Development and validation of a reversed‐phase HPLC method for CYP1A2 phenotyping by use of a caffeine metabolite ratio in saliva

CYP1A2 is important for metabolizing various clinically used drugs. Phenotyping of CYP1A2 may prove helpful for drug individualization therapy. Several HPLC methods have been developed for quantification of caffeine metabolites in plasma and urine. Aim of the present study was to develop a valid and simple HPLC method for evaluating CYP1A2 activity during exposure in xenobiotics by the use of human saliva. Caffeine and paraxanthine were isolated from saliva by liquid‐liquid extraction (chlorophorm/isopropanol 85/15v/v). Extracts were analyzed by reversed‐phase HPLC on a C₁₈ column with mobile phase 0.1% acetic acid/methanol/acetonitrile (80/20/2 v/v) and detected at 273nm. Caffeine and paraxanthine elution times were <13min with no interferences from impurities or caffeine metabolites. Detector response was linear (0.10–8.00µg/ml, R²>0.99), recovery was >93% and bias <4.47%. Intra‐ and inter‐day precision was <5.14% (n=6). The limit of quantitation was 0.10µg/ml and the limit of detection was 0.018±0.002µg/mL for paraxanthine and 0.032±0.002µg/ml for caffeine. Paraxanthine/caffeine ratio of 34 healthy volunteers was significantly higher in smokers (p<0.001). Saliva paraxanthine/caffeine ratios and urine metabolite ratios were highly correlated (r=0.85, p<0.001). The method can be used for the monitoring of CYP1A2 activity in clinical practice and in studies relevant to exposure to environmental and pharmacological xenobiotics. Copyright © 2015 John Wiley & Sons, Ltd.     

A topological investigation of the Quantum Adiabatic Phase

Using algebraic topology, the appearance of the Quantum Adiabatic Phase over various parameter manifolds is investigated. The relation with nontrivial gauge bundles (both abelian and non-abelian) is studied and it is shown that the phase appears as a result of homotopically non-trivial mappings, induced by the Hamiltonian in the space of wave-functions. The cohomological picture is developed and some topological considerations concerning field theory anomalies in the Hamiltonian picture are presented. A proof of the Nielsen-Ninomiya theorem is given inspired from the notion of the adiabatic phase.Work supported in part by the U.S. Department of Energy under contract DEAC 03-81-ER 40050     

Roles of SiH4 and SiF4 in growth and structural changes of poly-Si films

The structural properties of polycrystalline silicon films, prepared by plasma enhanced chemical vapor deposition system, with different flow rates of SiH₄/SiF₄ mixtures at 300 °C were investigated. This study indicates that the low hydrogen coverage on the growing surface, under optimum fluorine radicals, will be leaded to an improvement of crystallized area as compared with case of high hydrogen coverage surface. Moreover, the studies of the role of SiH₄ and SiF₄ radicals show that the SiH₄ radicals are important in the nucleation and growth of grains. However, SiF₄ radicals are effective in the structural change of grain boundaries regions and by this way, in the present system, establish the growth of grains under the dominant 〈1 1 0〉 direction. The stress investigation indicates that addition of high flow rate of SiF₄ in amorphous film, results in the nearly stress free films. Finally, we found that the changes in g-value reflect the changes in the intrinsic compressive and tensile stress in the both polycrystalline and amorphous silicon films.     

Asymptotic behavior of the distribution of the stock price in models with stochastic volatility: the Hull–White model

In the present Note, we study the asymptotic behavior of the distribution density of the stock price process in the Hull–White model. The leading terms in the asymptotic expansions at zero and infinity are found for such a density and the corresponding error estimates are given. Similar problems are solved for time averages of the volatility process, which are also of interest in the study of Asian options. To cite this article: A. Gulisashvili, E.M. Stein, C. R. Acad. Sci. Paris, Ser. I 343 (2006).     

Adaptive median filters: new algorithms and results

Based on two types of image models corrupted by impulse noise, we propose two new algorithms for adaptive median filters. They have variable window size for removal of impulses while preserving sharpness. The first one, called the ranked-order based adaptive median filter (RAMF), is based on a test for the presence of impulses in the center pixel itself followed by a test for the presence of residual impulses in the median filter output. The second one, called the impulse size based adaptive median filter (SAMF), is based on the detection of the size of the impulse noise. It is shown that the RAMF is superior to the nonlinear mean L(p) filter in removing positive and negative impulses while simultaneously preserving sharpness; the SAMF is superior to Lin's (1988) adaptive scheme because it is simpler with better performance in removing the high density impulsive noise as well as nonimpulsive noise and in preserving the fine details. Simulations on standard images confirm that these algorithms are superior to standard median filters.     

Local polynomial fitting under association

We consider the estimation of multivariate regression functions r(x₁,…,x_d) and their partial derivatives up to a total order p1 using high-order local polynomial fitting. The processes {Y_i,X_i} are assumed to be (jointly) associated. Joint asymptotic normality is established for the estimates of the regression function r and all its partial derivatives up to the total order p. Expressions for the bias and variance/covariance matrix (of the asymptotic distribution) are given.     

Characterisation of aperture coupled microstrip patch antenna withthick ground plane

The feasibility of using a thick ground plane with an aperture coupled microstrip patch antenna while maintaining reasonable antenna performance is demonstrated using moment method and reciprocity analyses in the spectral domain. The thick ground plane, which may serve as a heatsink for active MMIC circuitry, or as a mechanical support for thin substrates, is particularly advantageous in millimetre wave phased array applications. It is found that the effect of ground plane thickness is to reduce the level of coupling from the feed line to the patch     

InGaAs/AlAs/InGaAsP resonant tunneling hot electron transistorsgrown by chemical beam epitaxy

InP-based resonant tunneling hot electron transistors (RHET's) were studied systematically using chemical beam epitaxy (CBE) for the first time. All the RHET's studied have a highly strained AlAs/In_0.75Ga_0.25As/AlAs resonant tunneling double barrier as a hot electron injector, and an InP collector barrier with or without InGaAsP graded layers. The highest transport ratio (α) observed is 0.98, and the highest peak-to-valley current ratios (PVR's) measured are 20 and 200 in the collector current and base current, respectively, at 80 K. A self-consistent simulation is used as a reference to optimize the hot electron injector and to explain the ballistic transport. An energy spectrometer technique was applied to the RHET's for resolving the hot electron energy distribution which showed a full width at half maximum (FWHM) of around 58 meV, indicating ballistic transport of electrons. Finally, room temperature transistor action was also observed with a β of 4 and a cutoff frequency of 31 GHz     

Determination of the gamma self-attenuation correction factors using intensity ratios

Summary The possible correlation between the self-attenuation correction in gamma-spectrometric assay of uranyl nitrate samples and spectral line intensity ratios was investigated experimentally and simulated numerically using MCNP code. The characteristic gamma- and X-lines of uranium were measured using a low energy Ge gamma-spectrometer. The simulation results agreed with the experimental data and showed obvious correlation between the self-attenuation correction and the intensity ratios [(185.7 keV)/(143.8 keV), (98.44 keV)/(185.7 keV) and (185.7 keV)/(63.23 keV)]. This correlation greatly simplifies the determination of the self-attenuation correction and reduces the troublesome traditional procedures used to determine this coefficient.