Neutrophil extracellular traps are networks of DNA and associated proteins produced by nucleosome release from activated neutrophils in response to infection stimuli and have recently been identified as key mediators between innate immunity, inflammation, and hemostasis. The interaction of DNA and histones with a number of hemostatic factors has been shown to promote clotting and is associated with increased thrombosis, but little is known about the effects of DNA and histones on the regulation of fibrin stability and fibrinolysis. Here we demonstrate that the addition of histone-DNA complexes to fibrin results in thicker fibers (increase in median diameter from 84 to 123 nm according to scanning electron microscopy data) accompanied by improved stability and rigidity (the critical shear stress causing loss of fibrin viscosity increases from 150 to 376 Pa whereas the storage modulus of the gel increases from 62 to 82 pascals according to oscillation rheometric data). The effects of DNA and histones alone are subtle and suggest that histones affect clot structure whereas DNA changes the way clots are lysed. The combination of histones + DNA significantly prolongs clot lysis. Isothermal titration and confocal microscopy studies suggest that histones and DNA bind large fibrin degradation products with 191 and 136 nm dissociation constants, respectively, interactions that inhibit clot lysis. Heparin, which is known to interfere with the formation of neutrophil extracellular traps, appears to prolong lysis time at a concentration favoring ternary histone-DNA-heparin complex formation, and DNase effectively promotes clot lysis in combination with tissue plasminogen activator.
30 June 2013 in Journal of Thrombosis and Haemostasis
Cell‐derived or extracellular vesicles, including microparticles and exosomes, are abundantly present in body fluids such as blood. Although such vesicles have gained strong clinical and scientific interest, their detection is difficult because many vesicles are extremely small with a diameter of less than 100 nm, and, moreover, these vesicles have a low refractive index and are heterogeneous in both size and composition. In this review, we focus on the relatively high throughput detection of vesicles in suspension by flow cytometry, resistive pulse sensing, and nanoparticle tracking analysis, and we will discuss their applicability and limitations. Finally, we discuss four methods that are not commercially available: Raman microspectroscopy, micro nuclear magnetic resonance, small‐angle X‐ray scattering (SAXS), and anomalous SAXS. These methods are currently being explored to study vesicles and are likely to offer novel information for future developments.
1 July 2001 in Nuclear Instruments and Methods in Physics Research Section A: Accelerators, Spectrometers, Detectors and Associated Equipment
The Avogadro constant links the atomic and the macroscopic properties of matter. Since the molar Planck constant is well known via the measurement of the Rydberg constant, it is also closely related to the Planck constant. In addition, its accurate determination is of paramount importance for a definition of the kilogram in terms of a fundamental constant. We describe a new approach for its determination by counting the atoms in 1 kg single-crystal spheres, which are highly enriched with the isotope. It enabled isotope dilution mass spectroscopy to determine the molar mass of the silicon crystal with unprecedented accuracy. The value obtained, , is the most accurate input datum for a new definition of the kilogram.
1 July 2001 in Nuclear Instruments and Methods in Physics Research Section A: Accelerators, Spectrometers, Detectors and Associated Equipment
We have developed different types of photodetectors that are based on the photoionization of a gas at a low target density. The almost transparent devices were optimized and tested for online photon diagnostics at current and future x-ray free-electron laser facilities on a shot-to-shot basis with a temporal resolution of better than 100 ns. Characterization and calibration measurements were performed in the laboratory of the Physikalisch-Technische Bundesanstalt at the electron storage ring BESSY II in Berlin. As a result, measurement uncertainties of better than 10% for the photon-pulse energy and below for the photon-beam position were achieved at the Free-electron LASer in Hamburg (FLASH). An upgrade for the detection of hard x-rays was tested at the Sub-Picosecond Photon Source in Stanford.