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     

Eye tissue structure and refraction alterations upon nondestructive laser action

A new approach to alterations in eye refraction upon nondestructive laser action on the sclera and cornea is studied. It is demonstrated in in vivo experiments on rabbit eyes that sequential laser irradiation of the sclera and cornea yields a significant alteration in the eye refraction. The collagen structure of the sclera and cornea is studied after the nondestructive laser action with noninvasive polarization-sensitive optical coherence tomography. It is demonstrated that collagen fibers that provide for the cornea tension and applanation partially survive in the zone of the local denaturation of sclera. An irradiation mode that corresponds to an increase in the cornea’s plasticity and does not cause visible structural changes is chosen. The simplest theoretical model for alterations in the eye refraction upon the nonablative laser action on sclera is analyzed. The alteration in the cornea curvature upon stretching resulting from the local sclera coagulation and the corresponding decrease in its volume is calculated. The model makes it possible to approximately estimate the laser irradiation modes that provide the desired alterations in eye refraction.     

Modification of the surface state of rough substrates by two different varnishes and influence on the reflected light

Modification of the visual appearance when a rough surface is covered by a varnish is mostly attributed to the levelling of the substrate surface, which depends on the molecular weight of the varnish. The topography of varnished surfaces, however, has never been measured directly. Surfaces of varnishes applied over glass substrates of varying roughness were studied, therefore, using mechanical profilometry. Two different varnishes made with a low and a high molecular weight resin were studied. Both varnishes lower the r.m.s. roughness of the substrates and filter the high spatial frequencies. These results are amplified for the varnish containing the low molecular weight resin. The light reflected by the varnished samples is modelled from these topographical data. Its angular distribution, calculated from the probability density of slopes is presented, taking into account separately the air/varnish and the varnish/substrate interfaces. These analyses are presented in a back-scattering configuration. They show that varnishing significantly reduces the angular width of the reflected light and that this effect is magnified for the low molecular weight resin. Modelling furthermore shows that the influence of the roughness of the varnish/substrate interface is negligible in the total reflected light.     

Sensitivity of depolarized lidar signals to cloud and aerosol particle properties

Measurements from depolarized lidars provide a promising method to retrieve both cloud and aerosol properties and a versatile complement to passive satellite-based sensors. For lidar observations of clouds and aerosols, multiple scattering plays an important role in the scattering process. Monte Carlo simulations are carried out to investigate the sensitivity of lidar backscattering depolarization to cloud and aerosol properties. Lidar parameters are chosen to be similar to those of the upcoming space-based CALIPSO lidar. Cases are considered that consist of a single cloud or aerosol layer, as well as a case in which cirrus clouds overlay different types of aerosols. It is demonstrated that besides thermodynamic cloud phase, the depolarized lidar signal may provide additional information on ice or aerosol particle shapes. However, our results show little sensitivity to ice or aerosol particle sizes. Additionally, for the case of multiple but overlapping layers involving both clouds and aerosols, the depolarized lidar contains information that can help identify the particle properties of each layer.     

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).     

Interpreting Observables in a Quantum World from the Categorial Standpoint

We develop a relativistic perspective on structures of quantum observables, in terms of localization systems of Boolean coordinatizing charts. This perspective implies that the quantum world is comprehended via Boolean reference frames for measurement of observables, pasted together along their overlaps. The scheme is formalized categorically, as an instance of the adjunction concept. The latter is used as a framework for the specification of a categorical equivalence signifying an invariance in the translational code of communication between Boolean localizing contexts and quantum systems. Aspects of the scheme semantics are discussed in relation to logic. The interpretation of coordinatizing localization systems, as structure sheaves, provides the basis for the development of an algebraic differential geometric machinery suited to the quantum regime.     

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.