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.     

Wavelet Collocation Methods for a First Kind Boundary Integral Equation in Acoustic Scattering

In this paper we consider a wavelet algorithm for the piecewise constant collocation method applied to the boundary element solution of a first kind integral equation arising in acoustic scattering. The conventional stiffness matrix is transformed into the corresponding matrix with respect to wavelet bases, and it is approximated by a compressed matrix. Finally, the stiffness matrix is multiplied by diagonal preconditioners such that the resulting matrix of the system of linear equations is well conditioned and sparse. Using this matrix, the boundary integral equation can be solved effectively.     

Analytic calculation of scaling dimensions: Tricritical hard squares and critical hard hexagons

The finite-size corrections, central chargesc, and scaling dimensionsx of tricritical hard squares and critical hard hexagons are calculated analytically. This is achieved by solving the special functional equation or inversion identity satisfied by the commuting row transfer matrices of these lattice models at criticality. The results are expressed in terms of Rogers dilogarithms. For tricritical hard squares we obtainc=7/10,x=3/40, 1/5, 7/8, 6/5 and for hard hexagons we obtainc=4/5,x=2/15, 4/5, 17/15, 4/3, 9/5, in accord with the predictions of conformal and modular invariance.     

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.     

Aspects of Generic Entanglement

We study entanglement and other correlation properties of random states in high-dimensional bipartite systems. These correlations are quantified by parameters that are subject to the ``concentration of measure' phenomenon, meaning that on a large-probability set these parameters are close to their expectation. For the entropy of entanglement, this has the counterintuitive consequence that there exist large subspaces in which all pure states are close to maximally entangled. This, in turn, implies the existence of mixed states with entanglement of formation near that of a maximally entangled state, but with negligible quantum mutual information and, therefore, negligible distillable entanglement, secret key, and common randomness. It also implies a very strong locking effect for the entanglement of formation: its value can jump from maximal to near zero by tracing over a number of qubits negligible compared to the size of the total system. Furthermore, such properties are generic. Similar phenomena are observed for random multiparty states, leading us to speculate on the possibility that the theory of entanglement is much simplified when restricted to asymptotically generic states. Further consequences of our results include a complete derandomization of the protocol for universal superdense coding of quantum states.     

A Bicriterial Optimization Problem of Antenna Design

In this paper we consider a special optimization problem withtwo objectives which arises in antenna theory. It is shown that thisabstract bicriterial optimization problem has at least one solution.Discretized versions of this problem are also discussed, and therelationships between these finite dimensional problems and the infinitedimensional problem are investigated. Moreover, we presentnumerical results for special parameters using a multiobjectiveoptimization method.