Development and validation of a simple and rapid capillary zone electrophoresis method for determination of nnrti nevirapine in pharmaceutical formulations

A simple and fast capillary zone electrophoresis (CZE) method has been developed and validated for quantification of a non-nucleoside reverse transcriptase inhibitor (NNRTI) nevirapine, in pharmaceuticals. The analysis was optimized using 10 mmol L-1 sodium phosphate buffer pH 2.5, +25 kV applied voltage, hydrodynamic injection 0.5 psi for 5 s and direct UV detection at 200 µm. Diazepam (50.0 µg mL-1) was used as internal standard. Under these conditions, nevirapine was analyzed in approximately less than 2.5 min. The analytical curve presented a coefficient of correlation of 0.9994. Limits of detection and quantification were 1.4 µg mL-1 and 4.3 µg mL-1, respectively. Intra- and inter-day precision expressed as relative standard deviations were 1.4% and 1.3%, respectively and the mean recovery was 100.81%. The active pharmaceutical ingredient was subjected to hydrolysis (acid, basic and neutral) and oxidative stress conditions. No interference of degradation products and tablet excipients were observed. This method showed to be rapid, simple, precise, accurate and economical for determination of nevirapine in pharmaceuticals and it is suitable for routine quality control analysis since CE offers benefits in terms of quicker method development and significantly reduced operating costs.

A positional FEM Formulation for geometrical non-linear analysis of shells

This work presents a fully non-linear finite element formulation for shell analysis comprising linear strain variation along the thickness of the shell and geometrically exact description for curved triangular elements. The developed formulation assumes positions and generalized unconstrained vectors as the variables of the problem, not displacements and finite rotations. The full 3D Saint-Venant-Kirchhoff constitutive relation is adopted and, to avoid locking, the rate of thickness variation enhancement is introduced. As a consequence, the second Piola-Kirchhoff stress tensor and the Green strain measure are employed to derive the specific strain energy potential. Curved triangular elements with cubic approximation are adopted using simple notation. Selected numerical simulations illustrate and confirm the objectivity, accuracy, path independence and applicability of the proposed technique.

Placebo Response of Non-Pharmacological and Pharmacological Trials in Major Depression: A Systematic Review and Meta-Analysis

Background: Although meta-analyses have shown that placebo responses are large in Major Depressive Disorder (MDD) trials; the placebo response of devices such as repetitive transcranial magnetic stimulation (rTMS) has not been systematically assessed. We proposed to assess placebo responses in two categories of MDD trials: pharmacological (antidepressant drugs) and non-pharmacological (device-rTMS) trials. Methodology/Principal Findings: We performed a systematic review and meta-analysis of the literature from April 2002 to April 2008, searching MEDLINE, Cochrane, Scielo and CRISP electronic databases and reference lists from retrieved studies and conference abstracts. We used the keywords placebo and depression and escitalopram for pharmacological studies; and transcranial magnetic stimulation and depression and sham for non-pharmacological studies. All randomized, double-blinded, placebo-controlled, parallel articles on major depressive disorder were included. Forty-one studies met our inclusion criteria-29 in the rTMS arm and 12 in the escitalopram arm. We extracted the mean and standard values of depression scores in the placebo group of each study. Then, we calculated the pooled effect size for escitalopram and rTMS arm separately, using Cohen's d as the measure of effect size. We found that placebo response are large for both escitalopram (Cohen's d-random-effects model-1.48; 95% C.I. 1.26 to 1.6) and rTMS studies (0.82; 95% C.I. 0.63 to 1). Exploratory analyses show that sham response is associated with refractoriness and with the use of rTMS as an add-on therapy, but not with age, gender and sham method utilized. Conclusions/Significance: We confirmed that placebo response in MDD is large regardless of the intervention and is associated with depression refractoriness and treatment combination (add-on rTMS studies). The magnitude of the placebo response seems to be related with study population and study design rather than the intervention itself.

