Mass spectral reference libraries: an ever-expanding resource for chemical identification

The basic principles, practices, and pitfalls in the process of compound identification by searching mass spectral reference libraries are presented. Factors affecting the identification process are discussed as members of one of three major contributors to identification confidence: prior probability, risk of false negative results, and risk of false positive results. More general concerns and the problem of "unknown unknowns" are then explored.     

Tomographic alignment algorithm for an extremely large three-mirror telescope: invisible modes

We analyze the optical effects due to distortions of a three-mirror telescope that is sufficiently large that all three mirrors must be actively controlled. Numerical experiments on telescopes with both monolithic and segmented primary mirrors reveal the existence of telescope misalignment configurations (modes) that are invisible to a fixed focal station wavefront sensor, even for highly redundant multidirectional tomographic measurement schemes. We describe these modes and give a theoretical explanation for them.     

Single actuator alignment control for improved frequency stability of a cavity-based optical frequency reference

We demonstrate a method of controlling the alignment of a laser beam to a Fabry-Perot resonator through synchronous detection of the misalignment arising from modulating the orientation of a single beam-steering mirror. The horizontal and vertical tilt of the mirror are modulated in quadrature to drive a circular motion of the beam orientation. A corresponding modulation of the intensity of the optical field circulating in the cavity is measured at either the reflected or transmitted port and demodulated synchronously to derive two error signals to indicate the vertical and horizontal misalignment. These signals are fed back to the beam-steering mirror to suppress fluctuations below 30 Hz. This method avoids the complexity of monitoring off-axis cavity modes and is particularly effective in the case where unwanted pointing fluctuations are introduced by one or two elements in the optical setup. We have applied the technique to two Fabry-Perot resonators in use as precision frequency references, delivering a result of 10 dB suppression of alignment fluctuations at 1 Hz and an improvement in frequency stability by up to a factor of 4.     

XCMS: processing mass spectrometry data for metabolite profiling using nonlinear peak alignment, matching, and identification

Metabolite profiling in biomarker discovery, enzyme substrate assignment, drug activity/specificity determination, and basic metabolic research requires new data preprocessing approaches to correlate specific metabolites to their biological origin. Here we introduce an LC/MS-based data analysis approach, XCMS, which incorporates novel nonlinear retention time alignment, matched filtration, peak detection, and peak matching. Without using internal standards, the method dynamically identifies hundreds of endogenous metabolites for use as standards, calculating a nonlinear retention time correction profile for each sample. Following retention time correction, the relative metabolite ion intensities are directly compared to identify changes in specific endogenous metabolites, such as potential biomarkers. The software is demonstrated using data sets from a previously reported enzyme knockout study and a large-scale study of plasma samples. XCMS is freely available under an open-source license at http://metlin.scripps.edu/download/.     

Application of fast Fourier transform cross-correlation for the alignment of large chromatographic and spectral datasets

Preprocessing of chromatographic and spectral data is an important aspect of analytical sciences. In particular, recent advances in proteomics have resulted in the generation of large data sets that require analysis. To assist accurate comparison of chemical signals, we propose two methods for the alignment of multiple spectral data sets. Based on methods previously described, each chromatograph or spectrum to be aligned is divided and aligned as individual segments to a reference. However, our methods make use of fast Fourier transform for the rapid computation of a cross-correlation function that enables alignments between samples to be optimized. The proposed methods are demonstrated in comparison with an existing method on a chromatographic and a mass spectral data set. It is shown that our methods provide an advantage of speed and a reduction of the number of input parameters required. The software implementations for the proposed alignment methods are available under the downloads section at http://ptcl.chem.ox.ac.uk/~jwong/specalign.     

Objective data alignment and chemometric analysis of comprehensive two-dimensional separations with run-to-run peak shifting on both dimensions.

