A hard x ray split and delay unit for the HED experiment at the European XFEL

For the High Energy Density HED experiment [1] at the European XFEL [2] an x ray split and delay unit SDU is built covering photon energies from 5 keV up to 20 keV [3]. This SDU will enable time resolved x ray pump x ray probe experiments [4,5] as well as sequential diffractive imaging [6] on a femtosecond to picosecond time scale. Further, direct measurements of the temporal coherence properties will be possible by making use of a linear autocorrelation [7,8]. The set up is based on geometric wavefront beam splitting, which has successfully been implemented at an autocorrelator at FLASH [9]. The x ray FEL pulses are split by a sharp edge of a silicon mirror coated with multilayers. Both partial beams will then pass variable delay lines. For different photon energies the angle of incidence onto the multilayer mirrors will be adjusted in order to match the Bragg condition. For a photon energy of h amp; 957; 20 keV a grazing angle of amp; 952; 0.57 has to be set, which results in a footprint of the beam 6 amp; 963; on the mirror of l 98 mm. At this photon energy the reflectance of a Mo B4C multi layer coating with a multilayer period of d 3.2 nm and N 200 layers amounts to R 0.92. In order to enhance the maximum transmission for photon energies of h amp; 957; 8 keV and below, a Ni B4C multilayer coating can be applied beside the Mo B4C coating for this spectral region. Because of the different incidence angles, the path lengths of the beams will differ as a function of wavelength. Hence, maximum delays between 2.5 ps at h amp; 957; 20 keV and up to 23 ps at h amp; 957; 5 keV will be possibl

Glial cell type-specific changes in spinal dipeptidyl peptidase 4 expression and effects of its inhibitors in inflammatory and neuropatic pain

Altered pain sensations such as hyperalgesia and allodynia are characteristic features of various pain states, and remain difficult to treat. We have shown previously that spinal application of dipeptidyl peptidase 4 (DPP4) inhibitors induces strong antihyperalgesic effect during inflammatory pain. In this study we observed low level of DPP4 mRNA in the rat spinal dorsal horn in physiological conditions, which did not change significantly either in carrageenan-induced inflammatory or partial nerve ligation-generated neuropathic states. In naive animals, microglia and astrocytes expressed DPP4 protein with one and two orders of magnitude higher than neurons, respectively. DPP4 significantly increased in astrocytes during inflammation and in microglia in neuropathy. Intrathecal application of two DPP4 inhibitors tripeptide isoleucin-prolin-isoleucin (IPI) and the antidiabetic drug vildagliptin resulted in robust opioid-dependent antihyperalgesic effect during inflammation, and milder but significant opioid-independent antihyperalgesic action in the neuropathic model. The opioid-mediated antihyperalgesic effect of IPI was exclusively related to mu-opioid receptors, while vildagliptin affected mainly delta-receptor activity, although mu- and kappa-receptors were also involved. None of the inhibitors influenced allodynia. Our results suggest pathology and glia-type specific changes of DPP4 activity in the spinal cord, which contribute to the development and maintenance of hyperalgesia and interact with endogenous opioid systems

Design of an x-ray split- and delay-unit for the European XFEL

For the European XFEL [1] an x ray split and delay unit SDU is built covering photon energies from 5 keV up to 20 keV. This SDU will enable time resolved x ray pump x ray probe experiments as well as sequential diffractive imaging [2] on a femtosecond to picosecond time scale. Further, direct measurements of the temporal coherence properties will be possible by making use of a linear autocorrelation. The set up is based on geometric wavefront beam splitting, which has successfully been implemented at an autocorrelator at FLASH [3]. The x ray FEL pulses will be split by a sharp edge of a silicon mirror coated with Mo B4C multi layers. Both partial beams will then pass variable delay lines. For different wavelengths the angle of incidence onto the multilayer mirrors will be adjusted in order to match the Bragg condition. For a photon energy of hn 20 keV a grazing angle of q 0.57 has to be set, which results in a footprint of the beam 6s on the mirror of l 345 mm. At this photon energy the reflectance of a Mo B4C multi layer coating with a multi layer period of d 3 nm and N 200 layers amounts to R 0.92. For a photon energy of hn 5 keV a smaller size of the footprint of l 244 mm is calculated due to the steeper grazing angle of q 2.28 . In order to enhance the maximum transmission for photon energies of hn 8 keV and below, a Ni B4C multilayer coating can be applied beside the Mo B4C coating for this spectral region. Because of the different incidence angles, the path lengths of the beams will differ as a function of wavelength. Hence, maximum delays between 3.7 ps at hn 20 keV and up to 44 ps at hn 5 keV will be possibl