Non-exhaustive tests for critical power estimation

Objective. - The aim of this study was to propose a new method that allows for the estimation of critical power (CP) from non-exhaustive tests using ratings of perceived exertion (RPE). Methods. - Twenty-two subjects underwent two practice trials for ergometer and Borg 15-point scale familiarization, and adaptation to severe exhaustive exercise. After then, four exercise bouts were performed on different days for the estimation of CP and anaerobic work capacity (AWC) by linear work-time equation, and CP(15), CP(17), AWC(15) and AWC(17) were estimated using the work and time to attainment of RPE15 and RPE17 based on the Borg 15-point scale. Results. - The CP, CP(15) and CP(17) (170-177W) were not significantly different (P>0.05). However, AWC, AWC(15) and AWC(17) were all different from each other. The correlations between CP(15) and CP(17), with CP were strong (R=0.871 and 0.911, respectively), but the AWC(15) and AWC(17) were not significantly correlated with AWC. Conclusion. - Sub-maximal. RPE responses can be used for the estimation of CP from non-exhaustive exercise protocols. (C) 2009 Elsevier Masson SAS. All rights reserved.

Power imbalance application region method for distributed synchronous generator anti-islanding protection design and evaluation

This paper presents a novel graphical approach to adjust and evaluate frequency-based relays employed in anti-islanding protection schemes of distributed synchronous generators, in order to meet the anti-islanding and abnormal frequency variation requirements, simultaneously. The proposed method defines a region in the power mismatch space, inside which the relay non-detection zone should be located, if the above-mentioned requirements must be met. Such region is called power imbalance application region. Results show that this method can help protection engineers to adjust frequency-based relays to improve the anti-islanding capability and to minimize false operation occurrences, keeping the abnormal frequency variation utility requirements satisfied. Moreover, the proposed method can be employed to coordinate different types of frequency-based relays, aiming at improving overall performance of the distributed generator frequency protection scheme. (C) 2011 Elsevier B.V. All rights reserved.

Automatic tuning method for the design of supplementary damping controllers for flexible alternating current transmission system devices

The design of supplementary damping controllers to mitigate the effects of electromechanical oscillations in power systems is a highly complex and time-consuming process, which requires a significant amount of knowledge from the part of the designer. In this study, the authors propose an automatic technique that takes the burden of tuning the controller parameters away from the power engineer and places it on the computer. Unlike other approaches that do the same based on robust control theories or evolutionary computing techniques, our proposed procedure uses an optimisation algorithm that works over a formulation of the classical tuning problem in terms of bilinear matrix inequalities. Using this formulation, it is possible to apply linear matrix inequality solvers to find a solution to the tuning problem via an iterative process, with the advantage that these solvers are widely available and have well-known convergence properties. The proposed algorithm is applied to tune the parameters of supplementary controllers for thyristor controlled series capacitors placed in the New England/New York benchmark test system, aiming at the improvement of the damping factor of inter-area modes, under several different operating conditions. The results of the linear analysis are validated by non-linear simulation and demonstrate the effectiveness of the proposed procedure.

Non-linear boundary element formulation applied to contact analysis using tangent operator

This work presents a non-linear boundary element formulation applied to analysis of contact problems. The boundary element method (BEM) is known as a robust and accurate numerical technique to handle this type of problem, because the contact among the solids occurs along their boundaries. The proposed non-linear formulation is based on the use of singular or hyper-singular integral equations by BEM, for multi-region contact. When the contact occurs between crack surfaces, the formulation adopted is the dual version of BEM, in which singular and hyper-singular integral equations are defined along the opposite sides of the contact boundaries. The structural non-linear behaviour on the contact is considered using Coulomb`s friction law. The non-linear formulation is based on the tangent operator in which one uses the derivate of the set of algebraic equations to construct the corrections for the non-linear process. This implicit formulation has shown accurate as the classical approach, however, it is faster to compute the solution. Examples of simple and multi-region contact problems are shown to illustrate the applicability of the proposed scheme. (C) 2011 Elsevier Ltd. All rights reserved.

