Diffusion modeling of percutaneous absorption kinetics: 2. Finite vehicle volume and solvent deposited solids

The diffusion model for percutaneous absorption is developed for the specific case of delivery to the skin being limited by the application of a finite amount of solute. Two cases are considered; in the first, there is an application of a finite donor (vehicle) volume, and in the second, there are solvent-deposited solids and a thin vehicle with a high partition coefficient. In both cases, the potential effect of an interfacial resistance at the stratum corneum surface is also considered. As in the previous paper, which was concerned with the application of a constant donor concentration, clearance limitations due to the viable eqidermis, the in vitro sampling rate, or perfusion rate in vivo are included. Numerical inversion of the Laplace domain solutions was used for simulations of solute flux and cumulative amount absorbed and to model specific examples of percutaneous absorption of solvent-deposited solids. It was concluded that numerical inversions of the Laplace domain solutions for a diffusion model of the percutaneous absorption, using standard scientific software (such as SCIENTIST, MicroMath Scientific software) on modern personal computers, is a practical alternative to computation of infinite series solutions. Limits of the Laplace domain solutions were used to define the moments of the flux-time profiles for finite donor volumes and the slope of the terminal log flux-time profile. The mean transit time could be related to the diffusion time through stratum corneum, viable epidermal, and donor diffusion layer resistances and clearance from the receptor phase. Approximate expressions for the time to reach maximum flux (peak time) and maximum flux were also derived. The model was then validated using reported amount-time and flux-time profiles for finite doses applied to the skin. It was concluded that for very small donor phase volume or for very large stratum corneum-vehicle partitioning coefficients (e.g., for solvent deposited solids), the flux and amount of solute absorbed are affected by receptor conditions to a lesser extent than is obvious for a constant donor constant donor concentrations. (C) 2001 Wiley-Liss, Inc. and the American Pharmaceutical Association J Pharm Sci 90:504-520, 2001.

A dynamic model with on-line identification for rotary sugar drying processes

A dynamic modelling methodology, which combines on-line variable estimation and parameter identification with physical laws to form an adaptive model for rotary sugar drying processes, is developed in this paper. In contrast to the conventional rate-based models using empirical transfer coefficients, the heat and mass transfer rates are estimated by using on-line measurements in the new model. Furthermore, a set of improved sectional solid transport equations with localized parameters is developed in this work to reidentified on-line using measurement data, the model is able to closely track the dynamic behaviour of rotary drying processes within a broad range of operational conditions. This adaptive model is validated against experimental data obtained from a pilot-scale rotary sugar dryer. The proposed modelling methodology can be easily incorporated into nonlinear model based control schemes to form a unified modelling and control framework.place the global correlation for the computation of solid retention time. Since a number of key model variables and parameters are identified on-line using measurement data, the model is able to closely track the dynamic behaviour of rotary drying processes within a broad range of operational conditions. This adaptive model is validated against experimental data obtained from a pilot-scale rotary sugar dryer. The proposed modelling methodology can be easily incorporated into nonlinear model based control schemes to form a unified modelling and control framework.

Quaternary continental weathering geochronology by laser-heating Ar-40/Ar-39 analysis of supergene cryptomelane

Incremental laser-heating analyses of supergene cryptomelane clusters extracted from three distinct weathering profiles from the Mary Valley region, southeast Queensland, Australia, yield reproducible and well-defined plateau ages ranging from 346 +/- 15 to 291 +/- 14 ka (2 a). Precipitation of supergene cryptomelane in this period implies that relative humid climate prevailed in southeast Queensland from 340 to 290 ha, a result consistent with oxygen isotope analyses of marine sediments from Ocean Drilling Program Site 820 and with regional pollen and spore records. These results, the first report on the precise Ar-40/Ar-39 dating of Quaternary supergene cryptomelane, indicate that Ar-40/Ar-39 analysis of pedogenic minerals provides a reliable geochronometer for the study of Quaternary surficial processes useful in the study of soil formation rates, continental paleoclimates, and archaeological sites devoid of datable volcanic minerals.

Step size control for efficient discrete element simulation

The step size determines the accuracy of a discrete element simulation. The position and velocity updating calculation uses a pre-calculated table and hence the control of step size can not use the integration formulas for step size control. A step size control scheme for use with the table driven velocity and position calculation uses the difference between the calculation result from one big step and that from two small steps. This variable time step size method chooses the suitable time step size for each particle at each step automatically according to the conditions. Simulation using fixed time step method is compared with that of using variable time step method. The difference in computation time for the same accuracy using a variable step size (compared to the fixed step) depends on the particular problem. For a simple test case the times are roughly similar. However, the variable step size gives the required accuracy on the first run. A fixed step size may require several runs to check the simulation accuracy or a conservative step size that results in longer run times. (C) 2001 Elsevier Science Ltd. All rights reserved.

