The stereospecific synthesis of leukotriene A4 (LTA4), 5-epi-LTA4, 6-epi-LTA4 and 5-epi,6-epi-LTA4

The stereospecific syntheses of the four isomers of 6-formyl-5,6-epoxy hexanoic acid methyl ester $\text{8}$, $\text{15}$, $\text{23}$ and $\text{30}$ from Z-deoxy-D-ribose have allowed the preparation of methyl esters of LTA₄, $\text{1}$, and its three unnatural isomers.     

Field emission tip as a nanometer source of free electron femtosecond pulses

We report a source of free electron pulses based on a field emission tip irradiated by a low-power femtosecond laser. The electron pulses are shorter than 70 fs and originate from a tip with an emission area diameter down to 2 nm. Depending on the operating regime we observe either photofield emission or optical field emission with up to 200 electrons per pulse at a repetition rate of 1 GHz. This pulsed electron emitter, triggered by a femtosecond oscillator, could serve as an efficient source for time-resolved electron interferometry, for time-resolved nanometric imaging and for synchrotrons.     

Four-body Efimov effect for three fermions and a lighter particle

We study three same-spin-state fermions of mass M interacting with a distinguishable particle of mass m in the unitary limit where the interaction has a zero range and an infinite s-wave scattering length. We predict an interval of mass ratio 13.384相似文献   

Algebraic analysis of two‐grid methods: The nonsymmetric case

Two‐grid methods constitute the building blocks of multigrid methods, which are among the most efficient solution techniques for solving large sparse systems of linear equations. In this paper, an analysis is developed that does not require any symmetry property. Several equivalent expressions are provided that characterize all eigenvalues of the iteration matrix. In the symmetric positive‐definite (SPD) case, these expressions reproduce the sharp two‐grid convergence estimate obtained by Falgout, Vassilevski and Zikatanov (Numer. Linear Algebra Appl. 2005; 12 :471–494), and also previous algebraic bounds, which can be seen as corollaries of this estimate. These results allow to measure the convergence by checking ‘approximation properties’. In this work, proper extensions of the latter to the nonsymmetric case are presented. Sometimes approximation properties for the SPD case are summarized in loose terms; e.g.: Interpolation must be able to approximate an eigenvector with error bound proportional to the size of the eigenvalue (SIAM J. Sci. Comp. 2000; 22 :1570–1592). It is shown that this can be applied to nonsymmetric problems too, understanding ‘size’ as ‘modulus’. Eventually, an analysis is developed, for the nonsymmetric case, of the theoretical foundations of ‘compatible relaxation’, according to which a Fine/Coarse partitioning may be checked and possibly improved. Copyright © 2009 John Wiley & Sons, Ltd.     

Passive acoustic detection and localization of whales: effects of shipping noise in Saguenay-St. Lawrence Marine Park

The performance of large-aperture hydrophone arrays to detect and localize blue and fin whales' 15-85 Hz signature vocalizations under ocean noise conditions was assessed through simulations from a normal mode propagation model combined to noise statistics from 15 960 h of recordings in Saguenay-St. Lawrence Marine Park. The probability density functions of 2482 summer noise level estimates in the call bands were used to attach a probability of detection/masking to the simulated call levels as a function of whale depth and range for typical environmental conditions. Results indicate that call detection was modulated by the calling depth relative to the sound channel axis and by modal constructive and destructive interferences with range. Masking of loud infrasounds could reach 40% at 30 km for a receiver at the optimal depth. The 30 dB weaker blue whale D-call were subject to severe masking. Mapping the percentages of detection and localization allowed assessing the performance of a six-hydrophone array under mean- and low-noise conditions. This approach is helpful for optimizing hydrophone configuration in implementing passive acoustic monitoring arrays and building their detection function for whale density assessment, as an alternative to or in combination with the traditional undersampling visual methods.     

