In vitro biotransformation of (R)- and (S)-thalidomide: application of circular dichroism spectroscopy to the stereochemical characterization of the hydroxylated metabolites

Circular dichroism (CD) spectroscopy was successfully used for the stereochemical characterization of the hydroxylated metabolites formed during the in vitro biotransformation of (R)- and (S)-thalidomide. Incubation extracts of the individual enantiomers were analyzed by HPLC on an achiral stationary phase combined with CD detection. The CD data of the almost enantiopure eluates of the metabolites were compared with the CD spectra quantum chemically calculated for the respective structures. The results allowed us a reliable determination of the absolute stereostructure for all of the metabolites. The chiral center of thalidomide is unaffected by the stereoselective biotransformation process. (3'R,5'R)-trans-5'-hydroxythalidomide is the main metabolite of (R)-thalidomide, which epimerizes spontaneously to give the more stable (3'S,5'R)-cis isomer. On the contrary, (S)-thalidomide is preferentially metabolized by hydroxylation in the phthalimide moiety, resulting in the formation of (S)-5-hydroxythalidomide.     

Phase-stepping interferometry: methods for reducing errors caused by camera nonlinearities

Phase errors that arise in phase-stepping interferometry are discussed. Investigations were performed by use of a Twyman-Green interferometer equipped with a compensation plate with a variable and servo-controlled tilt angle. With this instrument, phase-stepping errors can be reduced to a negligible level. There are, however, phase errors that are caused by camera nonlinearities. Two methods for minimizing these errors are presented. The first method is based on the simple idea that the interference intensity at the output of a two-beam interferometer has an exact cosine shape. The camera signals were monitored as a function of the tilt angle of the compensation plate, and the deviation from the cosine form was used to produce a correction. The second method is based on the idea that, under specific conditions, errors of an average of two phase measurements may compensate for each other. Numerical calculations were performed and give evidence of this hypothesis. Each method, the signal-correction and the averaging method, drastically reduces errors in evaluation of phases. The combination of both methods is a powerful tool that allows precise phase data to be obtained with an uncertainty, in the range lambda/2000 approximately 0.3 nm, that is caused mainly by signal noise.     

Iterative solution of algebraic matrix Riccati equations in open loop Nash games

In this note we study a fixed point iteration approach to solve algebraic Riccati equations as they appear in general two player Nash differential games on an infinite time horizon, where the information structure is of open loop type. We obtain conditions for existence and uniqueness of non‐negative solutions. The performance of the numerical algorithm is shown in an example. Copyright © 2005 John Wiley & Sons, Ltd.     

Edge-Cut Bounds on Network Coding Rates

Active networks are network architectures with processors that are capable of executing code carried by the packets passing through them. A critical network management concern is the optimization of such networks and tight bounds on their performance serve as useful design benchmarks. A new bound on communication rates is developed that applies to network coding, which is a promising active network application that has processors transmit packets that are general functions, for example a bit-wise XOR, of selected received packets. The bound generalizes an edge-cut bound on routing rates by progressively removing edges from the network graph and checking whether certain strengthened d-separation conditions are satisfied. The bound improves on the cut-set bound and its efficacy is demonstrated by showing that routing is rate-optimal for some commonly cited examples in the networking literature.     

(Ba,Ca)TiO3 PTCR Ceramics with LaNiO3 Thin-Film Electrodes: Preparation and Characterization of the Interface

Conductive LaNiO₃ thin film electrodes were deposited by chemical solution deposition (CSD) from nitrate solutions onto polycrystalline Al₂O₃ and (Ba,Ca)TiO₃ PTCR ceramic substrates. The electrical properties of the LaNiO₃ thin film on Al₂O₃ and of the interface consisting of LaNiO₃ and the semiconductive oxide ceramic were investigated. The deposited LaNiO₃ films were about 250 nm thick and consisted of nanosized particles. The resistivity of the LaNiO₃ film was about 3 × 10^-3cm at 20°C. The PTCR ceramic consisted of m sized particles and exhibited an electronic resistivity of about 10 cm at 20°C and a steep increase of the resistivity of a few orders of magnitude above the Curie point at about 120°C. The electrical properties of the LaNiO₃/PTCR interface were dominated by the properties of a barrier layer between the PTCR ceramic and the LaNiO₃ electrode. The potential dependence of the impedance indicated that the barrier layer consisted of a depletion layer within the PTCR ceramic, when the flat band potential of LaNiO₃ on the PTCR ceramic at about –250 mV was exceeded. Additionally the formation of an insulating layer at the LaNiO₃ electrode has to be taken into account.     

