Vacuum-compatible low-loss Faraday isolator for efficient squeezed-light injection in laser-interferometer-based gravitational-wave detectors.

In this paper, we present, to the best of our knowledge, the first low-loss vacuum-compatible thermally controlled Faraday isolator able to retain a good isolation factor under high-vacuum working conditions. The throughput that can be obtained with the developed device is as high as 99%, retaining an isolation factor higher than 40 dB. That very high isolation ratio can be kept over long time periods independently from external temperature conditions with a few Celsius degrees of variation due to thermal active control. The mechanical and optical configuration is detailed, and the performances achieved with this device are presented.

Gold(I)-Catalysed Asymmetric Hydroamination of Alkenes: A†Silver- and Solvent-Dependent Enantiodivergent Reaction.

In the present study, we report the first silver-dependent enantiodivergent gold-catalysed reaction. The asymmetric intramolecular hydroamination of alkenes catalysed by the combination of a single chiral binuclear gold(I) chloride complex and silver perchlorate can afford both enantiomers of the products by a simple solvent change from toluene to methanol. Such an enantiodivergent reaction is strictly independent of the reaction temperature or of the nature of the catalyst anion and displays the same first-order kinetic rate law with respect to substrate concentration in both solvents. Beyond a simple solvent effect the enantioinversion is controlled by gold-silver chloride adducts which occur only in methanol and allow a dual activation of the reagent. While one single gold atom activates the alkene moiety, the other gold atom forms an oxophilic gold-silver chloride adduct which is likely to interact with the carbamate function. By comparison with toluene, which affords (S)-enantiomer, this proximal and bimetallic activation would allow an opposite stereodifferentiation of the two diastereomeric intermediates during the final protodeauration step and lead therefore to the (R)-enantiomer.

Tuning of a high magnification compact parabolic telescope for centimeter-scale laser beams.

Off-axis parabolic telescopes, widely used in astronomy and laser optics, if perfectly tuned, are virtually free from aberrations along the parabola's axis direction, but their alignment is very critical. We present a detailed method to align a high magnification off-axis afocal parabolic telescope. The method is composed of two steps: an initial pre-alignment using autocollimators, followed by a fine tuning with a collimated laser beam. Due to the large telescope magnification, the outcoming beam cannot be measured without being refocused. The beam is therefore reflected on a flat mirror and sent back through the telescope. This double-pass configuration allows the measurement of the beam quality without the need for large additional optics. In the fine-tuning step, a numerical simulation is also used to identify the degrees of freedom to be adjusted. The experimental results presented are obtained with one of the mode-matching parabolic telescopes of the gravitational wave interferometric detector Advanced Virgo.

Quantitative monitoring of tamoxifen in human plasma extended to 40 metabolites using liquid-chromatography high-resolution mass spectrometry: new investigation capabilities for clinical pharmacology.

Liquid-chromatography (LC) high-resolution (HR) mass spectrometry (MS) analysis can record HR full scans, a technique of detection that shows comparable selectivity and sensitivity to ion transitions (SRM) performed with triple-quadrupole (TQ)-MS but that allows de facto determination of "all" ions including drug metabolites. This could be of potential utility in in vivo drug metabolism and pharmacovigilance studies in order to have a more comprehensive insight in drug biotransformation profile differences in patients. This simultaneous quantitative and qualitative (Quan/Qual) approach has been tested with 20 patients chronically treated with tamoxifen (TAM). The absolute quantification of TAM and three metabolites in plasma was realized using HR- and TQ-MS and compared. The same LC-HR-MS analysis allowed the identification and relative quantification of 37 additional TAM metabolites. A number of new metabolites were detected in patients' plasma including metabolites identified as didemethyl-trihydroxy-TAM-glucoside and didemethyl-tetrahydroxy-TAM-glucoside conjugates corresponding to TAM with six and seven biotransformation steps, respectively. Multivariate analysis allowed relevant patterns of metabolites and ratios to be associated with TAM administration and CYP2D6 genotype. Two hydroxylated metabolites, α-OH-TAM and 4'-OH-TAM, were newly identified as putative CYP2D6 substrates. The relative quantification was precise (<20 %), and the semiquantitative estimation suggests that metabolite levels are non-negligible. Metabolites could play an important role in drug toxicity, but their impact on drug-related side effects has been partially neglected due to the tremendous effort needed with previous MS technologies. Using present HR-MS, this situation should evolve with the straightforward determination of drug metabolites, enlarging the possibilities in studying inter- and intra-patients drug metabolism variability and related effects.