Data from comprehensive two-dimensional (2-D) separation techniques, such as comprehensive 2-D gas chromatography (GC x GC), liquid chromatography/liquid chromatography (LC x LC) and liquid chromatography/ capillary electrophoresis (LC x CE) can be readily analyzed by various chemometric methods to increase chemical analysis capabilities. A retention time alignment, preprocessing method is presented that objectively corrects for run-to-run retention time variations on both separation dimensions of comprehensive 2-D separations prior to application of chemometric data analysis algorithms. The 2-D alignment method corrects for run-to-run shifting of a sample data matrix relative to a standard data matrix on both separation time axes in an independent, stepwise fashion. After 2-D alignment, the generalized rank annihilation method (GRAM) is successfully applied, substantiating the performance of the alignment method. The alignment method should have important implications, because most 2-D separation techniques exhibit, in the context of chemometric data analysis, considerable run-to-run retention time shifting on both dimensions. Even when there are only three to four points/peak, that is, with three to four separations on the second dimension (column 2) per peak width from the first dimension (column 1), the 2-D alignment coupled with GRAM provides dependable analyte peak identification capabilities and adequate quantitative precision for unresolved analyte peaks. Thus, the 2-D alignment algorithm is applicable to lower data density conditions, which broadens the scope of chemometric analysis to high-speed 2-D separations.     

Speedy component resolution: an improved tool for processing diffusion-ordered spectroscopy data

Diffusion-based NMR techniques (e.g., diffusion-ordered spectroscopy, DOSY), which can be used to distinguish between the signals of different components of a mixture, are steadily gaining in popularity. When processing data from a DOSY experiment it is often desirable to reconstruct the spectra of individual components; here, multivariate methods that take advantage of the covariance between the resonances of a given component can often be advantageous. This paper presents a minor variation on the established CORE method, speedy component resolution (SCORE), that gives a major improvement in performance. In common with CORE it can use any experimental sampling scheme and is adaptable to different experimental decay shapes, but unlike CORE it is very fast and relatively insensitive to starting guesses. The method is demonstrated on a mixture of quinine, geraniol, and camphene in deuteriated methanol, where all four component spectra can be extracted in less than 15 s.     

SRD1000 with improved reference points for thermometry below 1K

No Heading Reference samples of improved quality were prepared and tested for a new series of the Superconductive Reference Devices SRD1000 for thermometry below 1K. In the past years prototypes of the device were evaluated by the PTB in Berlin, the NPL in London, BNM-INM in Paris and the CNRS-CRTBT in Grenoble. The evaluation proved that the SRD1000 is a convenient and reliable means of transferring the Provisional Low Temperature Scale 2000 (PLTS-2000). For the new series the quality of the transitions of Cd at 520 mK and Zn at 850 mK was significantly improved by preparing new crystals and applying better surface etching and attachment procedures to the samples. We report on the results of the characterization of the reference samples.PACS numbers: 07.20.Dt, 07.20.Mc. 74.62.–c, 74.70.Ad     

Suggestions for an improved system for statistical data about road accidents and road traffic

Data information systems for road accidents and road traffic must satisfy high standards of relevance and quality. The general outline of an improved system for collecting road accident data is given. The system is characterized by the use of statistical sampling methods. The police, the insurance companies and the hospitals are recommended as sources of information about the total accident population. A statistical sample of all identified accidents is then investigated in more detail by special local investigation groups. A hypothetical numerical example is given to show how the suggested system would work in practise. Road accident data should not be isolated from road traffic data. An improved system for collecting information on road traffic is also discussed. This consists of a basic system (founded on statistical sampling methods) for estimation of the total volume of traffic and a few other essential variables such as the volume divided into speed and vehicle types.     

Fast convergence with spectral volume integral equation for crossed block-shaped gratings with improved material interface conditions

For block-shaped dielectric gratings with two-dimensional periodicity, a spectral-domain volume integral equation is derived in which explicit Fourier factorization rules are employed. The Fourier factorization rules are derived from a projection-operator framework and enhance the numerical accuracy of the method, while maintaining a low computational complexity of O(NlogN) or better and a low memory demand of O(N).     

