Signal-to-noise ratio for source determination and for a comodulated masker in goldfish, Carassius auratus

The masking effects of white and amplitude comodulated noise were studied with respect to simple signal detection and sound source determination in goldfish. A stimulus generalization method was used to determine the signal-to-noise ratio required to completely determine the signal's characteristics. It was found that the S∕N required for this determination is about 4 dB greater than that required for signal detection, or was about 4 dB greater than the critical masking ratio. This means that the potential harm to fish of a given masking noise is at least 4 dB greater than previously thought, based on critical masking ratios. However, for amplitude comodulated noise between 10 and 50 Hz modulation rate, the potential harmful effects are up to 5.3 dB less than would be predicted from the critical masking ratio for unmodulated noise.     

On the evaluation of strategies for branching bandit processes

Glazebrook [1] has given an account of improved procedures for strategy evaluation for resource allocation in a stochastic environment. These methods are extended in the paper in such a way that they can be applied to problems which, for example, have precedence constraints and/or an arrivals process of new jobs. Theoretical results, backed up by numerical studies, show that quasi-myopic heuristics often perform well.     

Tuning Tetrazole Photochemistry for Protein Ligation and Molecular Imaging

Photochemistry provides a wide range of alternative reagents that hold potential for use in bimolecular functionalisation of proteins. Here, we report the synthesis and characterisation of metal ion binding chelates derivatised with disubstituted tetrazoles for the photoradiochemical labelling of monoclonal antibodies (mAbs). The photophysical properties of tetrazoles featuring extended aromatic systems and auxochromic substituents to tune excitation toward longer wavelengths (365 and 395 nm) were studied. Two photoactivatable chelates based on desferrioxamine B (DFO) and the aza-macrocycle NODAGA were functionalised with a tetrazole and developed for protein labelling with ⁸⁹Zr, ⁶⁴Cu and ⁶⁸Ga radionuclides. DFO-tetrazole ( 1 ) was assessed by direct conjugation to formulated trastuzumab and subsequent radiolabelling with ⁸⁹Zr. Radiochemical studies and cellular-based binding assays demonstrated that the radiotracer remained stable in vitro retained high immunoreactivity. Positron emission tomography (PET) imaging and biodistribution studies were used to measure the tumour specific uptake and pharmacokinetic profile in mice bearing SK-OV-3 xenografts. Experiments demonstrate that tetrazole-based photochemistry is a viable approach for the light-induced synthesis of PET radiotracers.     

Simultaneous analysis of 13C‐glutathione as its dimeric form GSSG and its precursor [1‐13C]glycine using liquid chromatography/isotope ratio mass spectrometry

Determination of glutathione kinetics using stable isotopes requires accurate measurement of the tracers and tracees. Previously, the precursor and synthesized product were measured with two separate techniques, liquid chromatography/isotope ratio mass spectrometry (LC/IRMS) and gas chromatography/combustion/isotope ratio mass spectrometry (GC/C/IRMS). In order to reduce sample volume and minimize analytical effort we developed a method to simultaneously determine ¹³C‐glutathione as its dimeric form (GSSG) and its precursor [1‐¹³C]glycine in a small volume of erythrocytes in one single analysis. After having transformed ¹³C‐glutathione into its dimeric form GSSG, we determined both the intra‐erythrocytic concentrations and the ¹³C‐isotopic enrichment of GSSG and glycine in 150 µL of whole blood using liquid chromatography coupled to LC/IRMS. The results show that the concentration (range of µmol/mL) was reliably measured using cycloleucine as internal standard, i.e. with a precision better than 0.1 µmol/mL. The ¹³C‐isotopic enrichment of GSSG and glycine measured in the same run gave reliable values with excellent precision (standard deviation (sd) <0.3‰) and accuracy (measured between 0 and 5 APE). This novel method opens up a variety of kinetic studies with relatively low dose administration of tracers, reducing the total cost of the study design. In addition, only a minimal sample volume is required, enabling studies even in very small subjects, such as preterm infants. Copyright © 2009 John Wiley & Sons, Ltd.     

Gas chromatography/tandem mass spectrometry analysis of alkylresorcinols in red blood cells

Erythrocyte alkylresorcinols (5‐alkyl‐1,3‐dihydroxybenzenes) are potential biomarkers of wholegrain wheat and rye intake. However, their high‐throughput quantitative analysis by gas chromatography/mass spectrometry (GC/MS) is hindered by the time‐consuming sample preparation and, more importantly, by interfering compounds that still remain after sample cleanup. In the present work we describe a gas chromatography/tandem mass spectrometry (GC/MS/MS) method for the rapid and reliable quantification of alkylresorcinols in erythrocyte samples. The performance of the GC/MS/MS method is compared with that of GC/MS. The main characteristics of the method are: lower limits of detection: 2–10 µg/L standard solution; lower limits of quantification: 6–30 µg/L standard solution; linearity coefficients: 0.9611–0.9888; linear ranges: 2–20 µg/L in erythrocytes; and intra‐day precisions (n = 6): 4–13% at endogenous analyte levels in non‐spiked erythrocytes. Tandem mass spectrometry showed greatly improved selectivity over single‐stage mass spectrometry in the case of erythrocyte samples, eliminating all interferences detectable in single‐stage MS and enabling simple peak integration for quantification. Moreover, increased selectivity resulted in GC separation speeded up by a factor of two, allowing the duplicate analysis of over 40 samples per day. This GC/MS/MS method is suggested as an improved alternative to GC/MS for the quantification of alkylresorcinols in erythrocytes for assessing wholegrain wheat and rye intake. Copyright © 2008 John Wiley & Sons, Ltd.