Prediction of mortality using dobutamine echocardiography

OBJECTIVES We sought to find out whether dobutamine echocardiography (DbE) could provide independent prediction of total and cardiac mortality, incremental to clinical and angiographic variables. BACKGROUND Existing outcome studies with DbE have examined composite end points, rather than death, over a relatively short follow-up. METHODS Clinical and stress data were collected in 3,156 patients (age 63 +/- 12 years, 1,801 men) undergoing DbE. Significant stenoses (>50% diameter) were identified in 70% of 1,073 patients undergoing coronary angiography. Total and cardiac mortality were identified over nine years of follow-up (mean 3.8 +/- 1.9). Cox models were used to analyze the effect of ischemia and other variables, independent of other determinants of mortality. RESULTS The dobutamine echocardiogram was abnormal in 1,575 patients (50%). Death occurred in 716 patients (23%), 259 of whom (8%) were thought to have died from cardiac causes. Patients with normal DbE had a total mortality of 8% per year and a cardiac mortality of 1% per year over the first four years of follow-up. Ischemia and the extent of abnormal wall motion were independent predictors of cardiac death, together with age and heart failure. In sequential Cox models, the predictive power of clinical data alone (model chi-square 115) was strengthened by adding the resting left ventricular function (model chi-square 138) and the results of DbE (model chi-square 181). In the subgroup undergoing coronary angiography, the power of the model was increased to a minor degree by the addition of coronary anatomy data. CONCLUSIONS Dobutamine echocardiography is an independent predictor of death, incremental to other data. While a normal dobutamine echocardiogram predicts low risk of cardiac death ton the order of 1% per year), this risk increases with the extent of abnormal wall motion at rest and stress, (J Am Coil Cardiol 2001;37:754-60) (C) 2001 by the American College of Cardiology.

Continuous quantum measurement of two coupled quantum dots using a point contact: A quantum trajectory approach

We obtain the finite-temperature unconditional master equation of the density matrix for two coupled quantum dots (CQD's) when one dot is subjected to a measurement of its electron occupation number using a point contact (PC). To determine how the CQD system state depends on the actual current through the PC device, we use the so-called quantum trajectory method to derive the zero-temperature conditional master equation. We first treat the electron tunneling through the PC barrier as a classical stochastic point process (a quantum-jump model). Then we show explicitly that our results can be extended to the quantum-diffusive limit when the average electron tunneling rate is very large compared to the extra change of the tunneling rate due to the presence of the electron in the dot closer to the PC. We find that in both quantum-jump and quantum-diffusive cases, the conditional dynamics of the CQD system can be described by the stochastic Schrodinger equations for its conditioned state vector if and only if the information carried away from the CQD system by the PC reservoirs can be recovered by the perfect detection of the measurements.

Complex natural resonances of conducting planar objects buried in a dielectric half-space

A scheme is presented to incorporate a mixed potential integral equation (MPIE) using Michalski's formulation C with the method of moments (MoM) for analyzing the scattering of a plane wave from conducting planar objects buried in a dielectric half-space. The robust complex image method with a two-level approximation is used for the calculation of the Green's functions for the half-space. To further speed up the computation, an interpolation technique for filling the matrix is employed. While the induced current distributions on the object's surface are obtained in the frequency domain, the corresponding time domain responses are calculated via the inverse fast Fourier transform (FFT), The complex natural resonances of targets are then extracted from the late time response using the generalized pencil-of-function (GPOF) method. We investigate the pole trajectories as we vary the distance between strips and the depth and orientation of single, buried strips, The variation from the pole position of a single strip in a homogeneous dielectric medium was only a few percent for most of these parameter variations.

The effect of moderate aerobic exercise and relaxation on secretory immunoglobulin A

A deficiency in secretory immunoglobulin A (sIgA) is associated with recurrent upper respiratory tract infections both in the general community and in elite athletes. The aim of this paper was to investigate the effect of aerobic exercise and relaxation on various indices of sIgA in 12 male and 8 female adults who varied in levels of recreational activity. Salivary samples were obtained before, immediately after and 30 minutes after an incremental cycle ergometer test to fatigue. after 30 minutes of cycling at 30% or 60 % of maximum heart rate, and after 30 minutes of relaxation with guided imagery. Each session was run on a separate day. When expressed in relation to changes in salivary flow rate, sIgA did not change after exercise. However, both the absolute concentration and secretion rate of sIgA increased during relaxation (167 +/- 179 mug ml(-1), p < 0.001: and 37 +/- 71 g(.)min(-1), p < 0.05 respectively). Nonspecific protein increased more than sIgA during incremental exercise to fatigue (decrease in the sIgA/protein ratio 92 +/- 181 g(.)mg protein(-1), p(0.05), but sIgA relative to protein did not change during relaxation. Our findings suggest that sIgA secretion rate is a more appropriate measure of sIgA than sIgA relative to protein, both for exercise and relaxation. These data suggest the possibility of using relaxation to counteract the negative effects of intense exercise on sIgA levels.

