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.     

Precision steering of an optical trap by electro-optic deflection

We designed, constructed, and tested a single-beam optical trapping instrument employing twin electro-optic deflectors (EODs) to steer the trap in the specimen plane. Compared with traditional instruments based on acousto-optic deflectors (AODs), EOD-based traps offer a significant improvement in light throughput and a reduction in deflection-angle (pointing) errors. These attributes impart improved force and position resolution, making EOD-based traps a promising alternative for high-precision nanomechanical measurements of biomaterials.     

Explosions of xenon clusters in ultraintense femtosecond x-ray pulses from the LCLS free electron laser

Explosions of large Xe clusters ( ~ 11,000) irradiated by femtosecond pulses of 850 eV x-ray photons focused to an intensity of up to 10(17) W/cm(2) from the Linac Coherent Light Source were investigated experimentally. Measurements of ion charge-state distributions and energy spectra exhibit strong evidence for the formation of a Xe nanoplasma in the intense x-ray pulse. This x-ray produced Xe nanoplasma is accompanied by a three-body recombination and hydrodynamic expansion. These experimental results appear to be consistent with a model in which a spherically exploding nanoplasma is formed inside the Xe cluster and where the plasma temperature is determined by photoionization heating.     

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.     

The porous structure of pulp fibres with different yields and its influence on paper strength

The porous structure of the interior of papermaking fibres is a well-known important property of the fibres. Changes of this structure will influence tensile and burst strength of paper formed from the fibres and a change in pore size of the pores within the fibre wall is also important for the ability of molecules to diffuse in and out of the fibre wall. Relevant examples of this latter effect are the removal of lignin during cooking and the addition of performance chemicals during papermaking. In this paper, pore sizes and the pore size distribution of unbleached softwood fibres have been studied. A well-characterised fibre material consisting of laboratory cooked spruce and pine pulp of various lignin contents was used. Pore size and pore size distribution were measured by studies of the relaxation behaviour of ²H in fibres saturated with ²H₂O. Beside this the total and surface charge of the fibres were also measured together with strength properties of papers from unbeaten fibres. For both pulps, there is a maximum in pore radius at a yield around 46%. Calculations of fibre wall volume from water retention values and yield levels show that there is a discontinuity in pore radius as a function of the fibre wall volume around a yield of 51%. It is suggested that this discontinuity is caused by the breakdown of the hemicellulose/lignin matrix within the fibre wall at this yield level. The strength of the papers formed from the fibres shows a correlation with the surface charge of the fibres. Based on the change in surface charge with yield and the change in total charge with yield, this correlation is suggested to be due to an opening up of the external part of the fibre wall. This stresses the importance of the chemical composition and physical structure of the outer layer of the fibre wall.     

Multicompartmentalized polymersomes for selective encapsulation of biomacromolecules

Multicompartmentalized polymersomes are formed using block co-polymers PMOXA-PDMS-PMOXA and PS-PIAT, and are subsequently proven to be capable of selective encapsulation of biomacromolecules. This architecture mimics the compartmentalization found in cells and may serve as a simple, albeit robust, model system.     

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.