323,119 research outputs found
Spatial characterization of extreme ultraviolet plasmas generated by laser excitation of xenon gas targets
At Laser-Laboratorium Gottingen laser-plasma sources were tested, which are going to be used for characterization of optical components and sensoric devices in the wavelength region from 11 to 13 nm. In all cases extreme ultraviolet (EUV) radiation is generated by focusing a Q-switched Nd:YAG laser into a pulsed gas puff target. By the use of xenon or oxygen as target gas, broadband as well as narrowband EUV radiation is obtained, respectively. Different types of valves and nozzles were tested in order to optimize the emitted radiation with respect to maximum EUV intensities, small source diameters, and positional stability. The investigation of these crucial source parameters was performed with specially designed EUV pinhole cameras, utilizing evaluation algorithms developed for standardized laser beam characterization. In addition, a rotatable pinhole camera was developed which allows both spatially and angular resolved monitoring of the soft x-ray emission characteristics. With the help of this camera a strong angular dependence of the EUV intensity was found. The data were compared with fluorescence measurements for visualization of the target gas jet. The experimental observations can be explained by reabsorption of the generated EUV radiation in the surrounding target gas, as supported by semiempirical model calculations based on the attenuation in the three-dimensional gas density according to Lambert-Beer's law. As a consequence of the presented investigations, an optimization of the EUV source with respect to intensity, plasma shape, and angular dependence is achieved, resulting in a spherical plasma of 200 mum diameter and a 50% increase of the EUV pulse energy. (C) 2003 American Institute of Physics
Characterization of gas targets for laser produced extreme ultraviolet plasmas with a Hartmann-Shack sensor
A table top extreme ultraviolet (EUV)-source was developed at Laser-Laboratorium Gottingen for the characterization of optical components and sensoric devices in the wavelength region from 11 to 13 nm. EUV radiation is generated by focusing the beam of a Q-switched Nd:YAG laser into a pulsed xenon gas jet. Since a directed gas jet with a high number density is needed for an optimal performance of the source, conical nozzles with different cone angles were drilled with an excimer laser to produce a supersonic gas jet. The influence of the nozzle geometry on the gas jet was characterized with a Hartmann-Shack wave front sensor. The deformation of a planar wave front after passing the gas jet was analyzed with this sensor, allowing a reconstruction of the gas density distribution. Thus, the gas jet was optimized resulting in an increase of EUV emission by a factor of two and a decrease of the plasma size at the same time. (C) 2004 American Institute of Physics
Development and application of an LC-MS method for the alcohol biomarker phosphatidylethanol (PEth) in blood
Objective biomarkers tracing alcohol consumption are demanded in many situations when alcohol drinking is in focus, e.g. during monitoring of patient in a treatment program, in forensic medicine, workplace testing or biochemical validation of self-report in research. Phosphatidylethanol (PEth) is an abnormal phospholipid formed only in the presence of ethanol that can be used as a sensitive and specific alcohol biomarker to detect current risky alcohol consumption. The aim of this project was to develop an liquid chromatography-mass spectrometry (LC-MS) method for PEth that is suitable for routine use.PEth was extracted from whole blood and separated by LC-MS using a C4 column in a reversed phase system by gradient elution. The limit of detection (S/N ≥ 3) and limit of quantification (S/N ≥ 10) were ≤ 0.02 and ≤ 0.1 μmol/L, respectively. The calibration curve was linear in the concentration range 0.2-20 μmol/L and the intra-assay CV % for total PEth was ≤ 8.6 % and the inter-assay CV was Nine of the most common PEth forms were evaluated by both LC-MS and LC-MS/MS. PEth-16:0/18:1 and PEth-16:0/18:2 were found to be the major forms in blood from alcoholic patients. The correlations of PEth-16:0/18:1 and PEth-16:0/18:2 to total PEth were good (R2 = 0.973) and PEth-16:0/18:2 (R2= 0.983) but together they