1,3-Dipolar cycloadditions with azomethine ylide species generated from aminocyclopropanes

Two types of bicyclic N-cyclopropyl glycine ester derivatives have been prepared and put under scrutiny as possible precursors of azomethine ylides. The results demonstrate that they can indeed participate in 1,3-dipolar cycloaddition reactions with dipolarophiles, as illustrated in the cases of phenyl vinyl sulfone, N-phenylmaleimide, diethyl fumarate and diethyl maleate. The relative configurations of the major diastereoisomers produced are consistent with the predicted generation of azomethine ylide species, reacting in concerted cycloaddition processes. This unprecedented way of generating such 1,3-dipoles provides access to functionalised pyrrolizidine and pyrrolidine derivatives, that would be difficult to make directly by more classic methods. It was also found that using phenyl vinyl sulfone or N-phenylmaleimide as the dipolarophile reactant, a domino nucleophilic conjugate addition/1,3-dipolar cycloaddition process may operate competitively.     

Robust cross-validation of linear regression QSAR models

A quantitative structure-activity relationship (QSAR) model is typically developed to predict the biochemical activity of untested compounds from the compounds' molecular structures. "The gold standard" of model validation is the blindfold prediction when the model's predictive power is assessed from how well the model predicts the activity values of compounds that were not considered in any way during the model development/calibration. However, during the development of a QSAR model, it is necessary to obtain some indication of the model's predictive power. This is often done by some form of cross-validation (CV). In this study, the concepts of the predictive power and fitting ability of a multiple linear regression (MLR) QSAR model were examined in the CV context allowing for the presence of outliers. Commonly used predictive power and fitting ability statistics were assessed via Monte Carlo cross-validation when applied to percent human intestinal absorption, blood-brain partition coefficient, and toxicity values of saxitoxin QSAR data sets, as well as three known benchmark data sets with known outlier contamination. It was found that (1) a robust version of MLR should always be preferred over the ordinary-least-squares MLR, regardless of the degree of outlier contamination and that (2) the model's predictive power should only be assessed via robust statistics. The Matlab and java source code used in this study is freely available from the QSAR-BENCH section of www.dmitrykonovalov.org for academic use. The Web site also contains the java-based QSAR-BENCH program, which could be run online via java's Web Start technology (supporting Windows, Mac OSX, Linux/Unix) to reproduce most of the reported results or apply the reported procedures to other data sets.     

Evaluation of polymeric methacrylate-based monoliths in capillary electrochromatography for their potential to separate pharmaceutical compounds

Polymeric methacrylate-based monoliths are evaluated in capillary electrochromatography (CEC) and pressurized capillary electrochromatography (p-CEC) for their potential in pharmaceutical analysis. Using a given polymerization mixture as a basis for the monolith synthesis, different mobile phase pH at constant organic modifier concentrations are tested in both CEC and p-CEC. The test set consists of basic, acidic, amphoteric, and neutral compounds, which are mainly pharmaceuticals. Because of the mainly hydrophobic character of the stationary phase, the interactions are largest when the compounds appear in an uncharged state, but some ion-exchange phenomena with negatively charged compounds can also be observed. In CEC, acidic substances are most retained at low pH. For amphoteric and neutral compounds, no preference regarding analyzing pH can be derived from these experiments. For basics, a high pH is chosen, but a reduced solvent strength is needed to enhance the retention of these compounds. The retention mechanism in p-CEC can also be assigned to both hydrophobic and ionic interactions. For acidic, amphoteric, and neutral compounds, acceptable retention is seen. For the basic compounds, the retention with a mobile phase containing 50% organic modifier is low, as in CEC. However, when the organic modifier content in the mobile phase is decreased, retention increases and the selectivity of the stationary phase is more pronounced. This mode of operation presents a possibility for separating some test mixtures, thus some potential for pharmaceutical analysis is seen. More efforts are needed to obtain higher efficiencies and better peak shapes, which might be solved by a further optimization of both the stationary phase synthesis and the mobile phase composition.     

Ruggedness and robustness testing

Due to the strict regulatory requirements, especially in pharmaceutical analysis, analysis results with an acceptable quality should be reported. Thus, a proper validation of the measurement method is required. In this context, ruggedness and robustness testing becomes increasingly more important. In this review, the definitions of ruggedness and robustness are given, followed by a short explanation of the different approaches applied to examine the ruggedness or the robustness of an analytical method. Then, case studies, describing ruggedness or robustness tests of high-performance liquid chromatographic (HPLC), capillary electrophoretic (CE), gas chromatographic (GC), supercritical fluid chromatographic (SFC), and ultra-performance liquid chromatographic (UPLC) assay methods, are critically reviewed and discussed. Mainly publications of the last 10 years are considered.