Detection of corneal fibrosis by imaging second harmonicgenerated signals in rabbit corneas treated with mitomycin C after excimer laser surface ablation,” Invest

PURPOSE. Recent studies have shown that confocal imaging of second harmonic-generated (SHG) signals can detect corneal collagen organization. The purpose of this study was to assess whether SHG signals can detect differences in corneal fibrosis after excimer laser surface ablation (photorefractive keratectomy [PRK]). METHODS. Rabbits received 9-D PRK in one eye followed by treatment with either mitomycin C (MMC) or vehicle. Corneal haze was measured by in vivo confocal microscopy before and 2, 4, 8, and 12 weeks after surgery. Animals were then killed and corneas were evaluated by visible and nonlinear confocal microscopy. RESULTS. PRK induced significant haze in vehicle-treated corneas that peaked at 2 weeks and remained elevated at 12 weeks after surgery. MMC treatment significantly (P Ͻ 0.05) reduced corneal haze at 2 weeks and was essentially normal by 12 weeks. Imaging of SHG signals in vehicle-treated eyes showed an anterior layer of collagen forming a honeycomb network blending into a dense mat of irregularly arranged collagen fibers that overlaid normal orthogonally arranged collagen lamellae. MMC treatment showed normal collagen organization at the surface. Fibrotic tissue was associated with a high cell density and alignment of intracellular actin filaments with collagen fiber bundles. In MMC-treated eyes, an anterior acellular zone overlaid a sparsely populated stroma containing isolated and enlarged keratocytes. CONCLUSIONS. Imaging of SHG signals provides a sensitive means for detection of corneal fibrosis after surface ablation and can be used to assess the effects of antifibrotic therapy on corneal healing after refractive surgery. (Invest Ophthalmol Vis Sci

The XUV split-and-delay unit at beamline BL2 at FLASH

For time-resolved extreme ultraviolet (XUV) pump–XUV probe experiments at the Free electron LASer in Hamburg (FLASH), a split-and-delay unit (SDU) has been built. It is implemented in beamline BL2 which provides a focal spot size of about 20 μm diameter in the experiment. The beam is divided geometrically into two paths which can be delayed from −3 to +15 ps with respect to each other. The transmission up to 200 eV photon energy is above 35% in one beam path and 74% in the other. The latter transmits the XUV beam again from 305 to 570 eV (>1% transmission). Thus almost the whole spectral range at FLASH is covered by the SDU with reasonable transmission, including the option to transport high-energy third harmonic radiation in one of the beam paths. Both beam paths are realigned into the original direction of the radiation at the end of the SDU. Thus the utilization of the divided as well as the original beam is enabled by simply moving the optical elements of the SDU into or out of the beam. Using the SDU, the coherence length and the average pulse duration at FLASH was determined to be 0.9–1.8 μm, depending on the wavelength, and about 30 fs, respectively, for the specific electron bunch parameters

Optical Design and Time-dependent Wavefront Propagation Simulation for a Hard X-Ray Split- and delay-unit for the European XFEL

For the European XFEL an x-ray split- and delay-unit (SDU) is built covering photon energies from 5 keV up to 20 keV. This SDU will enable time-resolved x-ray pump / x-ray probe experiments as well as sequentialdiffractive imaging on a femtosecond to picosecond time scale. The wavefront of the x-ray FEL pulses will be split by an edge of a silicon mirror coated with Mo/B4C and W/B4C multilayers. Both partial beams will then pass variable delay lines. For different wavelengths the angle of incidence onto the multilayer mirrors will be adjusted in order to match the Bragg condition. Hence, maximum delays between +/- 2.5 ps at hν = 20keV and up to +/- 33 ps at hν = 5 keV will be possible. The time-dependent wave-optics simulations have been done with SRW software, for the fundamental and the 3rd harmonic. The XFEL radiation was simulated bothin the Gaussian approximation as well as using an output of time-dependent SASE code FAST. Main features of the optical layout, including diffraction on the splitter edge, and optics imperfections were taken into account. Impact of these effects on the possibility to characterize spatial-temporal properties of FEL pulses are analyzed