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     

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).     

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.     

The axial Ward identity in the presence of a quark-condensing vacuum

Quark-condensate contributions to triangle amplitudes arising from the nonperturbative content of the QCD vacuum are shown to uphold the anomalous axial Ward identity to leading and next-to-leading order in both the expansion parameter [m _quark/momentum]², as well as in the expansion parameter [m _π/m _quark]² appropriate forπ ⁰→ kinematics.     

An externally cooled beetle type scanning tunneling microscope for imaging in cryogenic liquids

We describe a variable temperature cryogenic scanning tunneling microscope designed for imaging and research in cryogenic liquids. It has an external Dewar type large scale cooling system with a temperature control range of roughly 85-110 K using pressure controlled liquid nitrogen cooling. The liquid nitrogen is kept in a closed chamber surrounding the STM and maintained at a pressure to suit the chosen temperature. Several gases have triple points in this temperature range and can therefore be liquified, such as argon, methane, silane and germane. The STM is based on a beetle type design built into a small cube vacuum chamber to fit into the cooling dewar. The system has been used for atomic resolution of highly oriented graphite submerged in a methane liquid at a temperature of 100 K.     

A modular scanning tunneling microscope with an interchangeable elastic closed cell and external actuators

We introduce a novel modular cell based scanning tunneling microscope with external piezoelectric actuators. A tip and a sample are contained in a closed interchangeable cell, consisting of a stiff top plate and a bottom part, fastened together by an elastic material. The bottom part, containing a scanning tip, is fastened to a base unit while the top plate, containing a sample, is capable of scanning motion by external piezoelectric actuators mounted in the same base unit. The actuators are pre-loaded by the deformation of the elastic material of the cell, giving an increased stability. This design is expected to simplify the scanning tunneling microscope (STM) operation in difficult environments greatly by enclosing only the tip and sample in a small cell-module, which is pluggable to a scanning mechanism and other supportive functionalities. A frequency characterization and an image scan showing atomic resolution of highly oriented graphite in air, at room temperature, is presented.     

2-Dimension from the Topological Viewpoint

In this paper we study the 2-dimension of a finite poset from the topological point of view. We use homotopy theory of finite topological spaces and the concept of a beat point to improve the classical results on 2-dimension, giving a more complete answer to the problem of all possible 2-dimensions of an n-point poset.