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A method was developed for the precise and accurate determination of ovalbumin labelled with p-hydroxy-mercuribenzoic acid (pHMB) using polyacrylamide gel electrophoresis with ns-laser ablation–inductively coupled plasma mass spectrometry. Following systematic optimisation of the ablation process in terms of detection sensitivity, two different quantification strategies were applied: external calibration using standards of the derivatized protein after 13C+ normalization and, as a proof of concept, label-specific isotope dilution analysis (IDA) using pHMB enriched in the isotope 199Hg. Due to the inhomogeneous distribution of the protein within the gel bands, it could be demonstrated that the IDA approach was superior in terms of precision and accuracy. Furthermore, it permits a reliable quantification, if more complex separation protocols are applied, as typically occurring analyte loss and degradation can be compensated for as soon as complete mixture of spike and sample is achieved. The estimated limit of detection was 160 fmol in the case of ovalbumin. In contrast to earlier studies using metals naturally present in proteins, no loss of mercury was observed during separation under denaturing conditions and other sample preparation steps. Using label-specific IDA, the measured isotope ratios in the gel corresponded to recoveries between 95% and 103%.  相似文献   
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Ohne ZusammenfassungHerrn ProfessorAlexander Ostrowski zum achtzigsten Geburtstag gewidmet  相似文献   
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The platinum anticancer drug cisplatin has made a major contribution to the treatment of testicular and ovarian cancer. This chance discovery has been the stimulus for research into other metal-based drugs. Inorganic chemistry offers many opportunities for medicinal chemistry, and the discovery of metal-based drugs has moved on from chance discovery to rational drug design. There are however, many challenges associated with the drug discovery and development process. The aim of this review is to provide case histories exemplifying the role of rational drug design in modern inorganic medicinal chemistry in the context of these challenges. The evolution of platinum drugs from cisplatin to third generation drugs is described. The molecular target for the platinum agents is DNA. Alternative molecular targets such as thiol-containing proteins and redox processes are proposed. The example of a simple, safe, efficacious metal-based drug, Fosrenol, is reviewed.  相似文献   
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In this study,the three dimensional nanoscale organization in the photoactive layers of poly(3-hexylthiophene) (P3HT) and a methanofullerene derivative (PCBM) is revealed by transmission electron tomography.After annealing treatment,either at elevated temperature or during slow solvent evaporation,nanoscale interpenetrating networks are formed with high crystalline order and favorable concentration gradients of both components through the thickness of the photoactive layer.Such a tailored morphology acco...  相似文献   
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Peptides perform a wide number of physiological roles as signaling molecules between cells as well as other functions. The detection of peptides has generally relied on one of two distinct techniques: immunohistochemistry and mass spectrometry. In this issue of Chemistry & Biology, Neupert and colleagues describe an approach to combine these techniques.  相似文献   
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The paper deals with the fluid limits of some generalized M/G/∞ queues under heavy-traffic scaling. The target application is the modeling of Internet traffic at the flow level. Our paper first gives a simplified approach in the case of Poisson arrivals. Expressing the state process as a functional of some Poisson point process, an elementary proof for limit theorems based on martingales techniques and weak convergence results is given. The paper illustrates in the special Poisson arrivals case the classical heavy-traffic limit theorems for the G/G/∞ queue developed earlier by Borovkov and by Iglehart, and later by Krichagina and Puhalskii. In addition, asymptotics for the covariance of the limit Gaussian processes are obtained for some classes of service time distributions, which are useful to derive in practice the key parameters of these distributions.  相似文献   
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