Publications Repository - Helmholtz-Zentrum Dresden-Rossendorf

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35174 Publications

P1402 - Kontrolle einer therapeutischen Bestrahlung durch eine Bestrahlungseinrichtung mit einem mikrogepulsten Teilchenstrahl

Enghardt, W.; Fiedler, F.; Helmbrecht, S.

Die Erfindung betrifft Verfahren und Einrichtungen zur Kontrolle einer therapeutischen Bestrahlung durch eine Bestrahlungseinrichtung mit einem mikrogepulsten Teilchenstrahl mittels eines Positronen-Emissions-Tomografen. Diese zeichnen sich insbesondere dadurch aus, dass eine therapeutische Bestrahlung durch eine Bestrahlungseinrichtung mit einem mikrogepulsten Teilchenstrahl mittels eines Positronen-Emissions-Tomografen während der Bestrahlung kontrollierbar ist. Dazu werden wahre Koinzidenzen mittels – des durch die erlaubte Zeitdifferenz des Auftreffens zweier Photonen in verschiedenen Detektoren des Tomografen bestimmten Koinzidenzzeitfensters und – der Differenz zwischen prompten Fenster und verzögerten Fenster ohne wahre Koinzidenzen ermittelt. Dabei sind sowohl das Koinzidenzzeitfenster als auch die Zeitdifferenz zwischen prompten und verzögerten Fenster ein ganzzahliges Vielfaches der durch die Frequenz der beschleunigenden Wechselspannung des Hochfrequenzbeschleunigers gegebenen Zeitdauer einer Mikropulsperiode des Teilchenstrahls. Die Mikropulsperiode ist durch den Mikropuls und die Pause zwischen Mikropulsen definiert. Diese Zeitdauer ist durch die Frequenz der die Teilchen des Teilchenstrahls beschleunigenden Wechselspannung gegeben und damit zu wählen.

  • Patent
    DE102014202828 - Erteilung 02.07.2015, Nachanmeldung: WO, JP

Publ.-Id: 22178

Grid studies for the simulation of resolved structures in an Eulerian two-fluid framework

Gauss, F.; Lucas, D.; Krepper, E.

The influence of the grid size on the rise velocity of a single bubble simulated with an Eulerian two-fluid method is investigated. This study is part of the development of an elaborated Eulerian two-fluid framework, which is able to predict complex flow phenomena as arising in nuclear reactor safety research issues. Such flow phenomena cover a wide range of interfacial length scales. An important aspect of the simulation method is the distinction into small flow structures, which are modeled, and large structures, which are resolved. To investigate the requirements on the numerical grid for the simulation of such resolved structures the velocity of rising gas bubbles is a good example since theoretical values are available. It is well known that the rise velocity of resolved bubbles is clearly underestimated in a one-fluid approach if they span over only few numerical cells. In the present paper it is shown that in the case of the two-fluid model the bubble rise velocity depends only slightly on the grid size. This is explained with the use of models for the gas–liquid interfacial forces. Good approximations of the rise velocity and the bubble shape are obtained with only few grid points per bubble diameter. This result justifies the resolved treatment of flow structures, which cover only few grid cells. Thus, a limit for the distinction into resolved and modeled structures in the two-fluid context may be established.

Keywords: multiphase flow; grid study; single rising bubble; Eulerian two-fluid method; Volume of Fluid method; terminal rise velocity

Publ.-Id: 22177

Biomimetic Magnetic Silk Scaffolds

Samal, S. K.; Dash, M.; Shelyakova, T.; Declercq, H. A.; Uhlarz, M.; Banobre-Lopez, M.; Dubruel, P.; Cornelissen, M.; Herrmannsdörfer, T.; Rivas, J.; Padeletti, G.; de Smedt, S.; Braeckmans, K.; Kaplan, D. L.; Dediu, V. A.

Magnetic silk fibroin protein (SFP) scaffolds integrating magnetic materials and featuring magnetic gradients were prepared for potential utility in magnetic-field assisted tissue engineering. Magnetic nanoparticles (MNPs) were introduced into SFP scaffolds via dip-coating methods, resulting in magnetic SFP scaffolds with different strengths of magnetization. Magnetic SFP scaffolds showed excellent hyperthermia properties achieving temperature increases up to 8 °C in about 100 s. The scaffolds were not toxic to osteogenic cells and improved cell adhesion and proliferation. These findings suggest that tailored magnetized silk-based biomaterials can be engineered with interesting features for biomaterials and tissue-engineering applications.

Publ.-Id: 22176

Capture Gamma-Ray Spectroscopy and Related Topics, Proceedings of the Fifteenth International Symposium

Schwengner, R.; Zuber, K.; (Editors)

The Fifteenth International Symposium on Capture Gamma-Ray Spectroscopy and Related Topics (CGS15) was organized by the Helmholtz-Zentrum Dresden-Rossendorf (HZDR) and the Technische Universität (TU) Dresden and held at TU Dresden from August 25 to August 29, 2014.
CGS15 was the fifteenth symposium in a series that started in 1969.
This conference continued the general themes of earlier meetings with special emphasis on gamma-ray spectroscopy used in neutron capture and also in a wider context in nuclear structure, nuclear reactions, nuclear astrophysics, statistical properties of nuclei, nuclear probes for fundamental physics, nuclear data, novel techniques and applications.
These proceedings include a collection of articles from all these topics.

Keywords: Gamma-ray spectroscopy

  • Open Access Logo Book (Editorship)
    France: EDP Sciences, 2015
    ISBN: 978-2-7598-1794-8


Publ.-Id: 22175

Design of a 18F-labeled purinergic P2Y1 receptor (P2Y1R) ligand for brain imaging

Moldovan, R.-P.; Dukic-Stefanovic, S.; Wenzel, B.; Teodoro, R.; Deuther-Conrad, W.; Brust, P.

Objectives: Purine nucleotides such as ATP and ADP are important extracellular signaling molecules in almost all tissues. Via P2Y1R activation they mediate brain functions by trophic effects like differentiation and proliferation but also via fast synaptic transmission. The understanding of its role in brain disorders is limited because of lack of suitable brain-penetrating P2Y1R-selective drugs. Chao and co workers recently reported the first non-nucleotidic, diarylurea ligands with high affinity and selectivity for the P2Y1R[1]. We selected this scaffold for the development a 18F labeled P2Y1R ligand for brain imaging.

Methods: Based on the lead compounds 1-3 (Ki = 6-8 nM),[1] we designed derivative 5, suitable for aliphatic radiofluorination using the corresponding tosyl precursor 4. The radiolabeling was systematically optimized (eg. phase transfer catalyst, solvent, temperature, amount of precursor and heating method) and [18F]5 successfully provided for subsequent evaluation. The lead structure was further modified by fluorinating pyridine at the 2-position, replacing the urea subunit C with 2 aminothiazole, and substituting ring D with various fluoroaromatic and non-aromatic rings.

Results: Reference compound 5 has been synthesized from the tosylate 4 in 62% yield. Under optimized conditions, [18F]5 has been obtained in high radiochemical yield (30%) and purity (≥99%) at a specific activity of ~182 GBq/µmol. A series of 30 new fluorinated derivatives has been synthesized.

Conclusions: The first 18F-labeled P2Y1R ligand, [18F]5 has been successfully synthesized. To evaluate the newly designed compounds, an in vitro binding assay using stably transfected P2Y1R-1321N1 cells and [18F]5 is currently developed.

Literature: [1] Chao et al. J. Med. Chem. 2013, 56, 1704−1714

  • Lecture (Conference)
    23. Jahrestagung der AG Radiochemie / Radiopharmazie, 10.-12.09.2015, Erlangen, Deutschland

Publ.-Id: 22174

Network-like arrangement of mixed-valence uranium oxide nanoparticles after glutathione-induced reduction of uranium(VI)

Kretzschmar, J.; Haubitz, T.; Hübner, R.; Weiss, S.; Husar, R.; Brendler, V.; Stumpf, T.

Glutathione (GSH), a ubiquitous intracellular reducing tripeptide, is able to reduce hexavalent uranium, U(VI), to its tetravalent form, U(IV), in aqueous media in vitro, inducing the formation of nanocrystalline mixed-valence uranium oxide particles. After initial reduction to U(V) and subsequent dismutation, yielded U(IV) rapidly hydrolyses at near-neutral conditions forming 2–5 nm sized nanoparticles. The latter further aggregate to 20–40 nm chain-like building blocks that finally arrange as network-like structures.

Keywords: glutathione; uranium; redox reaction; uraninite; nanocrystal; TEM; environmental science

Publ.-Id: 22173

Advanced tomographic imaging for multi-phase flow investigations in industrial apparatuses

Bieberle, M.; Barthel, F.; Rabha, S.; Schubert, M.; Bieberle, A.; Hampel, U.

Investigations on two- and multiphase flow phenomena inside technical apparatuses or feedings are of highest interest for designers and operators since the knowledge helps to understand the fundamental physics behind processes, e.g. in chemical and process engineering. It expedites the development of safer and more efficiently operated industrial facilities. Furthermore, measured data are used to validate new models developed for multiphase flow simulation, e.g. CFD. For non-intrusive two-phase flow investigations, two radiation-based computed tomography (CT) scanners are operated at the Helmholtz-Zentrum Dresden - Rossendorf (HZDR) at the department of Fluid Dynamics: a high-resolution gamma-ray computed tomography scanner (HireCT) and an ultrafast electron beam X-ray CT scanner (ROFEX). They are able to recover non-superimposed cross-sectional material distributions of the scanned plane or volume section within the flow as time averaged images or time resolved image sequences. The capabilities of both CT systems are demonstrated exemplarily at experiments on an industrial scale bubble column, a fluidized bed and a static mixer.

Keywords: computed tomography; multi-phase flow; CFD

  • Contribution to proceedings
    Fachtagung “Lasermethoden in der Strömungsmesstechnik”, 08.-10.09.2015, Dresden, Deutschland
    Lasermethoden in der Strömungsmesstechnik, Karlsruhe: Deutsche Gesellschaft für Laser-Anemometrie, 978-3-9816764-1-9, 8-1-8-8
  • Lecture (Conference)
    Fachtagung “Lasermethoden in der Strömungsmesstechnik”, 08.-10.09.2015, Dresden, Deutschland

Publ.-Id: 22172

Commissioning and first RF results of the second 3.5 cell SRF gun for ELBE

Arnold, A.; Lu, P.; Murcek, P.; Teichert, J.; Vennekate, H.; Xiang, R.; Eremeev, G. V.; Kneisel, P.; Stirbet, M.; Turlington, L.

As in 2007 the first 3.5 cell superconducting radio frequency (SRF) gun was taken into operation at Helmholtz-Zentrum Dresden-Rossendorf, it turned out that the specified performance to realize an electron energy of 9.4 MeV has not been achieved. Instead, the resonator of the gun was limited by field emission to about one third of this value and the measured beam parameters remained significantly below its expectations.

However, to demonstrate the full potential of this electron source for the ELBE linear accelerator, a second and slightly modified SRF gun was developed and built in collaboration with Thomas Jefferson National Accelerator Facility.

We will report on commissioning and first RF results of this new SRF gun. This includes in particular the characterization of the most important RF properties as well as their comparison with previous vertical test results. Additionally, investigations are presented that try to explain a particle contamination that happened recently during the first cathode transfer.

Keywords: SRF gun; superconducting radio frequency electron injector; ELBE linear accelerator

  • Lecture (Conference)
    The 56th ICFA Advanced Beam Dynamics Workshop on Energy Recovery Linacs, 07.-12.06.2015, Stony Brook, NY 11794, USA

Publ.-Id: 22171

Radiation Effects in Solid Nitrogen and Nitrogen-Containing Matrices: Fingerprints of N4+ Species

Savchenko, E. V.; Khyzhniy, I. V.; Uyutnov, S. A.; Barabashov, A. P.; Gumenchuk, G. B.; Beyer, M. K.; Ponomaryov, A. N.; Bondybey, V. E.

The radiation effects and relaxation processes in solid N2 and N2-doped Ne matrices, preirradiated by an electron beam, have been studied in the temperature range of 5–40 and 5–15 K, respectively. The study was performed using luminescence methods: cathodoluminescence CL and developed by our group nonstationary luminescence NsL, as well as optical and current activation spectroscopy methods: spectrally resolved thermally stimulated luminescence TSL and exoelectron emission TSEE. An appreciable accumulation of N radicals, N+, N2 + ions, and trapped electrons is found in nitrogen-containing Ne matrices. Neutralization reactions were shown to dominate relaxation scenario in the low-temperature range, while at higher temperatures diffusion-controlled reactions of neutral species contribute. It was conceived that in α-phase of solid N2, the dimerization reaction (N2 + + N2 → N4 +) proceeds: “hole self-trapping”. Tetranitrogen cation N4 + manifests itself by the dissociative recombination reaction with electron: N4 + + e → N2*(a’1Σu ) + N2 → N2 + N2 + hν. In line with this assumption, we observed a growth of the a’1Σu → X1Σg + transition intensity with an exposure time in CL spectra and the emergence of this emission in the course of electron detrapping on sample heating in the TSL and NsL experiments.

Publ.-Id: 22170

Dependence of the inverse magnetocaloric effect on the field-change rate in Mn3GaC and its relationship to the kinetics of the phase transition

Scheibel, F.; Gottschall, T.; Skokov, K.; Gutfleisch, O.; Ghorbani-Zavareh, M.; Skourski, Y.; Wosnitza, J.; Cakir, Ö.; Farle, M.; Acet, M.

We study the dependence of the magnetocaloric effect on the magnetic field-change-rate the first order magnetostructural transition in Mn3GaC by measuring the adiabatic temperature change ΔT at three different time scales: 11 mTs-1, 700 mTs-1, and ~1000 Ts-1. We find that the Maximum adiabatic temperature-change of about 5 K is reached in the 11 mTs-1 and 700 mTs-1 rates, whereas for the ~1000 Ts-1 the transition lags the change in the magnetic field so that the maximum adiabatic temperature-change is not attained.

Publ.-Id: 22169

Optical conductivity evidence of clean-limit superconductivity in LiFeAs

Lobo, R. P. S. M.; Chanda, G.; Pronin, A. V.; Wosnitza, J.; Kasahara, S.; Shibauchi, T.; Matsuda, Y.

We measured the optical conductivity of superconducting LiFeAs. In the superconducting state, the formation of the condensate leads to a spectral-weight loss and yields a penetration depth of 225 nm. No sharp signature of the superconducting gap is observed. This suggests that the system is likely in the clean limit. A Drude-Lorentz parametrization of the data in the normal state reveals a quasiparticle scattering rate supportive of spin fluctuations and proximity to a quantum critical point.

Publ.-Id: 22168

Doping effects of Sb in FeTe1-xSbx single crystals

Wang, X. F.; Zhang, Z. T.; Chen, X. L.; Kan, X. C.; Li, L.; Sun, Y. P.; Zhang, L.; Xi, C. Y.; Pi, L.; Yang, Z. R.; Zhang, Y. H.

We investigated the doping effects of Sb on the magnetic, transport and structural properties in FeTe1-xSbx single crystals. Resistivity, magnetic susceptibility and heat capacity experiments consistently reveal that the magnetic/structural transition temperature TN ~ 70 K in undoped Fe1.05Te is gradually suppressed by Sb doping, but no superconductivity is observed for x up to 10%. It is found that the electronic heat capacity coefficient gamma increases with Sb content, implying the increase of the density of states at Fermi level. Referring to previous calculation reports, this means that the Sb substituent plays a role of hole carrier doping, which is consistent with our measurements on Hall coefficient. Structural Analysis shows that Sb doping induces an expansion of the lattice along the a axis and a shrinkage along the c axis. Our work suggests that the antiferromagnetism in Fe1+yTe may be different in nature with other parent compounds of FeAs-based systems.

Publ.-Id: 22167

Experimental and numerical investigation of flow structure and heat transfer during high pressure condensation in a declined pipe at COSMEA facility

Geißler, T.; Szijarto, R.; Beyer, M.; Hampel, U.; Prasser, H.-M.; Walther, M.; Leyer, S.

Reliability and safety are perpetual topics in the development of nuclear installations. Generation III reactor concepts contain additional passive safety systems for improved accident control and mitigation. Main aspect of these passive systems is to operate with a minimum of external energy and signals. One example is the emergency condenser of the KERENA reactor concept, which removes heat from the core passively, e.g. after a station blackout. The governing natural circulation flow with condensation is only coarsely understood and current simulation methods need to be improved. During the condensation process a complex interaction between flow structure and heat transfer takes places and this determines the total efficiency of the passive safety system and hence the reliability in managing an incident.
The experimental facility COSMEA (condensation test rig for flow morphology and heat transfer studies) at HZDR is designated to provide experimental results to support the further development of CFD calculation methods. The test rig consists of a 3 m long emergency condenser pipe (ID 43 mm) which is 0.76° inclined and cooled by forced water flow. The experiments are conducted in a pressure range between 5 bar and 65 bar with steam mass flow rates up to 1 kg/s. Measurements of pressure, temperature, flow rate and condensation rate deliver integral understanding of the process. To investigate the details of the resulting stratified flow structures, x-ray tomography is applied. Parallel temperature measurements inside the heat transferring wall provide information about the azimuthal distribution of the heat flux.
A phase injection system was developed to operate the experiment in a stepwise condensation mode, which allows the measuring of condensation rates, flow morphologies and heat transfer distribution for different steam fraction values. The combination between cross sectional images from x-ray tomography and the azimuthally resolved heat transfer clarify the coupling between flow structure and heat transfer during condensation.
The experimental results are supported by a system code calculation. The COSMEA facility was modeled with the RELAP5 code. The original condensation model of the code was modified such that the heat transfer coefficient depends on the local mass fraction of the flow field. The experimental and calculation results agreed well for the steady state condensation process in the condensation rate, secondary side temperature and the heat flux data.

Keywords: two-phase flow; passive safety system; TOPFLOW; heat transfer; condensation; COSMEA; x-ray tomography

  • Contribution to proceedings
    NURETH-16, 16th International Topical Meeting on Nuclear Reactor Thermalhydraulics, 30.08.-04.09.2015, Chicago, USA
    Proceedings of NURETH-16
  • Lecture (Conference)
    NURETH-16, 16th International Topical Meeting on Nuclear Reactor Thermalhydraulics, 30.08.-04.09.2015, Chicago, USA

Publ.-Id: 22166

First evidence of low energy enhancement in Ge isotopes

Renström, T.; Nyhus, H.-T.; Utsunomiya, H.; Larsen, A. C.; Siem, S.; Guttormsen, M.; Filipescu, D. M.; Gheorghe, I.; Goriely, S.; Bernstein, L. A.; Bleuel, D. L.; Glodariu, T.; Görgen, A.; Hagen, T. W.; Lui, Y.-W.; Negi, D.; Ruud, I. E.; Sahin, E.; Schwengner, R.; Shima, T.; Takahisa, K.; Tesileanu, O.; Tornyi, T. G.; Tveten, G. M.; Wiedeking, M.

The γ-strength functions and level densities of 73,74 Ge have been extracted from particle-γ coincidence data using the Oslo method. In addition the γ-strength function of 74 Ge above the neutron separation threshold, Sn = 10.196 MeV has been extracted from photoneutron measurements. When combined, these two experiments give a γ-strength function covering the energy range of ~ 1-13 MeV for 74 Ge. This thorough investigation of 74Ge is a part of an international campaign to study the previously reported low energy enhancement in this mass region in the γ-strength function from ~ 3 MeV towards lower γ energies. The obtained data show that both 73,74 Ge display an increase in strength at low γ energies.

Keywords: gamma-ray strength

Publ.-Id: 22165

Analysis of pion production data measured by HADES in proton-proton collisions at 1.25 GeV

Agakishiev, G.; Balanda, A.; Belver, D.; Belyaev, A. V.; Blanco, A.; Böhmer, M.; Boyard, J. L.; Braun-Munzinger, P.; Cabanelas, P.; Castro, E.; Chernenko, S.; Christ, T.; Destefanis, M.; Díaz, J.; Dohrmann, F.; Dybczak, A.; Fabbietti, L.; Fateev, O. V.; Finocchiaro, P.; Fonte, P.; Friese, J.; Fröhlich, I.; Galatyuk, T.; Garzón, J. A.; Gernhäuser, R.; Gil, A.; Gilardi, C.; Göbel, K.; Golubeva, M.; González-Díaz, D.; Guber, F.; Gumberidze, M.; Hennino, T.; Holzmann, R.; Ierusalimov, A.; Iori, I.; Ivashkin, A.; Jurkovic, M.; Kämpfer, B.; Karavicheva, T.; Kirschner, D.; Koenig, I.; Koenig, W.; Kolb, B. W.; Kotte, R.; Krizek, F.; Krücken, R.; Kühn, W.; Kugler, A.; Kurepin, A.; Kurilkin, A.; Kurilkin, P.; Ladygin, V.; Lang, S.; Lange, J. S.; Lapidus, K.; Liu, T.; Lopes, L.; Lorenz, M.; Maier, L.; Mangiarotti, A.; Markert, J.; Metag, V.; Michalska, B.; Michel, J.; Morinière, E.; Mousa, J.; Müntz, C.; Naumann, L.; Otwinowski, J.; Pachmayer, Y. C.; Palka, M.; Parpottas, Y.; Pechenov, V.; Pechenova, O.; Pietraszko, J.; Przygoda, W.; Ramstein, B.; Reshetin, A.; Rustamov, A.; Sadovsky, A.; Salabura, P.; Schmah, A.; Schwab, E.; Sobolev, Y. G.; Spataro, S.; Spruck, B.; Ströbele, H.; Stroth, J.; Sturm, C.; Tarantola, A.; Teilab, K.; Tlusty, P.; Traxler, M.; Trebacz, R.; Tsertos, H.; Wagner, V.; Vasiliev, T.; Weber, M.; Wisniowski, M.; Wojcik, T.; Wüstenfeld, J.; Yurevich, S.; Zanevsky, Y.; Zhou, P.

