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Organisationseinheit der BAM
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Purine nucleotides such as ATP and ADP are important extracellular signaling molecules in almost all tissues activating various subtypes of purinoreceptors. In the brain, the P2Y1 receptor (P2Y1R) subtype mediates trophic functions like differentiation and proliferation, and modulates fast synaptic transmission, both suggested to be affected in diseases of the central nervous system. Research on P2Y1R is limited because suitable brain-penetrating P2Y1R-selective tracers are not yet available. Here, we describe the first efforts to develop an 18F-labeled PET tracer based on the structure of the highly affine and selective, non-nucleotidic P2Y1R allosteric modulator 1-(2-[2-(tert-butyl)phenoxy]pyridin-3-yl)-3- [4-(trifluoromethoxy)phenyl]urea (7). A small series of fluorinated compounds was developed by systematic modification of the p-(trifluoromethoxy)phenyl, the urea and the 2-pyridyl subunits of the lead compound 7. Additionally, the p-(trifluoromethoxy)phenyl subunit was substituted by carborane, a boron-rich cluster with potential applicability in boron neutron capture therapy (BNCT). By functional assays, the new fluorinated derivative 1-{2-[2-(tert-butyl)phenoxy]pyridin-3-yl}-3-[4-(2-fluoroethyl) phenyl]urea (18) was identified with a high P2Y1R antagonistic potency (IC50 ¼10 nM). Compound [18F] 18 was radiosynthesized by using tetra-n-butyl ammonium [18F]fluoride with high radiochemical purity, radiochemical yield and molar activities. Investigation of brain homogenates using hydrophilic interaction chromatography (HILIC) revealed [18F]fluoride as major radiometabolite. Although [18F]18 showed fast in vivo metabolization, the high potency and unique allosteric binding mode makes this class of compounds interesting for further optimizations and investigation of the theranostic potential as PET tracer and BNCT agent.
Mn0.75Ga0.25As crystallites, partially embedded on and fully embedded within a single crystalline matrix of GaAs formed during metal organic vapor phase epitaxy (MOVPE) of Mn-rich (Mn,Ga)As on (001) oriented GaAs wafers. Phase and orientation analysis of these crystallites were performed with scanning nano beam electron diffraction (SNBED). The investigation of plan-view specimens using a liquid nitrogen cooling stage enabled the phase and orientation analysis of partially embedded ferromagnetic a-phase particles. In all specimens the following two orientation relationships (O) between the a-phase particles and the GaAs matrix were determined:
O1:
[1-2.0] Mn0.75Ga0.25As || [110] GaAs and
[10.2] Mn0.75Ga0.25As || [-110] GaAs
O2:
[10.2] Mn0.75Ga0.25As || [110] GaAs and
[1-2.0] Mn0.75Ga0.25As || [-110] GaAs.
The study of cross-sectional specimens enabled the analysis of fully embedded crystallites. It could be unambiguously detected that a fully embedded crystallite has the structure of the atomically ordered monoclinic β' phase. The β' phase crystallite consists of two domains which are related in twin positions to each other. The orientation relations of the different particles are illustrated by color coded stereographic projections.
Metal organic vapor phase epitaxy (MOVPE) of Mn-rich (Mn,Ga)As on (001) oriented GaAs wafers resulted in atomically ordered (Mn,Ga)As crystallites of two morphological kinds, partially embedded on the wafer surface and fully embedded within the single crystalline matrix. While the former were apparently free of defects (other than unavoidable point defects), the latter contained two domains separated by a grain boundary. Since atomic ordering can be modeled by space group symmetry descent considerations (Bärnighausen trees) that start with the space group of the known crystallographic phases of random (Mn,Ga)As alloys with specified chemical compositions, reasonable structure hypotheses have been derived for two atomically ordered Mn0.75Ga0.25As phases that we call the trigonal α' and the monoclinic β' phases. The implications of these structure hypotheses are in agreement with the results of a range of scanning transmission electron microscopy (STEM) and parallel illumination electron diffraction (ED) studies that include quantitative energy dispersive X-ray spectroscopy, X-ray spectroscopic imaging, as well nanobeam diffraction and high angle precession ED. The coexistence of two domains within the fully embedded crystallites is predicted by the corresponding Bärnighausen tree and observed experimentally for the fully embedded crystallites.
Time dependence of y/y' Lattice Mismatch in Creep-deformed Single Crystal Superalloy SC16 at 1173 K
(2007)
Specimens of single crystal superalloy SC16 were creep deformed at 1223 K along [0 0 1] up to ±0.5% creep strain using stresses of -150 MPa and +150 MPa, respectively. Line widths and peak positions of superlattice reflections were measured by means of X-ray diffraction parallel and perpendicular to the load axis in the temperature range between 293 K and 1173 K. The line widths were found to decrease with the increase of temperature for both directions on the two specimens after tensile and compressive creep deformation. After both kinds of creep deformation the crystal lattice showed tetragonal distortion which decreased with increasing temperature. The tetragonality after tensile creep deformation was larger than unity while it was smaller than unity after compressive creep deformation. The peak positions and widths restored after cooling back to room temperature. The experimental results can qualitatively be explained by the creation of dislocations during deformation and their anisotropic arrangement at the γ/γ' interfaces.
High-resolution diffraction using synchrotron x-ray radiation was applied to study γ´ precipitates with an L12 superlattice crystal structure in the single crystal superalloy SC16 after creep deformation at 1223 K with a creep strain of ±0.5% for tensile and compressive loads, respectively. The measurements of full width at half maximum (FWHM) of 001 and 100 γ´ superlattice reflections were performed at various temperatures from ambient temperature to 1173 K in vacuum. The experimental results revealed that the FWHM of both reflections decrease with increasing temperature. It is well-known that changes in particle size and lattice distortion in materials could lead to a variation of FWHM. The observed behaviour is discussed in the light of both the above-mentioned aspects. The decrease in the peak width is mainly attributed to the temperature dependence of the internal strain state.