Totally Order-disconnected Compact Topologies

Posets with property DINT which are Priestely spaces with respect interval topologies are characterized. Also, posets which are Priestley spaces with respect to bi-Scott topologies are characterized.     

Simultaneous quantitation of etoricoxib, salicylic acid, valdecoxib, ketoprofen, nimesulide and celecoxib in plasma by high-performance liquid chromatography with UV detection

A specific, accurate, precise and reproducible high performance liquid chromatography (HPLC) method was developed and validated for the simultaneous quantitation of etoricoxib, salicylic acid, valdecoxib, ketoprofen, nimesulide and celecoxib in human plasma. The method employed a simple liquid-liquid extraction of etoricoxib, salicylic acid, valdecoxib, ketoprofen, nimesulide and celecoxib and internal standard (IS, DRF-4367) from human plasma (500 microL) into acetonitirile. The organic layer was separated and evaporated under a gentle stream of nitrogen at 40 degrees C. The residue was reconstituted in the mobile phase and injected onto a Kromasil KR 100-5C18 column (4.6 x 250 mm, 5 microm). The chromatographic separation was achieved by gradient elution consisting of 0.05 M formic acid (pH 3)-acetonitrile-methanol-water at a flow rate of 1.0 mL/min. The eluate was monitored using an ultraviolet (UV) detector set at 235 nm. The ratio of peak area of each analyte to IS was used for quantification of plasma samples. Nominal retention times of etoricoxib, salicylic acid, valdecoxib, ketoprofen, nimesulide, IS and celecoxib were 15.63, 17.20, 21.66, 24.95, 26.27, 30.24 and 32.22 min, respectively. The standard curve for etoricoxib, salicylic acid, valdecoxib, ketoprofen and celecoxib was linear (r2 > 0.999) in the concentration range 0.1-50 microg/mL and for nimesulide (r2 > 0.999) in the concentration range 0.5-50 microg/mL. Absolute recovery was >83% from human plasma for all the analytes and IS. The lower limit of quantification (LLOQ) of nimesulide was 0.5 microg/mL and for etoricoxib, salicylic acid, valdecoxib, ketoprofen and celecoxib the LLOQ was 0.1 microg/mL. The inter- and intra-day precisions in the measurement of QC samples, 0.1, 0.3, 15.0 and 40.0 microg/mL (for all analytes except nimesulide), were in the range 2.29-9.37% relative standard deviation (RSD) and 0.69-10.28% RSD, respectively. For nimesulide the inter- and intra-day precisions in the measurement of quality control (QC) samples, 0.5, 1.5, 15.0 and 40.0 microg/mL, were in the range 3.21-7.37% RSD and 0.97-7.06% RSD, respectively. Accuracy in the measurement of QC samples for all analytes was in the range 91.03-106.38% of the nominal values. All analytes including IS were stable in the battery of stability studies, viz. bench top, autosampler and freeze-thaw cycles. Stability of all analytes was established for 21 days at -20 degrees C. The application of the assay in an oral pharmacokinetic study in rats co-administered with celecoxib and valdecoxib is described.     

The role of molecular recognition in charge transport properties of doped polyaniline

Molecular recognition plays a significant role in the counterion-induced processibility, morphological features, and physical properties of doped polyaniline (PANI). The interaction of the counterion and solvent controls the chain conformation and, as a result, the formation of extended and localized electronic states; hence, it holds the key for tuning a wide range of electrical and optical properties of doped PANI. The combined effects of counterion, solvent, and processing conditions tune the metal-insulator transition, temperature dependence of conductivity, magnetoresistance, and so forth in doped PANI. The typical examples are shown in the case of PANI doped by camphor sulfonic acid, 2-acrylamido-2-methyl-1-propane sulfonic acid, and dodecylbenzoyl sulfonic acid.     

An unsteady incompressible Navier–Stokes solver for large eddy simulation of turbulent flows

An unsteady incompressible Navier–Stokes solver that uses a dual time stepping method combined with spatially high‐order‐accurate finite differences, is developed for large eddy simulation (LES) of turbulent flows. The present solver uses a primitive variable formulation that is based on the artificial compressibility method and various convergence–acceleration techniques are incorporated to efficiently simulate unsteady flows. A localized dynamic subgrid model, which is formulated using the subgrid kinetic energy, is employed for subgrid turbulence modeling. To evaluate the accuracy and the efficiency of the new solver, a posteriori tests for various turbulent flows are carried out and the resulting turbulence statistics are compared with existing experimental and direct numerical simulation (DNS) data. Copyright © 1999 John Wiley & Sons, Ltd.     

