Stability properties of nonlinear systems with fluctuating parameters: I. Nonlinear oscillators

We have determined the stability properties of nonlinear oscillators with fluctuating potential parameters and a fluctuating additive driving force. It is shown that nonlinearities in general stabilize moments known to diverge in the corresponding linear system.     

Proton dynamics in hydrogen-bonded systems

We discuss a simplified version of an ice lattice which consists of an alternating sequence of heavy and light masses. The light masses (protons) are each subject to a bistable potential caused by the heavy masses (oxygens). The protons interact with one another, as do the heavy ions. The interactions between the protons and the oxygens modulate the bistable proton potential. This system is known to exhibit kink and antikink solutions associated with mobile ionic defects accompanied by a lattice distortion. We show that at finite temperatures and in the presence of a constant external field on the protons, the defect velocity is a nonmonotonic function of the temperature, reflecting an interesting interplay of thermal effects (noise) and the constant deterministic external forcing in this nonlinear system. We discuss extensions of the model to higher dimensions, and present preliminary results for the proton motion in such networks.     

Order statistics for first passage times in diffusion processes

We consider the problem of the first passage times for absorption (trapping) of the firstj (j = 1,2, ....) ofk, j <k, identical and independent diffusing particles for the asymptotic case k?>1. Our results are a special case of the theory of order statistics. We show that in one dimension the mean time to absorption at a boundary for the first ofk diffusing particles, μ_1,k , goes as (lnk)^?1 for the set of initial conditions in which none of thek particles is located at a boundary and goes ask ^?2 for the set of initial conditions in which some of thek particles may be located at the boundary. We demonstrate that in one dimension our asymptotic results (k21) are independent of the potential field in which the diffusion takes place for a wide class of potentials. We conjecture that our results are independent of dimension and produce some evidence supporting this conjecture. We conclude with a discussion of the possible import of these results on diffusion-controlled rate processes.     

Determination of Triton X-100 in influenza vaccine by high-performance liquid chromatography and capillary electrophoresis

Triton X-100 is applied to influenza vaccines at different stages of the manufacturing process to prevent aggregation and precipitation of biomolecules. Furthermore it is used to disintegrate the virus particles in split vaccine and to guarantee the homogeneity during production and utilisation. The final concentration of Triton X-100 has to be determined because the concentration changes in manufacturing process. The determination of the total amount of Triton X-100 as well as the separation of its ethylene oxide oligomers was possible with high-performance liquid chromatography (HPLC) and capillary electrophoresis (CE). In HPLC a change of the column and eluent was necessary, in CE different electrolytes were used for the various separation effects. The HPLC method for the analysis of total Triton was preferred for the quantification of Triton X-100 in influenza vaccine because of better linearity, reproducibility and detection sensitivity compared to CE. In the end products an average concentration of 0.117 mg/mL was found. Received: 19 December 1996 / Revised: 27 February 1997 / Accepted: 6 March 1997     

In vitro metabolic profiling of synthetic cannabinoids by pooled human liver microsomes,cytochrome P450 isoenzymes,and Cunninghamella elegans and their detection in urine samples

As synthetic cannabinoids are extensively metabolized, there is an urgent need for data on which metabolites can be used for successful urine screening. This study examines the in vitro metabolism of EG-018 and its 5F-analogue EG-2201 by means of comparing three different in vitro models: pooled human liver microsomes, cytochrome P450 isoenzymes, and a fungal approach utilizing the filamentous fungus Cunninghamella elegans LENDNER, which is known for its ability to mimic human biotransformation of xenobiotics. In addition, this study includes the screening of two authentic urine samples from individuals with proven EG-018 consumption, for the evaluation of in vitro–in vivo extrapolations made in the study. Incubation with pooled human liver microsomes yielded 15 metabolites of EG-018 belonging to six different metabolite subgroups, and 21 metabolites of EG-2201 belonging to seven different metabolite subgroups, respectively. Incubation with cytochrome P450 isoenzymes incubation yielded a further three EG-018 and five EG-2201 metabolites. With reference to their summed metabolite peak abundancies, the isoenzymes CYP2C9, CYP2C19, CYP2D6, CYP3A4, and CYP3A5 were shown to contribute most to the microsomal metabolism of EG-018 and EG-2201. CYP2B6 was shown to make the lowest contribution, by far. As the phase I metabolism of both synthetic cannabinoids was shown to be distributed over a substantial number of different cytochrome P450 isoenzymes, it was concluded that it is likely to not be significantly affected by co-consumption of other drugs. Although fungal incubation with Cunninghamella elegans yielded an additional three EG-018 and four EG-2201 metabolites not observed after microsomal incubation, metabolites generated by Cunninghamella elegans were in good correlation with those generated by microsomal incubations. The fungal model demonstrated its ability to be an independent in vitro model in synthetic cannabinoid metabolism research. The three tested in vitro models enable sufficient predictive in vitro–in vivo extrapolations, comparable to those obtained from hepatocyte incubation published in the literature. In addition, with regard to the screening of authentic urine samples and comparison with the literature, one monohydroxylated EG-018 metabolite and two monohydroxylated EG-2201 metabolites can be recommended as urinary targets, on the basis of the tested in vitro models.

Graphical abstract

     

Quantifying the effect of membrane potential in chemical osmosis across bentonite membranes by virtual short-circuiting

Clay liners are charged membranes and show semipermeable behavior regarding the flow of fluids, electrical charge, chemicals and heat. At zero gradients of temperature and hydrostatic pressure, a salt concentration gradient across a compacted clay sample induces not only an osmotic flux of water and diffusion of salt across the membrane but also an electrical potential gradient, defined as membrane potential. Laboratory experiments were performed on commercially available bentonite samples in a rigid-wall permeameter connected to two electrically insulated fluid reservoirs filled with NaCl solutions of different concentrations and equipped with Ag/AgCl electrodes to measure the electrical potential gradient. The effect of membrane potential could be cancelled out by short-circuiting the clay with the so-called virtual shortcut. The potential gradient across the sample is brought to zero with a negative feedback circuit. It was observed that the water flux and the diffusion of Cl- were hindered by the occurrence of a membrane potential, indicating that an electroosmotic counterflow is induced. Flow parameters were calculated with modified coupled flow equations of irreversible thermodynamics. They were in excellent agreement with values reported in the literature. Comparing the method of short-circuiting with a study elsewhere, where the electrodes were physically short-circuited, it was shown that the virtual shortcut is more appropriate because physically short-circuiting induces additional effects that are attributed to the fluxes.     

Unusual properties of the first copper complex containing a pi(eta 2)-coordinated phosphorus-carbon double bond moiety

The first stable phosphaarene pi-complex of copper displays unusual 31P NMR data that suggest a novel interpretation of 31P coordination shifts in pi-complexes of phosphorus containing multiple bonds.     

Palladium(0)-catalyzed cycloisomerization of enallenes

A novel palladium(0)-catalyzed cycloisomerization of enallenes has been developed. This reaction, catalyzed by [Pd(dba)2] (dba=dibenzylideneacetone) in acetic acid, results in the formation of cyclopentene derivatives and [n.3.0]bicyclic systems (n=3, 4) in good to high yields. The carbon-carbon bond-forming step is highly stereoselective to give cis-fused bicyclic systems. The presence of acetic acid as solvent and dba as ligand for palladium(0) turned out to be essential for the reaction in order to provide good reactivity and regioselectivity.