Structural revision and absolute configuration of lateritin

‘Lateritin’ (1), a morpholine-2,5-dione (depsipeptide), was reinvestigated for its structure and absolute configuration. On the basis of thorough 1D and 2D NMR and mass spectrometrical analyses, the structure of 1 was revised to be identical with beauvericin (8) and confirmed that beauvericin (8) is the trimeric lactone of ‘lateritin’ (1). The absolute configuration was determined by acidic hydrolysis, followed by application of Marfey’s method, menthyl ester derivatization, and GC–MS analysis. In addition, the specific optical rotation values of the hydrolysis products were compared with those of available standards.     

Visualizing elements of order two in the Weil-Châtelet group

Let E be an elliptic curve over an infinite field K with characteristic ≠2, and σ∈H¹(G_K,E)[2] a two-torsion element of its Weil-Châtelet group. We prove that σ is always visible in infinitely many abelian surfaces up to isomorphism, in the sense put forward by Cremona and Mazur in their article (J. Exp. Math. 9(1) (2000) 13). Our argument is a variant of Mazur's proof, given in (Asian J. Math. 3(1) (1999) 221), for the analogous statement about three-torsion elements of the Shafarevich-Tate group in the setting where K is a number field. In particular, instead of the universal elliptic curve with full level-three-structure, our proof makes use of the universal elliptic curve with full level-two-structure and an invariant differential.     

The photocurrent response of human cones is fast and monophasic

Background  

The precise form of the light response of human cone photoreceptors in vivo has not been established with certainty. To investigate the response shape we compare the predictions of a recent model of transduction in primate cone photoreceptors with measurements extracted from human cones using the paired-flash electroretinogram method. As a check, we also compare the predictions with previous single-cell measurements of ground squirrel cone responses.     

Estimating the domain of applicability for machine learning QSAR models: a study on aqueous solubility of drug discovery molecules

We investigate the use of different Machine Learning methods to construct models for aqueous solubility. Models are based on about 4000 compounds, including an in-house set of 632 drug discovery molecules of Bayer Schering Pharma. For each method, we also consider an appropriate method to obtain error bars, in order to estimate the domain of applicability (DOA) for each model. Here, we investigate error bars from a Bayesian model (Gaussian Process (GP)), an ensemble based approach (Random Forest), and approaches based on the Mahalanobis distance to training data (for Support Vector Machine and Ridge Regression models). We evaluate all approaches in terms of their prediction accuracy (in cross-validation, and on an external validation set of 536 molecules) and in how far the individual error bars can faithfully represent the actual prediction error.     

Paclitaxel solubility in aqueous dispersions and mixed micellar solutions of lecithin

The aim of this study was to find a biocompatible, lecithin-based carrier for paclitaxel (PTX) suitable for intravenous infusion and ensuring a soluble PTX concentration of 100 mg/100 ml or higher for at least 24 h. Aqueous dispersions of egg or soya lecithin (water-lecithin dispersions, WLD), mixed micellar (MM) solutions of egg lecithin and sodium deoxycholate, and formulations containing lecithin plus the co-surfactants and co-solvents poloxamer, polysorbate, Span, benzalkonium chloride, and macrogol were investigated. Amorphous PTX was prepared by lyophilization. PTX co-lyophilized with surfactants was also studied. Unlike crystalline PTX, the drug in an amorphous form is easily soluble in 1-5% (w/w) WLD or in MM. The highest solubility (up to 570 mg/100 ml) was achieved in 5% WLD. Dissolved PTX precipitated from all tested formulations over 24 h. Despite this, concentrations of dissolved PTX of 100 mg/100 ml or higher were observed after 24 h in 5% egg WLD, 1-5% soya WLD, and in 5% MM (lecithin : deoxycholate ratio 1 : 1 w/w). When four different batches of 5% egg WLD were prepared, containing PTX in clinically relevant concentration of 100 mg/100 ml, no precipitation of PTX was observed within 24 h and this formulation is the most promising candidate for further in vivo studies. Neither additional surfactants nor co-lyophilization increased PTX solubility in the lecithin-based carriers. The use of parenteral emulsions as solvents for the co-lyophilized PTX also failed to increase the solubility of the drug up to the target concentration.     

Distribution of Chlorinated Hydrocarbons in Different Ecosystems in Germany

Abstract

The German Environmental Specimen Bank (GESB) was established in 1985 as a permanent institution for the systematic collection, processing, characterization and storage of representative environmental samples from different ecosystems throughout Germany. Immediately after the reunification a special sampling campaign was performed in representative areas of the former GDR focusing on the assessment of the environmental pollution situation. These samples can be regarded as a basis for monitoring the development of spatial and temporal trends in Eastern Germany. Selected results about the determination of chlorinated hydrocarbons (CHC) in various bioindicators (earthworms, pigeon eggs, poplar leaves, pine shoots, breams) are presented. Particular emphasis is given to the comparsion of the CHC burden in East and West Germany with respect to different contamination sources.     

Mechanism of the initial stage of silicate oligomerization

The mechanism of the initial stage of silicate oligomerization from solution is still not well understood. Here we use an off-lattice kinetic Monte Carlo (kMC) approach called continuum kMC to model silicate oligomerization in water solution. The parameters required for kMC are obtained from density functional theory (DFT) calculations. The evolution of silicate oligomers and their role in the oligomerization process are investigated. Results reveal that near-neutral pH favors linear growth, while a higher pH facilitates ring closure. The silicate oligomerization rate is the fastest at pH 8. The temperature is found to increase the growth rate and alter the pathway of oligomerization. The proposed pH and temperature-dependent mechanism should lead to strategies for the synthesis of silicate-based materials.     

Heterogeneous reactions of HONO formation from NO2 and HNO3: a review

The photolysis of nitrous acid (HONO) is an important reaction of atmospheric chemistry due to the fact that it can be the source of OH radical in the troposphere. Despite its role as a radical precursor, the chemical mechanisms leading to HONO formation are not well understood. It is commonly assumed that HONO formation is due to both homogeneous and heterogeneous processes involving NO_x (mixture of NO and NO₂) in which the kinetic and mechanistic details are still under investigation. In this discussion, we would like to highlight the formation of HONO from NO₂ and nitric acid (HNO₃) in the presence of organic particulate. We understood that in the real case, many parameters can influence the reaction mechanism; however, this is just an effort to have a better understanding of the study of HONO formation in the atmospheric process.     

On-line immunoaffinity column-liquid chromatography-tandem mass spectrometry method for trace analysis of diuron in wastewater treatment plant effluent sample

An on-line immunoaffinity column with liquid chromatography/tandem mass spectrometry (IAC-LC-MS/MS) method for the determination of diuron in water matrices was described. This method used a sol-gel immunoaffinity column (20 mm x 4 mm I.D.) for on-line sample cleanup and enrichment, a monolithic analytical column (100 mm x 4.6 mm I.D.) for separation, and a triple quadrupole mass spectrometer for quantitation. The major challenges for the on-line set-up were discussed. The optimized on-line protocol was emphasized by the fact that low limit of quantitation (LOQ) of 1.0 ng/L was achieved with only 2.5-mL sample. In addition, a satisfactory accuracy ( approximately 90% of recovery) and precision (<6% of relative standard deviation) at 50 ng/L concentration were also obtained. Due to the ability of the sol-gel immunoaffinity column to eliminate matrix effect, the on-line IAC-LC-MS/MS analysis method can reliably determine diuron in wastewater treatment plant effluent sample.