correlated even better with total PEth. In 200 blood samples from blood donors and 3023 from the routine pool, the majority had a total PEth concentration ≤ 0.5 μmol/L. The amount of PEth formed in whole blood samples that were incubated in the presence of ethanol varied considerably between individuals. The value of PEth as an alcohol biomarker was compared with ethyl glucuronide (EtG), ethyl sulfate (EtS) and carbohydrate deficient transferrin (CDT) in an outpatient treatment program for alcohol-dependent subjects. Compared with CDT, PEth was found to be a more sensitive biomarker.In conclusion, a sensitive and specific LC-MS method was developed for the routine measurement of PEth in whole blood samples. The measurement of PEth-16:0/18:1 alone or in combination with PEth-16:0/18:2 did not affect test sensitivity compared with total PEth. The use of PEth in combination with other biomarker is preferred, due to inter-individual variation in PEth formation.List of scientific papersI. Molecular species of the alcohol biomarker phosphatidylethanol in human blood measured by LC-MS. A. Helander, Y. Zheng. Clin Chem. 2009;55:1395-405. https://doi.org/10.1373/clinchem.2008.120923 II. Method development for routine liquid chromatography-mass spectrometry measurement of the alcohol biomarker phophatidylethanol (PEth) in blood. Y. Zheng, O. Beck, A. Helander. Clin Chim Acta. 2011;412:1428-35. https://doi.org/10.1016/j.cca.2011.04.022 III. Inter-individual variability of in-vitro formation of phosphatidylethanol (PEth) in blood. Y. Zheng, O. Beck, A. Helander. [Manuscript]IV. Monitoring of the alcohol biomarkers PEth, CDT and EtG/EtS in an outpatient treatment setting. A. Helander, O. Péter, Y. Zheng. [Submitted]</p
Development and application of an LC-MS method for the alcohol biomarker phosphatidylethanol (PEth) in blood [Elektronisk resurs]
Objective biomarkers tracing alcohol consumption are demanded in many situations when alcohol drinking is in focus, e.g. during monitoring of patient in a treatment program, in forensic medicine, workplace testing or biochemical validation of self-report in research. Phosphatidylethanol (PEth) is an abnormal phospholipid formed only in the presence of ethanol that can be used as a sensitive and specific alcohol biomarker to detect current risky alcohol consumption. The aim of this project was to develop an liquid chromatography-mass spectrometry (LC-MS) method for PEth that is suitable for routine use. PEth was extracted from whole blood and separated by LC-MS using a C4 column in a reversed phase system by gradient elution. The limit of detection (S/N ≥ 3) and limit of quantification (S/N ≥ 10) were ≤ 0.02 and ≤ 0.1 μmol/L, respectively. The calibration curve was linear in the concentration range 0.2-20 μmol/L and the intra-assay CV % for total PEth was ≤ 8.6 % and the inter-assay CV was < 11 %. The CV was lower using isotope labeled PEth as internal standard in the MS/MS mode. Nine of the most common PEth forms were evaluated by both LC-MS and LC-MS/MS. PEth-16:0/18:1 and PEth-16:0/18:2 were found to be the major forms in blood from alcoholic patients. The correlations of PEth-16:0/18:1 and PEth-16:0/18:2 to total PEth were good (R2 = 0.973) and PEth-16:0/18:2 (R2= 0.983) but together they correlated even better with total PEth. In 200 blood samples from blood donors and 3023 from the routine pool, the majority had a total PEth concentration ≤ 0.5 μmol/L. The amount of PEth formed in whole blood samples that were incubated in the presence of ethanol varied considerably between individuals. The value of PEth as an alcohol biomarker was compared with ethyl glucuronide (EtG), ethyl sulfate (EtS) and carbohydrate deficient transferrin (CDT) in an outpatient treatment program for alcohol-dependent subjects. Compared with CDT, PEth was found to be a more sensitive biomarker. In conclusion, a sensitive and specific LC-MS method was developed for the routine measurement of PEth in whole blood samples. The measurement of PEth-16:0/18:1 alone or in combination with PEth-16:0/18:2 did not affect test sensitivity compared with total PEth. The use of PEth in combination with other biomarker is preferred, due to inter-individual variation in PEth formation
Differentiation and quantification of synthetic phosphatidylethanol (PEth) homologues by (1)H- and (13)C-NMR in polar organic solvents.
