Comprehensive Profiling by Non-targeted Stable Isotope Tracing Capillary Electrophoresis-Mass Spectrometry: A New Tool Complementing Metabolomic Analyses of Polar Metabolites

Mass spectrometry (MS) driven metabolomics is a frequently used tool in various areas of life sciences; however, the analysis of polar metabolites is less commonly included. In general, metabolomic analyses lead to the detection of the total amount of all covered metabolites. This is currently a major limitation with respect to metabolites showing high turnover rates, but no changes in their concentration. Such metabolites and pathways could be crucial metabolic nodes (e.g., potential drug targets in cancer metabolism). A stable-isotope tracing capillary electrophoresis–mass spectrometry (CE-MS) metabolomic approach was developed to cover both polar metabolites and isotopologues in a non-targeted way. An in-house developed software enables high throughput processing of complex multidimensional data. The practicability is demonstrated analyzing [U-¹³C]-glucose exposed prostate cancer and non-cancer cells. This CE-MS-driven analytical strategy complements polar metabolite profiles through isotopologue labeling patterns, thereby improving not only the metabolomic coverage, but also the understanding of metabolism.     

Universality at the edge of the spectrum for unitary,orthogonal, and symplectic ensembles of random matrices

We prove universality at the edge of the spectrum for unitary (β = 2), orthogonal (β = 1), and symplectic (β = 4) ensembles of random matrices in the scaling limit for a class of weights w(x) = e^?V(x) where V is a polynomial, V(x) = κ_2mx^2m + · · ·, κ_2m > 0. The precise statement of our results is given in Theorem 1.1 and Corollaries 1.2 and 1.4 below. For the same class of weights, a proof of universality in the bulk of the spectrum is given in [12] for the unitary ensembles and in [9] for the orthogonal and symplectic ensembles. Our starting point in the unitary case is [12], and for the orthogonal and symplectic cases we rely on our recent work [9], which in turn depends on the earlier work of Widom [46] and Tracy and Widom [42]. As in [9], the uniform Plancherel‐Rotach‐type asymptotics for the orthogonal polynomials found in [12] plays a central role. The formulae in [46] express the correlation kernels for β = 1, 4 as a sum of a Christoffel‐Darboux (CD) term, as in the case β = 2, together with a correction term. In the bulk scaling limit [9], the correction term is of lower order and does not contribute to the limiting form of the correlation kernel. By contrast, in the edge scaling limit considered here, the CD term and the correction term contribute to the same order: this leads to additional technical difficulties over and above [49]. © 2006 Wiley Periodicals, Inc.     

Comparative investigation of ruthenium-based metathesis catalysts bearing N-heterocyclic carbene (NHC) ligands

Exchange of one PCy3 unit of the classical Grubbs catalyst 1 by N-heterocyclic carbene (NHC) ligands leads to "second-generation" metathesis catalysts of superior reactivity and increased stability. Several complexes of this type have been prepared and fully characterized, six of them by X-ray crystallography. These include the unique chelate complexes 13 and 14 in which the NHC- and the Ru-CR entities are tethered to form a metallacycle. A particularly favorable design feature is that the reactivity of such catalysts can be easily adjusted by changing the electronic and steric properties of the NHC ligands. The catalytic activity also strongly depends on the solvent used; NMR investigations provide a tentative explanation of this effect. Applications of the "second-generation" catalysts to ring closing alkene metathesis and intramolecular enyne cycloisomerization reactions provide insights into their catalytic performance. From these comparative studies it is deduced that no single catalyst is optimal for different types of applications. The search for the most reactive catalyst for a specific transformation is facilitated by IR thermography allowing a rapid and semi-quantitative ranking among a given set of catalysts.     

Multiparametric microsensor chips for screening applications

The identification of drug targets for pharmaceutical screening can be greatly accelerated by gene databases and expression studies. The identification of leading compounds from growing libraries is realized by high throughput screening platforms. Subsequently, for optimization and validation of identified leading compounds studies of their functionality have to be carried out, and just these functionality tests are a limiting factor. A rigorous preselection of identified compounds by in vitro cellular screening is necessary prior to using the drug candidates for the further time consuming and expensive stage, e.g. in animal models. Our efforts are focused to the parallel development, adaptation and integration of different microelectronic sensors into miniaturized biochips for a multiparametric, functional on-line analysis of living cells in physiologically environments. Parallel and on-line acquisition of data related to different cellular targets is required for advanced stages of drug screening and for economizing animal tests.     

Einkristalle von CoNbO4 mit AlNbO4-Struktur

Single Crystals of CoNbO₄ with AlNbO₄ Structure The hitherto unknown single crystals of CoNbO₄ were prepared. CoNbO₄ has AlNbO₄ structure with monoclinic symmetry (space group C?C2/m; a = 1212.9; b = 374.9; c = 651.2 pm; β = 107.6°). X-ray investigations shows on ordered arrangement of Co³⁺ and Nb⁵⁺ with well defined differences in respect to oxocobaltates with Columbite type (CoNb₂O₆ = Co_0.33Nb_O.66O₂) and Rutil type (CoNbO₄ = Co_0.5-xNb_0.5+xO₂; 0 ? × ? 0.166) structure.     

Molekulargewichtsbestimmung durch Gelchromatographie von Oligoimidophosphorsäureamiden

Determination of Molecular Weights by Gel Chromatography of Oligoimidoamides of Phosphoric Acid. Oligoimidoamides of phosphoric acid were eluted with nonionic water on a Sephadex LH-20 column. The measured distribution coefficient of the oligoimidoamides of phosphoric acid was independent of sample concentration and pH of the eluent. Andrews equation was obeyed: a linear relation exist between elution volume and logarithm of molecular weight both cyclic and acyclic oligoimidoamides of phosphoric acid.     

Anomalous behaviour of the Landé factors and the chemical shift close to the dissociation limit of the B state of molecular iodine

Resonances in a modulated light beam have been observed on five transitions in the visible band system of I₂. Landé factors g_J and chemical shifts g₁ have been measured for levels very close to the dissociation limit of the B state.     

Five-membered ring formation in unimolecular reactions of peptides: a key structural element controlling low-energy collision-induced dissociation of peptides

Unimolecular fragmentation reactions of peptides in low-energy collision-induced dissociation are reviewed in the mechanistic context of five-membered ring formation. This structure of intermediates or of fragment ions is recognized as a key element that governs unimolecular peptide fragmentation within the structural framework determined by the peptide backbone and its side-chains. A collection of collision-induced dissociation reactions is presented covering (i) b-ion formation, (ii) the fragmentation of N-terminally acylated peptides, (iii) neutral loss of the C-terminal amino acid in alkali or silver cationized peptides, (iv) the fragmentation of isoAsp-containing peptides and (v) the fragmentation of negatively charged Asp- or Glu-containing peptides. It appears that for all possible nucleophile-electrophile interactions leading to a five-membered ring structure an associated unimolecular peptide fragmentation reaction can be observed.