Verification of a mixed high-order accurate DNS code for laminar turbulent transition by the method of manufactured solutions

This paper presents results on a verification test of a Direct Numerical Simulation code of mixed high-order of accuracy using the method of manufactured solutions (MMS). This test is based on the formulation of an analytical solution for the Navier-Stokes equations modified by the addition of a source term. The present numerical code was aimed at simulating the temporal evolution of instability waves in a plane Poiseuille flow. The governing equations were solved in a vorticity-velocity formulation for a two-dimensional incompressible flow. The code employed two different numerical schemes. One used mixed high-order compact and non-compact finite-differences from fourth-order to sixth-order of accuracy. The other scheme used spectral methods instead of finite-difference methods for the streamwise direction, which was periodic. In the present test, particular attention was paid to the boundary conditions of the physical problem of interest. Indeed, the verification procedure using MMS can be more demanding than the often used comparison with Linear Stability Theory. That is particularly because in the latter test no attention is paid to the nonlinear terms. For the present verification test, it was possible to manufacture an analytical solution that reproduced some aspects of an instability wave in a nonlinear stage. Although the results of the verification by MMS for this mixed-order numerical scheme had to be interpreted with care, the test was very useful as it gave confidence that the code was free of programming errors. Copyright (C) 2009 John Wiley & Sons, Ltd.

Wavelet-Galerkin method for one-dimensional elastoplasticity and damage problems: Constitutive modeling and computational aspects

This work presents an analysis of the wavelet-Galerkin method for one-dimensional elastoplastic-damage problems. Time-stepping algorithm for non-linear dynamics is presented. Numerical treatment of the constitutive models is developed by the use of return-mapping algorithm. For spacial discretization we can use wavelet-Galerkin method instead of standard finite element method. This approach allows to locate singularities. The discrete formulation developed can be applied to the simulation of one-dimensional problems for elastic-plastic-damage models. (C) 2007 Elsevier Inc. All rights reserved.

Matrix Method for Acoustic Levitation Simulation

A matrix method is presented for simulating acoustic levitators. A typical acoustic levitator consists of an ultrasonic transducer and a reflector. The matrix method is used to determine the potential for acoustic radiation force that acts on a small sphere in the standing wave field produced by the levitator. The method is based on the Rayleigh integral and it takes into account the multiple reflections that occur between the transducer and the reflector. The potential for acoustic radiation force obtained by the matrix method is validated by comparing the matrix method results with those obtained by the finite element method when using an axisymmetric model of a single-axis acoustic levitator. After validation, the method is applied in the simulation of a noncontact manipulation system consisting of two 37.9-kHz Langevin-type transducers and a plane reflector. The manipulation system allows control of the horizontal position of a small levitated sphere from -6 mm to 6 mm, which is done by changing the phase difference between the two transducers. The horizontal position of the sphere predicted by the matrix method agrees with the horizontal positions measured experimentally with a charge-coupled device camera. The main advantage of the matrix method is that it allows simulation of non-symmetric acoustic levitators without requiring much computational effort.

Application of the essential work of fracture method in ranking the performance in service of high-density polyethylene resins employed in pressure pipes

High-density polyethylene resins have increasingly been used in the production of pipes for water- and gas-pressurized distribution systems and are expected to remain in service for several years, but they eventually fail prematurely by creep fracture. Usual standard methods used to rank resins in terms of their resistance to fracture are expensive and non-practical for quality control purposes, justifying the search for alternative methods. Essential work of fracture (EWF) method provides a relatively simple procedure to characterize the fracture behavior of ductile polymers, such as polyethylene resins. In the present work, six resins were analyzed using the EWF methodology. The results show that the plastic work dissipation factor, beta w(p), is the most reliable parameter to evaluate the performance. Attention must be given to specimen preparation that might result in excessive dispersion in the results, especially for the essential work of fracture w(e).

