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101.
Erick Kindt Sandra Bak Mueller Christine Castle Carine M. Boustany‐Kari 《Biomedical chromatography : BMC》2010,24(7):752-758
Biomarkers are an increasingly important constituent of the drug development process, offering the potential of increased efficiency through reduced compound attrition and earlier proof of mechanism and/or efficacy. Assays developed for compound screening that can be directly translated for clinical trials are especially valuable, but their successful adoption requires a careful balance between assay performance and implementation costs. One such ‘fit‐for‐purpose’ biomarker assay, the indirect measurement of pharmacological modulation of sphingolipid biosynthesis and disposition, is presented here. Among spingolipids, numerous ceramide species are readily detectable in different lipoprotein fractions of mammalian plasma, but their parallel quantification can be prohibitively expensive and time consuming. Ceramides differ in their fatty acid moiety, which is readily removed by hydrolysis, yielding a common sphingosine derivative, the measurement of which serves as an indicator of total ceramide. When followed by liquid chromatography tandem mass spectrometry (LC/MS/MS) for detection, robust analyte quantification becomes relatively straightforward. The practical utility of a method developed to be fit for the purpose of rapidly and quantitatively measuring treatment‐induced variations in total ceramide from hamster plasma and individual lipoprotein fractions is described. With a linear calibration range from 0.003 to 33.4 μm sphingosine, precision and accuracy error in plasma‐based quality controls spiked with ceramides was less than 15%. The specificity of the assay for ceramides was also assessed. The simplicity of the method would allow for its potential translation to other preclinical species, as well as for clinical applications in later‐stage drug development. Copyright © 2009 John Wiley & Sons, Ltd. 相似文献
102.
Carl Mueller 《Probability Theory and Related Fields》1991,87(3):365-388
Summary A connection is given between various functional laws of the iterated logarithm for Brownian motion due to Donsker and Varadhan, Csáki, Chung, Strassen, and the author.Supported by an NSF grant 相似文献
103.
104.
Th. W. Richards E. Mueller Krickmeyer und Baxter 《Fresenius' Journal of Analytical Chemistry》1911,50(4-5):331-336
Ohne Zusammenfassung 相似文献
105.
Jannik Matuschke S. Thomas McCormick Gianpaolo Oriolo Britta Peis Martin Skutella 《Operations Research Letters》2017,45(1):53-59
We present a new robust optimization model for the problem of maximizing the amount of flow surviving the attack of an interdictor. Given some path flow, our model allows the interdictor to specify the amount of flow removed from each path individually. In contrast to previous models, for which no efficient algorithms are known, the most important basic variants of our model can be solved in poly-time. We also consider extensions where there is a budget to set the interdiction costs. 相似文献
106.
Bates CM Strahan JR Santos LJ Mueller BK Bamgbade BO Lee JA Katzenstein JM Ellison CJ Willson CG 《Langmuir : the ACS journal of surfaces and colloids》2011,27(5):2000-2006
The orientation of cylinder-forming poly(styrene-block-methyl methacrylate) [P(S-b-MMA)] was investigated on two sets of polymeric surface treatments: 10 para-substituted polystyrene derivatives with <10 mol % poly(4-vinylbenzyl azide) and a series of poly(styrene-random-4-vinylbenzyl azide) [P(S-r-VBzAz)] copolymers with 5-100 mol % poly(4-vinylbenzyl azide). The copolymers were spin-coated to form thin films and then cross-linked by heating. The resulting films exhibited a range of surface tensions from 21 to 45 dyn/cm. Perpendicular orientation of P(S-b-MMA) cylinders was achieved with poly(p-bromostyrene) and all the [P(S-r-VBzAz)] copolymer surface treatments, most notably the homopolymer of poly(4-vinylbenzyl azide). Films made from these simple copolymers are as effective as random terpolymer alignment layers commonly made from both block monomers and a cross-linkable monomer. 相似文献
107.
