Practical synthesis of (2'R)-2'-deoxy-2'-C-methyluridine by highly diastereoselective homogeneous hydrogenation

Diastereoselective hydrogenation of 2'-deoxy-2'-exo-methyleneuridine was carried out under homogeneous conditions using a low loading of a chiral Rh catalyst. This, coupled with improvements in the synthesis of the substrate, allowed the smooth pilot plant preparation of the title compound on >10 kg scale.     

Understanding anomalous delays in a model of intracellular calcium dynamics

In many cell types, oscillations in the concentration of free intracellular calcium ions are used to control a variety of cellular functions. It has been suggested [J. Sneyd et al., "A method for determining the dependence of calcium oscillations on inositol trisphosphate oscillations," Proc. Natl. Acad. Sci. U.S.A. 103, 1675-1680 (2006)] that the mechanisms underlying the generation and control of such oscillations can be determined by means of a simple experiment, whereby a single exogenous pulse of inositol trisphosphate (IP(3)) is applied to the cell. However, more detailed mathematical investigations [M. Domijan et al., "Dynamical probing of the mechanisms underlying calcium oscillations," J. Nonlinear Sci. 16, 483-506 (2006)] have shown that this is not necessarily always true, and that the experimental data are more difficult to interpret than first thought. Here, we use geometric singular perturbation techniques to study the dynamics of models that make different assumptions about the mechanisms underlying the calcium oscillations. In particular, we show how recently developed canard theory for singularly perturbed systems with three or more slow variables [M. Wechselberger, "A propos de canards (Apropos canards)," Preprint, 2010] applies to these calcium models and how the presence of a curve of folded singularities and corresponding canards can result in anomalous delays in the response of these models to a pulse of IP(3).     

Interpretation of ghost lines in secondary-electron spectra determined by XPS

The photoelectron energy corresponding to the Fermi level of an investigated specimen and the onset energy for detection of secondary electrons are two characteristic energy values that can be used for work-function evaluation. Secondary-electron onset measurements are usually carried out by applying an acceleration voltage between the specimen and the spectrometer entrance, giving a structured secondary-electron spectrum showing three types of secondary electrons: those from the specimen, those from the entrance-slit system, and those from the X-ray tube window. For the latter electrons the electrical field built up in the sample chamber acts as an energy analyzer, imaging a discrete energy interval onto the spectrometer entrance slit. The variation of energy and intensity of these “ghost-lines” is discussed as a function of the applied acceleration voltage and the specimen tilting angle, leading to optimized experimental parameters for recording of secondary-electron spectra.     

Molecular Organization of Various Collagen Fragments as Revealed by Atomic Force Microscopy and Diffusion‐Ordered NMR Spectroscopy

Heterogeneous mixtures of collagen fragments can be used as nutrition supplement or as key ingredients for ointments with therapeutic relevance in wound healing. Some mixtures of collagen fragments are referred to as collagen hydrolysates owing to the production process with hydrolytic enzymes. Since the precise composition of collagen hydrolysates is generally unknown, it is of interest to analyze samples containing various collagen fragments with appropriate biophysical methods. Any product optimization without a profound knowledge concerning the size and the molecular weight distribution of its components is nearly impossible. It turned out that a combination of AFM methods with NMR techniques is exceptionally suited to examine the size range and the aggregation behavior of the collagen fragments in the hydrolysates of fish, jellyfish, chicken, porcine and bovine collagen. Supported by molecular modeling calculations, the AFM and NMR experiments provide a detailed knowledge about the composition of collagen hydrolysates and collagen ointments. Furthermore, the data allow a correlation between the size of the fragments and their potential bioactivity.     

Multiple Timescales, Mixed Mode Oscillations and Canards in Models of Intracellular Calcium Dynamics

A range of representative models of intracellular calcium dynamics are surveyed, with the aim of determining which model characteristics are qualitatively unchanged by changes to details of the model components. Techniques from geometric singular perturbation theory are used to investigate the role of separation of timescales in determining model dynamics, with particular emphasis on identifying parameter regimes in which mixed mode oscillations are present as a result of the separation of timescales. We find that the number of distinct timescales and the number of variables evolving on each timescale varies between models and depends on both the model assumptions and on the parameter regime of interest within the model, but in all cases, the presence of canards and associated mixed mode oscillations provides a mechanism by which the models can robustly exhibit complex oscillations, with the frequency of oscillation depending sensitively on parameter values. We find that analysis of the number and nature of the distinct timescales in a model allows us to make useful predictions about the dynamics associated with the model, and that this may give us more information about the model dynamics than a classification according to the modelling assumptions made about different cellular mechanisms in deriving the models.     

Elucidation of lignin structure by quantitative 2D NMR

Quick quantitative HSQC (QQ‐HSQC) was applied to quantitative evaluation of different inter‐unit linkages in an array of milled softwood and hardwood and technical lignins by using the guaiacyl C2 and syringyl C2–C6 signals as internal standards. The results were found to be highly reproducible and comparable with earlier literature reports. The advantage of QQ‐HSQC NMR analysis of lignin is contemporary detection and quantification of lignin inter‐unit linkages with a direct, non‐destructive method requiring short acquisition times.     

The selection of mixed-mode oscillations in a Hodgkin-Huxley model with multiple timescales

In recent work [J. Rubin and M. Wechselberger, Biol. Cybern. 97, 5 (2007)], we explained the appearance of remarkably slow oscillations in the classical Hodgkin-Huxley (HH) equations, modified by scaling a time constant, using recently developed theory about mixed-mode oscillations (MMOs). This theory is only rigorously valid, however, for epsilon sufficiently small, where epsilon is a parameter that arises from nondimensionalization of the HH system. Here, we illustrate how the parameter regime over which MMOs exist, and the features of the MMO patterns within this regime, vary with respect to several key parameters in the nondimensionalized HH equations, including epsilon. Moreover, we explain our findings in terms of the effects that these parameters are expected to have on certain organizing structures within the corresponding flow, generalized from analysis done previously in the singular limit.