Dynamics of a mesoscopic charge quantum bit under continuous quantum measurement

We present the conditional quantum dynamics of an electron tunneling between two quantum dots subject to a measurement using a low transparency point contact or tunnel junction. The double dot system forms a single qubit and the measurement corresponds to a continuous in time readout of the occupancy of the quantum dot. We illustrate the difference between conditional and unconditional dynamics of the qubit. The conditional dynamics is discussed in two regimes depending on the rate of tunneling through the point contact: quantum jumps, in which individual electron tunneling current events can be distinguished, and a diffusive dynamics in which individual events are ignored, and the time-averaged current is considered as a continuous diffusive variable. We include the effect of inefficient measurement and the influence of the relative phase between the two tunneling amplitudes of the double dot/point contact system.

Materialized view selection under the maintenance time constraint

A data warehouse is a data repository which collects and maintains a large amount of data from multiple distributed, autonomous and possibly heterogeneous data sources. Often the data is stored in the form of materialized views in order to provide fast access to the integrated data. One of the most important decisions in designing a data warehouse is the selection of views for materialization. The objective is to select an appropriate set of views that minimizes the total query response time with the constraint that the total maintenance time for these materialized views is within a given bound. This view selection problem is totally different from the view selection problem under the disk space constraint. In this paper the view selection problem under the maintenance time constraint is investigated. Two efficient, heuristic algorithms for the problem are proposed. The key to devising the proposed algorithms is to define good heuristic functions and to reduce the problem to some well-solved optimization problems. As a result, an approximate solution of the known optimization problem will give a feasible solution of the original problem. (C) 2001 Elsevier Science B.V. All rights reserved.

Effect of propionyl-L-carnitine on exercise performance in peripheral arterial disease

Background: Supplementation with propionyl-L-carnitine (PLC) may be of use in improving the exercise capacity of people with peripheral arterial disease. Methods: After a 2-wk exercise familiarization phase, seven subjects displaying intermittent claudication were studied over a 12-wk period consisting of three 4-wk phases, baseline (B), supplementation (S), and placebo (P). PLC was supplemented at 2 g(.)d(-1), and subjects were blinded to the order of supplementation. Unilateral calf strength and endurance were assessed weekly. Walking performance was assessed at the end of each phase using an incremental protocol, during which respiratory gases were collected. Results: Although there was not a significant increase in maximal walking time (similar to 14%) in the whole group, walking time improved to a greater extent than the individual baseline coefficient of variation in four of the seven subjects. The changes in walking performance were correlated with changes in the respiratory exchange ratio both at steady state (r = 0.59) and maximal exercise (r = 0.79). Muscle strength increased significantly from 695 +/- 198 N to 812 +/- 249 N by the end of S. Changes in calf strength from B to S were modestly related to changes in walking performance (r = 0.56). No improvements in calf endurance were detected throughout the study. Conclusions: These preliminary data suggest that, in addition to walking performance, muscle strength can be increased in PAD patients after 4 wk of supplementation with propionyl-L-carnitine.

On the fast approximation of Green's functions in MPIE formulations for planar layered media

The numerical implementation of the complex image approach for the Green's function of a mixed-potential integralequation formulation is examined and is found to be limited to low values of k(0) rho (in this context k(0) rho = 2 pirho/ lambda(0), where rho is the distance between the source and the field points of the Green's function and lambda(0) is the free space wavelength). This is a clear limitation for problems of large dimension or high frequency where this limit is easily exceeded. This paper examines the various strategies and proposes a hybrid method whereby most of the above problems can be avoided. An efficient integral method that is valid for large k(0) rho is combined with the complex image method in order to take advantage of the relative merits of both schemes. It is found that a wide overlapping region exists between the two techniques allowing a very efficient and consistent approach for accurately calculating the Green's functions. In this paper, the method developed for the computation of the Green's function is used for planar structures containing both lossless and lossy media.

Entanglement creation using quantum interrogation

We present some applications of high-efficiency quantum interrogation (interaction-free measurement) for the creation of entangled states of separate atoms and of separate photons. The quantum interrogation of a quantum object in a superposition of object-in and object-out leaves the object and probe in an entangled state. The probe can then be further entangled with other objects in subsequent quantum interrogations. By then projecting out those cases in which the probe is left in a particular final state, the quantum objects can themselves be left in various entangled states. In this way, we show how to generate two-, three-, and higher-qubit entanglement between atoms and between photons. The effect of finite efficiency for the quantum interrogation is delineated for the various schemes.

A monolithic smoothing-gap algorithm for contact-impact based on the signed distance function

A new algorithm has been developed for smoothing the surfaces in finite element formulations of contact-impact. A key feature of this method is that the smoothing is done implicitly by constructing smooth signed distance functions for the bodies. These functions are then employed for the computation of the gap and other variables needed for implementation of contact-impact. The smoothed signed distance functions are constructed by a moving least-squares approximation with a polynomial basis. Results show that when nodes are placed on a surface, the surface can be reproduced with an error of about one per cent or less with either a quadratic or a linear basis. With a quadratic basis, the method exactly reproduces a circle or a sphere even for coarse meshes. Results are presented for contact problems involving the contact of circular bodies. Copyright (C) 2002 John Wiley Sons, Ltd.