Baryon resonance production in proton-proton collisions at a kinetic beam energy of 1.25 GeV is investigated. The multi-differential data were measured by the HADES collaboration. Exclusive channels with one pion in the final state (nπ+ and pπ0) were put to extended studies based on various observables in the framework of a one-pion exchange model and with solutions obtained within the framework of a partial wave analysis (PWA) of the Bonn-Gatchina group. The results of the PWA confirm the dominant contribution of the Δ(1232), yet with a sizable impact of the N(1440) and non-resonant partial waves. The obtained resonance production cross sections provide a useful normalization for the further analysis of the Δ+ -> pe+e- Dalitz decay.

Publ.-Id: 22164

Low-Energy Magnetic Radiation

Frauendorf, S.; Beard, M.; Mumpower, M.; Schwengner, R.; Wimmer, K.

A pronounced spike at low energy in the strength function for magnetic radiation (LEMAR) is found by means of Shell Model calculations, which explains the experimentally observed enhancement of the dipole strength. LEMAR originates from statistical low-energy M1-transitions between many excited complex states.
Re-coupling of the proton and neutron high-j orbitals generates the strong magnetic radiation. LEMAR is predicted for nuclides with A ~ 132 participating in the r-process of element synthesis. It increases the reaction rates by a factor of 2.5. The spectral function of LEMAR follows Planck's Law. A power law for the size distribution of the B(M1) values is found.

Keywords: Magnetic dipole radiation; shell model

Publ.-Id: 22163

Poly-disperse simulation of condensing steam-water flow inside a large vertical pipe

Liao, Y.; Lucas, D.

The condensation of saturated steam bubbles in sub-cooled water inside a vertical pipe is studied by poly-disperse CFD simulations. Six test cases with varied pressure, liquid sub-cooling and diameter of the gas injection orifices are investigated. Baseline closures presented for non-drag forces in previous work are found to be reliable also in non-isothermal cases. The effect of bubble coalescence and breakup is negligible in cases with small orifice diameter. The Ranz-Marshall correlation leads to a global under-estimation of the condensation rate, especially at high pressure levels.

Keywords: Poly-disperse; CFD simulation; Condensation; Steam-Water

Publ.-Id: 22162

Experimental and theoretical study on the co-current two-phase downflow regime transition in open solid foam packed reactors

Möller, F.

The main objective of this Diploma thesis was to determine the regime transition between trickling and pulsing flow for solid ceramic foams made of silicium carbid with extra silicium coating (SiSiC). Two pressure transducers were used in order to determine this transition. Additional to the experimental determination, a predictive model was developed after the idea of Grosser et al. (1988) as well as Attou and Ferschneider (2000). Therefore, bed specific parameters (specific surface area, pressure drop parameters, static liquid holdup, porosity of the bed) and fluid specific parameters (gas and liquid density and viscosity, surface tension) had to be known. Since these models were only validated for conventional FBRs with a packing of spheres, modifications have been carried out in order to fit the model to foam related parameters.
In order to describe the regime transition through the models, further experiments had been carried out. The static liquid holdup as well as the singe phase (gas phase) pressure drop were investigated and afterwards modeled though different approaches.
To obtain the influences of changing the surface tension as well as the viscosity on the regime transition, additional experiments with tergitol and glycerin were carried out.
Three different pore sizes (20 PPI, 30 PPI and 45PPI) as well as two different foam diameters (0.05m and 0.1 m) were investigated with two different spray systems. For the change of viscosity and surface tension, only foams with a diameter of 0.1m had been used.

Keywords: Solid foam packing; trickle-bed reactor; flow regime transition; relative permeability concept; static holdup

  • Diploma thesis
    TU Dresden, 2015
    Mentor: Zalucky, J., Schubert, M.
    124 Seiten

Publ.-Id: 22161

Neutron-capture experiment on 77Se with EXILL at ILL Grenoble

Lorenz, C.; John, R.; Massarczyk, R.; Schwengner, R.; Blanc, A.; de France, G.; Jentschel, M.; Köster, U.; Mutti, P.; Simpson, G.; Soldner, T.; Urban, W.; Valenta, S.; Belgya, T.

The neutron capture reaction at 77 Se has been studied with cold neutrons in the course of the EXILL campaign at the high-flux reactor of the Institut Laue-Langevin Grenoble. A simulation of the detector array with Geant4 has been accomplished and evaluated. The detector response has been deduced and measured spectra were unfolded, which have been compared with simulations using γDex to determine strength functions.

Keywords: Neutron capture; gamma-spectroscopy

Publ.-Id: 22160

Investigation of dipole strength up to the neutron separation energy at γELBE

Massarczyk, R.; Schwengner, R.; Bemmerer, D.; Beyer, R.; Hannaske, R.; Junghans, A. R.; Kempe, M.; Kögler, T.; Schramm, G.; Wagner, A.

The bremsstrahlung facility at the ELBE accelerator offers the possibility to investigate dipole strength distributions up to the neutron-separation energies with photon up to 16 MeV in energy. The facility and various results for nuclides measured during recent years are presented. One example is the study of the N = 80 nuclide 136 Ba. The other presented example is the study of the chain of xenon isotopes from N = 70 to N = 80 which aimed to investigate the influence of nuclear deformation an neutron excess on the dipole strength in the pygmy region. An overview of the analysis is given. GEANT4 simulations were performed to determine the non-nuclear background that has to be removed from the measured spectra. This opens up the possibility to take into account also the strength of unresolved transitions. Simulations of gamma-ray cascades were carried out that consider the transitions from states in the quasi-continuum and allow us to estimate their branching ratios. As a result, the photoabsorption cross sections obtained from corrected intensities of ground-state transitions are compared with theoretical predictions and results within the chain of isotopes. With the help of the measured dipole distribution it is possible to describe gamma-ray spectra following neutron capture more precisely.

Keywords: photon scattering; nuclear structure; photon strength

Publ.-Id: 22159

Combined study of the gamma-ray strength function of 114Cd with (n,γ) and (γ,γ’) reactions

Belgya, T.; Massarzyk, R.; Szentmiklósi, L.; Schramm, G.; Schwengner, R.; Junghans, A. R.; Wagner, A.; Grosse, E.

Collaboration on strength function measurements and level density determinations is ongoing between the Budapest Prompt Gamma Neutron Activation Analysis and the ELBE Nuclear Physics groups within the framework of EU FP6 EFNUDAT project. The idea is to prove that good theoretical fits to the measured gamma-ray spectra collected in the (n,γ) and (γ,γ’) reactions can be carried out using common photon strength and level density functions over a wide spectral energy range from 1 to 10 MeV for the same residual nucleus. Here, preliminary results on the isotope pair of 113,114Cd are presented for which the neutron capture state in 114Cd has 1+ or 0+ spin and parity.

Keywords: electromagnetic strength function; neutron capture; resonance fluorescence

Publ.-Id: 22158

Spin decoherence processes in the S=1/2 scalene triangular cluster (Cu3(OH))

Ponomaryov, A. N.; Kim, N.; Jang, Z. H.; van Tol, J.; Koo, H.-J.; Law, J. M.; Suh, B. J.; Yoon, S.; Choi, K. Y.

We report the synthesis and magnetic properties of the molecular cluster Cu33−OH)(μ-OH)(μ-O2Ar4F-Ph)2(py)3(OTf)2, abbreviated as (Cu3(OH)). Using magnetization, electron paramagnetic resonance and spin dimer analysis, we derive a microscopic magnetic model of (Cu3(OH)) and measure the electron T1 and T2 relaxation times. The Cu2+ ions are arranged to form a distorted triangular structure with the three different exchange coupling constants J1 = −43.5 K, J2 = −53.0 K, and J3 = −37.7 K. At T = 1.5 K T1 is of the order of 10−4 s and T2 is evaluated to be 0.26 μs. We find that the temperature dependence of 1/T1 and 1/T2 is governed by Orbach process and spin bath fluctuations, respectively. We discuss the role of spin–phonon mechanism in determining a spin decoherence time in a class of spin triangular clusters.

Publ.-Id: 22157

Paramagnetic moments and time effects in melt-textured NdBaCuO system with Nd422 inclusions

Dias, F. T.; Vieira, V. N.; Silva, D. L.; Wolff-Fabris, F.; Kampert, E.; Almeida, M. L.; Mesquita, F.; Hneda, M.; Roa, J. J.

We have performed magnetic measurements in two melt-textured NdBa2Cu3O7-δ samples with Nd422 inclusions under magnetic fields from 0.05 up to 14 T, applied parallel to the ab planes. The measurements were made with a superconducting quantum interference device (SQUID) and a vibrating sample magnetometer (VSM). Paramagnetic moments could be observed during FCC (field-cooled cooling) and FCW (field-cooled warming) experiments. This effect, known as Paramagnetic Meissner Effect (PME), persisted up to 14 T and strong irreversibilities were observed among FCC and FCW experiments, revealing the presence of time effects. These time effects were confirmed by specific magnetic relaxation experiments in different cooling rates and temperatures, showing an anomalous and curious paramagnetic behavior. We explain our results based on the flux-compressed state generated within nonsuperconducting regions of the sample, such as the Nd422 inclusions dispersed into the superconducting matrix. These inclusions may produce a strong vortex pinning that stabilize the paramagnetic state, allowing the admission of extra vortices into the sample responsible for the positive moments during the relaxation experiments.

Publ.-Id: 22156

Electron-tunneling measurements of low-Tc single-layer Bi2+xSr2−yCuO6+δ: Evidence for a scaling disparity between superconducting and pseudogap states

Jacobs, T.; Katterwe, S. O.; Motzkau, H.; Rydh, A.; Maljuk, A.; Helm, T.; Putzke, C.; Kampert, E.; Kartsovnik, M. V.; Krasnov, V. M.

We experimentally study intrinsic tunneling and high magnetic field (up to 65 T) transport characteristics of the single-layer cuprate Bi2+xSr2−yCuO6+δ, with a very low superconducting critical temperature Tc ≲ 4 K. It is observed that the superconducting gap, the collective bosonic mode energy, the upper critical field, and the fluctuation temperature range are scaling down with Tc, while the corresponding pseudogap characteristics remain the same as in high-Tc cuprates with 20 to 30 times higher Tc. The observed disparity of the superconducting and pseudogap scales clearly reveals their different origins.

Publ.-Id: 22155

Charakterisierung der Oberflächenkomplexe der Oxoanionen von Se(VI) und Tc(VII) an Mineral-Waser Grenzflächen

Foerstendorf, H.; Heim, K.; Franzen, C.; Jordan, N.

79Se und 99Tc sind als Spaltprodukte im nuklearen Brennstoffkreislauf für die Sicherheitsanalyse eines zukünftigen Endlagers von besonderem Interesse. Eine Abschätzung der Migration dieser Elemente im Nah- und Fernfeld eines geologischen Tiefenlagers ist nur möglich auf der Basis der umfassenden Kenntnis der Wechselwirkungen der Spezies mit mineralischen Oberflächen. Insbesondere die Oxoanionen Se(VI)O4 2– und Tc(VII)O4 gelten auf Grund ihrer hohen Löslichkeit und negativen Ladung als besonders mobile Spezies in Aquiferen.
Die Oberflächenreaktionen von in Wasser gelösten Oxoanionen an Mineraloberflächen können mittels in situ Schwingungsspektroskopie dezidiert untersucht werden. Dabei können sowohl die Sorptions- als auch die Desorptionsreaktionen der gelösten Ionen an einer stationären mineralischen Phase in Echtzeit erfasst werden. [1–2]
Für das Selenation wurden an zwei verschiedenen Mineralphasen unterschiedliche Arten von außersphärischen Oberflächenkomplexen gefunden. Obwohl die makroskopischen Eigenschaften dieser Oberflächenkomplexe an beiden Mineralen auf eine außersphärische Anbindung (Physisorption) schließen lassen, zeigen die Infrarotspektren eine signifikant abweichende spektrale Signatur, die nur mit unterschiedlichen Molekülsymmetrien erklärt werden kann. So zeigen die Spektren je nach Mineraloberfläche, dass das Selenat mit einer leicht verzerrten – der aquatischen Spezies sehr ähnlichen – tetraedrischen bzw. mit einer bidendaten C2v Symmetrie an die Oberfläche sorbiert wird. Diese Spezies können demnach als „erweiterte“ bzw. als „klassische“ außersphärische Komplexe bezeichnet werden. [3–4]
Entsprechende Experimente mit dem isostrukturellen Tc(VII)O4 -Anion zeigen, dass auch dieses Ion vorwiegend außersphärische Oberflächenkomplexe an verschiedenen Mineraloberflächen bildet. Dabei weisen die ersten Ergebnisse auf eine geringere Spezifizität des TcO4 bei der Anbindung an die verschiedenen Oberflächen hin.

[1] Foerstendorf, H. et al. (2012) J. Colloid Interface Sci. 377, 299–306. [2] Müller, K. et al. (2015) Environ. Sci. Technol. 49, 2560–2567. [3] Jordan, N. et al. (2011) Geochim. Cosmochim. Acta 75, 1519–1530. [4] Jordan, N. et al. (2013) Geochim. Cosmochim. Acta 103, 63–75.

  • Poster
    GDCh-Wissenschaftsforum Chemie 2015 Chemie verbindet, 30.08.-02.09.2015, Dresden, Deutschland

Publ.-Id: 22154

Sub-pixel resolution with a color X-ray camera

Nowak, S. H.; Bjeoumikhov, A.; von Borany, J.; Buchriegler, J.; Munnik, F.; Petric, M.; Radtke, M.; Renno, A. D.; Reinholz, U.; Scharf, O.; Wedell, R.

The color X-ray camera SLcam® is a full-field, single photon detector providing scanning-free, energy and spatially resolved X-ray imaging. Spatial resolution is achieved with the use of polycapillary optics guiding Xray photons from small regions on a sample to distinct energy dispersive pixels on a charged-coupled device detector. Applying sub-pixel resolution, signals from individual capillary channels can be distinguished. Therefore, the SLcam® spatial resolution, which is normally limited to the pixel size of the charge-coupled device, can be improved to the size of individual polycapillary channels. In this work a new approach to a sub-pixel resolution algorithm comprising photon events also from the pixel centers is proposed. The details of the employed numerical method and several sub-pixel resolution examples are presented and discussed.

Publ.-Id: 22153

Analysis of mononuclear uranyl(VI) hydroxo complexes using TRLFS and PARAFAC

Drobot, B.; Bauer, A.; Steudtner, R.; Tsushima, S.; Raff, J.; Brendler, V.

Speciation analysis of fast equilibrium processes is often challenging. Metal hydrolysis is one example of such a system. It is the basis for more complex aquatic systems and thus a deep understanding of those systems is indispensable. In the case of uranyl(VI) hydrolysis spectroscopic studies are hindered by low solubility over an wide pH range. Additionally occurrence of polynuclear complexes further complicates the system when working close to the solubility limit (e.g. 10-5 M uranyl(VI)). In a previous study we demonstrated that a combination of luminescence spectroscopic methods together with state of the art data analysis (parallel factor analysis; PARAFAC) and quantum chemical calculations is a powerful setup to gain information on that system [1]. Since uranyl(VI) has high affinities to several minerals and biopolymers systems containing trace metal concentrations have to be considered. In the present study we focus on this low concentration range (10-8 M uranyl(VI)).
We were able to extract thermodynamic constants for this system [(UO2(OH)(H2O)4+), (UO2(OH)2(H2O)3), (UO2(OH)3(H2O)2-)] using optimized data processing. Furthermore, advanced deconvolution of individual luminescence spectra demonstrates the correlation of luminescence spectroscopy and vibrational spectroscopy. Raman frequencies result from symmetrical stretching of the uranyl(VI) unit. We could show that features of individual emission spectra are separated by the same energy. Thus a further luminescence signal to chemical structure correlation is demonstrated which was missing for that system.

  • Poster
    GDCh-Wissenschaftsforum Chemie 2015, 30.08.-02.09.2015, Dresden, Deutschland

Publ.-Id: 22152

Repeatability of tumor SUV quantification: the role of variable blood SUV

van den Hoff, J.; Hofheinz, F.

kein Abstract verfügbar

Publ.-Id: 22151

Novel (pyrazolyl)benzenesulfonamides with a nitric oxide-releasing moiety as selective cyclooxygenase-2 inhibitors

Bechmann, N.; Kniess, T.; Köckerling, M.; Pigorsch, A.; Steinbach, J.; Pietzsch, J.

Inhibition of cyclooxygenase-2 (COX-2) is a promising anti-inflammatory therapeutic strategy, but longterm medication with COX-2-inhibitors (coxibs) may be associated with adverse cardiovascular effects. Functionalization of existing lead structures with nitric oxide (NO)-releasing moieties is an auspicious approach to minimize these effects. In this regard, an organic nitrate (–O–NO2) substituent was introduced at a (pyrazolyl)benzenesulfonamide lead structure. The novel NO-coxibs selectively inhibited COX-2 in a low micromolar range (IC50(COX-2): 0.22–1.27 lM) and are supposed to be promising antiinflammatory compounds with, in parallel, positive effects on vascular homeostasis.

Keywords: Anti-inflammatory therapy; Cardiovascular side effects; Celecoxib; Direct/indirect NO coupling; Griess assay; Organic nitrate

Publ.-Id: 22150

Rational design of dual peptides targeting ghrelin and Y2 receptors to regulate food intake and body weight

Kilian, T. M.; Klöting, N.; Bergmann, R.; Els-Heindl, S.; Babilon, S.; Clément-Ziza, M.; Zhang, Y.; Beck-Sickinger, A. G.; Chollet, C.

Ghrelin and Y2 receptors play a central role in appetite regulation inducing opposite effects. The Y2 receptor induces satiety, while the ghrelin receptor promotes hunger and weight gain. However, the food regulating system is tightly controlled by interconnected pathways where redundancies can lead to poor efficacy and drug tolerance when addressing a single molecule. We developed a multitarget strategy to synthesize dual peptides simultaneously inhibiting the ghrelin receptor and stimulating the Y2 receptor. Dual peptides showed dual activity in vitro, and one compound induced a slight diminution of food intake in a rodent model of obesity. In addition, stability studies in rats revealed different behaviors between the dual peptide and its corresponding monomers. The Y2 receptor agonist was unstable in blood, while the dual peptide showed an intermediate stability compared to that of the highly stable ghrelin receptor inverse agonist.

Publ.-Id: 22149

On the relation between Kaiser-Bessel blob and tube of response based modelling of the system matrix in iterative PET image reconstruction

Lougovski, A.; Hofheinz, F.; Maus, J.; Schramm, G.; van den Hoff, J.

We investigate the question of how the blob approach is related to tube of response based modelling of the system matrix. In our model, the tube of response (TOR) is approximated as a cylinder with constant density (TOR-CD) and the cubic voxels are replaced by spheres. Here we investigate a modification of the TOR model that makes it effectively equivalent to the blob model, which models the intersection of lines of response (LORs) with radially variant basis functions ('blobs') replacing the cubic voxels. Implications of the achieved equivalence regarding the necessity of final resampling in blob-based reconstructions are considered. We extended TOR-CD to a variable density tube model (TOR-VD) that yields a weighting function (defining all system matrix elements) which is essentially identical to that of the blob model. The variable density of TOR-VD was modelled by a Gaussian and a Kaiser-Bessel function, respectively. The free parameters of both model functions were determined by fitting the corresponding weighting function to the weighting function of the blob model. TOR-CD and the best-fitting TOR-VD were compared to the blob model with a final resampling step (BLOB-RS) and without resampling (BLOB-NRS) in phantom studies. For three different contrast ratios and two different voxel sizes, resolution noise curves were generated. TOR-VD and BLOB-NRS lead to nearly identical images for all investigated contrast ratios and voxel sizes. Both models showed strong Gibbs artefacts at 4 mm voxel size, while at 2 mm voxel size there were no Gibbs artefacts visible.
The spatial resolution was similar to the resolution with TOR-CD in all cases. The resampling step removed most of the Gibbs artefacts and reduced the noise level but also degraded the spatial resolution substantially. We conclude that the blob model can be considered just as a special case of a TOR-based reconstruction. The latter approach provides a more natural description of the detection process and allows for modifications that are not readily representable within the blob framework.

Publ.-Id: 22148

Positron-Annihilation Lifetime Spectroscopy using Electron Bremsstrahlung

Wagner, A.; Anwand, W.; Butterling, M.; Cowan, T. E.; Fiedler, F.; Fritz, F.; Kempe, M.; Krause-Rehberg, R.