Performance of a thermally deformable mirror for correction of low-order aberrations in laser beams.

The thermally deformable mirror is a device aiming at correcting beam-wavefront distortions for applications where classical mechanical methods are precluded by noise considerations, as in advanced gravitational wave interferometric detectors. This moderately low-cost technology can be easily implemented and controlled thanks to the good reproducibility of the actuation. By using a flexible printed circuit board technology, we demonstrate experimentally that a device of 61 actuators in thermal contact with the back surface of a high-reflective mirror is able to correct the low-order aberrations of a laser beam at 1064 nm and could be used to optimize the mode matching into Fabry-Perot cavities.

Identification of new natural sweet compounds in wine using centrifugal partition chromatography-gustatometry and Fourier transform mass spectrometry.

Sweetness contributes notably to the taste-balance of dry wines and increases during oak-barrel aging owing to the release of natural sweeteners from wood. The search for such taste-active molecules, which are sometimes present at very low concentrations in wine or other complex matrixes, requires both reliable purification tools and powerful identification techniques. Here, we report the development of an original inductive method using centrifugal partition chromatography (CPC) and sensorial analysis. This method, called CPC-gustatometry, was implemented to isolate a sweet fraction with only four compounds from a complex oak wood extract. The recently developed Fourier transform mass spectrometry (FT-MS, Orbitrap analyzer) was used jointly with two-dimensional nuclear magnetic resonance (2D (1)H and (13)C NMR) to obtain the structural elucidation of the purified compounds. The tandem mass spectrometry (MS/MS) spectra obtained with resonant and nonresonant fragmentation modes were compared, thus providing complementary information about the molecular structure. Two oleanane-type triterpenoids substituted with galloyl and glucosyl moieties were identified, one of which exhibits sweet properties. We term these compounds which have never been reported, Quercotriterpenoside I and II.

Evaluation of accurate mass and relative isotopic abundance measurements in the LTQ-orbitrap mass spectrometer for further metabolomics database building.

Recently, high-resolution mass spectrometry has been largely employed for compound identification, thanks to accurate mass measurements. As additional information, relative isotope abundance (RIA) is often needed to reduce the number of candidates prior to tandem MS(n). Here, we report on the evaluation of the LTQ-Orbitrap, in terms of accurate mass and RIA measurements for building further metabolomics spectral databases. Accurate mass measurements were achieved in the ppm range, using external calibration within 24 h, and remained at <5 ppm over a one-week period. The experimental relative abundances of (M+1) isotopic ions were evaluated in different data sets. First of all, 137 solutions of commercial compounds were analyzed by flow injection analysis in both the positive and negative ion modes. It was found that the ion abundance was the main factor impacting the accuracy of RIA measurements. It was possible to define some intensity thresholds above which errors were systematically <20% of their theoretical values. The same type of results were obtained with analyses from two biological media. Otherwise, no significant effect of ion transmission between the LTQ ion trap and the Orbitrap analyzer on RIA measurement errors was found, whereas the reliability of RIA measurements was dramatically improved by reducing the mass detection window. It was also observed that the signal integration method had a significant impact on RIA measurement errors, with the most-reliable results being obtained with peak height integrations. Finally, automatic integrations using the data preprocessing software XCMS and MZmine gave results similar to those obtained by manual integration, suggesting that it is relevant to use the RIA information in automatic elemental composition determination software from metabolomic peak tables.

Direct introduction of biological samples into a LTQ-Orbitrap hybrid mass spectrometer as a tool for fast metabolome analysis.

We report the direct introduction of biological samples into a high-resolution mass spectrometer, the LTQ-Orbitrap, as a fast tool for metabolomic studies. A proof of concept study was performed on yeast cell extracts that were introduced into the mass spectrometer by using flow injection analysis, with an acquisition time of 3 min. Typical mass spectra contained a few thousand m/z signals, 400 of which were found to be analytically relevant (i.e., their intensity was 3-fold higher than that of the background noise and they occurred in at least 60% of the acquisition profiles under identical experimental conditions). The method was validated by studies of the matrix effect, linearity, and intra-assay precision. Accurate mass measurements in the Orbitrap discriminated between isobaric ions and also indicated the elemental composition of the ions of interest with mass errors below 5 ppm, for identification purposes. The proposed structures were then assessed by MSn experiments via the linear ion trap, together with accurate mass determination of the product ions in the Orbitrap analyzer. When applied to the study of cadmium toxicity, the method was as effective as that initially developed by using LC/ESI-MS/MS for a targeted approach. The same metabolic fingerprints were also subjected to multivariate statistical analyses. The results highlighted a reorganization of amino acid metabolism under cadmium conditions in order to increase the biosynthesis of glutathione.

