Computational singular perturbation with non-parametric tabulation of slow manifolds for time integration of stiff chemical kinetics

This paper presents a novel tabulation strategy for the adaptive numerical integration of chemical kinetics using the computational singular perturbation (CSP) method. The strategy stores and reuses CSP quantities required to filter out fast dissipative processes, resulting in a non-stiff chemical source term. In particular, non-parametric regression on low-dimensional slow invariant manifolds (SIMs) in the chemical state space is used to approximate the CSP vectors spanning the fast chemical subspace and the associated fast chemical time-scales. The relevant manifold and its dimension varies depending on the local number of exhausted modes at every location in the chemical state space. Multiple manifolds are therefore tabulated, corresponding to different numbers of exhausted modes (dimensions) and associated radical species. Non-parametric representations are inherently adaptive, and rely on efficient approximate-nearest-neighbor queries. As the CSP information is only a function of the non-radical species in the system and has relatively small gradients in the chemical state space, tabulation occurs in a lower-dimensional state space and at a relatively coarse level, thereby improving scalability to larger chemical mechanisms. The approach is demonstrated on the simulation of homogeneous constant pressure H₂–air and CH₄–air ignition, over a range of initial conditions. For CH₄–air, results are shown that outperform direct implicit integration of the stiff chemical kinetics while maintaining good accuracy.     

Stochastic optimization in supply chain networks: averaging robust solutions

We propose a novel robust optimization approach to analyze and optimize the expected performance of supply chain networks. We model uncertainty in the dema     

One‐Pot Synthesis of O‐Allylhydroxylamines through the Organocatalytic Oxidation of Tertiary Allylic Amines Followed by a [2,3]‐Meisenheimer Rearrangement

A cheap, green, and highly efficient one‐pot method for the synthesis of O‐protected allylic alcohols is described. By utilizing 2,2,2‐trifluoroacetophenone as the organocatalyst and H₂O₂ as the oxidant, a variety of allylic amine N‐oxides were synthesized, which upon heating are converted to the final products through a [2,3]‐Meisenheimer rearrangement.     

Magnetically modified single and turbostratic stacked graphenes from tris(2,2'-bipyridyl) iron(II) ion-exchanged graphite oxide

Loading of graphite oxide (GO) with tris(2,2'-bipyridyl) iron(II) ions and subsequent calcination affords a novel graphene-based composite with magnetic and electrically conductive properties. The pH of the starting aqueous suspension and the washing procedure play a crucial role in the successful immobilization of the iron precursor, which is mainly governed by ion exchange. The complex is intercalated between the graphene oxide layers, where it adopts a distorted conformation. Rapid heating of this solid results in the deflagration of GO and the formation of ultrafine ( d = 2-14 nm) Fe2O3 particles with maghemite as the dominant phase. The superparamagnetic maghemite crystals are dispersed uniformly in the high-surface-area diamagnetic matrix built up from single or turbostratic stacked graphenes.     

Affinity chromatography for the purification of therapeutic proteins from transgenic maize using immobilized histamine

Plant molecular pharming is a technology that uses plants as bioreactors to produce recombinant molecules of medical and veterinary importance. In the present study, we evaluated the ability of histamine (HIM), tryptamine (TRM), phenylamine (PHEM) and tyramine (TYRM) coupled to Sepharose CL-4B via a 1,4-butanediol diglycidyl ether spacer to bind and purify human monoclonal anti-HIV antibody 2F5 (mAb 2F5) from spiked maize seed and tobacco leaf extracts. Detailed studies were carried out to determine the factors that affect the chromatographic behaviour of mAb 2F5 and also maize seed and tobacco leaf proteins. All affinity adsorbents showed a reduced capacity to bind and a reduced ability to purify proteins from tobacco extract compared to maize extract. Under optimal conditions, HIM exhibited high selectivity for mAb 2F5 and allowed a high degree of purification (>95% purity) and recovery (>90%) in a single step with salt elution (0.4 M KCl) from spiked maize seed extract. Analysis of the purified antibody fraction by ELISA and Western blot showed that the antibody was fully active and free of degraded variants or modified forms. The efficacy of the system was assessed further using a second therapeutic antibody (human monoclonal anti-HIV antibody mAb 2G12) and a therapeutic enzyme (alpha-chymotrypsin). HIM may find application in the purification of a wide range of biopharmaceuticals from transgenic plants.     

A novel micellar PEGylated hyperbranched polyester as a prospective drug delivery system for paclitaxel

A hyperbranched aliphatic polyester has been functionalized with PEG chains to afford a novel water-soluble BH40-PEG polymer which exhibits unimolecular micellar properties, and is therefore appropriate for application as a drug-delivery system. The solubility of the anticancer drug paclitaxel was enhanced by a factor of 35, 110, 230, and 355 in aqueous solutions of BH40-PEG of 10, 30, 60, and 90 mg x mL(-1), respectively. More than 50% of the drug is released at a steady rate and release is almost complete within 10 h. The toxicity of BH40-PEG was assessed in vitro with A549 human lung carcinoma cells and found to be nontoxic for 3 h incubation up to a 1.75 mg x mL(-1) concentration while LD50 was 3.5 mg x mL(-1). Finally, it was efficiently internalized in cells, primarily in the absence of foetal bovine serum, while confocal microscopy revealed the preferential localization of the compound in cell nuclei. [Figure: see text].     

A self-organizing algorithm for molecular alignment and pharmacophore development

We present a method for simultaneous three-dimensional (3D) structure generation and pharmacophore-based alignment using a self-organizing algorithm called Stochastic Proximity Embedding (SPE). Current flexible molecular alignment methods either start from a single low-energy structure for each molecule and tweak bonds or torsion angles, or choose from multiple conformations of each molecule. Methods that generate structures and align them iteratively (e.g., genetic algorithms) are often slow. In earlier work, we used SPE to generate good-quality 3D conformations by iteratively adjusting pairwise distances between atoms based on a set of geometric rules, and showed that it samples conformational space better and runs faster than earlier programs. In this work, we run SPE on the entire ensemble of molecules to be aligned. Additional information about which atoms or groups of atoms in each molecule correspond to points in the pharmacophore can come from an automatically generated hypothesis or be specified manually. We add distance terms to SPE to bring pharmacophore points from different molecules closer in space, and also to line up normal/direction vectors associated with these points. We also permit pharmacophore points to be constrained to lie near external coordinates from a binding site. The aligned 3D molecular structures are nearly correct if the pharmacophore hypothesis is chemically feasible; postprocessing by minimization of suitable distance and energy functions further improves the structures and weeds out infeasible hypotheses. The method can be used to test 3D pharmacophores for a diverse set of active ligands, starting from only a hypothesis about corresponding atoms or groups.     

A convenient method for the assignment of relative configuration of acyclic alpha-alkyl-beta-hydroxy carbonyl compounds by (1)H NMR

The relative configuration of acyclic alpha-alkyl-beta-hydroxy carbonyl compounds can be determined by using (1)H NMR spectroscopy. The assignment can be achieved by recording the (1)H NMR spectrum of the syn-anti mixture. The upfield carbinol hydrogen signal belongs to the anti whereas the downfield to the syn stereoisomer.