Simultaneous quantitation of IC87114, roflumilast and its active metabolite roflumilast N‐oxide in plasma by LC‐MS/MS: application for a pharmacokinetic study

A sensitive and reliable high‐performance liquid chromatography–mass spectrometry (LC–MS/MS) was developed and validated for simultaneous quantification IC87114, roflumilast (RFM), and its active metabolite roflumilast N‐oxide (RFN) using tolbutamide as an internal standard. The analytes were extracted by using liquid–liquid extraction and separated on a reverse phase C₁₈ column (50 mm × 3 mm i.d., 4.6 µ) using methanol: 2 mM ammonium acetate buffer, pH 4.0 as mobile phase at a flow rate 1 mL/min in gradient mode. Selective reaction monitoring was performed using the transitions m/z 398.3 > 145.9, 403.1 >186.9, 419.1 > 187.0 and 271.1 > 155.0 to quantify quantification IC87114, RFM, RFN and tolbutamide, respectively. The method was validated over the concentration range of 0.1–60 ng.mL^?1 for RFM and RFN and 6 to 2980 ng.mL^?1 for IC87114. Intra‐ and inter‐day accuracy and precision of validated method were within the acceptable limits of <15% at all concentrations. Coefficients of correlation (r²) for the calibration curves were >0.99 for all analytes. The quantitation method was successfully applied for simultaneous estimation of IC87114, RFM and RFN in a pharmacokinetic drug–drug interaction study in Wistar rats. Copyright © 2012 John Wiley & Sons, Ltd.     

Signal design and convolutional coding for noncoherent space-timecommunication on the block-Rayleigh-fading channel

We consider the problem of designing signal constellations for the multiple transmit-multiple receive antenna Rayleigh-fading communication channel, when neither the transmitter nor the receiver know the fading. In particular, by employing the asymptotic union bound (AUB) on the probability of error, we give a new formulation of the problem of signal design for the noncoherent fading channel. Since unitary signals are optimal for this channel (in the limit of large signal-to-noise ratios SNRs), the problem can be posed in terms of packings on the Grassmanian manifold. A key difference in our approach from that of other authors is that we use a notion of distance on this manifold that is suggested by the union bound. As a consequence of our use of this distance measure, we obtain signal designs that are guaranteed to achieve the full diversity order of the channel, a result that does not hold when the chordal distance is used. We introduce a new method of recursively designing signals, termed successive updates, to approximately optimize this performance measure. We then examine the use of our signals with several convolutional codes over the fading channel. An upper bound on the bit error probability of the maximum-likelihood decoder is presented together with an asymptotic analysis of that bound     

Group detection for synchronous Gaussian code-divisionmultiple-access channels

The concept of group detection Is introduced to address the design of suboptimum multiuser detectors for code-division multiple-access (CDMA) channels. A group detection scheme consists of a bank of P group detectors, one each for detecting the information symbols of users in each group of a P group partition of the K simultaneously transmitting users. In a parallel group detection scheme, these group detectors operate independently, whereas in a sequential scheme, each group detector. Uses the decisions of the previous group detectors to successively cancel the interference from those users. Group detectors based on the generalized likelihood ratio test (GLRT) are obtained for the synchronous Gaussian CDMA channel. The complexity of these detectors is exponential in the group size, whereas that of the optimum detector is exponential in K. Since the partition of users is a design parameter, group sizes can be chosen to satisfy a wide range of complexity constraints. A key performance result is that the GLRT group detectors are optimally group near-far resistant. Furthermore, upper and lower bounds on the asymptotic efficiency of the sequential group detectors are derived. These bounds reveal that the sequential group detectors can, under certain conditions, perform as well as GLRT group detectors of much larger group sizes. Group detection provides a unifying approach to multiuser detection. When the users are partitioned into K single-user groups, the GLRT, a modified form of GLRT, and the sequential group detectors reduce to previously proposed suboptimal detectors; namely, the decorrelator, the two-stage detector, and the decorrelating decision-feedback detector, respectively. For the other nontrivial partitions, the group detectors are new and have a performance that is commensurate with their complexity     

Optimum multiuser noncoherent DPSK detection in generalized diversity Rayleigh-fading channels