Hydrolysis of acetic anhydride: Non-adiabatic calorimetric determination of kinetics and heat exchange

A simple calorimetric method to estimate both kinetics and heat transfer coefficients using temperature-versus-time data under non-adiabatic conditions is described for the reaction of hydrolysis of acetic anhydride. The methodology is applied to three simple laboratory-scale reactors in a very simple experimental setup that can be easily implemented. The quality of the experimental results was verified by comparing them with literature values and with predicted values obtained by energy balance. The comparison shows that the experimental kinetic parameters do not agree exactly with those reported in the literature, but provide a good agreement between predicted and experimental data of temperature and conversion. The differences observed between the activation energy obtained and the values reported in the literature can be ascribed to differences in anhydride-to-water ratios (anhydride concentrations). (C) 2010 Elsevier Ltd. All rights reserved.

Infinite horizon MPC with non-minimal state space feedback

In the MPC literature, stability is usually assured under the assumption that the state is measured. Since the closed-loop system may be nonlinear because of the constraints, it is not possible to apply the separation principle to prove global stability for the Output feedback case. It is well known that, a nonlinear closed-loop system with the state estimated via an exponentially converging observer combined with a state feedback controller can be unstable even when the controller is stable. One alternative to overcome the state estimation problem is to adopt a non-minimal state space model, in which the states are represented by measured past inputs and outputs [P.C. Young, M.A. Behzadi, C.L. Wang, A. Chotai, Direct digital and adaptative control by input-output, state variable feedback pole assignment, International journal of Control 46 (1987) 1867-1881; C. Wang, P.C. Young, Direct digital control by input-output, state variable feedback: theoretical background, International journal of Control 47 (1988) 97-109]. In this case, no observer is needed since the state variables can be directly measured. However, an important disadvantage of this approach is that the realigned model is not of minimal order, which makes the infinite horizon approach to obtain nominal stability difficult to apply. Here, we propose a method to properly formulate an infinite horizon MPC based on the output-realigned model, which avoids the use of an observer and guarantees the closed loop stability. The simulation results show that, besides providing closed-loop stability for systems with integrating and stable modes, the proposed controller may have a better performance than those MPC controllers that make use of an observer to estimate the current states. (C) 2008 Elsevier Ltd. All rights reserved.

Non-linear modal analysis for beams subjected to axial loads: Analytical and finite-element solutions

A rigorous derivation of non-linear equations governing the dynamics of an axially loaded beam is given with a clear focus to develop robust low-dimensional models. Two important loading scenarios were considered, where a structure is subjected to a uniformly distributed axial and a thrust force. These loads are to mimic the main forces acting on an offshore riser, for which an analytical methodology has been developed and applied. In particular, non-linear normal modes (NNMs) and non-linear multi-modes (NMMs) have been constructed by using the method of multiple scales. This is to effectively analyse the transversal vibration responses by monitoring the modal responses and mode interactions. The developed analytical models have been crosschecked against the results from FEM simulation. The FEM model having 26 elements and 77 degrees-of-freedom gave similar results as the low-dimensional (one degree-of-freedom) non-linear oscillator, which was developed by constructing a so-called invariant manifold. The comparisons of the dynamical responses were made in terms of time histories, phase portraits and mode shapes. (C) 2008 Elsevier Ltd. All rights reserved.

Thermally developing Brinkman–Brinkman forced convection in rectangular ducts with isothermal walls

The Extended Weighted Residuals Method (EWRM) is applied to investigate the effects of viscous dissipation on the thermal development of forced convection in a porous-saturated duct of rectangular cross-section with isothermal boundary condition. The Brinkman flow model is employed for determination of the velocity field. The temperature in the flow field was computed by utilizing the Green’s function solution based on the EWRM. Following the computation of the temperature field, expressions are presented for the local Nusselt number and the bulk temperature as a function of the dimensionless longitudinal coordinate. In addition to the aspect ratio, the other parameters included in this computation are the Darcy number, viscosity ratio, and the Brinkman number.