Modelling the metabolic action of human and rat CYP1A2 and its relationship with the carcinogenicity of heterocyclic amines

Cytochrome P450 (CYP) is a family of enzymes responsible for organism detoxification. However, some of the members of the CYP1A subfamily also catalyse the activation of heterocyclic amines (HAs), present in cooked meat, to carcinogenic compounds which have been shown to increase the risk of breast, colorectal and lung cancer. In humans, CYP1A2 is the enzyme with the most significant action in HA metabolism but in rodents CYP1A1 is also important in this biotransformation. Understanding the metabolic action of these enzymes is essential to predict the factors that enable the formation of the carcinogenic products. We have built two models of CYP1A2, one for the human enzyme and one for the rat homologue. The templates chosen include the only X-ray structure published to date for a mammal CYP, a quimeric C2A5 from rabbit, as well as CYPs belonging to Bacillus megaterium (CYPBm-3), Pseudomonas putida (CYPcam), Pseudomonas sp. (CYPterp), and Saccharopolyspora erythraea (CYPeryf). Two HAs, MeIQ (2-amino-3,4-dimethylimidazo[4,5-?]quinoline) and MeIQx (2-amino-3,8-dimethylimidazo[4,5-?]quinoxaline), known substrates of human and rat CYPIA2, were docked in the active site of the models, providing information regarding the different catalytic rates associated with the metabolisms in both enzymes. This is important for analysing the behaviour of animal models concerning the testing of anticancer drugs.     

ELECTROSTATIC EFFECTS IN THE PHOTOREDUCTION OF FLAVINS BY EDTA

The anaerobic photoreduction of riboflavin, flavin mononucleotide, N(3)-carboxymethylriboflavin, N(3)-methyl-lumiflavin, and lumiflavin by EDTA was studied in aqueous solution over the pH range 2.5–10. The electrostatic effects of the electron donor-acceptor pair produce a secondary effect on the reactivity, and this effect can be predicted from the product of the charges (Z_D x Z_A). The trianonic and tetraanonic species of EDTA have nitrogens which are free from intramolecular hydrogen bonding, and these species are potentially the most reactive. However, in some pH regions the electrostatic effect can become the dominant factor when both the electron donor and acceptor become negatively charged. The excited states of flavins are susceptible to charge effects whether the charge is localized on the side chain or involves the isoalloxazine ring system.     

Applications of Fiber Optic Grating Technology to Multi-Parameter Measurement

Abstract

In this article, approaches reported in the literature for multi-parameter measurement relying on fiber grating technology are reviewed. Due to its importance, the particular case of temperature/strain simultaneous measurement is addressed in further detail, as well as the techniques and sensing heads for temperature-independent strain measurement. Specific criteria are also proposed for sensing head classification in the context of multi-parameter measurement.     

Operators that admit a moment sequence, II

As the title indicates, this note is a continuation of a paper by Foias, Jung, Ko and Pearcy, in which it was shown that certain classes of operators on a Hilbert space admit moment sequences. Herein we extend these results.

     

Characterization of molecularly imprinted polymers for the extraction of tobacco alkaloids and their metabolites in human urine

Molecularly imprinted polymers (MIPs) are synthetic polymers designed to selectively extract target analytes from complex matrices (including biological matrices). The literature shows that MIPs have a degree of cross-selectivity from analytes within the same class of compounds. A commercially available MIP for tobacco-specific nitrosamines (TSNAs) is designed to be class selective for four TSNA compounds. This study sought to characterize the extent of cross-selectivity of the TSNA MIPs with other tobacco alkaloids. Cross-selectivity and recovery of the SupelMIP™ TSNA SPE cartridges was assessed with N-nitrosonornicotine (NNN), nicotine, cotinine and morphine. Their recoveries were compared with the recoveries of a nonimprinted polymer SPE cartridge, and two traditional SPE cartridges: a Waters mixed-mode cation exchange cartridge and a Waters hydrophilic–lipophilic balance cartridge. NNN and cotinine had the highest recoveries with the MIP cartridge, over 80%, and cotinine samples in urine had >80% recoveries. Nicotine had highly variable recoveries, possibly owing to differing chemical properties from the TSNAs. All three analytes had significantly different recoveries with the MIP cartridges compared with the traditional SPE cartridges. Morphine displayed nonspecific interactions with the MIP cartridges. Utilization of the TSNAs’ cross-selectivity allows for simultaneous extraction and identification of multiple tobacco biomarkers using one extraction technique.     

Search with the ATLAS detector for new physics with significant missing transverse energy and two isolated leptons

Results of searches for supersymmetry in events with significant missing transverse energy and two isolated leptons with the ATLAS experiment at the LHC are presented. Three analyses are presented here, the first two are analyses with leptons of opposite charge and same charge, respectively. The third one is an analysis that searches for an excess of same-flavour opposite-charge lepton pairs over those of different-flavour. Data corresponding to an integrated luminosity of 1 fb^?1 are analysed.     

Probability Density Function of the Output Current of Cascaded Multiplexer/Demultiplexers in Transparent Optical Networks

The influence of the concatenation of arbitrary optical multiplexers/demultiplexers (MUX/DEMUXs) on the probability density function (PDF) of the output current of a transparent optical network is assessed. All PDF results obtained analytically are compared with estimates from Monte Carlo simulation and an excellent agreement is achieved.

The non-Gaussian behavior of the PDFs, previously reported by other authors for square-law detectors, is significantly enhanced with the number of nodes increase due to the noise accumulation along the cascade of MUX/DEMUXs. The increase of the MUX/DEMUXs bandwidth and detuning also enhances the PDFs non-Gaussian behavior. The PDF shape variation with the detuning depends strongly on the number of nodes.

Explanations for the Gaussian approximation (GA) accuracy on the assessment of the performance of a concatenation of optical MUX/DEMUXs are also provided. For infinite extinction ratio and tuned MUX/DEMUXs, the GA error probabilities are, in general, pessimistic, due to the inaccurate estimation of the error probability for both bits. For low extinction ratio, the GA is very accurate due to a balance between the error probabilities estimated for the bits “1” and “0.” With the detuning increase, the GA estimates can become optimistic.