The jointly optimum multiuser noncoherent detector for differential phase-shift keying (DPSK) modulation over the generalized diversity Rayleigh-fading (GDRF) channel is derived and analyzed. The GDRF channel includes time/frequency/receiver antenna diversity and allows fading correlations between the various diversity branches of each user. Noncoherent detection here refers to the case where the receiver has neither knowledge of the instantaneous phases nor of the envelopes of the users' channels. Upper and lower bounds on the bit-error probability of the optimum detector are derived for a given user. For fast fading, when the fading coefficients vary from one symbol interval to the next (but are still essentially constant over one symbol interval), the detector asymptotically (for high signal-to-noise ratios (SNRs)) reaches an error floor, which is bounded from below and above for different fast fading scenarios. For slow fading, when the channel is constant for at least two consecutive symbol intervals, the upper bound is shown to converge asymptotically to the lower bound. Thus, the asymptotic efficiency of optimum multiuser DPSK detection can be determined and is found to be positive. In contrast to coherent detection, however, it is smaller than unity in general. Since the asymptotic efficiency is independent of the interfering users' signal strengths, the optimum detector is near-far resistant. While optimum multiuser detection is exponentially complex in the number of users, its performance provides the benchmark for suboptimal detectors. In particular, it is seen that the previously suggested post-decorrelative detectors can be far from satisfactory.     

RMS bandwidth constrained signature waveforms that maximize thetotal capacity of PAM-synchronous CDMA channels

Optimum time-limited signal sets of equal and unequal energies are obtained under root mean square (RMS) bandwidth constraints. The total capacity and the total asymptotic efficiency of the PAM synchronous Gaussian CDMA (PSG-CDMA) channel are considered as the optimality criteria. The latter measure is monotonic with the determinant of the correlation matrix, R, and the former is monotonic with det(I+σ ^-2R), where σ² represents the noise level. Average as well as maximum RMS bandwidth constraints are considered in the equal-energy case, and the energy-weighted RMS bandwidth constraint is considered for unequal energy signals. For the equal-energy problem, signal sets are found that simultaneously optimize the total asymptotic efficiency under both average and maximum RMS bandwidth constraints. For the total capacity measure, such simultaneously optimal signal sets are also obtained, albeit under the restriction that the number of signals n be a Hadamard matrix dimension. When the Hadamard dimension is in particular a power of two, we obtain optimum signal sets that are shown to yield equal optimum multiuser detector asymptotic efficiencies for all users of an uncoded PSG-CDMA channel. Unequal energy signal sets are also found under an energy-weighted RMS bandwidth constraint for both optimality criteria     

Inducing self-assembly of Y2BaCuO5 nanoparticles via Ca-doping for improved pinning in YBa2Cu3O7−x

Different mechanisms may exists as a means to provide additional or specialized enhancement of existing nanoparticulate pinning in YBa₂Cu₃O_7?x (YBCO) thin films. In the particular case of Y₂BaCuO₅ (Y211) nanoparticles, Ca-doping of these nanoparticles via addition to the Y211 target material provides an additional increase to the J_c(H). YBCO + Y211 samples were created by pulsed laser deposition with alternating targets of YBCO with Y211 and Y211 doped with Ca. Initial indications suggest that this improvement in pinning results from some scattered short-ranged self-assembly of the nanoparticles into short nanocolumns.     

Comment on the intensity and the temperature dependence of the nitrogen-broadened half-width of the P(6) line in the CO fundamental

The recent line-center absorption coefficient measurements on the P(6) line of the CO fundamental have been shown to be consistent with S_v(T) = 273(273/T)cm^-2atm^-1 and γ⁰(T) = 0.0652(300/T)^0.66 for the absolute intensity of the band and the nitrogen-broadened line width in the temperature range 300–800°K.     

Some arithmetically symmetrical bandpass filters

A combination of the conventional and Matthaei lowpass-bandpass transformations is shown to result in some bandpass filters with very good arithmetic symmetry.     

Facilitated transport in spherical shells: application of the combined damköhler number technique

In cell membranes, double emulsion drops, or other particles with spherical shell geometry, reversible carriers may be present which serve to facilitate transport of solutes into the particles. The physical phenomena taking place are both diffusion and chemical reaction. When the reaction deviates from chemical equilibrium, the solution of the conservation equations becomes difficult because the equations are non-linear. The combined Damköhler technique, recently devised by Hoofd and Kreuzer, is a simple analytical method to accurately predict facilitated mass transfer in the presence of non-equilibrium chemical reaction. The application of the combined Damköhler technique to spherical shell geometry gives accurate predictions of the facilitated flux over the full range of Damköhler numbers, when compared to results from a numerical analysis technique. The non-equilibrium facilitated flux depends on the sphericity of the spherical shell.