A new type of an intense source of positrons for materials research has been set up at the superconducting electron linear. The source employs hard X-rays from electron-bremsstrahlung production generating energetic electron-positron pairs inside the sample under investigation. CW-operation allows performing experiments with significantly reduced pile-up artefacts in the detectors compared to pulsed mode operation in conventional accelerators. The high-resolution timing of the accelerator with bunch lengths below 10 ps full width at half maximum (FWHM) allows positron annihilation lifetime spectroscopy (PALS) measurements with high time resolution. A single-component annihilation lifetime of Kapton has been measured as (381.3 ± 0.3) ps. Employing segmented detectors for the detection of both annihilation photons allows for the first time to perform a 4D tomographic reconstruction of the annihilation sites including the annihilation lifetime.

Keywords: positrons materials research ELBE linac superconducting tomography

Publ.-Id: 22147

Response of Multi-Strip Multi-gap Resistive Plate Chamber

Datta, U.; Chakraborty, S.; Rahaman, A.; Basu, P.; Basu, J.; Bemmerer, D.; Boretzky, K.; Elekes, Z.; Kempe, M.; Münzenberg, G.; Simon, H.; Sobiella, M.; Stach, D.; Wagner, A.; Yakorev, D.

A prototype of Multi-strip Multi-gap Resistive Plate chamber (MMRPC) with active area 40 cm x 20 cm has been developed at SINP, Kolkata. Detailed response of the developed detector was studied with the pulsed electron beam from ELBE at Helmholtz-Zentrum Dresden-Rossendorf. In this report the response of SINP developed MMRPC with different controlling parameters is described in details. The obtained time resolution of the detector after slew correction was 91.5 +- 3 ps. Position resolution measured along x and across y the strip was 2.8+-0.6 cm and 0.58 cm, respectively. The measured absolute efficiency of the detector for minimum ionizing particle like electron was 95.8+-1.3 %. Better timing resolution of the detector can be achieved by restricting the events to a single strip. The response of the detector was mainly in avalanche mode but a few percentage of streamer mode response was also observed. A comparison of the response of these two modes with trigger rate was studied.

Keywords: Multi-strip Multi-gap Resistive Plate chamber (MMRPC) ELBE

Publ.-Id: 22146

Combined phase distribution and particle velocity measurement in spout fluidized beds by ultrafast X-ray computed tomography

Bieberle, M.; Barthel, F.

The spout fluidized bed is a very successful combination of spouted and fluidized bed, which is most interesting for processing particles with larger or varying diameter. However, the more complex hydrodynamics of the combined configuration is yet not fully understood. Here, we propose the application of ultrafast X-ray computed tomography (CT), which has proven to be a valuable measurement technique for the analysis of highly dynamic processes, for example multiphase flows. It is able to resolve material distributions with up to 8,000 frames per second and a spatial resolution down to 1 mm. Especially for opaque systems, such as fluidized beds, ultrafast X-ray CT can reveal details, which are not recoverable by e.g. optical measurement techniques. Besides the recovering of the dynamic phase distribution, determining local particle velocities is essential to understand the complex flow in fluidized beds. As we will demonstrate here for the first time, this is possible via a dual-plane ultrafast X-ray CT by using suitable marker particles. In this article, the methodology for determining particle velocities under highly dynamic conditions within a cylindrical spout fluidized bed is presented. Complementary analysis techniques for different flow conditions have been combined to increase confidence in the velocity data.

Keywords: velocity; spout fluidized bed; ultrafast; X-ray; computed tomography

Publ.-Id: 22142

Coulomb Dissociation Experiment of P-27

Marganiec, J.; Beceiro-Novo, S.; Typel, S.; Wimmer, C.; Alvarez-Pol, H.; Aumann, T.; Boretzky, K.; Casarejos, E.; Chatillon, A.; Cortina Gil, D.; Datta-Pramanik, U.; Elekes, Z.; Fulop, Z.; Galaviz, D.; Geissel, H.; Giron, S.; Greife, U.; Hammache, F.; Heil, M.; Hoffman, J.; Johansson, H.; Kiselev, O.; Kurz, N.; Larsson, K.; Le Bleis, T.; Litvinov, Y.; Mahata, K.; Muentz, C.; Nociforo, C.; Ott, W.; Paschalis, S.; Plag, R.; Prokopowicz, W.; Rodriguez Tajes, C.; Rossi, D.; Simon, H.; Stanoiu, M.; Stroth, J.; Sümmerer, K.; Wagner, A.; Wamers, F.; Weick, H.

The 26Si(p;gamma)27P reaction, which might play an important role in the rp process, was studied by the Coulomb Dissociation method. The experiment was performed at GSI, Darmstadt. A secondary 27P ion beam of 500 MeV/nucleon was directed onto a Pb target. From this experiment, the Coulomb Dissociation cross section will be deduced and then converted to the photoabsorption cross section, and the radiative-capture cross section. Also information on the structure of 27P will be obtained. The analysis is in progress.

Keywords: Coulom dissociation; radiative-capture; radioactive beams

Publ.-Id: 22141

Depth-resolved slow positron beam analysis of ECR proton and argon implanted graphite and boron nitride system

Ganguly, B. N.; Menon, R.; Yalagoud, N. P.; Bandyopadhyay, S. K.; Anwand, W.; Brauer, G.

Layered materials and sp2 hybridized structures like graphite and hexagonal-boron nitride (h-BN) have been subjected to electron cyclotron resonance (ECR) ion beam implantation of proton and argon ions at different fluences and studied primarily employing slow positron beam technique using positron annihilation Doppler broadening spectroscopy (DBS). The results show remarkable structural perturbation effects in the implantation areas around the depth of 200–300 nm from the top surface, in both the systems but with glaring differences in the trends of the line shape analysis in terms of S and W parameters. Due to proton and argon ion implantation, structurally damaged lattice with open volume defects exists in graphite. But, for both the ion implantations at the high fluence, profound clustering effect of the respective atoms within the interstitial space are evident in h-BN. The structural effects of both graphite and h-BN lattice after the said implantation have been studied and corroborated through grazing incidence X-ray diffraction (GI-Xray) method and Raman scattering spectroscopy as complementary analytical techniques.

Keywords: BN; graphite; grazing incidence X-ray diffraction; positron beams; Raman spectroscopy; slow positrons

Publ.-Id: 22140

How radio-ecological research helps to develop innovative nanobiomaterials

Raff, J.; Weinert, U.; Matys, S.; Vogel, M.; Suhr, M.; Günther, T.; Drobot, B.; Lehmann, F.; Kutschke, S.; Pollmann, K.

The presentation introduces the Institute of Resource Ecology and the Helmholtz Institute Freiberg for Resource Technology and provides an insight into the work of the Biotechnology Group.

Keywords: radio-ecology; resource technology; nano-biotechnology

  • Lecture (others)
    Arbeitskreisseminar Technische Chemie, 03.07.2015, Paderborn, Deutschland

Publ.-Id: 22139

Investigating hadronic resonances in pp interactions with HADES

Przygoda, W.; Adamczewski-Musch, J.; Arnold, O.; Atomssa, E. T.; Behnke, C.; Berger-Chen, J. C.; Biernat, J.; Blanco, A.; Blume, C.; Böhmer, M.; Bordalo, P.; Chernenko, S.; Deveaux, C.; Dybczak, A.; Epple, E.; Fabbietti, L.; Fateev, O.; Fonte, P.; Franco, C.; Friese, J.; Fröhlich, I.; Galatyuk, T.; Garzón, J. A.; Gill, K.; Golubeva, M.; Guber, F.; Gumberidze, M.; Harabasz, S.; Hennino, T.; Hlavac, S.; Höhne, C.; Holzmann, R.; Ierusalimov, A.; Ivashkin, A.; Jurkovic, M.; Kämpfer, B.; Karavicheva, T.; Kardan, K.; Koenig, I.; Koenig, W.; Kolb, B. W.; Korcyl, G.; Kornakov, G.; Kotte, R.; Krása, A.; Krebs, E.; Kuc3, H.; Kugler, A.; Kunz, T.; Kurepin, A.; Kurilkin, A.; Kurilkin, P.; Ladygin, V.; Lalik, R.; Lapidus, K.; Lebedev, A.; Lopes, L.; Lorenz, M.; Mahmoud, T.; Maier, L.; Mangiarotti, A.; Markert, J.; Metag, V.; Michel, J.; Müntz, C.; Münzer, R.; Naumann, L.; Palka, M.; Parpottas, Y.; Pechenov, V.; Pechenova, O.; Petousis, V.; Pietraszko, J.; Ramstein, B.; Rehnisch, L.; Reshetin, A.; Rost, A.; Rustamov, A.; Sadovsky, A.; Salabura, P.; Scheib, T.; Schmidt-Sommerfeld, K.; Schuldes, H.; Sellheim, P.; Siebenson, J.; Silva, L.; Sobolev, Y. G.; Spataro, S.; Ströbele, H.; Stroth, J.; Strzempek, P.; Sturm, C.; Svoboda, O.; Tarantola, A.; Teilab, K.; Tlusty, P.; Traxler, M.; Tsertos, H.; Vasiliev, T.; Wagner, V.; Wendisch, C.; Wirth, J.; Wüstenfeld, J.; Zanevsky, Y.; Zumbruch, P.

In this paper we report on the investigation of baryonic resonance production in proton-proton collisions at the kinetic energies of 1.25 GeV and 3.5 GeV, based on data measured with HADES. Exclusive channels npπ+ and ppπ0 as well as ppe+e− were studied simultaneously in the framework of a one-boson exchange model. The resonance cross sections were determined from the one-pion channels for Δ(1232) and N(1440) (1.25 GeV) as well as further Δ and N* resonances up to 2 GeV/c2 for the 3.5 GeV data. The data at 1.25 GeV energy were also analysed within the framework of the partial wave analysis together with the set of several other measurements at lower energies. The obtained solutions provided the evolution of resonance production with the beam energy, showing a sizeable non-resonant contribution but with still dominating contribution of Δ(1232)P33. In the case of 3.5 GeV data, the study of the ppe+e− channel gave the insight on the Dalitz decays of the baryon resonances and, in particular, on the electromagnetic transition form-factors in the time-like region. We show that the assumption of a constant electromagnetic transition form-factors leads to underestimation of the yield in the dielectron invariant mass spectrum below the vector mesons pole. On the other hand, a comparison with various transport models shows the important role of intermediate ρ production, though with a large model dependency. The exclusive channels analysis done by the HADES collaboration provides new stringent restrictions on the parameterizations used in the models.

Publ.-Id: 22138

Specific binding biomolecules

Raff, J.; Weinert, U.; Matys, S.; Vogel, M.; Suhr, M.; Günther, T.; Hofinger, J.; Drobot, B.; Lehmann, F.; Kutschke, S.; Pollmann, K.

During evolution nature has evolved different kinds of specific binding macro-molecules being crucial for cell metabolism and their interaction with the environment. Most important examples therefore are proteins and nucleic acids. But beside biogenic molecules, specific proteins and nucleic acids can also be selected by doing an in vitro evolution using large molecule libraries. In this way specific ligands for various targets can be obtained allowing the development of new materials for different industrial applications.

Keywords: Sepcific binding; proteins; peptides; aptamers

  • Invited lecture (Conferences)
    Professur-Seminar Biomaterialien, 01.07.2015, Dresden, Deutschland

Publ.-Id: 22137

Developed turbulence and nonlinear amplification of magnetic fields in laboratory and astrophysical plasmas

Meinecke, J.; Tzeferacos, P.; Bell, A.; Bingham, R.; Clarke, R.; Churazov, E.; Crowston, R.; Doyle, H.; Drake, R. P.; Heathcote, R.; Koenig, M.; Kuramitsu, Y.; Kuranz, C.; Lee, D.; Macdonald, M.; Murphy, C.; Notley, M.; Park, H.-S.; Pelka, A.; Ravasio, A.; Reville, B.; Sakawa, Y.; Wan, W.; Woolsey, N.; Yurchak, R.; Miniati, F.; Schekochihin, A.; Lamb, D.; Gregori, G.

The visible matter in the universe is turbulent and magnetized. Turbulence in galaxy clusters is produced by mergers and by jets of the central galaxies and believed responsible for the amplification of magnetic fields. We report on experiments looking at the collision of two laser-produced plasma clouds, mimicking, in the laboratory, a cluster merger event. By measuring the spectrum of the density fluctuations, we infer developed, Kolmogorov-like turbulence. From spectral line broadening, we estimate a level of turbulence consistent with turbulent heating balancing radiative cooling, as it likely does in galaxy clusters. We show that the magnetic field is amplified by turbulent motions, reaching a nonlinear regime that is a precursor to turbulent dynamo. Thus, our experiment provides a promising platform for understanding the structure of turbulence and the amplification of magnetic fields in the universe.

Keywords: galaxy clusters; laboratory analogues; lasers; magnetic fields; turbulence

  • Proceedings of the National Academy of Sciences of the United States of America 112(2015)27, 8211-8215
    DOI: 10.1073/pnas.1502079112

Publ.-Id: 22136

Retention of trivalent Actinides by structural Incorporation

Schmidt, M.; Peschel, S.; Hofmann, S.; Walther, C.; Bosbach, D.; Stumpf, T.

The incorporation of radionuclides into a host mineral’s crystal structure is a particularly efficient means of retention, due to the fact that the incorporated radionuclide is removed from the water path. The process is relevant, both, naturally occurring under repository conditions[1], and as a technical means for the sequestration of actinide waste streams. Consequently, it is of utmost importance to understand the processes leading up to the incorporation, as well as the structural properties of the formed solid solution at the molecular level[2].
We will give an overview on the incorporation of trivalent actinides and lanthanides into Ca- and Ln-bearing mineral phases of technical and geochemical relevance. The minor actinides dominate the radiotoxicity in a nuclear waste storage site over hundreds of thousands of years. For Am and Cm the trivalent oxidation states is the only relevant oxidation in aqueous solutions, and even Pu may be present as Pu(III) under reducing repository conditions. The trivalent actinides have ionic radii closely matched to their lanthanides homologues as well as calcium, making mineral phases with these host cations ideal matrices for the incorporation of the trivalent minor actinides.
To identify and characterize actinides in solid solutions at the trace concentration level, we make use of time-resolved laser fluorescence spectroscopy (TRLFS). TRLFS allows for speciation of Cm(III) at concentrations below 10-9 mol/L, or 1 ppm in the solid state. Cm TRLFS can be complemented by experiments with Eu(III), which, while less sensitive, are more sensitive to changes in the local coordination geometry of the fluorescent probe.
An overview will be given on the characterization of solid solutions of secondary phases relevant under repository conditions. We will compare a phase formed close to equilibrium (calcite) with a metastable phase undergoing a phase transition (vaterite[3]), as well as a phase from high-temperature synthesis (powellite[4]). The effect of various reaction parameters on the reactions, and their implications for the stability of the formed solid solutions, and hence the retention of the radionuclides will be discussed.
[1] T. Stumpf and Th. Fanghänel, J. Colloid Interf. Sci. 249, 119 (2002).
[2] H. Geckeis, et al., Chem. Rev. 113, 1016 (2013).
[3] M. Schmidt, et al., J. Colloid Interf. Sci. 351, 50 (2010).
[4] M. Schmidt, et al., Dalton Trans. 42, 8387 (2013).

Keywords: acitnides; solid solutions; TRLFS; calcite

  • Poster
    MIGRATION 2015: 15th International Conference on the Chemistry and Migration Behaviour of Actinides and Fission Products in the Geosphere, 13.-18.09.2015, Santa Fe, USA

Publ.-Id: 22135

Recycling of magnesium chips

Ohmann, S.; Ditze, A.; Scharf, C.

Magnesium chips were processed by means of re-melting. An important requirement of re-melting the chips is the removal of oil and moisture. The results show that using acetone in a soxhlet as an organic solvent is a more efficient method to obtain good results compared to vacuum distillation with a rotational evaporator. The subsequent re-melting has been successfully performed without the addition of flux between temperatures of 580 °C and 600°C. At this temperature range, the exothermic reaction of magnesium with the oxygen present in the surrounding atmosphere was avoided. Results show that more than 95 % of the magnesium chips were able to be recovered as metal. Experiments were performed at different scales to obtain production parameters for the recycling process. Larger particle size of magnesium chips were able to be faster remelted than the smaller ones. In the case of added lime for oil removal, the yield of recovered magnesium was lower due to the reaction towards magnesium foam. The ability of re-melting at low temperatures without the need for flux demonstrates the possibility of recovering virtually all of the metal from the chips.

Keywords: Magnesium; Chips; Recycling; Remelting; Analysis

  • Contribution to proceedings
    European Metallurgical Conference, 14.-17.06.2015, Düsseldorf, Germany
    EMC 2015 Volume 1: GDMB Verlag GmbH, 978-3-940276-61-2, 429-442

Publ.-Id: 22134

Understanding Cu mobilisation from Kupfershale leaching: [64Cu]CuS: Ligand identification, kinetic rates and modelling Preliminary Results.

Lippmann-Pipke, J.; Barthen, R.; Gründig, M.; Karimzadeh, L.; Schössler, C.; Mansel, A.; Grenzer, J.; Scholz, A.; Bischoff, L.; Schymura, S.; Kulenkampff, J.; Franke, K.; Lippold, H.

Es ist kein Abstract vorhanden.

  • Poster
    General Meeting 3, Ecometals, 23.-24.06.2015, Halle/Saale, Deutschland

Publ.-Id: 22133

Liquid phase epitaxy of binary III-V nanocrystals in thin Si layers triggered by ion implantation and flash lamp annealing

Wutzler, R.; Rebohle, L.; Prucnal, S.; Bregolin, F.; Hübner, R.; Voelskow, M.; Helm, M.; Skorupa, W.

The integration of III-V compound semiconductors in Si is a crucial step towards faster and smaller devices in future technologies. In this work, we investigate the formation process of III-V compound semiconductor nanocrystals, namely, GaAs, GaSb, and InP, by ion implantation and sub-second flash lamp annealing in a SiO2/Si/SiO2 layer stack on Si grown by plasma-enhanced chemical vapor deposition. Raman spectroscopy, Rutherford Backscattering spectrometry, and transmission electron microscopy were performed to identify the structural and optical properties of these structures. Raman spectra of the nanocomposites show typical phonon modes of the compound semiconductors. The formation process of the III-V compounds is found to be based on liquid phase epitaxy, and the model is extended to the case of an amorphous matrix without an epitaxial template from a Si substrate. It is shown that the particular segregation and diffusion coefficients of the implanted group-III and group-V ions in molten Si significantly determine the final appearance of the nanostructure and thus their suitability for potential applications.

Keywords: ion implantation; flash lamp annealing; III-V integration into silicon; nanostructure; liquid phase epitaxy; compound semiconductor

Publ.-Id: 22132

Flash-Enhanced Atomic Layer Deposition: Basics, Opportunities, Review, and Principal Studies on the Flash-Enhanced Growth of Thin Films

Henke, T.; Knaut, M.; Hossbach, C.; Geidel, M.; Rebohle, L.; Albert, M.; Skorupa, W.; Bartha, J.

Within this work, flash lamp annealing (FLA) is utilized to thermally enhance the film growth in atomic layer deposition (ALD). First, the basic principles of this flash-enhanced ALD (FEALD) are presented in detail, the technology is reviewed and classified. Thereafter, results of our studies on the FEALD of aluminum-based and ruthenium thin films are presented. These depositions were realized by periodically flashing on a substrate during the precursor exposure. In both cases, the film growth is induced by the flash heating and the processes exhibit typical ALD characteristics such as layer-by-layer growth and growth rates smaller than one angstrom/cycle. The obtained relations between process parameters and film growth parameters are discussed with the main focus on the impact of the FLA-caused temperature profile on the film growth.

Similar, substrate-dependent growth rates are attributed to the different optical characteristics of the applied substrates. Regarding the ruthenium deposition, a single-source process was realized. It was also successfully applied to significantly enhance the nucleation behavior in order to overcome substrate-inhibited film growth. Besides, this work addresses technical challenges for the practical realization of this film deposition method and demonstrates the potential of this technology to extend the capabilities of thermal ALD.

Keywords: flash lamp annealing; atomic layer deposition

Publ.-Id: 22131

Uranyl(VI) hydrolysis studied by luminescence spectroscopy

Drobot, B.; Steudtner, R.; Raff, J.; Brendler, V.; Geipel, G.; Tsushima, S.

Speciation constitutes the basis for actinide complexation studies. These systems can be very complex and challenging especially because of the polynuclear species. An advanced combination of theoretical and experimental methods is proposed here. Continuous wave (CW) and time-resolved laser-induced fluorescence spectroscopy (TRLFS) data of uranyl(VI) hydrolysis were analyzed using parallel factor analysis (PARAFAC). Distribution patterns of five major species were thereby derived under a fixed uranyl concentration (10-5) over a wide pH range from 2 to 11. UV (180 nm to 370 nm) excitation spectra were extracted for individual species. Time-dependent density functional theory (TD-DFT) calculations revealed ligand excitation (water, hydroxo, oxo) in this region and ligand-to-metal charge transfer (LMCT) responsible for luminescence. Thus excitation in the UV is extreme ligand sensitive and highly specific. Combining findings from PARAFAC and DFT the [UO2(H2O)5]2+ cation (aquo complex, 1:0) and four hydroxo complexes (1:1, 3:5, 3:7 and 1:3) were identified. Refined structural and thermodynamical data of uranyl(VI) hydrolysis is thus acquired.