Novel Big Data-Driven Machine Learning Models for Drug Discovery Application

Most contemporary drug discovery projects start with a ‘hit discovery’ phase where small chemicals are identified that have the capacity to interact, in a chemical sense, with a protein target involved in a given disease. To assist and accelerate this initial drug discovery process, ’virtual docking calculations’ are routinely performed, where computational models of proteins and computational models of small chemicals are evaluated for their capacities to bind together. In cutting-edge, contemporary implementations of this process, several conformations of protein targets are independently assayed in parallel ‘ensemble docking’ calculations. Some of these protein conformations, a minority of them, will be capable of binding many chemicals, while other protein conformations, the majority of them, will not be able to do so. This fact that only some of the conformations accessible to a protein will be ’selected’ by chemicals is known as ’conformational selection’ process in biology. This work describes a machine learning approach to characterize and identify the properties of protein conformations that will be selected (i.e., bind to) chemicals, and classified as potential binding drug candidates, unlike the remaining non-binding drug candidate protein conformations. This work also addresses the class imbalance problem through advanced machine learning techniques that maximize the prediction rate of potential protein molecular conformations for the test case proteins ADORA2A (Adenosine A2a Receptor) and OPRK1 (Opioid Receptor Kappa 1), and subsequently reduces the failure rates and hastens the drug discovery process.     

Fluorescence Turn off Sensor for Brilliant Blue FCF- an Approach Based on Inner Filter Effect

A nanosensor with fluorometric readout based on L-cysteine capped cadmium sulphide quantum dots for discriminative detection and determination of Brilliant blue FCF (BB) (in 0.5 M Tris buffer solution of pH 9.5) over other synthetic food colourants is developed. Mechanism of the nanosensor is based on inner filter effect (IFE). The addition of BB into quantum dot solution might induce the quenching of fluorescence. The nanosensor described in this report reveals its simplicity and flexibility due to less laborious and more cost-effective synthesis. The developed fluorescence sensor showed excellent selectivity towards BB, and allows the detection as low as 3.50 × 10^?7 M. The developed sensor exhibited a linear concentration range of 4.00 × 10^?5 to 4.50 × 10^?6 M. More importantly, the proposed sensor exhibit sensitive responses toward BB in food samples such as sports drink and candies, demonstrating its potential in food analysis, which might be significant in food quality control in the future.     

Gradient Systems with Wiggly Energies¶and Related Averaging Problems

Gradient systems with wiggly energies of the form

$$

and A:? ^d →? wereproposed by Abeyaratne, Chu &; James [2] to study the kinetics of martensitic phase transitions. Their model may be recast in the framework of the theory of averaging as a dynamical system on ? ^d ×? ^d , with the slow variable x∈? ^d and fast variable θ∈? ^d . However, this problem lies completely outside the classical theory of averaging, since the vertical flow on ? ^d is not ergodic for sets of positive measure, and we must interpret averages to mean weak limits.

We obtain rigorous averaging results for d= 2. We use Schwartz's generalization of the Poincaré-Bendixson theorem [37] to heuristically derive homogenized equations for the weak limits. These equations depend on the ω-limit sets for the vertical flow on fibres. When the vertical flow is structurally stable, we use the persistence of hyperbolic structures to prove that these are the correct equations. We combine these theorems with a study of two-parameter bifurcations of flows on ?² to characterize the weak limits. Our results may be interpreted as follows. The space ?² breaks into: (˙1) a bounded open set surrounding {?F ^?1 (0)} where there is only sticking, (˙2) a transition region outside this set, where the dynamics is a combination of sticking and slipping, and (˙3) the rest of the plane, which contains a countable number of resonance zones, with nonempty interior, and their nowhere dense complement. Inside a resonance zone the direction of the weak limits is given by the rotation number ρ∈?. The Cantor set structure of the resonance zones is described by well-known results of Arnol'd [7] and Herman [27] in the theory of circle diffeomorphisms. Consequently, the homogenized equations vary on all scales. We also study the linear transport equation associated with the wiggly gradient flow, and show that its homogenization limit is not well posed.Smyshlyaev has studied this problem independently, and some of our results are similar [39].