Radiofluorinated Pyrimidine‐2,4,6‐triones as Molecular Probes for Noninvasive MMP‐Targeted Imaging

Matrix metalloproteinases (MMPs) are zinc‐ and calcium‐dependent endopeptidases. Representing a subfamily of the metzincin superfamily, MMPs are involved in the proteolytic degradation of components of the extracellular matrix. Unregulated MMP expression, MMP dysregulation and locally increased MMP activity are common features of various diseases, such as cancer, atherosclerosis, stroke, arthritis, and others. Therefore, activated MMPs are suitable biological targets for the specific visualization of such pathologies, in particular by using radiolabeled MMP inhibitors (MMPIs). The aim of this work was to develop a radiofluorinated molecular probe for noninvasive in vivo imaging for the detection of up‐regulated levels of activated MMPs in the living organism. Fluorinated MMPIs ( 26 , 31 and 38 ) based on the pyrimidine‐2,4,6‐trione lead structure RO 28‐2653 ( 1 ) were synthesized, and their MMP inhibition potency was evaluated in vitro. The radiosynthesis and the in vivo biodistribution of the first ¹⁸F‐labeled prototype, MMP‐targeted tracer [¹⁸F] 26 , suitable for molecular imaging by means of positron emission tomography (PET) were realized.     

Residual Stresses in Alumina/Zirconia Composites: Effect of Cooling Rate and Grain Size

Alumina/zirconia composites with various compositions at the zirconia-rich part of the phase diagram have been prepared with various grain sizes of the starting alumina powders. After firing under identical conditions, the pellets have been cooled systematically, changing the cooling rates from 0.5 to 8000 K/min. Subsequently, the residual stresses in alumina have been determined by monitoring the frequency shifts of the R ₂ luminescence line of alumina (14 430 cm⁻¹). The data indicate that the stress in alumina is compressive in all cases, with increasing absolute values of the stress with decreasing alumina content. Within the same composition, the residual stress as a function of the cooling rate presents a minimum for values between 10 and 100 K/min, with no clear dependence on the alumina or zirconia grain size. An interpretation of the experimental data in terms of a Coble-type diffusional relaxation applies for intermediate cooling rates (from 10 to 800 K/min), but it fails to account for the large stresses at low cooling rates. The width of the stress distribution is narrow (∼150 MPa) and constant for all compositions and grain sizes at low cooling rates, but it increases for cooling rates >10 K/min, depending on the grain size but not on the composition. For fast cooling rates, a correlation is found when reporting the average width of the stress distribution as function of the average sintered grain-size distribution of alumina. Overall, zirconia grain size seems to influence the average stress, whereas alumina grain size determines the stress distribution.     

Mechanical stability of trimethylolpropane trimethacrylate-based polymers

Trimethylolpropane trimethacrylate (TRIM) was homopolymerized and copolymerized with methyl methacrylate (MMA), glycidyl methacrylate (GMA), and acrylamide (AA), respectively, in various solvents and at various temperatures. For comparison, poly(styrene-co-divinyl benzene) [poly(S-co-DVB)] gels were selected. The mechanical stability was measured by compression of the swollen gels. The porogen served as swelling agent. The compression moduli increased with increasing TRIM concentration in the polymerization. The compression moduli of poly(TRIM) could be increased by copolymerization with low concentrations of comonomer. Low polymerization temperature decreased the mechanical strength of poly(TRIM). A good solvent increased the compression modulus. TRIM-based gels were at least as mechanically stable as were poly(S-co-DVB) gels.     

On the interrelation of rubber elastic stress-strain curves under different types of strain

With specially shaped samples it is possible to study the stress-strain relation σ(γ) in simple shear up to large shear deformation γ. Measurements of σ(γ) on synthetic polyisoprene, IR 305, differently crosslinked with dicumylperoxide, are reported and compared with those for uniaxial extension on the same materials. Using the simple deformation geometry including shearbands proposed in the meander model (1), both stress-strain relations can be converted into each other. These results favor the applied superstructural model and moreover show that the deformation behavior of rubbers is governed by one material law, σ(γ).     

Numerische Magnetfeldberechnung durch Diskretisierungsverfahren

Übersicht Zur Berechnung von Magnetfeldern mit beliebigen Materialverteilungen und beliebigen Anregungen wird die Differentialgleichung für das Vektorpotential angegeben und mit Hilfe der finiten Elemente Methode in ein algebraisches Gleichungssystem umgewandelt. Die Anwendung des Durchflutungsgesetzes führt wesentlich einfacher zu identischen Bestimmungsgleichungen. Eine Berücksichtigung der Nichtlinearitäten geschieht mit dem Newton Raphson Verfahren. Für den Sonderfall von anisotropen Stoffeigenschaften werden die Transformationsmatrizen angegeben. Zum Schluß wird ein Lösungsverfahren für schwach besetzte Gleichungssysteme beschrieben.

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Numerical magnetic field calculations using discretization methods

Contents To calculate magnetic fields with arbitrary material distributions and excitations the given vector potential differential equation is transformed into an algebraic system of equations (Finite Element Method). The application of the ampere turns rule leads (considerably more simply) to identical equations. Allowance for non-linearities is provided by the Newton-Raphson method. The transformation matrices are given for anisotropic material properties. Finally, a solver for sparsely populated matrices is deseribed.

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Verzeichnis der verwendeten Symbole A,A Vektorpotential - a, b, c Koeffizienten - B,B magnetische Induktion - b Anregungsvektor - f Formfunktion - G, F Gebiet - H,H magnetische Feldstärke - J Dreiecksfläche - K Integrationsweg - K Koeffizientenmatrix - L Dreieckskoordinaten - M,M Magnetische Polarisation - S Stromdichte - t Zeitkoordinate - v,v Geschwindigkeit - x, y, z Ortskoordinaten - elektrische Leitfähigkeit - =1/ Permeabilität - Reluktivität     

The effect of levitated water on fermentation kinetics

The rate of anaerobic glucose fermentation by baker's yeast is found to be altered when tap water is replaced with "levitated" (i.e., hydrodynamically processed) water. To analyze the effect in more detail, we developed a fermentation kinetics model that differentiates between (i) nutrient transport into the cell, (ii) the "catabolic" and (iii) the "anabolic" reactions. As a result, the levitated water affects specifically the glucose uptake kinetics, whereas the other kinetic parameters remain unchanged. Remarkably, the sign of the effect changes with the water used to prepare the culture. When levitated water is used for both the culture preparation and the fermentation, the rate constant of glucose transport is increased by (67+/-25)%, relative to ordinary tap-water. When the culture is prepared in ordinary water and only the fermentation is performed in levitated water, the rate constant of glucose transport decreased by (50+/-12)%. Three-week old levitated water has no discernable effect any more.