  • Poster
    Second Joint Student Workshop on f-Element Chemistry, 09.-10.06.2015, Karlsruhe, Deutschland

Publ.-Id: 22130

Mikoskopische Lithiumverteilung in Pfadfinder-Mineralien

Neri, G.; Gernhäuser, R.; Lichtinger, J.; Renno, A. D.; Rugel, G.; Kudejova, P.; Revay, S.; Winkler, S.; Seiler, D.; Bendel, M.

Keywords: FRM II; Prompte Neutronenaktivierung; Lithium

  • Poster
    Tag der Physikerinnen, 23.06.2015, Garching, Deutschland

Publ.-Id: 22129

Flow regime transition in open-cell solid foam packed reactors: Adaption of the relative permeability concept and experimental validation

Zalucky, J.; Möller, F.; Schubert, M.; Hampel, U.

The trickle-to-pulse flow regime transition in silicon-infiltrated silicon carbide (SiSiC) foam packed fixed bed reactors has been investigated. Based on the film stability concepts of Grosser et al.1 (DOI: 10.1002/aic.690341111) as well as Attou and Ferschneider2 (DOI: 10.1016/S0009-2509(99)00344-9), two predictive models have been adapted to foams’ specific geometric parameters. To account for the different nature of solid foams and their interactions with various fluids, the fixed bed characteristics (specific surface area and bed porosity) and fluid specific parameters (gas and liquid density, liquid viscosity, surface tension) have been incorporated in the model. Ergun parameters and static liquid holdup which are required for the modelling of the prevailing tractive forces were determined experimentally.
The modelling results were compared to regime transition measurements performed for SiSiC solid foams with different linear pore densities (20, 30 and 45 PPI), for different reactor diameters (50 and 100 mm) and initial liquid distributors (spray cone nozzle and multipoint distributor) as well as liquids with various physicochemical properties (water, Tergitol®, 50% glycerin) under ambient operating conditions. Compared to conventional random fixed bed reactors, the onset of pulsing in solid foam packed fixed beds is significantly shifted towards larger liquid and gas fluxes allowing high throughputs in the trickle regime. Moreover, the homogeneity of initial liquid distribution strongly affects the trickle-to-pulse flow transition.

Keywords: Solid foam packing; trickle-bed reactor; flow regime transition; relative permeability concept; static holdup

Publ.-Id: 22128

Mineralogical investigations of agates from Cordón de Lila, Chile

Richter, S.; Götze, J.; Niemeyer, H.; Möckel, R.

In the present study a first found of agates in Chile is reported from the Cordón de Lila region in northern Chile. The agates occur as veins and lenses in altered Permian volcanic rocks. The rock composition is rhyodacitic/dacitic consisting of a fine-grained K-feldspar-quartz groundmass with phenocrysts of plagioclase (An50-60) and pyroxene (augite). The volcanic host rocks show strong features of alteration and brecciation.
Results of XRD, polarizing microscopy and cathodoluminescence (CL) microscopy and spectroscopy point to a late- to postvolcanic formation of the agates by hydrothermal fluids and SiO2 which was released during the alteration of unstable minerals and volcanic glass. Strongly varying agate micro-textures and the appearance of euhedral quartz crystals with μm-sized growth lamellae (so called Bambauer quartz) indicate fluctuations in the physico-chemical conditions (SiO2 concentration, pH) during alteration and agate formation. Another indication for the alteration processes is the occurrence of secondary calcite in the agate-bearing rocks.

Publ.-Id: 22127

XAS and XMCD studies of magnetic properties modifications of Pt/Co/Au and Pt/Co/Pt trilayers induced by Ga+ ions irradiation

Mazalski, P.; Sveklo, I.; Kurant, Z.; Ollefs, K.; Rogalev, A.; Wilhelm, F.; Fassbender, J.; Baczewski, L.; Wawro, A.; Maziewski, A.

Magnetic and magneto-optical properties of Pt/Co/Au and Pt/Co/Pt trilayers subjected to 30 keV Ga+ ion irradiation are compared. In two-dimensional maps of these properties as a function of cobalt thickness and ion fluence, two branches with perpendicular magnetic anisotropy (PMA) for Pt/Co/Pt trilayers are well distinguished. The replacement of the Pt capping layer with Au results in the two branches still being visible but the in-plane anisotropy for the low-fluence branch is suppressed whereas the high-fluence branch displays PMA. The X-ray absorption spectra and X-ray magnetic circular dichroism (XMCD) spectra are discussed and compared with non-irradiated reference samples. The changes of their shapes and peak amplitude, particularly for the high-fluence branch, are related to the modifications of the local environment of Co(Pt) atoms and the etching effects induced by ion irradiation. Additionally, in irradiated trilayers the XMCD measurements at the Pt L-2,L-3-edge reveal an increase of the magnetic moment induced in Pt atoms.

Publ.-Id: 22126

P1317 - Vorrichtung und Verfahren zur Gewinnung von 2- und 3-wertigen Metallionen aus primären und sekundären Rohstoffen mit Hilfe von mikrobiellen Metaboliten

Gutzmer, J.; Kutschke, S.; Pollmann, K.; Raff, J.

Die vorliegende Erfindung betrifft eine Vorrichtung und ein Verfahren zur Gewinnung von Metallen aus primären und sekundären Rohstoffen, basierend auf der Nutzung von organischen Säuren und anderen mikrobiellen Metaboliten.
Die Gewinnung von 2- und/oder 3-wertigen Metallionen erfolgt aus primären und/oder sekundären Rohstoffen, erfolgt mittels einer Vorrichtung mit zwei Kompartimenten. Das erste Kompartiment enthält ein heterogenes Gemisch aus einem oder mehreren primären und/oder sekundären Rohstoffen mit einer wässrigen Lösung. Das zweite Kompartiment ist vom ersten Kompartiment durch eine Membran abgetrennt und enthält Mikroorganismen oder einen Kulturüberstand oder einen oder mehrere Komplexbildner.

  • Patent
    DE102013226042 - Offenlegung 18.06.2015, Nachanmeldung: WO, EP

Publ.-Id: 22125

Kinematic dynamos resulting from the interaction of high permeability material and flows of liquid sodium

Giesecke, A.; Stefani, F.

We perform numerical simulations of the dynamo effect driven by various flow fields of a conducting liquid interacting with "magnetic material" characterized by a large relative permeability. The examinations are motivated by the key role of soft iron impellers for the Von-Kármán-Sodium (VKS) dynamo [1] and by the repeatedly expressed idea to make use of Oxide Dispersion Strengthened (ODS) ferritic/martensitic alloys in the core of a fast reactor which may exhibit a permeability much larger than one [2].

The results of our simulations that consider a localized distribution with finite permeability clearly differ from computations using simplyfying pseudo-vacuum boundary conditions (vanishing tangential field conditions) in order to mimic the impact of infinite permeability. Our kinematic simulations of an axisymmetric model of the VKS dynamo show a close connection between the exclusive occurrence of dynamo action in the presence of soft iron impellers and the observed axisymmetry of the magnetic field [3]. We qualitatively explain this effect by paramagnetic pumping at the fluid-disk interface and propose a simplified analytical model that quantitatively reproduces numerical results. In order to fully explain the observation of growing magnetic fields in the VKS dynamo we resort to mean-field dynamo theory [4] in terms of an α-effect caused by helical outflows between adjacent blades attached to the impeller disks.

In order to examine the properties of the α- and β-effect (which is closely related to the turbulent diffusivity) under influence of magnetic material [5] we use an idealized helical flow field (a modified Roberts flow). We compute the mean-field coefficients using the test-field method [6] and proof that the corresponding mean-field models are indeed capable to reproduce growth-rates and principle field structure of the fully resolved model by requiring much less computational efforts.

Further remarkable results are the observed reduction of the critical magnetic Reynolds number by roughly 30 percent independently of configuration or flow geometry when the permeability is sufficiently large. However, this universality is not reflected in the behavior of the mean-field coefficients. In particular, the β-effect strongly depends on the geometry and the permeability. A striking feature is the occurrence of negative β which has previously been observed in simulations [7] and, more recently, in experiments [8].

Our results for the mean-field coefficients allow the development of dynamo models for nearly arbitrary systems of various sizes consisting of a large number of helical small scale flow cells embedded into some large flow structure.

[1]Monchaux, R. et al., Phys. Rev. Lett. 98 (2007), 044502
[2]Dubuisson, P., de Carlan, Y., Garat, V. and Blat, M., J. Nucl. Mater. 428 (2012), 6–12
[3]Giesecke, A. et al., New J. Phys. 14 (2012), 053005
[4]Krause, F. and Rädler, K.-H. Mean-field Magnetohydrodynamics and dynamo theory, Pergamon Press 1980
[5]Giesecke, A. et al., New J. Phys. 16 (2014), 073034
[6]Schrinner, M. et al., Astron. Nachr. 326 (2005), 245-249
[7]Rädler, K.-H. and Brandenburg, A., Phys. Rev. E 67 (2003), 026401
[8]Frick, P., Noskov, V., Denisov, S. and Stepanov ,R., Phys. Rev. Lett. 105 (2010), 184502

Keywords: dynamo

  • Lecture (Conference)
    Russian Conference on Magnetohydrodynamics, 22.-25.06.2015, Perm, Russia

Publ.-Id: 22124

Influence of calcium on the uranium(VI) interaction with mineral surfaces

Richter, C.; Brendler, V.; Steudtner, R.; Drobot, B.

Many minerals have a strong tendency to sorb ions from the surrounding environment. An understanding of this process allows a realistic prediction of distribution and transport of the elements in nature. In case of uranium this is of high importance with respect to former mining sites or envisaged deposits. In this work, sorption of uranium(VI) onto orthoclase and muscovite, representing important components (feldspars and micas) of the earth crust, was investigated in absence and presence of calcium under aerobic conditions.
Batch experiments with both minerals were performed as triplicates in 0.01 M NaClO4 in the pH range of 5 to 8, with solid-to-liquid ratios of 1/20 and 1/80 g/mL, uranium concentrations of 10-5 and 10-6 M, with and without 1.5×10-3 M Ca. Furthermore time-resolved laser-induced fluorescence spectroscopy (TRLFS) was performed at batch samples with orthoclase (pH 4 to 9, with 10-5 M U and 1.5×10-3 M Ca). There, the aquatic solutions as well as the mineral suspensions were investigated as described in [1].
Uranium sorption shows its maximum at circumneutral pH values. At pH ≥ 8 in presence of calcium a reduced uranium(VI) sorption was observed which is due to the formation of the non-sorbing neutral Ca2UO2(CO3)3 complex. The evaluation of the spectroscopic results by Parallel factor analysis (PARAFAC) indicates the formation of three surface species. In detail the sorption of U(VI) onto orthoclase indicate two surface species. Based on the peak positions given in [2] they can be attributed to the formation of ≡SiO2UO20 and ≡SiO2UO2OHCO33– surface complexes. In presence of Ca2+ the ≡SiO2UO2OHCO33– surface complex disappears and instead the ≡SiO2UO2OH– surface complex also given in [2] can be observed. It occurs at lower pH values than the carbonate complex and shows different peak positions of the fluorescence bands.
The results improve the basis for a mechanistic modeling of the U(VI) sorption onto orthoclase and muscovite, which is important for long-term safety analysis of nuclear waste repositories.
With regard to the U(VI) sorption onto mica and feldspars not only the binary systems have to be understood because in natural systems many more components are present. For calcium this work already showed a significant influence on the speciation and thus on the potential transport of U(VI). But many other elements leached from surrounding minerals or contained in the groundwater may affect the overall sorption, too. Thus future work has to focus on more complex systems representing natural conditions as well as on the generation of surface complexation parameters for predictions of the U(VI) speciation.

  • Poster
    GDCh Wissenschaftsforum 2015, 30.08.-02.09.2015, Dresden, Deutschland

Publ.-Id: 22123

Numerical Modelling of the FCC Regenerator Reactor Based on Shrinkage Reaction Rate Model

Azizi, S.; Schubert, M.

Fluid catalytic cracking (FCC) reactors are applied to convert gas oils and residues to lighter, higher-value products. Circulating fluidized bed technologies are used in modern FCC units, where cracking reactions take place in the riser with co-current upflow of the vaporized gasoil feed and the catalyst. After the disengagement from the product gas, the catalyst needs to be regenerated to compensate the deactivation due to coke deposition. The deactivation of the FCC catalyst can occur already in a few seconds and regeneration of the deactivated catalyst plays an important role for the yield of the FCC unit. For an effective regeneration, burning of deposited coke in the fluidized bed solves the early decay time of the catalysts. During the process the heavy hydrocarbons deposit on the catalyst, which subsequently block the active sites. To restore the activity, deposited hydrocarbons are oxidized with air in the regenerator reactor. The performance of the regenerator as well as its coupling with the cracking reactor are important to reach a high overall yield in the FCC unit. Usually, Geldart-A particles are used as catalyst in the FCC reactors. As the aeration rate of the FCC catalyst is low and the particles are cohesive, big bubbles are formed, channeling occurs and fluidization is often nonhomogeneous, which makes the hydrodynamic modeling a challenge. The clustering behavior of the fluidizing gas also increases the complexity of the reactor design. The complicated hydrodynamic behavior of gas phase and solid particles is a critical point to model coupled heat and mass transfer phenomena inside the fluidized reactors. The aim of the work is to develop an Eulerian-Eulerian numerical model for the FCC regenerator reactor operated as a fluidized bed based on the kinetic theory of granular flows to consider the clustering effect of the FCC catalysts in the regeneration process. In addition, the model shall consider the impact of the shrinkage of the deposited coke on FCC catalyst regeneration time, product yield, and temperature history of the regenerator reactor.

Keywords: Numerical Modeling; Two-Fluid Model; Fluidized Bed Reactor; Hydrodynamics; FCC Catalyst Regeneration

  • Lecture (Conference)
    12th International Conference on Gas-Liquid & Gas-Liquid-Solid Reactor Engineering (GLS12), 28.06.-01.07.2015, New York, USA

Publ.-Id: 22122

The Breakup and Coalescence of Bubbles Considering Interphase Turbulence Transfer in Bubbly Flows

Azizi, S.; Lau, Y. M.; Schubert, M.

The ability to accurately predict the bubble size distribution in bubble column reactors is a requirement for any process design as well as for scale-up. The bubble size distribution depends mainly on the magnitude of bubble breakup and coalescence. Several breakup and coalescence models have been developed assuming different driving mechanisms, such as turbulence dissipation and shear rate of the liquid phase. The proposed breakup and coalescence models contain turbulence contributions in breakup and coalescence of the bubbles and also the relative velocity of the bubbles. The realistic expressionfor the mentioned terms is missing for the implementation of the breakup and coalescence models due to poor knowledge on the turbulence behavior of the bubbly flows. Here, bubble-liquid turbulence interactions of the bubbly flows are considered to predictparticipating turbulence energy in breakup and also relative velocity of the bubbles at coalescence of the bubbles.

Keywords: Breakup and Coalescence; Bubbly Flows; Numerical Modeling; Turbulence; Bubbles Fluctuation

  • Poster
    12th International Conference on Gas-Liquid & Gas-Liquid-Solid Reactor Engineering (GLS12), 28.06.-01.07.2015, New York, USA

Publ.-Id: 22121

Pyrolysis of Biomass Particles Using Circulating Fluidized Bed reactor with Heat loop of the Heat Carrier Particles

Salar, A.

Conversion of biomass into fuel and chemicals is currently receiving a great deal of attention because of the reduction of greenhouse gas emissions and national energy security and sustainability. The design of the pyrolysis process is important to reach higher bio-oil products and a key factor to produce higher bio-oil than char, is supplying high heat transfer rate to the biomass particles (fast pyrolysis) and fast removal of the volatiles. Although fluidized bed reactors provide higher heat transfer than conventional pyrolysis reactors, the heat transfer is limited by the convection at particle surface and conduction inside particle. The added inert particles to the fluidized bed improve heat transfer rate and fluidization properties of the biomass to reach desired fluidization velocity and good mixing of the particles. In this work, instead of using heated wall, performance of a circulating fluidized bed reactor with the heating loop of inert particles at the circulation path is investigated for pyrolysis of biomass.

Keywords: Numerical Modeling; Algae Biomass; Flash pyrolysis; Fluidized Bed Reactor; Heat Carrier Particles; Heat Transfer

  • Lecture (Conference)
    12th International Conference on Gas-Liquid & Gas-Liquid-Solid Reactor Engineering (GLS12), 28.06.-01.07.2015, New York, USA

Publ.-Id: 22120

Methods to increase the metabolic stability of 18F-radiotracers

Kuchar, M.; Mamat, C.

The majority of pharmaceuticals and other organic compounds including radiotracers that are considered foreign to the body undergo metabolic changes in vivo. Most of these compounds are metabolic degraded by a system of enzymes of low substrate specificity requirement which is present mainly in the liver but drug metabolism may also take place in the kidneys or other organs. Thus, radiotracers and all other pharmaceuticals are faced with enormous challenges to maintain their stability in vivo implicating a high requirement on their structure. Often in practice, such biologically active molecules with manifested properties are found in vitro but these results could not be confirmed in vivo due to an increased metabolism within minutes. Many pharmacologically and biologically interesting compounds fail for further application due to their lack of stability.
One of the most important issues of radiotracers development based on fluorine-18 is the stability in vitro and in vivo. Sometimes, the metabolism of 18F-radiotracers goes along with the cleavage of the F-C bond and with the rejection of [18F]fluoride mostly combined with high background and accumulation in the skeleton. This review deals with the impact of radiodefluorination and with approaches to stabilize the F-C bond to avoid the cleavage between fluorine and carbon.

Publ.-Id: 22119

In vivo Demonstration of an Active Tumor Pretargeting Approach with Peptide Nucleic Acid Bioconjugates as Complementary System

Leonidova, A.; Foerster, C.; Zarschler, K.; Schubert, M.; Pietzsch, H.-J.; Steinbach, J.; Bergmann, R.; Metzler-Nolte, N.; Stephan, H.; Gasser, G.

A novel, promising strategy for cancer diagnosis and therapy is the use of a pretargeting approach. For this purpose, the non-natural DNA/RNA analogues Peptide Nucleic Acids (PNAs) are ideal candidates as in vivo recognition units due to their high metabolic stability and lack of unspecific accumulation. In the pretargeting approach, an unlabeled, highly specific antibody-PNA conjugate has sufficient time to target a tumor before administration of a small fast-clearing radiolabeled complementary PNA that hybridizes with the antibody-PNA conjugate at the tumor site. Herein, we report the first successful application of this multistep process using a PNA-modified epidermal growth factor receptor (EGFR) specific antibody (Cetuximab) and a complementary 99mTc-labeled PNA. In vivo studies on tumor bearing mice demonstrated a rapid and efficient in vivo hybridization of the radiolabeled PNA with the antibody-PNA conjugate. Decisively, a high specific tumor accumulation was observed with a tumor-to-muscle ratio of >8, resulting in a clear visualization of the tumor by single photon emission computed tomography (SPECT).

Publ.-Id: 22118

Optimizing a stepwise fractionation chain in mineral processing or metallurgy

Tolosana-Delgado, R.; van den Boogaart, K. G.; Konsulke, S.; Scholz, A.; Matos Camacho, S.; Christesen, C.; Rudolph, M.; Scharf, C.

This paper presents a framework of optimization of design and operation of a chain of identical cells or operator units that splits a raw input stream into two streams, increasing their total monetary value. This can be seen as a simplified conceptualization of several mineral processing or metallurgical techniques, where a cell itself badly separates the stream, hence its repeated operation seems appropriate. The solution is based on standard theory of linear differential equations. Uncertainty in the composition of the feed can be accounted for by Monte Carlo techniques.

  • Contribution to proceedings
    Annual Conference of the International Association of Mathematical Geosciences, 07.-10.09.2015, Freiberg, Deutschland
    Proceedings of the Annual Conference of the International Association of Mathematical Geosciences, 978-3-00-050337-5

Publ.-Id: 22117

Geostatistical Fisher discriminant analysis

Tolosana-Delgado, R.; Mckinley, J.; van den Boogaart, K. G.

A geostatistical version of the classical Fisher rule (linear discriminant analysis) is presented. This method is applicable when a large dataset of multivariate observations is available within a domain split in several known subdomains, and it assumes that the variograms (or covariance functions) are comparable between subdomains, which only differ in the mean values of the available variables. The method consists on finding the eigen-decomposition of the matrix inv(W) B, where W is the matrix of sills of all direct- and cross-variograms, and B is the covariance matrix of the vectors of weighted means within each subdomain, obtained by generalized least squares. The method is used to map peat blanket occurrence in Northern Ireland, with data from the Tellus survey, which requires a minimal change to the general recipe: to use compositionally-compliant variogram tools and models, and work with log-ratio transformed data.