Development of an analytical methodology using Fourier transform mass spectrometry to discover new structural analogs of wine natural sweeteners.

Volatile and non-volatile molecules are directly responsible for the thrill and excitement provided by wine-tasting. Their elucidation requires powerful analytical techniques and innovative methodologies. In a recent work, two novel sweet compounds called quercotriterpenosides (QTT) were identified in oak wood used for wine-ageing. The aim of the present study is to discover structural analogs of such natural sweeteners in oak wood. For this purpose, an analytical approach was developed as an alternative to chemical synthesis. Orbitrap mass spectrometry proved to be a crucial technique both to demonstrate the presence of QTT analogs in oak wood by targeted screening and to guide the purification pathway of these molecules using complementary chromatographic tools. Four compounds were isolated and identified for the first time: two isomers, one glucosyl derivative and one galloyl derivative of QTT. Their tasting showed that only the two new isomers were sweet, thus demonstrating both the pertinence of the strategy and the influence of functional groups on gustatory properties. Finally, this paper presents some developments involving multistage Fourier transform mass spectrometry (FTMS) to provide solid structural information on these functional groups prior to any purification of compounds. Such analytical developments could be particularly useful for research on taste-active or bio-active products.

Wide-scope analysis of pesticide and veterinary drug residues in meat matrices by high resolution MS: detection and identification using Exactive-Orbitrap.

A multiresidue and multiclass method for the simultaneous determination of more than 350 compounds including pesticides, biopesticides and veterinary drugs in different meat matrices (beef, pork and chicken) by ultra-high performance liquid chromatography coupled to Orbitrap MS has been developed. In the present study, the determination of fragments was accomplished as an essential tool for a reliable identification of compounds using high resolution MS. To obtain these fragments, different strategies have been carried out in order to ensure an appropriate fragment assignment and identification. The analytical method is suitable for qualitative analysis, and it was also evaluated for quantitative analysis. Generic extraction conditions were optimized, obtaining adequate recovery and precision values for most of the studied analytes (>290). The limits of detection ranged from 2 to 16 µg kg(-1). Limits of quantification were 10 µg kg(-1) with the exception of few compounds with a higher value (50 or 100 µg kg(-1)). Limits of identification were also established, and they ranged from 2 to 150 µg kg(-1). This method was applied to the analysis of 18 meat samples and some veterinary drugs as enrofloxacin and sulfadiazine were detected and further identified/quantified (with triple quadrupole) in two different samples at 33 µg kg(-1) and trace levels, respectively. No pesticides were detected in the analyzed samples.

Identification and characterization of a novel antimicrobial peptide from the venom of the ant Tetramorium bicarinatum.

A novel antimicrobial peptide, named Bicarinalin, has been isolated from the venom of the ant Tetramorium bicarinatum. Its amino acid sequence has been determined by de novo sequencing using mass spectrometry and by Edman degradation. Bicarinalin contained 20 amino acid residues and was C-terminally amidated as the majority of antimicrobial peptides isolated to date from insect venoms. Interestingly, this peptide had a linear structure and exhibited no meaningful similarity with any known peptides. Antibacterial activities against Staphylococcus aureus and S. xylosus strains were evaluated using a synthetic replicate. Bicarinalin had a potent and broad antibacterial activity of the same magnitude as Melittin and other hymenopteran antimicrobial peptides such as Pilosulin or Defensin. Moreover, this antimicrobial peptide has a weak hemolytic activity compared to Melittin on erythrocytes, suggesting potential for development into an anti-infective agent for use against emerging antibiotic-resistant pathogens.

Demonstration of a chaos generator with two time delays.

We demonstrate a chaos generator involving two time delays and two nonlinear functions. Dynamic behaviors are numerically and experimentally observed. The complexity of the dynamics is discussed in terms of Lyapunov exponents and dimensions. The setup can provide a new architecture for enhancing message security in chaos encryption systems.