A mass spectrometric study on meloxicam metabolism in horses and the fungus Cunninghamella elegans,and the relevance of this microbial system as a model of drug metabolism in the horse

This paper describes a study where the metabolism of the non‐steroidal anti‐inflammatory drug meloxicam was investigated in six horses and in the filamentous fungus Cunninghamella elegans. The metabolites identified were compared between the species, and then the fungus was used to produce larger amounts of the metabolites for future use as reference material. C. elegans proved to be a good model of phase I meloxicam metabolism in horses since all four metabolites found were the same in both species. Apart from the two main metabolites, 5′‐hydroxymethylmeloxicam and 5′‐carboxymeloxicam, a second isomer of hydroxymeloxicam and dihydroxylated meloxicam were detected for the first time in horse urine and the microbial incubations. Phase II metabolites were not discovered in the C. elegans samples but hydroxymeloxicam glucuronide was detected intact in horse urine for the first time in this study. Urine from six horses was further analyzed in a semi‐quantitative sense and 5′‐hydroxymethylmeloxicam gave peaks with much higher intensity compared to the parent drug and the other metabolites, and was detected for at least 14 days after the last given dose in some of the horses. From the results presented in this article, we suggest that analytical methods developed for the detection of meloxicam in horse urine after prohibited use should focus on the 5′‐hydroxymethyl metabolite and that C. elegans can be used to produce large amounts of this metabolite for potential future use as a reference compound. Copyright © 2009 John Wiley & Sons, Ltd.     

Direct analysis in real time (DART) mass spectrometry of nucleotides and nucleosides: elucidation of a novel fragment [C<Subscript>5</Subscript>H<Subscript>5</Subscript>O]<Superscript>+</Superscript> and its in-source adducts

Direct analysis in real time (DART) mass spectrometry is a recently developed innovative technology, which has shown broad applications for fast and convenient analysis of complex samples. Due to the ease of sample preparation, we have recently initiated an investigation of the feasibility of detecting nucleotides and nucleosides using the DART-AccuTOF instrument, which we will refer to as the DART mass spectrometer. Our experimental results reveal that the ions representing the intact molecules of nucleotides are not detectable in either positive-ion or negative-ion mode. Instead, all four natural nucleotides fragment in the DART ion source, and a common fragment ion, [C₅H₅O]⁺ (1), is observed, which is probably formed via multiple-elimination reactions. Interestingly, 1 can form adducts with nucleobases in different molar ratios in the DART ion source. In contrast to nucleotides, the ions representing the intact molecules of nucleosides are detected in both positive-ion and negative-ion mode using DART mass spectrometry. Surprisingly, the fragmentation pattern of nucleosides is different from that of nucleotides in the DART ion source. In the cases of nucleosides (under positive-ion conditions), the production of 1 is not observed, indicating that the phosphate group plays an important role for the multiple eliminations observed in the spectra of nucleotides. The in-source reactions described in the present work show the complexity of the conditions in the DART ion source, and we hope that our results illustrate a better understanding about DART mass spectrometry.     

Pulse shape analysis to reduce the background of BEGe detectors

A simple technique for pulse shape discrimination in HPGe-detectors of the so-called BEGe type, based on just one parameter obtained from one signal read out, is presented here. This technique allows discriminating between pulses generated when the deposited energy is located within a small region of about 1 mm³ from the pulses generated when the energy is deposited at different locations several mm or cm apart. Two possible applications using this technique are: (i) experiments that look for neutrinoless double β decay in ⁷⁶Ge, such as GERDA; (ii) γ spectrometry measurements where the Compton continuum can be reduced and the efficiency for cascading γ-rays can remain high. With this active background reduction technique a Compton suppression factor of about 3 was obtained. The detector response may be influenced by the detector size. The detector used for this study had a diameter of 6 cm, a thickness of 2.6 cm and a relative efficiency of 19%. The results obtained with this detector were consistent with the results obtained by Budjá? et al. [J Instrum 4:10, 2009] with a 50% relative efficiency BEGe detector.     

Connections Between Classical and Generalised Trajectories of a State/Signal System

In our earlier article “Well-posed state/signal systems in continuous time”, we originally defined the notion of a trajectory of a state/signal system by means of a generating subspace. However, it was left as an open problem whether the generating subspace is uniquely determined by a given family of all generalised trajectories of a well-posed state/signal system. In this article we give a positive answer to this question and show how this insight simplifies some formulations in the theory of well-posed state/signal systems. The main contribution of the article is an explicit convolution scheme for constructing classical trajectories approximating an arbitrary generalised trajectory. We apply this scheme by studying relationships between classical and generalised trajectories of continuous-time state/signal systems under very weak assumptions. Among others, we show that there exists a space of classical trajectories that is invariant under differentiation and dense in the space of generalised trajectories. Some of our results generalise known results for strongly continuous semigroups and input/state/output systems, but we make no use of decompositions of the signal space into an input space and an output space, and in particular, none of our results depend on well-posedness.     

Quasi-steady model of the acoustic scattering properties of a T-junction

T-junctions are common elements in flow duct networks. It is shown that for low Strouhal numbers, based on the duct diameter, their acoustic scattering properties can be described using an incompressible quasi-steady model. Models are derived for systems subjected to combinations of grazing and bias mean flow, and are shown to work in both the limiting cases—that is, grazing or bias flow alone—as well as for the joining or dividing flow configurations. The upper Strouhal number for which the quasi-steady models are applicable is limited by flow-acoustic interaction effects, which differ significantly between the different flow configurations. Generally the models are applicable up to Strouhal numbers of approximately 0.1-0.2, which is comparable with previous published models for other configurations such as bends and orifices. This range is sufficient to make the model useful in many important engineering applications.     

Pseudo-Hyperkähler Geometry and Generalized Kähler Geometry

We discuss the conditions for additional supersymmetry and twisted super-symmetry in N = (2, 2) supersymmetric nonlinear sigma models described by one left and one right semi-chiral superfield and carrying a pair of non-commuting complex structures. Focus is on linear non-manifest transformations of these fields that have an algebra that closes off-shell. We find that additional linear supersymmetry has no interesting solution, whereas additional linear twisted supersymmetry has solutions with interesting geometrical properties. We solve the conditions for invariance of the action and show that these solutions correspond to a bi-hermitian metric of signature (2, 2) and a pseudo-hyperkähler geometry of the target space.