  • Contribution to proceedings
    Annual Conference of the International Association of Mathematical Geosciences, 07.-10.09.2015, Freiberg, Deutschland
    Proceedings of the Annual Conference of the International Association of Mathematical Geosciences, 978-3-00-050337-5

Publ.-Id: 22116

Influence of oxygen impurities on growth morphology, structure and mechanical properties of Ti‐Al‐N thin films

Riedl, H.; Koller, C. M.; Munnik, F.; Hutter, H.; Mendez Martin, F.; Rachbauer, R.; Kolozsvári, S.; Bartosik, M.; Mayrhofer, P. H.

Unintended impurities, such as oxygen, can significantly influence the growth morphology, structure, and mechanical properties of many materials. Therefore, we study the origin and impact of oxygen impurities (between ~ 0.3 and 1.3 at.%) on sputtered Ti1‐xAlxN thin films by using targets with three different oxygen impurity levels and modifying the deposition conditions such as the base pressure. The oxygen impurity content of our coatings was always (by around ≥ 0.1 at.%) above that of the target used. Detailed atom probe tomography as well as secondary ion mass spectroscopy indicate a homogeneous distribution of the oxygen impurities across our face centred cubic structured Ti0.50Al0.50N coatings. Except for higher oxygen levels at the interface to the substrate, which is more pronounced when the target is not sputter‐cleaned prior to the deposition, and at the coating surface, there are no detectable oxygen variations at the grain or column boundaries. Based on our results we can conclude that the growth orientation of our coatings changes from random (for the cleanest coatings with ~ 0.3 at.% O) to pronounced 111 (for the coatings with the highest oxygen content of ~ 1.3 at.% O) with increasing oxygen impurity content. Thereby, also the coherently diffracting crystallite sizes increase from around 35 to 100 nm, the growth morphology changes from dense columnar grains to more open, porous columnar grains, and thus the hardness decreases from around 35 to 20 GPa.
Our study highlights the importance of well‐defined deposition conditions and high quality targets for developing high quality thin films.

Keywords: Ti‐Al‐N; Oxygen impurities; ERDA; SIMS; Texture; Grain Size; Hardness

Publ.-Id: 22115

Tomographic investigations on the effects of gas entrainment on centrifugal pumps

Schäfer, T.

High-resolution gamma-ray computed tomography (HireCT) was applied to clarify the two phase flow distribution inside the impeller wheel of a running pump. Thus, the accumulated gas holdup inside the impeller of an industrial centrifugal pump was investigated and analysed, depending on the suction side gas volume fraction and type of two phase flow regime. Using time-averaging rotation-synchronized tomographic imaging technique, effects on the conveying performance of the centrifugal pump could be clarified. The obtained results contributes to a better understanding of the flow behavior and its effects inside the impeller of a centrifugal pump, which is running under two phase flow conditions due to gas entrainment. Moreover, the results can help to develop improved pump designs to avoid loss of conveying performance due to gas entrainment.

Keywords: centrifugal pump; gas entrainment; two-phase flow; advanced gamma-ray computed tomography; phase fraction visualization

  • Contribution to proceedings
    46th Annual Meeting on Nuclear Technology (AMNT), 05.-07.05.2015, Berlin, Deutschland
    Proceedings of 46th Annual Meeting on Nuclear Technology
  • Lecture (Conference)
    46th Annual Meeting on Nuclear Technology (AMNT), 05.-07.05.2015, Berlin, Deutschland

Publ.-Id: 22114

Untersuchung von Zweiphasenströmungen in einer Kreiselpumpe mittels tomographischer Bildgebungsverfahren

Schäfer, T.; Neumann, M.; Bieberle, A.; Hampel, U.

Zentrifugalpumpen sind sehr weitverbreitet und werden in vielfältiger Weise unter anderem in der Prozessindustrie oder im Kraftwerksbereich eingesetzt. Beispielweise nutzt man Kreiselpumpen in Raffinerien als Speisepumpen oder in Kraftwerken als Umwälzpumpen in Kühlkreisläufen. Erfolgt der Einsatz auch in sicherheitsrelevanten Bereichen, wie z.B. in der Reaktornotkühlung von Kernkraftwerken, muss unbedingt ein störungsfreier und zuverlässiger Betrieb gewährleistet werden. Obwohl diese Pumpen einfach aufgebaut sind, bieten sie eine Reihe von Vorteilen, wie zum Beispiel hohe Effizienz bei geringem Energieverbrauch, ruhiger und kontinuierlicher Förderstrom und hohe Haltbarkeit und Beständigkeit. Es ist bekannt, dass sowohl Gaseintrag als auch Dampfbildung durch Kavitation schädlich und kritisch für den Betrieb von Kreiselpumpen sind, welche eigentlich für den einphasigen Betrieb ausgelegt sind. Gaseintrag kann beispielsweise in Situationen entstehen, wo Flüssigkeiten aus Reservoirs mit einem zu niedrigen Füllstand gefördert werden. Hier können sich als Konsequenz aus der unzureichenden Überdeckung des Pumpenansaugstutzens und der Anwesenheit von Initialwirbeln an der Flüssigkeitsoberfläche Hohlwirbel ausprägen. Derartige Situationen sind insbesondere in Kernkraftwerken, wo beispielsweise Notkühlmittel aus einem Reservoir wie der Kondensationskammer gefördert wird, unbedingt zu vermeiden. Der Gaseintrag führt zu einer verminderten Förderleistung der Pumpe, bis hin zum vollständigen Zusammenbruch der Förderrate. Außerdem kann vorhandenes Gas in Pumpen unter anderem zum Verlust der Kühlung der Lager und der Gleitringdichtung führen, was zu einer früheren Abnutzung bis hin zum Versagen der Pumpe führt. Auch starke Vibrationen welche ebenfalls zur Schädigung der Lager beitragen, sowie Abnutzungserscheinungen an den Laufradschaufeln können eintreten. Die vorgestellte Arbeit leistet mit quantitativen Messungen, Visualisierungen und Analysen der Gas-Flüssigkeits-Phasenverteilungen innerhalb des Laufrades und des umgebenden Pumpengehäuses einer fördernden Kreiselpumpe einen Beitrag zum fundamentalen Verständnis der Auswirkungen von Gaseintrag in Zentrifugalpumpen.

Keywords: Kreiselpumpe; Gaseintrag; Zweiphasenströmung; erweiterte Gammastrahlen-Computertomographie; Visualisierung der Phasenanteile; centrifugal pump; gas entrainment; two-phase flow; advanced gamma-ray computed tomography; phase fraction visualization

  • Invited lecture (Conferences)
    2. Projektstatusgespräch zur BMBF-geförderten Nuklearen Sicherheitsforschung, 25.-26.03.2015, Dresden, Deutschland

Publ.-Id: 22113

Liquid Metal Ultrasound Velocimetry in a High Current Environment

Starace, M.; Weber, N.; Seilmayer, M.; Weier, T.; Stefani, F.; Eckert, S.

Ultrasound Doppler velocimetry is an important tool for the characterization of liquid metal flows, including those caused by magnetohydrodynamic instabilities. Here we consider the Tayler Instability (TI), which is driven by a high current flowing through the system. This can entail a great deal of electromagnetic noise, which must be decoupled from the signal produced by ultrasound scatterers within the liquid metal. In the experiment described herein, two ultrasound transducers encased within a copper electrode are in contact with a cylindrical liquid GaInSn column. Currents in the order of several kA produced by a switching-mode power supply flow through the electrode and the liquid GaInSn, resulting in the TI, which causes vortices with vertical velocity components in the range of several mm/s to appear. Noise produced by the power supply was significantly reduced by adding film capacitors and toroidal cores, including a common-mode choke to the circuit. Electromagnetic interference was further reduced by adding toroidal and split cores to the coaxial cables connecting the ultrasound transducers to the velocimeter, with the latter drawing power through an isolating transformer. These precautions permitted the retrieval of reliable velocity data, which generally agree with previously conducted B_z-measurements.

Keywords: Liquid metals; magnetohydrodynamics; Tayler Instability; noise suppression

  • Open Access Logo Contribution to proceedings
    9th International Symposium on Ultrasonic Doppler Methods for Fluid Mechanics and Fluid Engineering, 27.-29.08.2014, Strasbourg, France
    Proceedings of the 9th International Symposium on Ultrasonic Doppler Methods for Fluid Mechanics and Fluid Engineering, Straßburg, Frankreich: iCUBE, Ubertone, 161-164
  • Lecture (Conference)
    9th International Symposium on Ultrasonic Doppler Methods for Fluid Mechanics and Fluid Engineering, 27.-29.08.2014, Strasbourg, France


Publ.-Id: 22112

Synthesis and First Evaluation of [18F]Fluorocyano- and [18F]Fluoronitroquinoxalinedione as Putative AMPA Receptor Antagonists

Olma, S.; Ermert, J.; Sihver, W.; Coenen, H.-H.

Derivatives of quinoxalinedione (QX) were chosen as chemical lead for the development of new radioligands of the AMPA receptor, since there are several examples of QX-derivatives with high affinity. The radiosyntheses of the new compounds 6-[18F]fluoro-7-nitro-QX ([18F]FNQX) and 7-[18F]fluoro-6-cyano-QX ([18F]FCQX) with radiochemical yields of 8 ± 2 and 3 ± 2 %, respectively, as well as the evaluation of their binding properties to the AMPA-receptor were performed. A comparison of the Ki-values of the new QX-derivatives FCQX and FNQX with mono-substituted cyanoand nitro-QX shows negligibly small differences of affinity (within the range of 1.4 to 5 µM), but exhibits a tenfold lower affinity than derivatives with two electron withdrawing groups like the 7-cyano-6-nitro-compound CNQX and the 6,7- dinitro compound DNQX. Thus, with respect to the low affinity and a high non-specific binding with in vitro and ex vivo autoradiographic studies, the new compounds do not lend themselves for in vivo imaging.

Keywords: AMPA receptor; fluorine-18; glutamate receptor; positron emission tomography; quinoxalinedione; radiofluorination

Publ.-Id: 22111

Ultrasound Velocimetry in High Current Driven Liquid Metal Flow

Starace, M.; Weber, N.; Seilmayer, M.; Kasprzyk, C.; Stefani, F.; Weier, T.; Eckert, S.

The understanding of magnetohydrodynamic phenomena in liquid metals relies heavily on measurement techniques such as ultrasound Doppler velocimetry that can be used to characterize flow patterns within them. The Tayler instability (TI), as well as electro-vortex flow (EVF) in a liquid GaInSn column whose top and bottom are bounded by copper current collectors connected to a switching mode power supply are considered here. The TI is driven by currents above a critical value of 2.7 kA and results in a number of vortices with vertical velocity components of the order of several mm s^−1 , whereas EVF is caused by inhomogeneities in the current density from the current collectors. Ultrasound transducers embedded within the top current collector are in direct contact with the liquid metal. At the high currents required to investigate the TI such a configuration is problematic, because the electromagnetic noise the transducers are exposed to greatly overshadows the signal from ultrasound echoes, if left unchecked. The noise generated by the power supply was significantly damped with the addition of toroidal cores and film capacitors to the current circuit. Moreover, coiling the coaxial cables connecting the transducers to the velocimeter around ring and split cores reduced the noise further. The velocimeter itself drew power through an isolation transformer and was thus prevented from being disturbed by ground loops. Reliable velocity data could be obtained from the experiment after these measures were taken and will be discussed here.

  • Poster
    3rd International Workshop on Measuring Techniques for Liquid Metal Flows (MTLM2015), 15.-17.04.2015, Dresden, Deutschland

Publ.-Id: 22110

Nichtinvasive Zustandsüberwachung von Kernreaktoren zur Detektion von Füllstandsänderungen und Deformationen des Kerns

Hampel, U.; Brachem, C.; Lange, C.; Kratzsch, A.; Schmidt, S.; Fiß, D.; Härtel, S.; Konheiser, J.

Der Vortrag stell das laufende BMBF-Vorhaben "Nichtinvasive Zustandsüberwachung von Kernreaktoren zur Detektion von Füllstandsänderungen und Deformationen des Kerns" vor. Berichtet wird über den Hintergrund des Vorhabens, Zielstellungen im Rahmen der Reaktorsicherheitsforschung und Nachwuchsförderung in der Kerntechnik sowie über aktuelle Projektergebnisse.

Keywords: Nuclear Safety; Reactor Safety; Reactor Monitoring; Monte-Carlo Simulation

  • Invited lecture (Conferences)
    Projektstatusgespräch zu BMBF-geförderten FuE-Arbeiten auf dem Gebiet der Nuklearen Sicherheits- und Entsorgungsforschung sowie Strahlenforschung, 25.03.2015, Dresden, Deutschland

Publ.-Id: 22109

Numerische Untersuchungen zur Strömungsdynamik von Flüssigmetallbatterien

Kasprzyk, C.

Due to global shortage of fossil fuels, the well known danger of nuclear-energy and the growing threats of climate change the interest in a full switch to renewable based energy-supply is still growing.
The fluctuating and unpredictable character of the power gained from renewable energy-sources, especially sun and wind, is an important fact when considering a turnaround in energy-policy. Therefore, the use of effective storage-technologies is unavoidable to ensure a stable energy-supply.
A promising candidate for cheap electro-chemical storage is the liquid-metal-battery. Coming up from a stable density-stratification of a molten salt in between an alkali metal and an alloy the battery is easy to assemble because of its fully liquid content.
The entirely liquid configuration allows the application of high current densities. By exceeding a critical total current value the so-called Tayler-instability could force a fluid movement in the cell. The instability can cause a mixing or in worst case a short-circuit of the electrodes. An experimental proof of the Tayler-instability shows also a characteristic velocity distribution below the critical current value.
Aim of the present work is a numerical analysis investigating the sub-critical fluid movement.
Possible causes are natural convection as a result of Joule heating or electro-vortex-flow induced by inhomogeneous current density distribution. Central parts of the investigation are the creation of a consistent model including the model validation and the application of the generated setup on the experimental case. An adapted in-house OpenFOAM version for the prediction of magnetohydrodynamics is available.
In a last step a multiphase system, made of a realistic material selection under the influence of electro-vortex-flow, is studied.
Each part of the study is concluded with a summary of the findings.

Keywords: Liquid Metal Battery; Electro-Vortex Flow; OpenFOAM; Rayleigh-Benard; Multiphase-Flow

  • Diploma thesis
    TU Dresden, 2015
    Mentor: Prof. Fröhlich, Martin Niemann, Tom Weier
    89 Seiten

Publ.-Id: 22108

Toward polarized antiprotons: Machine development for spin-filtering experiments

Weidemann, C.; Rathmann, F.; Stein, H.; Lorentz, B.; Bagdasarian, Z.; Barion, L.; Barsov, S.; Bechstedt, U.; Bertelli, S.; Chiladze, D.; Ciullo, G.; Contalbrigo, M.; Dymov, S.; Engels, R.; Gaisser, M.; Gebel, R.; Goslawski, P.; Grigoriev, K.; Guidoboni, G.; Kacharava, A.; Kamerdzhiev, V.; Khoukaz, A.; Kulikov, A.; Lehrach, A.; Lenisa, P.; Lomidze, N.; Macharashvili, G.; Maier, R.; Martin, S.; Mchedlishvili, D.; Meyer, H.; Merzliakov, S.; Mielke, M.; Mikirtychiants, M.; Mikirtychiants, S.; Nass, A.; Nikolaev, N.; Oellers, D.; Papenbrock, M.; Pesce, A.; Prasuhn, D.; Retzlaff, M.; Schleichert, R.; Schroer, D.; Seyfarth, H.; Soltner, H.; Statera, M.; Steffens, E.; Stockhorst, H.; Stroher, H.; Tabidze, M.; Tagliente, G.; Engblom, P.; Trusov, S.; Valdau, Y.; Vasiliev, A.; Wustner, P.

The paper describes the commissioning of the experimental equipment and the machine studies required for the first spin-filtering experiment with protons at a beam kinetic energy of 49.3 MeV in COSY. The implementation of a low-β insertion made it possible to achieve beam lifetimes of τb=8000  s in the presence of a dense polarized hydrogen storage-cell target of areal density dt=(5.5±0.2)×1013  atoms/cm2. The developed techniques can be directly applied to antiproton machines and allow the determination of the spin-dependent p¯p cross sections via spin filtering.

Publ.-Id: 22107

Analysing powers and spin correlations in deuteron–proton charge exchange at 726 MeV

Dymov, S.; Azaryan, T.; Bagdasarian, Z.; Barsov, S.; Carbonell, J.; Chiladze, D.; Engels, R.; Gebel, R.; Grigoryev, K.; Hartmann, M.; Kacharava, A.; Khoukaz, A.; Komarov, V.; Kulessa, P.; Kulikov, A.; Kurbatov, V.; Lomidze, N.; Lorentz, B.; Macharashvili, G.; Mchedlishvili, D.; Merzliakov, S.; Mielke, M.; Mikirtychyants, M.; Mikirtychyants, S.; Nioradze, M.; Ohm, H.; Prasuhn, D.; Rathmann, F.; Serdyuk, V.; Seyfarth, H.; Shmakova, V.; Stroeher, H.; Tabidze, M.; Trusov, S.; Tsirkov, D.; Uzikov, Y.; Valdau, Y.; Weidemann, C.; Wilkin, C.

The charge exchange of vector polarised deuterons on a polarised hydrogen target has been studied in a high statistics experiment at the COSY-ANKE facility at a deuteron beam energy of Td=726 MeV. By selecting two fast protons at low relative energy Epp, the measured analysing powers and spin correlations are sensitive to interference terms between specific neutron–proton charge-exchange amplitudes at a neutron kinetic energy of Tn≈1/2 Td=363 MeV. An impulse approximation calculation, which takes into account corrections due to the angular distribution in the diproton, describes reasonably the dependence of the data on both Epp and the momentum transfer. This lends broad support to the current neutron–proton partial wave solution that was used in the estimation.

Publ.-Id: 22106

Preclinical small animal PET/MRI for radiopharmaceutical dosimetry

Kranz, M.; Sattler, B.; Patt, M.; Deuther-Conrad, W.; Fischer, S.; Smits, R.; Hoepping, A.; Sabri, O.; Brust, P.

To assess the radiation risk after injection of new PET radiotracers small animal PET/MRI provides the essential whole body biodistribution data for image based dosimetry (ibD). In this study, we investigate ((S)-(-)# and (R)-(+)##-[18F]fluspidine, a PET radioligand for neuroimaging of σ1 receptors in mice. Organ doses (OD) and the effective dose (ED) were determined using PET/MR ibD to assess the radiation risk to humans. The results will be compared to those previously acquired for (-)-*and (+)-** [18F]flubatine , to proof the concept of small animal PET/MRI for incorporation dosimetry to assess the radiation exposure to humans by radiopharmaceuticals.

Materials and methods
Six female CD1 mice (weight: 30.9±1.3 g) were injected i.v. with 13.2±3.0 MBq (#, n=3) or 12.6±1.4 MBq (##, n=3), respectively. A dynamic 2 h animal PET/MRI protocol was performed (MEDISO nanoScan®, Hungary). All relevant organs were defined by volumes of interest. Time- and mass-scales were adapted to the human anatomy; exponential curves were fitted to the time-activity-data (%ID/organ). The ODs were computed using the adult male model with OLINDA and the ED using tissue weighting factors (ICRP103). The results were compared to previously acquired data of post mortem biodistribution (PMB) studies in mice for (-)-[18F]flubatine (n=27, Ø28.2 g) and [18F]fluspidine (n=28#/n=22##, Ø29.6 g).

The excreting organs (kidneys, liver and urinary bladder) received the highest ODs. Subsequently, these organs provide the largest contribution to the ED. The overall radiation risk to humans based on animal biodistribution data acquired with ibD would be 12.9# and 14.0## (16.7#; 18.4## based on PMB). Comparable results were estimated for [18F]flubatine: 12.5*(PMB), 12.1**.

ibD of [18F]fluspidine reveals major differences between the two enantiomers. The tracer with higher affinity and slower kinetics (##) causes a higher radiation exposure than its enantiomeric counterpart (#) both in ibD and PMB. Furthermore, the ibD shows lower ED values compared to the PMB due to the intrinsic methodological differences. Small animal ibB is feasible and its reliability needs to be further investigated and confirmed.

  • Poster
    Annual Congress of the European Association of Nuclear Medicine - EANM 2015, 09.-14.10.2015, Hamburg, Deutschland
  • Abstract in refereed journal
    European Journal of Nuclear Medicine and Molecular Imaging 42(2015), 347-348

Publ.-Id: 22105

Biodistribution, cellular localization, and in vivo tolerability of S-35-labeled antiinflammatory dendritic polyglycerol sulfate amine

Holzhausen, C.; Groger, D.; Mundhenk, L.; Donat, C. K.; Schnorr, J.; Haag, R.; Gruber, A. D.

Antiinflammatory dendritic polyglycerol sulfate (dPGS) holds great potential in the treatment and imaging of inflammatory processes. Here, we studied its biokinetic behavior, biodistribution, target cells, and in vivo toxicology. Following intravenous or subcutaneous application of (35)sulfur-labeled dPGS amine with a molecular weight of 10.05 kDa and a hydrodynamic diameter of 5.7 +/- 1.5 nm to mice, tissues were collected at specific time points (2, 15 min; 1, 24 h; 5, 21 days) and analyzed by liquid scintillation counting, autoradiography, radioluminography, and light microscopic autoradiography. The blood half-life of dPGS amine was 12 days. The major route of elimination was via the bile and feces.
Elimination via the kidney and urine was only initially observed after i.v., but not after s.c. injection. Regardless of the administration mode, liver and spleen were late target organs where dPGS amine accumulated in phagocytic cells. Despite bioaccumulation, toxicological histopathology failed to identify any adverse effects at any time and in any tissues examined suggesting a high in vivo biocompatibility and encouraging future investigation for biomedical applications.