A. Al-Kahlout S. Heusing T. Mueller N. Aldahoudi M. Quilitz P. W. de Oliveira 《Journal of Sol-Gel Science and Technology》2011,59(3):532-538
Transparent semiconducting ITO:Ti thin films, prepared by a sol–gel process, has been deposited by spin-coating technique
onto alkali-free glass substrates. The as-coated films were annealed in ambient air at 550 °C for 1 h and further annealed
in a reducing atmosphere. The influences of the Ti content in the sol on the surface morphology, microstructure, optical properties
and electrical resistivity have been investigated. These properties were found to depend on the Ti content in the coating
sol. Ti addition led to dense smooth layers with larger crystallite size (20–30 nm). Double layers synthesized with Ti:ITO = 0.53 wt%
and submitted to reducing treatment in forming gas exhibited the lowest sheet resistance R□ = 60 Ω□ with an average transmittance of 87% at 550 nm. 相似文献
108.
An automated real-time method for determination of ISE steady state value and response time is developed, following most recent IUPAC recommendations. Specifically, detection of the ‘steady state’ is related to (1) the time derivative of the emf as it reaches a limiting value (ΔE/Δtlimit, e.g., 0.1–1.0 mV min−1) and (2) the duration of time for which the absolute value of the time derivative remains less than this limiting value (stability window, denoted winst). A suite of representative ISEs, including glass, solid state, and polymer-based electrodes, is examined to determine sensitivity of results to parameterization choice. Measurements taken over a wide range of concentration values and in un-processed samples (i.e., without use of ionic strength adjustment) provide insight into behavior of ISEs in applications where analyte concentrations span a wide range and/or sample pre-processing may not be an option, e.g., use of sensors for in situ environmental sampling. Results show that declared steady state emf is strongly sensitive to variations in ΔE/Δtlimit but relatively unaffected by changes in the stability window when winst ≥30 s. Linearity of calibration curves produced, quantified by root mean squared error (RMSE) against a linear fit, improves as ΔE/Δtlimit decreases, however the percentage of measurements which reach a declared steady state within the prescribed sample window (∼6.5 min) falls with corresponding decreases in the ΔE/Δtlimit parameter. Response time, defined as the time required to reach declared steady emf, is also a strong function of parameterization. Dependence of response times on sample composition and/or ISE membrane composition and type are also discussed; results for ISEs in samples comprised exclusively of interfering ions are included. In general, limiting emf derivatives of {0.25–0.4 mV min−1} and stability windows of {30–40 s} achieve both good analytical accuracy and compliance with potentially short sampling window requirements. Methodology based on use of these parameters can improve sampling speed and accuracy as well as promote inter-comparison of data and ISE characterizations among research teams. 相似文献
109.
Ciobanu M Huang KT Daguer JP Barluenga S Chaloin O Schaeffer E Mueller CG Mitchell DA Winssinger N 《Chemical communications (Cambridge, England)》2011,47(33):9321-9323
We report the synthesis of a nucleic acid-encoded carbohydrate library, its combinatorial self-assembly into 37,485 pairs and a screen against DC-SIGN leading to the identification of consensus ligand motifs. A prototypical example from the selected pairs was shown to have enhanced binding. A dendrimer incorporating the selected motifs inhibited gp120's binding to dendritic cells with higher efficiency than mannan. 相似文献
110.
Hans J. Mueller Felix Beckmann David P. Dobson Simon A. Hunt Christian Lathe Nicole Stroncik 《高压研究》2013,33(3):345-354
Here we report recent technical advances that enable viscosity measurements in two DIA-type multi-anvil apparatus with a maximum of 250 tons and 1750 tons. We anticipate that this system will enable viscosity measurements for the pressures up to about 30 GPa. The deformation of the cell assemblies were analyzed by X-ray absorption tomography at beamline W II at DESY/HASYLAB after the high pressure runs. This analysis gave considerable insights into strategies for improving the cell assembly with the result that the optimized assemblies could be used at much higher pressures without blow-outs. We demonstrate using of X-ray transparent cubic boron nitride-anvils (single-stage DIA) and slotted carbide anvils (double-stage DIA) to make the whole melting chamber accessible for the high pressure X-radiography system. Results are demonstrated with viscosity measurements following Stokes’ Law by evaluation of X-radiography sequences taken by a camera equipped with a charge-coupled device sensor (CCD-camera) at pressures of 5 GPa as well as 10 GPa and temperatures of 1890 K. 相似文献