Extension of an improved one-fluid conformal solution theory to real fluid mixtures with large size differences

Conformal solution theories have been shown to be inadequate as the size ratio of the molecules in a mixture increases. We present an improved van der Waals-1 fluid conformal solution theory which incorporates a correction term developed using statistical mechanical perturbation theory. The correction addresses the effect of different size molecules on the Helmholtz free energy of the mixture. Results of the new model are compared with other conformal solution theories for model Lennard-Jones systems. We also show how to extend the model to perform computations on real fluid mixtures. Results for selected hydrocarbon mixtures are given.Paper presented at the Tenth Symposium on Thermophysical Properties, June 20–23, 1988, Gaithersburg, Maryland, U.S.A.FormerlyNational Bureau of Standards     

Model reference adaptive control-based adaptive current control scheme of a PM synchronous motor with an improved servo performance

A model reference adaptive control (MRAC)-based current control scheme of a PM synchronous motor with an improved servo performance is presented. Although the predictive current control is known to give ideal transient and steady-state responses among various PWM inverter-fed current control schemes for a PM synchronous motor, its steady-state response may be degraded under the motor parameter variations. To overcome such a limitation, the disturbances caused by the parameter variations will be estimated using an MRAC technique and compensated by a feedforward manner. Thus, the steady-state control performance can be effectively improved, while retaining its good dynamic performance. The proposed control scheme does not require the measurement of the phase voltage unlike the conventional disturbance estimation scheme using observer. This can be an effective way considering the phase voltage contains much harmonics as well as noise. The asymptotic stability of the overall system is proved and the adaptation laws are derived by the Lyapunov stability theory. The proposed scheme is implemented using DSP TMS320C31 and the effectiveness is verified through the comparative simulations and experiments.     

Statistical total correlation spectroscopy: an exploratory approach for latent biomarker identification from metabolic 1H NMR data sets

We describe here the implementation of the statistical total correlation spectroscopy (STOCSY) analysis method for aiding the identification of potential biomarker molecules in metabonomic studies based on NMR spectroscopic data. STOCSY takes advantage of the multicollinearity of the intensity variables in a set of spectra (in this case 1H NMR spectra) to generate a pseudo-two-dimensional NMR spectrum that displays the correlation among the intensities of the various peaks across the whole sample. This method is not limited to the usual connectivities that are deducible from more standard two-dimensional NMR spectroscopic methods, such as TOCSY. Moreover, two or more molecules involved in the same pathway can also present high intermolecular correlations because of biological covariance or can even be anticorrelated. This combination of STOCSY with supervised pattern recognition and particularly orthogonal projection on latent structure-discriminant analysis (O-PLS-DA) offers a new powerful framework for analysis of metabonomic data. In a first step O-PLS-DA extracts the part of NMR spectra related to discrimination. This information is then cross-combined with the STOCSY results to help identify the molecules responsible for the metabolic variation. To illustrate the applicability of the method, it has been applied to 1H NMR spectra of urine from a metabonomic study of a model of insulin resistance based on the administration of a carbohydrate diet to three different mice strains (C57BL/6Oxjr, BALB/cOxjr, and 129S6/SvEvOxjr) in which a series of metabolites of biological importance can be conclusively assigned and identified by use of the STOCSY approach.     

Concept for facilitating analyst-mediated interpretation of qualitative chromatographic-mass spectral data: an alternative to manual examination of extracted ion chromatograms

A chemometrics-based data analysis concept has been developed as a substitute for manual inspection of extracted ion chromatograms (XICs), which facilitates rapid, analyst-mediated interpretation of GC- and LC/MS(n) data sets from samples undergoing qualitative batchwise screening for prespecified sets of analytes. Automatic preparation of data into two-dimensional row space-derived scatter plots (row space plots) eliminates the need to manually interpret hundreds to thousands of XICs per batch of samples while keeping all interpretation of raw data directly in the hands of the analyst-saving great quantities of human time without loss of integrity in the data analysis process. For a given analyte, two analyte-specific variables are automatically collected by a computer algorithm and placed into a data matrix (i.e., placed into row space): the first variable is the ion abundance corresponding to scan number x and analyte-specific m/z value y, and the second variable is the ion abundance corresponding to scan number x and analyte-specific m/z value z (a second ion). These two variables serve as the two axes of the aforementioned row space plots. In order to collect appropriate scan number (retention time) information, it is necessary to analyze, as part of every batch, a sample containing a mixture of all analytes to be tested. When pure standard materials of tested analytes are unavailable, but representative ion m/z values are known and retention time can be approximated, data are evaluated based on two-dimensional scores plots from principal component analysis of small time range(s) of mass spectral data. The time-saving efficiency of this concept is directly proportional to the percentage of negative samples and to the total number of samples processed simultaneously.     