Publ.-Id: 22104

Felsenkeller shallow-underground accelerator laboratory for nuclear astrophysics (at p-process workshop)

Szücs, T.

A very low background level is a key requirement for low-energy nuclear astrophysics experiments. A series of detailed high energy (E> 3 MeV) laboratory gamma-background study with escape-suppressed HPGe detectors has been performed at the surface of the Earth [1,2], at shallow underground (110 m w. e.) in the Felsenkeller laboratory in Dresden, Germany [2,3], at medium deep underground (400 m w. e.) in the Reiche Zeche mine in Freiberg, Germany [3], and at deep underground (3800 m w. e.) in LNGS in Gran Sasso, Italy [1]. The data show that already a shallow underground site has sufficiently low gamma-background for many nuclear astrophysics studies when an additional active shield is used to veto the remaining muon flux [2,3].
Benefiting from these low background conditions, a used 5 MV Pelletron tandem accelerator with external high-current sputter ion source for hydrogen and carbon beams is currently being refurbished for installation in Felsenkeller [4]. Installation of an additional radio-frequency ion source on the high voltage terminal is under way. The ions will be injected into the acceleration tube by an electrostatic deflector, thus the tandem mode of operation will be kept. With the RF-source up to 100A alpha beam is foreseen. Similarly high proton current either from the external or the internal source will be available. In addition, also a large, well-shielded HPGe detector for offline counting will be included in the new laboratory, enabling activation experiments.

The Felsenkeller accelerator will be used in part for in-house research by HZDR and TU Dresden, aiming for complementarity with the LUNA-MV project and science program. In addition, external users from any field of science will be highly welcome at Felsenkeller. Users are to be selected based on the recommendations of an independent group of outside advisers judging the scientific merits of the proposals.
Owing to the high current of the 5 MV Pelletron and the low laboratory background, the Felsenkeller laboratory may be suited to study p-process related nuclear reactions.

In addition to the detailed introduction of the new Felsenkeller accelerator laboratory, the talk will flash the recent status of the KADoNiS-p database [5].

  • Supported by the Helmholtz Association (HGF) through the Nuclear Astrophysics Virtual Institute (NAVI, HGF VH-VI-417)

[1] T. Szücs et al., Eur. Phys. J. A 44, (2010) 513
[2] T. Szücs et al., Eur. Phys. J. A 48, (2012) 8
[3] T. Szücs et al., Eur. Phys. J. A 51, (2015) 33
[4] D. Bemmerer et al., Procc. of Sciences NIC XIII, (2015) 044
[5] T.Szücs et al., Nucl. Data Sheets 120, (2014) 191

Keywords: Felsenkeller; Underground; accelerator; nuclear astrophysics

  • Lecture (Conference)
    p-process workshop 2015: status and outlook, 10.-13.06.2015, Limassol, Cyprus

Publ.-Id: 22103

Active Site Mapping of Human Cathepsin F with Dipeptide Nitrile Inhibitors

Schmitz, J.; Furtmann, N.; Ponert, M.; Frizler, M.; Löser, R.; Bartz, U.; Bajorath, J.; Gütschow, M.

The cleavage of the invariant chain is the key event in the trafficking pathway of major histocompatibility complex class II. Cathepsin S constitutes the major processing enzyme of the invariant chain, but cathepsin F acts in macrophages as its functional synergist which is as potent as cathepsin S in invariant chain cleavage. Dedicated low molecular weight inhibitors for cathepsin F have not been developed so far. An active site mapping with 52 dipeptide nitriles, reacting as covalent-reversible inhibitors, was performed to draw structureactivity relationships for the non-primed binding region of human cathepsin F. In a stepwise process, new compounds with optimized fragment combinations were designed and synthesized. These dipeptide nitriles were evaluated on human cysteine cathepsins F, B, L, K and S. Compounds 10 (N-(4-phenylbenzoyl)-leucyl-glycine nitrile) and 12 (N-(4-phenylbenzoyl)-leucyl-methionine nitrile) were potent inhibitors of human cathepsin F with Ki values less than 10 nM. With all dipeptide nitriles from our study, a 3D activity landscape was generated to visualize structure-activity relationships for this
series of cathepsin F inhibitors.

Publ.-Id: 22102

Cysteine cathepsins: their role in tumor progression and recent trends in the development of imaging probes

Löser, R.; Pietzsch, J.

Papain-like cysteine proteases bear an enormous potential as drug discovery targets for both infectious and systemic human diseases. The considerable progress in this field over the last two decades has also raised interest in the visualization of these enzymes in their native context, especially with regard to tumor imaging.
After a short introduction to structure and general functions of human cysteine cathepsins, we highlight their importance for drug discovery and development and provide a critical update on the current state of knowledge towards their involvement in tumor progression, with a special emphasis on their role in therapy response. In accordance with a radiopharmaceutical point of view, the main focus of this review article will be the discussion of recently developed fluorescence and radiotracer-based imaging agents together with related molecular probes.

Keywords: Cancer; Carcinogenesis; extracellular enzymes; Fluorescence-based probes; Lysosomal cysteine proteases; metastasis; Molecular Imaging; radiotracers

Publ.-Id: 22101

Measuring techniques for experimental investigations and monitoring of liquid metal flows

Eckert, S.; Wondrak, T.; Franke, S.; Gundrum, T.; Ratajczak, M.; Stefani, F.; Gerbeth, G.

The safe and reliable operation of liquid metal systems requires corresponding measuring systems and control units, both for the liquid metal single-phase flow as well as for bubble-laden liquid metal two-phase flows. Moreover, significant research effort is permanently focused on the optimization of technologies and facilities for materials processing such as smelting, refining and casting of metals and alloys. The main objectives are an improvement of the final product quality, an enhancement of the process efficiency and an economical consumption of resources and energy. Further developments of processes involving metallic melts require a better, detailed knowledge about the flow structure and the transport properties of the flow. Numerical simulations could provide a better understanding of the complex flow behavior, but, experimental data are indispensable with respect to a validation of the respective CFD codes. The determination of flow quantities in liquid metals is considerably impeded by the special material properties. Powerful optical methods as used for measurements in transparent liquids are obviously not applicable in molten metals. Further serious restrictions arise from the high temperature or the chemical reactivity of the melt. As a consequence there is a very constrained choice of commercially available techniques to measure the velocity structure of fluid flows at elevated temperatures.
The presentation reports on established methods and new developments in the field of measuring techniques for liquid metal flows. This review is focused on measurements of the flow rate and the local velocity field as well as on the characterization of liquid metal two-phase flows and solidifying melts. During the last two decades considerable effort was spent by miscellaneous researcher groups to provide new solutions for measurements of flow fields in liquid metals. The presentation intends to summarize different approaches and attempts to account on perspectives, particularly in view of some recent developments.

Keywords: liquid metal; flow measurements; ultrasound Doppler method; inductive flow tomography

  • Invited lecture (Conferences)
    Heavy Metal Summer School, 15.-19.06.2015, Mol, Belgium

Publ.-Id: 22100

Flexible Antigen-Specific Redirection of Human Regulatory T Cells Via a Novel Universal Chimeric Antigen Receptor System

Koristka, S.; Cartellieri, M.; Feldmann, A.; Arndt, C.; Loff, S.; Michalk, I.; Aliperta, R.; von Bonin, M.; Bornhäuser, M.; Ehninger, A.; Ehninger, G.; Bachmann, M. P.

Based on compelling evidence from a vast number of in vitro and in vivostudies, Tregs have become an attractive cell population to treat or even prevent auto- and alloimmunity including Graft-versus-Host disease (GvHD). However, several safety concerns still exist as for example the risk of global immunosuppression using polyclonal Tregs. In fact, experiments in mice showed that adoptive transfer or induction of antigen-specific Tregs is more potent regarding suppression of pathogenic immune responses when compared to polyclonal Treg populations. Unfortunately, the isolation and expansion of naturally occurring antigen-specific Tregs is technically difficult, labour-intensive, and time-consuming. An attractive way to overcome these limitations and to endow polyclonal Treg populations with a desired antigen-specificity is their engraftment with chimeric antigen receptors (CARs). In this context, CAR-modification represents a promising approach to redirect polyclonal Tregs in an antigen-specific manner to suppress ongoing self-destructive immune responses at the site of inflammation.

Nevertheless, until now redirection of CAR-engineered T cells is limited to a single target antigen, restricting this approach to an unflexible monospecific therapy. Therefore, we developed a more flexible universal CAR (UCAR) platform that allows redirection of T cells to an in principal unrestricted number of surface antigens. T cells are engrafted with UCARs that bind to a small peptide epitope derived from a human nuclear protein. Cross-linkage to target cells is mediated by independent target modules that provide antigen-specificity and comprise the peptide epitope recognized by the UCAR. In order to target different tissue antigens, the target modules can easily be exchanged. Thereby, once established, the treatment strategy can easily be applied to various auto- and alloimmune diseases.

At present, the CD45RA+ population is the Treg subset of choice for a clinical application as these cells have the highest capacity to maintain phenotypic and functional Treg properties upon prolonged ex vivo expansion. Here we show that highly pure, sorted CD4+CD25+CD127lowCD45RA+ Tregs can be genetically manipulated using lentiviral gene transfer, resulting in approximately 70 % of UCAR-expressing Treg cells. The transduction procedure itself did not affect the phenotype of UCAR-engineered Tregs as it was similar to non-transduced wildtype cells. Both Treg populations presevered FOXP3 expression even after prolonged in vitro cultivation (> 95 % FOXP3+). Upon incubation with antigen-positive target cells and a respective target module UCAR-engineered Tregs upregulate the activation markers CD69 and LAP demonstrating that the cells can be restimulated antigen-specifically. Most importantly, UCAR-engrafted Tregs were functionally activated upon antigen encounter, demonstrated by suppression of proliferation and expansion of cocultured autologous T effector cells.

Taken together, our results pave the way towards an application of UCAR technology for a site-specific recruitment of CAR-modified Tregs into inflamed tissues aiming at re-establishing immune homeostasis. Due to its high flexibility UCAR-engrafted Tregs can easily and universally be used for treatment of various autoimmune diseases or GvHD just by exchanging the tissue-specific target modules.

Disclosures Cartellieri: Cellex Patient Treatment GmbH: Employment. Ehninger: GEMoaB GmbH: Employment, Patents & Royalties. Ehninger: GEMoaB GmbH: Consultancy, Patents & Royalties. Bachmann: GEMoaB GmbH: Consultancy, Patents & Royalties.

  • Abstract in refereed journal
    BLOOD 124(2014)21, 3494
  • Poster
    56th ASH Annual Meeting, 06.-09.12.2014, San Francisco, USA

Publ.-Id: 22099

Copper(II) cyclam complexes with N-propionic acid pendant arms

Kubeil, M.; Zarschler, K.; Pietzsch, J.; Kraus, W.; Comba, P.; Stephan, H.

Four cyclam (1,4,8,11-tetraazacyclotetradecane) ligands with different number of N-substituted propionic acid groups lead to penta-coordinated copper(II) complexes adopting trans-I configuration (4+1 geometry), i.e. the complexes have dx2−y2 ground state with significant rhombic distortion. From the structural data (X-ray, electron paramagnetic resonance, UV/vis, infrared), it appears that with increasing substitution of the secondary amines of the macrocyclic ring with propionic acid groups the distortion from square-pyramidal to trigonal-bipyramidal rises, and this is expected to lead to relatively low complex stabilities. This is confirmed by in vitro studies using superoxide dismutase (SOD) and human serum challenge experiments as well as by biodistribution data with the 64Cu-labelled ligands. 64Cu-labelled cyclam monopropionic and dipropionic acid show high in vitro and in vivo stability at which the latter provides a comparable biodistribution profile as 64Cu-TETA (1,4,8,11-tetraazacyclotetradecane-1,4,8,11-tetraacetic acid).

Publ.-Id: 22098

Synthesis and characterization of novel fluorescent sigma-2 receptor ligands

Ye, J.; Deuther-Conrad, W.; Steinbach, J.; Brust, P.; Jia, H.

Sigam-2 (σ2) receptors are overexpressed in a variety of human and rodent tumors and play a pivotal role in cancer biology. Furthermore, it has proved to be a unique biomarker of cell proliferation in solid tumors. With the aim of providing more potent and reliable tools to investigate the σ2 receptor biology, we report herein on the synthesis and characterization of novel fluorescent σ2 receptor ligands designed via an integrated approach by using N-(4-(6,7-dimethoxy-3,4-dihydroisoquinolin-2(1H)-yl)butyl)-2-(2- [18F]fluoroethoxy)-5-methylbenzamide ([18F]ISO-1, the only σ2 receptor radioligand used in clinical trials up to date) as the lead compound.
All the synthesized compounds possess the pharmacophore (6,7-dimethoxy-1,2,3,4-tetrahdyroxyisoquinoline) and a fluorophore directly connected via various carbon linkers as shown in Figure 1. The clog P values were calculated by On-line Lipophilicity in Virtual Computational Chemistry Laboratory as shown in Table 1 (compounds 2-5 vs SW116 and SW120, the clog P 4.24–5.05 vs 6.74 and 7.29). We measured the excitation/emission wavelength, the quantum yields (QY) and the absorbance in phosphate-buffered saline (PBS). The emission maxima of these compounds are about 450 nm. High QYs were observed for compounds 2–5 with 5.95%, 8.11%, 7.52% and 5.48%, respectively.
The affinities of ligands for the σ2 and σ1 receptors were determined with radioligand competition experiments. [3H]DTG in the presence of 10 μM dextrallorphan was used for the σ2 receptors and (+)-[3H]pentazocine for σ1 receptors. The results are presented in Table 1. In general, the fluorescent compounds preferred to bind to σ2 receptors. Compounds 2–5, containing a barbituric acid moiety as electron acceptor, possessed high affinity (10.9–22.3 nM) and subtype selectivity for σ2 receptors (Ki1)/Ki2) = 14–57).
In conclusion, fluorescent σ2 receptor ligands with high affinity and subtype selectivity have been developed and warrant further evaluation.

  • Lecture (Conference)
    World Molecular Imaging Congress 2015, 02.-05.09.2015, Hawaii, USA

Publ.-Id: 22097

Novel indole-based sigma-2 receptor ligands: synthesis, structure–affinity relationship and antiproliferative activity

Xie, F.; Kniess, T.; Neuber, C.; Deuther-Conrad, W.; Mamat, C.; Liebermann, B. P.; Liu, B.; Mach, R. H.; Brust, P.; Steinbach, J.; Pietzsch, J.; Jia, H.

We report the synthesis and biological evaluation of a series of indole-based σ2 receptor ligands derived from siramesine. In vitro competition binding assays showed that these analogues possessed high to moderate affinity and selectivity for σ2 receptors. Structure–affinity relationship analyses of these indole-based σ2 receptor ligands were performed. In the 3-(4,5-dimethythiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, 1a and 1b displayed significant and comparable antiproliferative activity in DU145, MCF7 and C6 cells to siramesine. In cell cycle analyses, compounds 1a, 1b and siramesine were found to induce a G1 phase cell cycle arrest in DU145 cells using flow cytometry. The combination of 5,6-dimethoxyisoindoline scaffold and N-(4-fluorophenyl)indole moiety was identified as a new σ2 receptor ligand deserving further investigation as an antitumor agent.

Publ.-Id: 22096

Two surface plasmon decay of plasma oscillations

Kluge, T.; Metzkes, J.; Zeil, K.; Bussmann, M.; Schramm, U.; Cowan, T. E.

The interaction of ultra-intense lasers with solid foils can be used to accelerate ions to high energies well exceeding 60MeV [Gaillard et al., Phys. Plasmas 18, 056710 (2011)]. The non-linear relativistic motion of electrons in the intense laser radiation leads to their acceleration and later to the acceleration of ions. Ions can be accelerated from the front surface, the foil interior region, and the foil rear surface (target normal sheath acceleration (TNSA), most widely used), or the foil may be accelerated as a whole if sufficiently thin (radiation pressure acceleration). Here, we focus on the most widely used mechanism for laser ion-acceleration of TNSA. Starting from perfectly flat foils, we show by simulations how electron filamentation at or inside the solid leads to spatial modulations in the ions. The exact dynamics depend very sensitively on the chosen initial parameters which has a tremendous effect on electron dynamics. In the case of step-like density gradients, we find evidence that suggests a two-surface-plasmon decay of plasma oscillations triggering a Raileigh-Taylor-like instability.

Publ.-Id: 22095

The origin and crust/mantle mass balance of Central Andean ignimbrite magmatism constrained by oxygen and strontium isotopes and erupted volumes

Freymuth, H.; Brandmeier, M.; Wörner, G.

Volcanism during the Neogene in the Central Volcanic Zone (CVZ) of the Andes produced 1) stratovolcanoes, 2) rhyodacitic to rhyolitic ignimbrites which reach volumes of generally less than 300 km3 and 3) large volume monotonous dacitic ignimbrites of up to several thousand cubic kilometres. We present models for the origin of these magma types using O and Sr isotopes to, constrain crust/mantle proportions for the large volume ignimbrites and explore the relationship to the evolution of the Andean crust.
Oxygen isotope ratios were measured on phenocrysts in order to avoid the effects of secondary alteration. Our results show a complete overlap in the Sr-O isotope compositions of lavas from stratovolcanoes and low-volume rhyolitic ignimbrites as well as older (>9 Ma) large-volume dacitic ignimbrites. This suggests that the mass balance of crustal and mantle components are largely similar. By contrast, younger (<10 Ma) large-volume dacitic ignimbrites from the southern portion of the Central Andes have distinctly more radiogenic Sr and heavier O isotopes and thus contrast with older dacitic ignimbrites in northernmost Chile and southern Peru.
Results of assimilation and fractional crystallization (AFC) models show that the largest chemical changes occur in the lower crust where magmas acquire a base-level geochemical signature that is later modified by middle to upper crustal AFC. Using geospatial analysis we estimated the volume of these ignimbrite deposits throughout the Central Andes during the Neogene and examined the spatiotemporal pattern of so- called "ignimbrite flare-ups". We observe a N-S migration of maximum ages of the onset of large volume "ignimbrite pulses" through time: Major pulses occurred at 19-24 Ma (e.g. Oxaya, Nazca Group), 13-14 Ma (e.g. Huaylillas and Altos de Pica ignimbrites), <10 Ma (Altiplano and Puna ignimbrites). Such "flare-ups" represent magmatic production rates of 25 to >70 km3 Ma-1 km-1 (assuming plutonic:volcanic ratios of 1:5) which are additional to, but within the order of, the arc background magmatic flux. Comparing our results to average shortening rates observed in the Andes, we observe a "lag-time" with large-volume eruptions occurring after accelerated shortening. A similar delay exists between the ignimbrite pulses and the subduction of the Juan-Fernandez ridge. This is consistent with the idea that large-volume ignimbrite eruptions occurred in the wake of the N-S passage of the ridge after slab steepening has allowed hot asthenospheric mantle to ascend into and cause the melting of the mantle wedge.
In our model, the older large-volume dacitic ignimbrites in the northern part of the CVZ have lower (15 to 37 %) crustal contributions because they were produced at times when the Central Andean crust was thinner and colder, and large-scale melting in the middle crust could not be achieved. Younger ignimbrite flare-ups further south (< 10 Ma, > 22°S) formed with a significantly higher crustal contribution (22 to 68 %) because at that time the Andean crust was thicker and hotter and, therefore primed for more extensive crustal melting. The rhyolitic lower-volume ignimbrites are more equally distributed in the Central Volcanic Zone (CVZ) in time and space and are produced by mechanisms similar to those operating below large stratovolcanoes, but at times of higher melt fluxes from the mantle wedge.

Publ.-Id: 22094

Solidification of pure aluminium affected by a pulsed electrical field and electromagnetic stirring

Zhang, Y.; Räbiger, D.; Eckert, S.

Pure aluminium (99.997 up to 99.9999 wt % Al) has been solidified under the influence of both electric current pulses and a traveling magnetic field for electromagnetic melt stirring. The electric current was applied by means of two parallel electrodes immersed into the melt through the free surface. In contradistinction to well-known investigations in solute-rich alloys or recently published studies for pure aluminium we did not find a grain refinement effect owing to the melt treatment here. It becomes obvious that a slight contamination of the basic raw material by an impure processing during melt preparation has a dramatic influence on the grain structure.

Keywords: Solidification; Metals and alloys; Pure aluminium; Grain refinement; Electric Current Pulses (ECP); Electromagnetic stirring

Publ.-Id: 22093

Reichweiteverifikation bei der Protonentherapie mit einer Prompt-Gamma-Schlitzkamera – Auf dem Weg zur klinischen Anwendung

Priegnitz, M.; Barczyk, S.; Golnik, C.; Janssens, G.; Smeets, J.; Vander Stappen, F.; Clementel, E.; Hotoiu, L.; de Xivry, J. O.; Baumann, M.; Enghardt, W.; Fiedler, F.; Krause, M.; Prieels, D.; Pausch, G.; Richter, C.