Various phosphatidylethanol (PEth) derivatives, the corresponding reversed positional isomers (RPI-PEths), lyso-PEth-16:0, and penta-deuterium-labeled PEth analogs (d5-PEths), were synthesized by enzyme-independent synthetic routes. A general solvent system consisting of a mixture of acetone-d6 and methanol-d4 (97:3; v/v) was found to provide a good solubilizing capacity and excellent hydrogen-1 NMR ((1)H-NMR) peak resolution of various PEth homologues. Analytical differentiation of PEth from the corresponding RPI-PEth by carbon-13 NMR ((13)C-NMR) was demonstrated by comparison of the (13)C-NMR signals of the carbonyl groups, the allylic positions, and of the β-carbons. An exemplary stable long-term room temperature, DMSO-d6-based, and proton-sensitive quantitative nuclear magnetic resonance ((1)H-qNMR) independently quantified calibrator comprising PEth-16:0/18:1 for liquid chromatography (tandem) mass spectrometry (LC-MS/MS) analytical applications were prepared by employment of sodium dodecyl sulfate (SDS) as a solubilizing additive. In summary, novel hypothetically occurring PEth derivatives, e.g., RPI-PEths, have been independently synthesized with regio- and stereochemical control. Use of polar organic solvents, e.g., mixtures of acetone-d6 and methanol-d4 or DMSO-d6, improves spectral line shapes as compared to traditional hydrophobic solvents and allow for analytical differentiation between closely related PEth derivatives, as well as LC-MS/MS-independent concentration determination of dissolved single species by employment of (1)H-qNMR
Phosphatidylethanol in blood (B-PEth): A marker for alcohol use and abuse.
Phosphatidylethanol (PEth) represents a group of glycerophospholipid homologues where ethanol by phospholipase D has been bound at the position that normally contains an amino-alcohol. Since the formation of PEth is specifically dependent on ethanol, the diagnostic specificity of PEth as an alcohol biomarker is theoretically 100%. The half-life of PEth in blood is approximately 4 days. The amount of alcohol consumed correlates to blood concentration of PEth and PEth has been shown to be a more sensitive indicator of alcohol consumption than traditional alcohol markers, such as CDT (carbohydrate-deficient transferrin), GGT (γ-glutamyl transferase), and MCV (mean corpuscular volume) or a combination of these. Almost all clinical data so far available are based on a high performance liquid chromatography (HPLC) method with limited analytical sensitivity. With the advent of methods with considerably higher analytical sensitivity (e.g. mass spectrometric methods), clinical sensitivity will increase correspondingly. The possibility of determining very low concentrations of PEth by new sensitive analytical techniques may, however, have both ethical and legal consequences that have to be considered. Copyright © 2011 John Wiley & Sons, Ltd
Study of measurement of the alcohol biomarker phosphatidylethanol (PEth) in dried blood spot (DBS) samples and application of a volumetric DBS device
Phosphatidylethanol (PEth) is a group of phospholipids formed in cell membranes following alcohol consumption. PEth measurement in whole blood samples is established as a specific alcohol biomarker with clinical and medico-legal applications. This study further evaluated the usefulness of dried blood spot (DBS) samples collected on filter paper for PEth measurement. Specimens used were surplus volumes of venous whole blood sent for routine LC–MS/MS quantification of PEth 16:0/18:1, the major PEth homolog. DBS samples were prepared by pipetting blood on Whatman 903 Protein Saver Cards and onto a volumetric DBS device (Capitainer). The imprecision (CV) of the DBS sample amount based on area and weight measurements of spot punches were 23–28%. Investigation of the relationship between blood hematocrit and PEth concentration yielded a linear, positive correlation, and at around 1.0–1.5 μmol/L PEth 16:0/18:1, the PEth concentration increased by ~ 0.1 μmol/L for every 5% increase in hematocrit. There was a close agreement between the PEth concentrations obtained with whole blood samples and the corresponding results using Whatman 903 (PEthDBS = 1.026 PEthWB + 0.013) and volumetric device (PEthDBS = 1.045 PEthWB + 0.016) DBS samples. The CV of PEth quantification in DBS samples at concentrations ≥ 0.05 μmol/L were ≤ 15%. The present results further confirmed the usefulness of DBS samples for PEth measurement.</p
Predicted values from linear mixed effects models evaluating the association between PEth and D-dimer.
Predicted values from linear mixed effects models evaluating the association between PEth and D-dimer.</p
Predicted values from linear mixed effects models evaluating the association between PEth and sCD14.
Predicted values from linear mixed effects models evaluating the association between PEth and sCD14.</p
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