling the monomers to be compared. The use of a partitioned space is central to this particular application as it facilitates the identification of regions of space which are not well represented by existing compounds. Several ways to extend the use of partitioned pharmacophore spaces are described. Applications of the approach in monomer acquisition and in library design are outlined.     

Global optimization for parameter estimation of differential-algebraic systems

The estimation of parameters in semi-empirical models is essential in numerous areas of engineering and applied science. In many cases, these models are described by a set of ordinary-differential equations or by a set of differential-algebraic equations. Due to the presence of non-convexities of functions participating in these equations, current gradient-based optimization methods can guarantee only locally optimal solutions. This deficiency can have a marked impact on the operation of chemical processes from the economical, environmental and safety points of view and it thus motivates the development of global optimization algorithms. This paper presents a global optimization method which guarantees ɛ-convergence to the global solution. The approach consists in the transformation of the dynamic optimization problem into a nonlinear programming problem (NLP) using the method of orthogonal collocation on finite elements. Rigorous convex underestimators of the nonconvex NLP problem are employed within the spatial branch-and-bound method and solved to global optimality. The proposed method was applied to two example problems dealing with parameter estimation from time series data.     

Mapping Enzyme Activity on Tissue by Functional Mass Spectrometry Imaging

Enzymes are central components of most physiological processes, and are consequently implicated in various pathologies. High‐resolution maps of enzyme activity within tissues therefore represent powerful tools for elucidating enzymatic functions in health and disease. Here, we present a novel mass spectrometry imaging (MSI) method for assaying the spatial distribution of enzymatic activity directly from tissue. MSI analysis of tissue sections exposed to phospholipid substrates produced high‐resolution maps of phospholipase activity and specificity, which could subsequently be compared to histological images of the same section. Functional MSI thus represents a new and generalisable method for imaging biological activity in situ.     

A new method for estimating the importance of hydrogen-bonding groups in the binding site of a protein

We introduce a new method to estimate the importance of hydrogen-bonding sitepoints in the binding site of a protein as part of a structure-based design strategy. Our method identifies hydrogen-bonding sitepoints within a binding pocket and ranks them according to both the accessibility of their hydrogen bonding regions to incoming ligands and their hydrogen-bonding strength. The combination of these components produces a prioritised list of sitepoints that are more likely to be involved in hydrogen bonding with an incoming ligand. A dataset of known protein-ligand interactions was used to compare the prioritisation of sitepoints identified by our method with those observed to be engaged in hydrogen bonding in their crystal structures. Our method was able to remove those sitepoints unable to bind the ligand due to a low accessibility or an unfavourable orientation and to award significantly higher hydrogen-bonding ranking values to those sitepoints observed to form hydrogen bonds. Our method can thus be used to identify hydrogen-bonding sitepoints that should be targeted preferentially in a drug design strategy.     

Parametrization of semiempirical models against ab initio crystal data: evaluation of lattice energies of nitrate salts

A method to estimate the lattice energies E(latt) of nitrate salts is put forward. First, E(latt) is approximated by its electrostatic component E(elec). Then, E(elec) is correlated with Mulliken atomic charges calculated on the species that make up the crystal, using a simple equation involving two empirical parameters. The latter are fitted against point charge estimates of E(elec) computed on available X-ray structures of nitrate crystals. The correlation thus obtained yields lattice energies within 0.5 kJ/g from point charge values. A further assessment of the method against experimental data suggests that the main source of error arises from the point charge approximation.     

Cost-effective interrogation of single nucleotide polymorphisms using the mismatch amplification mutation assay and capillary electrophoresis

The ability to characterize SNPs is an important aspect of many clinical diagnostic, genetic and evolutionary studies. Here, we designed a multiplexed SNP genotyping method to survey a large number of phylogenetically informative SNPs within the genome of the bacterium Bacillus anthracis. This novel method, CE universal tail mismatch amplification mutation assay (CUMA), allows for PCR multiplexing and automatic scoring of SNP genotypes, thus providing a rapid, economical and higher throughput alternative to more expensive SNP genotyping techniques. CUMA delivered accurate B. anthracis SNP genotyping results and, when multiplexed, saved reagent costs by more than 80% compared with TaqMan real-time PCR. When real-time PCR technology and instrumentation is unavailable or the reagents are cost-prohibitive, CUMA is a powerful alternative for SNP genotyping.     

Indirect determination of aqueous ozone concentrations via oxidation of iron(II)

A method is described for determination of ozone in clean aqueous solutions from the extent of oxidation of excess of iron (II); the excess is quantified spectrophotometrically by using 4,7-diphenyl-1,10-phenanthroline disulfonate. With suitable reaction conditions, the ozone concentrations thus determined agree within 1% with those determined by ultraviolet absorption for ozone concentrations near 3×10^?4 M and within 5% with those obtained by using the indigo dye bleaching method for ozone concentrations near 3×10^?5 M.     

Theoretical prediction of eutectic temperature and composition

An empirical method for the theoretical prediction of eutectic temperatures and compositions, for binary systems forming simple eutectics, from the reported values of freezing points and fusion enthalpies of the components is described. The eutectic temperatures and compositions thus predicted for systems involving organic compounds are found to be within ±2.5 K and ±0.03 of the experimental values, respectively. However, for binary metal systems this method is of limited success.