In der Radioonkologie gewinnt die Bestrahlung mit Protonen zunehmend an Bedeutung. Um die vorteilhaften strahlenphysikalischen Eigenschaften jedoch voll ausschöpfen zu können, ist eine Verifizierung der Protonenreichweite notwendig. Hierfür gibt es verschiedene Ansätze, wobei das Prompt Gamma Imaging (PGI) eine vielversprechende Methode ist. Eine Schlitzkamera, welche eine mögliche technische Realisierung für das PGI darstellt, ermöglicht die tiefenaufgelöste Messung von protoneninduzierten Prompt-Gamma-Emissionen und erlaubt Aussagen über die tatsächliche Reichweite der applizierten Protonen. An der Universitätsprotonentherapie Dresden (UPTD) wird in naher Zukunft eine klinische Studie zur Nutzung einer solchen Schlitzkamera im Patientenbetrieb beginnen. Hierfür erfolgen gegenwärtig die Vorbereitung der klinischen Implementierung sowie die systematische Charakterisierung des Kamerasystems.

  • Lecture (Conference)
    46. Jahrestagung der Deutschen Gesellschaft für Medizinische Physik, 09.-12.09.2015, Marburg, Deutschland
  • Contribution to proceedings
    46. Jahrestagung der Deutschen Gesellschaft für Medizinische Physik, 09.-12.09.2015, Marburg, Deutschland
    DGMP 2015 - 46. Jahrestagung der Deutschen Gesellschaft für Medizinische Physik - Abstractband, 978-3-9816508-8-4, 286-287

Publ.-Id: 22092

Melanoma targeting with [99mTcN(PNP3)]-labeled α-MSH peptide analogs: Preliminary studies

Gao, F.; Carta, D.; Salvarese, N.; Sihver, W.; Pietzsch, H.-J.; Biondi, B.; Ruzza, P.; Refosco, F.; Bolzati, C.

Objectives: The purpose of this study was to examine the effect of cyclization on the biological profiles of [99mTcN(PNP3)]-labeled α-MSH analogs.
Methods: The linear peptide H-Cys-Ahx-bAla-Nle-Asp-His-D-Phe-Arg-Trp-Gly-NH2 (NAP-NS1) (1) and a corresponding lactam bridge-cyclized peptide, H-Cys-Ahx-bAla3-c[Lys4-Glu-His-D-Phe-Arg-Trp-Glu10]-Arg11-Pro-Val-NH2 (NAP-NS2) (2), were synthesized, characterized by ESI-MS, and their melanocortin-1 receptor (MC1R) binding affinity was determined in B16F10 melanoma cells. In vitro stability and pharmacological parameters of [99mTc(N)(NAP-NS1)(PNP3)]+ (1a) and [99mTc(N)(NAP-NS2)(PNP3)]+ (2a) were assessed. Challenges with an excess of glutathione and cysteine and LogD values were also investigated. Furthermore, 1a and 2a were applied to study in vivo stability and the pharmacokinetic profiles on healthy rats.
Results: 1a and 2a were obtained in high yield (RCY > 90%). LogD values demonstrated the hydrophilic nature of the radiolabeled peptides: -1.43 for 1a; - 2.09 for 2a. No significant variations in RCPs of both the complexes were observed. Both complexes showed high stability after incubation in human and rat sera as well as in rat liver homogenate. A fast degradation of 2a was detected in kidneys homogenate. 1a retained a high receptor affinity (Kd: 7.1±0.5 nM). Biodistribution of 1a displayed a favorable pharmacokinetic profile with fast blood clearance and elimination from normal tissues. Rapid renal excretion of 1a was observed due to the high hydrophilic character. The pharmacokinetic profile of 2a was reflected in reduction of the blood clearance and the elimination from the other organs; especially the kidneys showed restraint elimination.
Conclusions: Compared with the linear peptide 1, cyclization affected the pharmacological properties of 2 negatively by reducing its stability, its binding affinity to MC1Rs (Ki: 0.9±0.3 nM for 1; 7.1±2.4 nM for 2) and decreasing the overall excretion rate of the corresponding [99mTcN(PNP3)]-labeled peptide from the body. Thus, only the linear labeled peptide 1a will be considered for further investigations in tumor bearing mice.

  • Poster
    21st International Symposium on Radiopharmaceutical Sciences (ISRS), 26.-31.05.2015, Columbia/Missouri, USA
  • Open Access Logo Abstract in refereed journal
    Journal of Labelled Compounds and Radiopharmaceuticals 58(2015), S359
    DOI: 10.1002/jlcr.3302_2

Publ.-Id: 22091

(Radio)pharmacological characterization of novel α-MSH derivatives

Gao, F.; Sihver, W.; Bergmann, R.; Haase-Kohn, C.; Steinbach, J.; Carta, D.; Bolzati, C.; Calderan, A.; Pietzsch, J.; Pietzsch, H.-J.

Objectives: Melanocortin-1 receptor (MC1R) is well known to be overexpressed in melanoma. Thus, it has been a great interest in targeting this receptor for diagnosis of human metastasized melanoma. We aimed at investigating
(radio)pharmacological properties of novel derivatives of the α-melanocyte-stimulating hormone (α-MSH) and selecting most promising candidates for further studies in melanoma models in vivo.
Methods: Linear and cyclic α-MSH derivatives (NAP-NS1(1), NOTA-NAP-NS1(2), natCu-NOTA-NAP-NS1(3), NAP-NS2(4), NOTA-NAP-NS2(5), natCu-NOTA-NAP-NS2(6), DPA-NAP-NS1(7) and Re-tricarbonyl-DPA-NAPNS1(8)) were investigated in competition assays in both murine B16F10 and human MeWo cells. In vitro stabilities of [64Cu]Cu-2, [64Cu]Cu-5 and 99mTc-tricarbonyl-7 were tested in phosphate buffer (pH=7.4) and human serum at 37°C for 1h and 24h. Transchelation and octanol/water partition coefficients of radiolabeled peptides were also investigated. Additionally, [64Cu]Cu-2, [64Cu]Cu-5 and 99mTc-tricarbonyl-7 with high radiochemical purities and specific activities were applied in saturation assays and kinetic studies.
Results: Linear α-MSH derivatives (1, 2, 3, 7 and 8) showed higher affinities on both murine and human cells than cyclic α-MSH derivatives (4, 5, 6). Linking the chelator to the peptide and coordinating the chelator-peptide with
natCu or Re were accompanied by some loss of affinity. [64Cu]Cu-2, [64Cu]Cu-5 and 99mTc-tricarbonyl-7 were stable in phosphate buffer and serum at 37°C after incubation for 1h and 24h. No transchelation of radiolabeled peptides was observed in cysteine and histidine challenge experiments. LogD values suggested that [64Cu]Cu-2 (-2.30±0.01) and [64Cu]Cu-5 (-3.39±0.04) had higher hydrophilicity than 99mTc-tricarbonyl-7 (-0.43±0.01). Saturation studies in both cell lines resulted in Kd values (nM) in the lower nanomolar ranges for [64Cu]Cu-2 (B16F10: 1.7±0.2; MeWo: 2.6±0.5) and 99mTc-tricarbonyl-7 (B16F10: 6.0±0.5; MeWo: 4.5±0.8). But Bmax (fmol/mg protein) of [64Cu]Cu-2 on murine and human cells (B16F10: 46.6±3.9; MeWo: 16.6±1.6) was notably lower than that of 99mTc-tricarbonyl-7 (B16F10: 403.5±46.1; MeWo: 50.3±6.4). Kinetic study of [64Cu]Cu-2 in murine cells showed rapid cellular association and dissociation in vitro.
Conclusions: [64Cu]Cu-2 showed high stability, hydrophilicity, binding affinities and rapid cellular association and dissociation in vitro, which made it promising for further investigations in melanoma models.

  • Poster
    21st International Symposium on Radiopharmaceutical Sciences (ISRS), 26.-31.05.2015, Columbia/Missouri, USA
  • Open Access Logo Abstract in refereed journal
    Journal of Labelled Compounds and Radiopharmaceuticals 58(2015), S345
    DOI: 10.1002/jlcr.3302_2

Publ.-Id: 22090

Synthesis, 18F-labeling and radiopharmacological characterization of a claudin-targeting peptide

Löser, R.; Bader, M.; Kuchar, M.; Wodtke, R.; Bergmann, R.; Lenk, J.; Haase-Kohn, C.; Pufe, J.; Steinbach, J.; Pietzsch, J.

Objectives: The cell surface receptor claudin-4 (Cld-4) is upregulated in various tumors and represents a promising target for both diagnosis and treatment of solid tumors of epithelial origin [1]. A suitable ligand to address Cld-4 in vivo seems to be the C-terminal fragment of the Clostridium perfringens enterotoxin cCPE(290-319) (1; Figure 1) [2].
Methods: 1 and N-terminally modified (fluorobenzoylated and FITC-conjugated) as well as other analogs were synthesized by microwave-assisted solid-phase peptide synthesis (SPPS). Their affinity to a protein construct containing both extracellular loops of Cld-4 was studied by surface plasmon resonance (SPR). Labeling of 1 with fluorine-18 was achieved on solid phase using [18F]SFB and 4-[18F]fluorobenzoyl chloride as 18F-acylating agents [3]. The stability of the resulting radiotracer was evaluated in different physiological media. Its cell binding was investigated using the HT29, A375 and A431 tumor cell lines. The in vivo behavior of 18F-labeled 1 was studied in NMRI nu/nu mice and Wistar rats by dynamic PET imaging and radiometabolite analyses, respectively. Furthermore, the binding of FITC-conjugated 1 was investigated by fluorescence microscopy.
Results: Among several approaches tried, sequential SPPS using three pseudoproline-dipeptide building blocks revealed as the most efficient one to afford 1 and its derivatives. Their affinities to the Cld-4 mimicking construct are in the low micromolar range. 18F-labeling was most advantageous when [18F]SFB was reacted with resin-bound 1 containing an N-terminal aminohexanoic spacer. The resulting radiotracer was sufficiently stable in cell supernatants and plasma. Its cell binding was time-dependent and higher to the Cld-4-positive A375 and A431 compared to the negative HT29 line. Results of confocal microscopy using FITC-1 and A431 cells are in accordance with these findings. 18F-labeled 1 is subject to substantial liver uptake and rapid metabolic degradation in vivo.
Conclusions: The synthesis and 18F-labeling of 1 was successfully established. Its binding to Cld-4 in vitro and in cellulo has been demonstrated. Initial radiopharmacological studies suggest the limited suitability of this peptide in its current form to target Cld-4 in vivo.
[1] Neese A, et al (2012) Arch. Biochem. Biophys. 524, 64–70.
[2] Ling J, et al (2008) J. Biol. Chem. 283, 30585–30595.
[3] Kuchar M, et al (2012) Amino Acids 43, 1431-1443.

  • Poster
    21st International Symposium on Radiopharmaceutical Sciences (ISRS), 26.-31.05.2015, Columbia/Missouri, USA
  • Open Access Logo Abstract in refereed journal
    Journal of Labelled Compounds and Radiopharmaceuticals 58(2015), S205
    DOI: 10.1002/jlcr.3302_2

Publ.-Id: 22089

Targeting lysyl oxidase for molecular imaging in breast cancer

Wuest, M.; Kuchar, M.; Sharma, S. K.; Richter, S.; Wankg, M.; Vos, L.; Mackey, J. R.; Wuest, F.; Löser, R.

Objectives: Lysyl oxidase (LOX, EC and its family members LOX-like 1-4 are copper-dependent matrixmodifying enzymes [1]. The expression of LOX is elevated in many human cancers, including breast cancer and correlates with tissue hypoxia. The enzyme plays a critical role in breast cancer metastasis [2]. The goal of the current study was to target LOX with fluorescent and radiolabeled oligopeptides to visualize LOX in preclinical models of breast cancer.
Methods: mRNA expression of all 5 LOX family members was analyzed by gene expression microarray analysis on samples from 176 breast cancer patients. The peptidic substrate GGGDPKGGGGG was selected to target LOX [3]. The peptide was labeled with either FITC for confocal microscopy experiments or with the positron emitter fluorine-18 for molecular imaging in vivo using positron emission tomography (PET) (Figure 1). The preclinical breast cancer models utilized were the murine breast cancer cell line EMT-6 and xenografts of MCF-7 and MDAMB-231.
Results: Immunofluorescence with a LOX-specific antibody confirmed that LOX protein expression is enhanced in hypoxic EMT-6 cells. FITC-labeled oligopeptide binds to several cell compartments of EMT6 cells under hypoxic conditions. After injection of 18F-labeled oligopeptide, radioactivity uptake was visible in all three breast cancer models in vivo with SUV5min values of: 0.70±0.07 (n=3) in EMT-6, 0.57±0.01 (n=3) in MCF-7 and 0.68 (n=2) in MDA-MB-231. The following continuous washout of radioactivity led to SUV60min values of: 0.18±0.03 (n=3) in EMT-6, 0.14±0.02 (n=3) in MCF-7 and 0.13 (n=2) in MDA-MB-231. Tumor uptake was reduced by pre-dosing with the irreversible LOX inhibitor BAPN 4 h and 24 h prior to injection of the radiotracer.
Conclusions: These data support further investigations towards the development of LOX-binding peptides as molecular probes for imaging of LOX expression in breast cancer.
Acknowledgements: The access to the Alberta Cancer Foundation-supported CBCF Tumor Bank is well appreciated.
[1] Payne SL, et al (2007) J. Cell. Biochem.101, 1338-54.
[2] Erler JT, et al (2006) Nature 440, 1222-6.
[3] Nagan N and Kagan HM (1994) J. Biol. Chem. 269, 22366-71.

  • Poster
    21st International Symposium on Radiopharmaceutical Sciences (ISRS), 26.-31.05.2015, Columbia/Missouri, USA
  • Open Access Logo Abstract in refereed journal
    Journal of Labelled Compounds and Radiopharmaceuticals 58(2015), S204
    DOI: 10.1002/jlcr.3302_2

Publ.-Id: 22088

Fast 18F-fluoroethylation without azeotropic drying in the radiosynthesis of cyclooxygenase-2 inhibitors

Kniess, T.; Laube, M.; Pietzsch, J.; Steinbach, J.

Objectives: 18F-Fluoroethylation is a basic approach in PET labeling chemistry and 2-[18F]fluoroethyl tosylate ([18F]FETs) is one of the mostly used agents. Usual protocols with [18F]FETs are covering the azeotropic drying of [18F]fluoride, nucleophilic substitution, purification and 18F-fluoroethylation within 60-90 min synthesis time. We developed a fast 18F-fluoroethylation avoiding azeotropic drying to yield e.g. 18F-fluoroethylated cyclooxygenase-2 (COX-2) inhibitors within 25 min.
Methods: Our approach is based on the finding that [18F]fluoride trapped on SAX cartridges can be completely eluted by a mixture of K222/K2CO3/acetonitrile/2% water and is bsufficiently reactive for 18F-labeling. [1,2] [18F]Fluoride, trapped on the SAX cartridge is eluted with 0.7 mL K222/K2CO3/acetonitrile/H2O into a vial containing 20 μmol bis-tosylate precursor. The vial is heated 10 min at 100°C, than 20 μmol hydroxyl precursor and 40 μmol Cs2CO3 dissolved in 0.5 mL DMF are added. Additional heating for 10 min at 110°C yields the 18Ffluoroethylated COX-2 radiotracers, by almost complete consumption of [18F]FETs. We used three different precursors to build COX-2 inhibitors (Fig) as model compounds to elucidate 18F-fluoroethylation.
Results: By elution of the SAX cartridge (46 mg) with K222/K2CO3/acetonitrile/H2O (42 μmol, 21 μmol, 679 μL, 21 μL) the adsorbed activity could be tranferred nearly quantitatively (93-95%). [18F]FETs was formed in 79-88% rcy as confirmed by radio-TLC. Subsequent 18F-fluoroethylation of the corresponding hydroxyl precursors resulted in yields of 77-92% (n=7) in case of the cyclopentene (1), 54-65% (n=3) for the pyrazolo[1,5-b]pyridazine (2), and 44-70% (n=3) for the indomethacine (3).
Conclusions: The [18F]KF/K222/K2CO3/H2O complex, formed without azeotropic drying is highly reactive to form [18F]FETs in yields up to 88%. Hence the reaction time can be shortened resulting in fast 18F-fluoethylations with total radiochemical yields up to 92% as exemplified for three radiolabeled COX-2 inhibitors.
[1] Wessmann S.H. et al., Nuklearmedizin, 2012, 51, 1-8
[2] Kolb H.C. et al., J.Label.Compd.Radiopharm.,2011, 54, S518

  • Poster
    21st International Symposium on Radiopharmaceutical Sciences (ISRS), 26.-31.05.2015, Columbia/Missouri, USA
  • Open Access Logo Abstract in refereed journal
    Journal of Labelled Compounds and Radiopharmaceuticals 58(2015), S169
    DOI: 10.1002/jlcr.3302_2

Publ.-Id: 22087

18F-Radiolabeling of Second Generation EphB4 Inhibitors Based on Bis-anilinopyrimidines

Mamat, C.; Wiemer, J.; Mosch, B.; Pietzsch, J.; Steinbach, J.

Objectives: Ephrins and its Eph receptors are dysregulated in several human tumor entities including malignant melanoma. In this regard, the EphB4/ephrinB2 system seems to play a major role in melanoma angiogenesis [1].
Thus,we developed a fluorine-18-containing peptide [2] extracellularly binding to EphB4 and a small 18F-labeled molecule which intracellularly binds to the EphB4 kinase domain with high affinity [3] in the past. However, the results showed low binding/uptake in A375EphB4 melanoma cells in vitro and in vivo. Therfore, a “second generation” lead structure based on bis-anilinopyrimidines (IC50 = 1.3 nM) [4] was chosen for novel EphB4-targeted radioligands.
Methods: The lead compound is based on two substructures (part A and B) which were synthesized independently. Two positions of the original inhibitor for the best position of the radiolabel were figured out using docking studies. Based on this, references 2 and 4 as well as precursors 1 and 3 were obtained. In order to introduce [18F]fluoride by ring opening, precursors 1 and 3 were prepared as azetidinium mesylates and lead to high RCYs.
The radiolabeling was done in anhydrous acetonitrile for 30 min at 100°C. Afterwards, the EOE protecting group, which is mandatory for the successful introduction, was cleaved under acidic conditions. The subsequent purification should be easy done by cartridges due to the ionic nature of the precursors [5].
Results: Interestingly, radiofluorination of the first precursor 1 did not lead to the desired tracer [18F]2. The delocalization of the positive charge over both aromatic rings might be the reason for this result. On the other hand, radiofluorination of diazaspirononane precursor 3 was successful and gives the desired [18F]4 in a radiochemical yield of 34% (n.d.c.) and high purity (>95%).
Conclusions: [18F]4 as novel potential EphB4-targeted radioligand based on the bis-anilinopyrimidine scaffold has been successfully synthesized and radiolabeled. Ongoing work is focused on the alternative preparation of radiotracer [18F]2 and on the biological evaluation of both radiotracers to be a suitable target for diagnostic applications.
[1] Mosch, B. et al. (2010), J. Oncol., DOI: 10.1155/2010/135285,
[2] Pretze, M., et al. (2013) ChemMedChem, 8, 935–945,
[3] Mamat, C., et al. (2012) ChemMedChem, 7, 1991–3002,
[4] Bardelle, C., et al. (2010) Bioorg. Med. Chem. Lett., 20, 6242–6245,
[5] Grosse-Gehling, P., et al. (2011) Radiochim. Acta 99, 365–373

  • Poster
    21st International Symposium on Radiopharmaceutical Sciences (ISRS), 26.-31.05.2015, Columbia/Missouri, USA
  • Open Access Logo Abstract in refereed journal
    Journal of Labelled Compounds and Radiopharmaceuticals 58(2015), S166
    DOI: 10.1002/jlcr.3302_2

Publ.-Id: 22086

18F-Labeling and Radiopharmacological Evaluation of Novel Purinedione Multi-Eph Inhibitors

Mamat, C.; Pretze, M.; Neuber, C.; Mosch, B.; Steinbach, J.; Pietzsch, J.

