Determination of Complex Small‐Molecule Structures Using Molecular Alignment Simulation

Correct structural assignment of small molecules and natural products is critical for drug discovery and organic chemistry. Anisotropy‐based NMR spectroscopy is a powerful tool for the structural assignment of organic molecules, but it relies on the utilization of a medium that disrupts the isotropic motion of molecules in organic solvents. Here, we establish a quantitative correlation between the atomic structure of the alignment medium, the molecular structure of the small molecule, and molecule‐specific anisotropic NMR parameters. The quantitative correlation uses an accurate three‐dimensional molecular alignment model that predicts residual dipolar couplings of small molecules aligned by poly(γ‐benzyl‐l ‐glutamate). The technique facilitates reliable determination of the correct stereoisomer and enables unequivocal, rapid determination of complex molecular structures from extremely sparse NMR data.     

ETD Allows for Native Surface Mapping of a 150 kDa Noncovalent Complex on a Commercial Q-TWIMS-TOF Instrument

Top-down approaches for the characterization of intact proteins and macromolecular complexes are becoming increasingly popular, since they potentially simplify and speed up the assignment process. Here we demonstrate how, on a commercially available Q-TWIMS-TOF instrument, we performed top-down ETD of the native form of tetrameric alcohol dehydrogenase. We achieved good sequence coverage throughout the first 81 N-terminal amino acids of ADH, with the exception of a loop located on the inside of the protein. This is in agreement with the exposed parts of the natively folded protein according to the crystal structure. Choosing the right precursor charge state and applying supplemental activation were found to be key to obtaining a high ETD fragmentation efficiency. Finally, we briefly discuss opportunities to further increase the performance of ETD based on our results.

Application of the page-equation on flat shaped viscose fibre handsheets

The influence of charged species on the relative bonded area (RBA) of flat shaped viscose fibre handsheets was investigated. For this purpose four samples, a reference fibre without any additives as well as three physical modified fibres, were studied. The RBA was determined by the light scattering method and by using the so called Page equation. To use the Page equation, the breaking length of handsheets, the optical bonded area of fibre-fibre joints as well as the bond strength of such fibre joints were determined. The optical bonded area was analysed by polarized light microscopy. Using a micro bond tester, the bond strength of fibre-fibre joints was determined. Both techniques, light scattering and calculation via the Page equation did not deliver absolute values for RBA. Quite contrary, they only give approximate values. However, an increase of relative bonded area due to anionic charges is clearly seen. Additionally, the breaking length is increased by both additives.     

Hyperfinite construction of G-expectation

The hyperfinite G-expectation is a nonstandard discrete analogue of G-expectation (in the sense of Robinsonian nonstandard analysis). A lifting of a continuous-time G-expectation operator is defined as a hyperfinite G-expectation which is infinitely close, in the sense of nonstandard topology, to the continuous-time G-expectation. We develop the basic theory for hyperfinite G-expectations and prove an existence theorem for liftings of (continuous-time) G-expectation. For the proof of the lifting theorem, we use a new discretization theorem for the G-expectation (also established in this paper, based on the work of Dolinsky et al. [Weak approximation of G-expectations, Stoch. Process. Appl. 122(2) (2012), pp. 664–675]).     

Leitf?higkeit

Ohne Zusammenfassung     

The partition function of an interacting many body system

Based on the path integral approach the partition function of a many body system with separable two body interaction is calculated in the sense of a semiclassical approximation. The commonly used Gaussian type of approximation, known as the perturbed static path approximation (PSPA), breaks down near a crossover temperature due to instabilities of the classical mean field solution. It is shown how the PSPA is systematically improved within the crossover region by taking into account large non-Gaussian fluctuations and an approximation applicable down to very low temperatures is carried out. These findings are tested against exact results for the archetypical cases of a particle moving in a one dimensional double well and the exactly solvable Lipkin-Meshkov-Glick model. The extensions should have applications in finite systems at low temperatures as in nuclear physics and mesoscopic systems, e.g. for gap fluctuations in nanoscale superconducting devices previously studied within a PSPA type of approximation. Received 28 March 2002 Published online 17 September 2002     

On the generation of circuits and minimal forbidden sets

We present several complexity results related to generation and counting of all circuits of an independence system. Our motivation to study these problems is their relevance in the solution of resource constrained scheduling problems, where an independence system arises as the subsets of jobs that may be scheduled simultaneously. We are interested in the circuits of this system, the so-called minimal forbidden sets, which are minimal subsets of jobs that must not be scheduled simultaneously. As a consequence of the complexity results for general independence systems, we obtain several complexity results in the context of resource constrained scheduling. On that account, we propose and analyze a simple backtracking algorithm that generates all minimal forbidden sets for such problems. The performance of this algorithm, in comparison to a previously suggested divide-and-conquer approach, is evaluated empirically using instances from the project scheduling library PSPLIB.Acknowledgement We appreciate the input of two anonymous referees. Particularly the deep remarks of one of them greatly improved our understanding of several issues; he also suggested the simplified Example 1. We thank Marc Pfetsch and Alexander Grigoriev for several enlightening discussions. Marc Pfetsch also pointed us to the paper [15]. Parts of this work were done while the authors were PhD students at the Technische Universität Berlin, Germany, where Frederik Stork was supported by DFG grant Mo 446/3-3, and Marc Uetz was supported by bmb+f grant 03-MO7TU1-3 and GIF grant I 246-304.02/97.     

Lead isotopic analysis of infant bone tissue dating from the Roman era via multicollector ICP–mass spectrometry

Archaeological samples originating from a cemetery of a Roman settlement, Pretorium Agrippinae (1st–3rd century A.D.), excavated near Valkenburg (The Netherlands) have been subjected to Pb isotopic analysis. The set of samples analysed consisted of infant bone tissue and possible sources of bone lead, such as the surrounding soil, garum, and lead objects (e.g., water pipes). After sample digestion with quantitative Pb recovery and subsequent quantitative and pure isolation of lead, the Pb isotopic composition was determined via multicollector ICP–mass spectrometry. The Pb isotope ratio results allowed distinction of three groups: bone, soil, and lead objects + garum. The ²⁰⁸Pb/²⁰⁶Pb ratio ranges were between 2.059 and 2.081 for the soils, between 2.067 and 2.085 for the bones, and between 2.087 and 2.088 for the lead objects. The garum sample is characterised by a ²⁰⁸Pb/²⁰⁶Pb ratio of 2.085. The bone group is situated on the mixing line between the soil and lead object groups, allowing the statement that diagenesis is not the main cause of the Pb found in the bones.