New method for spectral data classification: two-way moving window principal component analysis

Two-way moving window principal component analysis (TMWPCA), which considers all possible variable regions by using variable and sample moving windows, is proposed as a new spectral data classification method. In TMWPCA, the similarity between model function and the index obtained by variable and sample moving windows is defined as "fitness". For each variable region selected by a variable moving window, the fitness is obtained through the use of a model function. By maximizing the fitness, an optimal variable region can be searched. A remarkable advantage of TMWPCA is that it offers an optimal variable region for the classification. To demonstrate the potential of TMWPCA, it has been applied to the classification of visible-near-infrared (Vis-NIR) spectra of mastitic and healthy udder quarters of cows measured in a nondestructive manner. The misclassification rate of TMWPCA has been compared with those of other chemometric methods, such as principal component analysis (PCA), soft independent modeling of class analogies (SIMCA), and principal discriminant variate (PDV). TMWPCA has yielded the lowest misclassification rate. The result indicates that TMWPCA is a powerful tool for the classification of spectral data.     

An improved two-point calibration method for stereo vision with rotating cameras in large FOV

At present, binocular stereo vision is gradually being applied for 3D coordinate measurements in large fields of view (FOVs). In this study, a binocular stereo vision system with fixed and non-zooming cameras in a large FOV is constructed, in which cameras can rotate horizontally and vertically. All intrinsic parameters except the focal length of the cameras are set to default values and these focal lengths are calibrated offline in advance. Only the pitch angle and yaw angle of each camera need to be obtained during rotation. Therefore, we present a novel calibration method by using two control points and transform the imaging model of the pitch and yaw angles into a quadratic equation of the tangent value of the pitch angle so that the closed-form solutions of the pitch and yaw angles can be obtained. Computer simulation and real experiments demonstrate the effectiveness of the proposed method.     

移动自组网选播路由协议ARAD

针对移动自组(ad hoc)网的特点,提出了一种适合ad hoc移动网络的选播路由协议——ARAD协议.该协议在充分考虑选播路由特点的基础上,将ad hoc按需距离矢量路由(AODV)协议的路由发现机制与动态源路由(DSR)协议的缓存源路由技术相结合,在动态变化的ad hoc网络中实现了一种高效的选播路由.模拟结果表明,在动态的网络环境下,ARAD协议能够取得良好的性能.     

Robust algorithm for alignment of liquid chromatography-mass spectrometry analyses in an accurate mass and time tag data analysis pipeline

Liquid chromatography coupled to mass spectrometry (LC-MS) and tandem mass spectrometry (LC-MS/MS) has become a standard technique for analyzing complex peptide mixtures to determine composition and relative abundance. Several high-throughput proteomics techniques attempt to combine complementary results from multiple LC-MS and LC-MS/MS analyses to provide more comprehensive and accurate results. To effectively collate and use results from these techniques, variations in mass and elution time measurements between related analyses need to be corrected using algorithms designed to align the various types of data: LC-MS/MS versus LC-MS/MS, LC-MS versus LC-MS/MS, and LC-MS versus LC-MS. Described herein are new algorithms referred to collectively as liquid chromatography-based mass spectrometric warping and alignment of retention times of peptides (LCMSWARP), which use a dynamic elution time warping approach similar to traditional algorithms that correct for variations in LC elution times using piecewise linear functions. LCMSWARP is compared to the equivalent approach based upon linear transformation of elution times. LCMSWARP additionally corrects for temporal drift in mass measurement accuracies. We also describe the alignment of LC-MS results and demonstrate their application to the alignment of analyses from different chromatographic systems, showing the suitability of the present approach for more complex transformations.