Left ventricular radial tagging acquisition using gradient-recalled-echo techniques: sequence optimization

Myocardial tagging with magnetic resonance (MR) imaging offers unique possibilities for noninvasive left ventricular (LV) strain analysis. True three-dimensional strain analysis can be achieved with tags implemented in cardiac short axis and long axis images. Spin-echo (SE) techniques have been used for these studies. However, this approach is time-consuming: images at different phases of the cardiac cycle have to be obtained in successive measurements and hence the total number of measurements equals the number of time frames. Moreover, the images are often degraded by flow and motion artifacts. The purpose of this study was to optimize a faster and more robust MR tagging sequence for use on a clinical whole-body 1 T MR system with optimal persistence of the tags during the entire cardiac cycle. The tagging pulses were implemented in gradient-recalled-echo (GRE) sequences and compared to SE-based acquisitions. The effects of the use of flow-compensating gradients, the excitation angles, and the angles of the saturation pulses have been studied with MR signal simulations and in comparative measurements in volunteers. GRE acquisitions with flow-compensating gradients are robust techniques for myocardial tagging acquisitions. Use of optimized flip angles and saturation pulses can significantly improve delineation of the tag and can be used up to at least 700 ms after the R-wave. Therefore, LV tagging with GRE acquisitions using optimized MR parameters is a robust and promising technique.     

The Objective Conception of Context and Its Logic

In this paper, an objective conception of contexts based loosely upon situation theory is developed and formalized. Unlike subjective conceptions, which take contexts to be something like sets of beliefs, contexts on the objective conception are taken to be complex, structured pieces of the world that (in general) contain individuals, other contexts, and propositions about them. An extended first-order language for this account is developed. The language contains complex terms for propositions, and the standard predicate ist that expresses the relation that holds between a context and a proposition just in case the latter is true in the former. The logic for the objective conception features a global classical predicate calculus, a local logic for reasoning within contexts, and axioms for propositions. The specter of paradox is banished from the logic by allowing ist to be nonbivalent in problematic cases: it is not in general the case, for any context c and proposition p, that either ist(c,p) or ist(c, ¬ p). An important representational capability of the logic is illustrated by proving an appropriately modified version of an illustrative theorem from McCarthy's classic Blocks World example.     

Differences in the sterol composition of dominant antarctic zooplankton

The composition of free sterols was determined in Antarctic zooplankton species with various feeding behaviors. In the Southern Ocean, the dominant calanoid copepods Calanoides acutus, Calanus propinquus, Metridia gerlachei, and Euchaeta antarctica were investigated during different seasons and compared with the euphausiids Euphausia superba, E. crystallorophias, and Thysanoessa macrura. In addition, the Arctic copepods Calanus hyperboreus, C. glacialis, and C. finmarchicus were studied for comparison. Analyses were performed using gas chromatography and mass spectrometry. The zooplankton species exhibited a simple sterol content of up to six sterols. In the copepods, cholest-5-en-3β-ol (22.1 to 60.5%, range of sample means), cholesta-5,24-dien-3β-ol (22.3 to 45.2%), and cholesta-5,22E-dien-3β-ol (4.3 to 33.4%) contributed most, while in euphausiids the sterol composition was less complex with cholest-5-en-3β-ol always accounting for more than 75% of the total. Although sterols are membrane constituents and are expected not to vary considerably, differences in the abundance of sterols were observed between the species and the seasons. In herbivorous copepods, cholesta-5,24-dien-3β-ol increased by a factor of 1.5 to about 45% during the main feeding period in summer; this sterol is a metabolic precursor of cholest-5-en-3β-ol in the process of the dealkylation of dietary C-24 alkylated phytosterols. Cholest-5-en-3β-ol decreased by the same proportion. Omnivorous and carnivorous copepods showed average levels of cholesta-5,24-dien-3β-ol below 25%. These changes in sterol composition between copepod species seem to reflect their different feeding modes.