Objectives: The overexpression of various Eph receptors in tumors provokes the recent interest in highly affine inhibitors as attractive leads for the development of new targeted radioligands to image cancer [1]. Selective Ephtyrosine
kinase inhibitors based on the purinedione skeleton have been explored in the past as potential probes for imaging of EphB4 [2] and a SNEW peptide for EphB2 [3]. However up to now, there is still no optimal radiotracer
available. Herein, we report the synthesis, radiofluorination and biological evaluation of two novel purinedione derivatives as potential multi Eph inhibitor radioligands.
Methods: Based on known positions for affinity-related interactions of the lead structure with the receptor [4] two positions are favorable for the labeling with fluorine-18. Two precursors 1 and 3 as well as their reference compounds 2 and 4 were prepared. The radiolabeling was done in dry ACN at 100°C for 30 min. First cell association studies were performed using various Eph expressing melanoma cells (A375wt/mock, A375EphB4,
A375EphB6, A375EphB4) and Eph-negative controls (HL-60).
Results: After labeling, both tracers [18F]2 and [18F]4 were obtained in 10 – 15 % RCY (n.d.c.) after HPLC separation (RCP: > 95%). Cell experiments in vitro revealed a substantial cell association of both [18F]2 and [18F]4 ranging from 40 to 50 %ID/mg protein at 120 min in all cell lines used. The lack of any significant difference between wild type, recombinant and control cells is indicative for cell association of, as expected, low selectivity, but also of low specificity. The latter is consistent with the observation that preincubation with 100 μM of nonradioactive compound did not result in substantial inhibition of cell association.
Conclusions: [18F]2 and [18F]4 were synthesized successfully and first in vitro experiments were accomplished showing substantial cell association for both tracers in various melanoma cells. However, the cell experiments revealed data on specificity of purinedione derivatives that are contradictory to data from literature [4]. These observations will be elucidated in ongoing studies.
[1] Mosch, B. et al. (2010), J. Oncol., DOI: 10.1155/2010/135285;
[2] Mamat, C. et al. (2012), ChemMedChem, 7, 1991–2003;
[3] Pretze, M., et al. (2013) ChemMedChem, 8, 935–945; [4] Lafleur, K. et al.
(2009) J. Med. Chem., 52, 6433–6446.

  • Poster
    21st International Symposium on Radiopharmaceutical Sciences (ISRS), 26.-31.05.2015, Columbia/Missouri, USA
  • Open Access Logo Abstract in refereed journal
    Journal of Labelled Compounds and Radiopharmaceuticals 58(2015), S165
    DOI: 10.1002/jlcr.3302_2

Publ.-Id: 22085

First-in-human PET quantification study of cerebral α4β2* nicotinic acetylcholine receptors using the novel specific radioligand (−)-[18F]Flubatine

Sabri, O.; Becker, G.-A.; Meyer, P. M.; Hesse, S.; Wilke, S.; Graef, S.; Patt, M.; Luthardt, J.; Wagenknecht, G.; Hoepping, A.; Smits, R.; Franke, A.; Sattler, B.; Habermann, B.; Neuhaus, P.; Fischer, S.; Tiepolt, S.; Deuther-Conrad, W.; Barthel, H.; Schönknecht, P.; Brust, P.

α4β2* nicotinic receptors (α4β2* nAChRs) could provide a biomarker in neuropsychiatric disorders (e.g., Alzheimer's and Parkinson's diseases, depressive disorders, and nicotine addiction). However, there is a lack of α4β2* nAChR specific PET radioligands with kinetics fast enough to enable quantification of nAChR within a reasonable time frame. Following on from promising preclinical results, the aim of the present study was to evaluate for the first time in humans the novel PET radioligand (−)-[18F]Flubatine, formerly known as (−)-[18F]NCFHEB, as a tool for α4β2* nAChR imaging and in vivo quantification.
Dynamic PET emission recordings lasting 270 min were acquired on an ECAT EXACT HR+ scanner in 12 healthy male non-smoking subjects (71.0 ± 5.0 years) following the intravenous injection of 353.7 ± 9.4 MBq of (−)-[18F]Flubatine. Individual magnetic resonance imaging (MRI) was performed for co-registration. PET frames were motion-corrected, before the kinetics in 29 brain regions were characterized using 1- and 2-tissue compartment models (1TCM, 2TCM). Given the low amounts of metabolite present in plasma, we tested arterial input functions with and without metabolite corrections. In addition, pixel-based graphical analysis (Logan plot) was used. The model's goodness of fit, with and without metabolite correction was assessed by Akaike's information criterion. Model parameters of interest were the total distribution volume VT (mL/cm3), and the binding potential BPND relative to the corpus callosum, which served as a reference region.
The tracer proved to have high stability in vivo,with 90% of the plasma radioactivity remaining as untransformed parent compound at 90 min, fast brain kinetics with rapid uptake and equilibration between free and receptor bound tracer. Adequate fits of brain TACs were obtained with the 1TCM. VT could be reliably estimated within 90 min for all regions investigated, and within 30 min for low-binding regions such as the cerebral cortex.
The rank order of VT by region corresponded well with the known distribution of α4β2* receptors (VT [thalamus] 27.4±3.8, VT [putamen] 12.7±0.9, VT [frontal cortex] 10.0±0.8, and VT [corpus callosum] 6.3±0.8). The BPND, which is a parameter of α4β2* nAChR availability, was 3.41±0.79 for the thalamus, 1.04±0.25 for the putamen and 0.61 ± 0.23 for the frontal cortex, indicating high specific tracer binding. Use of the arterial input function without metabolite correction resulted in a 10% underestimation in VT, and was without important biasing effects on BPND.

Keywords: (−)-[18F]Flubatine [(−)-[18F]NCFHEB]; PET; α4β2* nicotinic acetylcholine receptors; Human brain; Kinetic modeling

Publ.-Id: 22084

Radiosynthesis of [18F]cabozantinib and [18F]fluoroethyl-sunitinib: two RTK-inhibitors of VEGFR-2

Schwebe, M.; Bergmann, R.; Steinbach, J.; Pietzsch, J.; Kniess, T.

Objectives: Radiolabeled inhibitors of the angiokinase VEGFR-2 might be suitable probes for monitoring induction of angiogenesis and anti-angiogenic therapy response in vivo with PET. [1,2]. We selected two VEGFR-2 inhibitors, cabozantinib (IC50, 0.03 nM) and sunitinib (IC50, 9.0 nM), both bearing a fluorine substituent, as lead structures for 18F-radiolabeled PET tracers.
Methods: [18F]Cabozantinib is synthesized by a 3-step radiosynthesis with final condensation of 4-[18F]fluoroaniline with an acyl chloride precursor. 4-[18F]Fluoroaniline is formed by substitution of 1,4-dinitrobenzene with [18F]fluoride, subsequent reduction of the intermediate 4-[18F]fluoro-nitrobenzene with Pd/C and NaBH4. Since [18F]sunitinib is not accessible via direct nucleophilic 18F-substitution, we developed the 5-fluoroethylated derivative (IC50, 9 nM) as well the corresponding radiolabeled analogue.
Results: 4-[18F]fluoroaniline was obtained in >60% rcy starting from [ 18F]fluoride after SPE purification. [18F]Cabozantinib was formed by reaction of 4-[18F]fluoroaniline with 10 mg of acyl precursor in THF at rt in >90% rcy. HPLC purification delivered [18F]cabozantinib in 95% purity and specific activity >20 GBq/μmol. Reaction of the methanesulfonyl-substituted sunitinib precursor with [18F]fluoride resulted in 8% 18F-incorporation. HPLC purification yielded [18F]fluoroethyl-sunitinib in 100 MBq scale. First in vitro investigations on VEGFR-2 expressing human A 2058 melanoma cell line showed cellular uptake of [18F]cabozantinib up to 790±100 %ID/mg protein at 60 min that could be significantly blocked by 46±3% by its non-radioactive counterpart (10 μM). For [18F]fluoroethyl-sunitinib the uptake reached 340±48 %ID/mg protein at 60 min. Stability tests in rat blood over 60 min revealed almost no metabolism for both radiotracers.
Conclusions: With the reliable radiosynthesis of [18F]cabozantinib and [18F]fluoroethyl-sunitinib two radiolabeled VEGFR-2 inhibitors with nano- and sub-nanomolar affinity and high in vivo stability are available.
References [1] Slobbe P. et al (2012) Drug Discov. Today, 17, 1175-1187
[2] Kniess T. (2012) Curr Pharm Des, 18, 2867-2874

  • Poster
    21st Internation Symposium on Radiopharmaceutical Sciences (ISRS), 26.-31.05.2015, Columbia/Missouri, USA
  • Open Access Logo Abstract in refereed journal
    Journal of Labelled Compounds and Radiopharmaceuticals 58(2015), S159
    DOI: 10.1002/jlcr.3302_2

Publ.-Id: 22083

An attractive method for radiolabeling antibodies with Tc-99m

Wunderlich, G.; Naumann, A.; Schubert, M.; Pietzsch, H.-J.

Objectives: Radiolabeled Cetuximab (C225, Ab) is an attractive tool for tumor targeting and delivering of particles for therapy or imaging applications of EGFR positive tumors. The labeling of Ab with radionuclides requires suitable chelating agents for a stable binding of the radionuclides. Well known is the Ab labeling with In-111 (imaging) and Y-90 (therapy). The aim of the present study was to develop a sufficient radiolabeling technique of this Ab with Tc-99m for SPECT imaging. A second label with a fluorescent dye (Alexa 488) enables to track the uptake of the compound with fluorescent microscopy.
Methods: NOTA (2,2',2''-(1,4,7-triazonane-1,4,7-triyl)triacetic-acid) was linked to C225 and labeled with the [Tc-99m]Tc(H2O)3(CO)3 complex that was made by a standard tricarbonylkit preparation [1]. For preparation of [Tc-99m]Tc(CO)3-NOTA-C225-Alexa(488) (figure 1) and [Tc-99m]Tc(CO)3-NOTA-C225 1 nM of the modified antibody was incubated with up to 1 GBq [Tc-99m]Tc(H2O)3(CO)3 complex and was shaken for 2 h at 40°C. The product was isolated by gelfiltration and tested for yield and stability with ITLC (Silica gel impregnated glass fiber sheets, Varian) in 5% acetic acid. The cell membrane binding and cell uptake of the compound was detected with Cetuximab receptor positive A431 cells and Cetuximab negative MDA cells. For comparison the pure NOTA ligand and unmodified Cetuximab were labeled with [Tc-99m]Tc(H2O)3(CO)3.
Results: NOTA-C225-Alexa(488), NOTA-C225 and NOTA ligand were successfully labeled with [Tc-99m]Tc(H2O)3(CO)3. Sufficient radiolabeling of Cetuximab was achieved and determined by ITLC. Yields: [Tc-99m]Tc-NOTA-C225-Alexa(488) 25-30% and [Tc-99m]Tc-NOTA-C225 50-60%. After purification the labeled compound is stable in cell culture medium and phosphate buffered saline to 24 h with a release of about 20%. Maximum membrane uptake at A431cells is determined after 1 h followed by a partly internalization into the cells. The affinity constant was found Kd = 3.71 nM and Bmax = 35 nM. Already after 1 h the localisation of NOTAC225-Alexa(488) is visualized with fluorescence microscope at cell membrane.
Conclusions: NOTA-Cetuximab can be radiolabeled with Tc-99m which is an interesting approach for SPECT studies in Nuclear Medicine besides the Ab labeling with Ga-68 or Cu-64.
References [1] Alberto, R. et al. (1998) J. Am. Chem. Soc., 120, 7987-7988.

  • Poster
    21st Internatioonal Symposium on Radiopharmaceutical Sciences (ISRS), 26.-31.05.2015, Columbia/Missouri, USA
  • Open Access Logo Abstract in refereed journal
    Journal of Labelled Compounds and Radiopharmaceuticals 58(2015), S105
    DOI: 10.1002/jlcr.3302_2

Publ.-Id: 22082

Potential labeling strategies with NCA 197(m)Hg

Walther, M.; Wang, C.; Bergmann, R.; Pietzsch, H.-J.; Steinbach, J.

Objectives: The decay properties of both nuclear isomers, like convenient half life 197mHg (T1/2 = 23.8 h, Eγ 133.98 keV, 33.5%) and 197Hg (T1/2 = 64.14 h, Eγ 77.4 keV, 18.7%), low energy gamma radiations for imaging and numerous Auger- and conversion electrons useful for therapy combined with unique chemical and physical properties of mercury and its compounds represent the motivation for this project. The no carrier added (NCA) radionuclide 197(m)Hg is accessible in sufficient quantity and quality for radiopharmaceutical research by irradiation of gold with protons using a cyclotron [1]. As the following logical step after examination of the production feasibility, the search for a suitable labeling tool was intensified.
Methods: Three different approaches to prepare a stable labeling unit at NCA level with 197(m)Hg were studied. The reactivity of the mercury(II) ions towards sulfur containing ligands (a), solvomercuration of alkenes (b) and electrophilic aromatic substitution (c) were investigated in this context. Prepared characteristic representatives of all three groups are shown in Figure 1.
Results: For all studied reactions the desired 197(m)Hg labeled compounds were detected. The mercury thiolate complexe (a) and the product of solvomercuration (b) show low stability in the presence of competing thiol ligands and therefore the suitability for radiopharmaceutical applications is not given. In contrast, diphenylmercury (c) as the simplest representative for symmetric diarylmercury compounds shows high stability against competing
Conclusions: As a basis for the development of a convenient labeling method different kinds of mercury compounds were prepared and characterized at NCA level. After nuclide production this was the required succeeding part of the evaluation of the cyclotron-based NCA 197(m)Hg regarding their suitability for diagnostics and therapy of tumors. First promising results of investigations concerning the development of mercury compounds stable in vivo will be reported.

References: [1] Walther, M., Preusche, S., Bartel, S., Wunderlich, G., Freudenberg, R., Steinbach, J., Pietzsch, H.-J., Theranostic mercury: 197(m)Hg with high specific activity for imaging and therapy (2014) Appl. Radiat. Isot. submitted

  • Poster
    21st International Symposium on Radiopharmaceutical Sciences (ISRS), 26.-31.05.2015, Columbia/Missouri, USA
  • Open Access Logo Abstract in refereed journal
    Journal of Labelled Compounds and Radiopharmaceuticals 58(2015), S99
    DOI: 10.1002/jlcr.3302_2

Publ.-Id: 22081

68Ga-DATATOC: Synthesis, radiolabeling and first in vivo studies

Waldron, B.; Seemann, J.; Sinnes, J.-P.; Bergmann, R.; Nagel, J.; Rösch, F.

Objectives: 68 Ga-DOTATOC is currently used as standard for diagnostic imaging of neuroendocrine tumors (NETs) and its metastases. Radiolabeling can be performed manually and automated at 95 °C. In order to approach application of 68 Ga following a kit-type procedure, a DATA-based chelator (6-Amino-1,4-diazepine-triacetate) was used as it has shown to radiolabel under very mild conditions. Conjugation with TOC may enable radiolabeling of the peptide at room temperature.
Methods: DATATOC was synthesized in a seven step synthesis. Radiolabeling with 68 Ga was performed manually at room temperature and stability was assessed in human serum. An automated setup was also examined, using the Modular-Lab eazy (Eckert & Ziegler, Berlin, Germany). First in vivo studies using MPC-mCherry tumor bearing mice were performed and compared with 68 Ga-DOTATATE.
Results: Radiolabeling was performed at room temperature using N2 solution, NaOAc-buffer and 14 nmol DATATOC. Within 3 min a RCY of 96.3 ± 1.2 % was obtained. Stability was tested in human serum over a period
of 2 h (Δ = 1.3 %). Automated labeling with 23 nmol precursor achieved quantitative complexation of 68 Ga (> 99 %). In vivo PET/CT-studies with 68Ga-DATATOC indicate a high specific uptake in the tumor region after 10 min (SUV of 3.73 ± 1.49). In a blocking study with OC, the SUV in the tumor was reduced to 0.45 ± 0.15. In addition, 68 Ga-DATATOC showed high stability in mouse plasma with 93.7 % of the tracer remaining intact after 120 min. Compared to 68 Ga-DOTATATE a faster renal excretion of the tracer was observed.
Conclusions: DATATOC can be labeled with 68 Ga in a manual or automated setup rapidly at room temperature, offering significant advantages over similar DOTA-based derivatives. Because of quantitative labeling yields, product purification is unnecessary. Furthermore, first in vivo studies confirm excellent targeting and excretion characteristics for the novel tracer. With the perspective towards a kit-type formulation, the superior characteristics
of this new compound pave the way for a new generation of 68 Ga radiopharmaceuticals.

  • Lecture (Conference)
    21st International Symposium on Radiopharmaceutical Sciences (ISRS), 26.-31.05.2015, Columbia/Missouri, USA
  • Open Access Logo Abstract in refereed journal
    Journal of Labelled Compounds and Radiopharmaceuticals 58(2015), S15
    DOI: 10.1002/jlcr.3302_1

Publ.-Id: 22080

A novel pretargeting system based on complementary L-oligonucleotides

Schubert, M.; Foerster, C.; Bergmann, R.; Sihver, W.; Vonhoff, S.; Klussmann, S.; Bethge, L.; Walther, M.; Pietzsch, J.; Pietzsch, H.-J.; Steinbach, J.

Objectives: High metabolic stability, low immunogenicity and negligible specificity for naturally binding partners are predominant characteristics of L-configured oligonucleotides. These advantages predestine this substance class
for its use in pretargeted radioimmunotherapy as in vivo recognition system between a tumor-specific antibody and a radiolabeled chelate. We evaluated this new pretargeting system consisting of 64Cu labeled NOTA-L-DNA-10kDa-PEG and c-L-DNA modified Cetuximab (C225) in vitro and in vivo.
Methods: C225 was functionalized with NOTA, maleimide moieties and thiol-bearing c-L-DNA. Competition studies were carried out against 64Cu labeled standard NOTA3-C225 in FaDu and A431-cell lysates. In vitro pretargeting studies were done in intact FaDu and A431 cells. PET and biodistribution studies were performed both in FaDu and A431 tumor bearing mice by intravenous injection of 4 nmol NOTA3-C225-(c-L-DNA)1,5 and 1 nmol [64Cu]Cu-NOTA-L-DNA-10kDa-PEG 24 h later.
Results: We synthesized two Cetuximab derivatives with 1.5 and respective 5 c-L-DNA molecules per antibody. Competition assays showed that affinities are not affected as a result of conjugation with NOTA and c-L-DNA.
PET studies injecting only [64Cu]Cu-NOTA3-C225-(c-L-DNA)1.5 revealed that a pretargeting interval of 24 h is the best compromise between tumor accumulation, blood background as well as liver uptake. Biodistribution in pretargeted A431 tumor mice is characterized by decreased tumor uptake (see figure). Internalization of antibody within waiting period is the obvious reason and could be confirmed by cellular uptake studies. After 24 h over 2/3 of surface bound antibody was internalized.
Conclusions: The present pretargeting concept shows high potential for further preclinical studies. Use of a noninternalizing antibody is necessary to enhance both tumor uptake and tumor to background ratios.

  • Lecture (Conference)
    21st International Symposium on Radiopharmaceutical Sciences (ISRS), 26.-31.05.2015, Columbia/Missouri, USA
  • Open Access Logo Abstract in refereed journal
    Journal of Labelled Compounds and Radiopharmaceuticals 58(2015), S14
    DOI: 10.1002/jlcr.3302_1

Publ.-Id: 22079

An Image Reconstruction Framework and Camera Prototype Aimed for Compton Imaging for In-vivo Dosimetry of Therapeutic Ion Beams

Schoene, S.; Enghardt, W.; Fiedler, F.; Golnik, C.; Pausch, G.; Rohling, H.; Kormoll, T.

Prompt gamma-ray imaging in hadron therapy is a novel approach for range verification. Due to the high energy of prompt gamma-rays emitted during therapeutic irradiation in the order of MeV, Compton imaging is a feasible method. In this work, an imaging prototype together with a data handling and an image reconstruction framework are presented. Data and reconstructed images from laboratory measurements are shown and evaluated. A spatial resolution of 7 mm in a distance of 7 cm has been achieved. More importantly, current limitations were identified for further work. It has been shown that an assumption on the unknown initial photon energy can considerably improve the imaging result.

Keywords: Compton camera; dosimetry; dose monitoring; Compton camera imaging; hadron therapy; cadmium zinc telluride; image reconstruction; system matrix

Publ.-Id: 22078

Evidence of a distinct Permian thermal event by EMP-Th-Pb-monazite ages in metapelites of the polymetamorphic Austroalpine basement

Schulz, B.; Zimmermann, R.; Krenn, E.

During the Alpine orogeny, the Austroalpine basement complex of the Eastern Alps was thrusted upon the Penninic ophiolites and the European basement, now exposed in the Tauern and Engadine tectonic windows. The Austroalpine basement underwent a polymetamor- phic evolution since the Early Paleozoic. An Ordovi- cian-Silurian event, the Devonian-Carboniferous Var- iscan orogeny, as well as the Cretaceous and Tertiary Alpine orogenic periods have been recognised in many parts. Although a wealth of radiometric data on these events exist, a distinct Permian metamorphic episode has not yet been established. Corresponding mica cool- ing ages were considered as Variscan-to-Alpine “mixed ages” in this polymetamorphic frame. However, the intrusion of Permian pegmatites between 270-250 Ma is an important marker of the tectonic and magmatic activity (Schuster et al. 2001).

The Permian pegmatites can be traced from the Ortler- Campo basement through the basement to the south of the Tauern Window toward the East into the Saualpe and Koralpe units. The electron microprobe (EMP) Th-U-Pb monazite dating method (Montel et al. 1996) has been applied to the garnet-bearing metapelitic host rocks of these Permian pegmatites. In the Saualpe, the Permian pegmatites were strongly deformed during the eclogite-facies Cretaceous event. In the metapelitic host rocks, the Permian monazites have the largest grain sizes and abundance. They are often character- ised by spectacular coronas of apatite and allanite of a partial decomposition.

In the Schobergruppe and the Defereggen Alps to the south of the Tauern Window, the Permian monazites are a less prominent population, but clearly distinct from the Carboniferous monazites (Krenn et al. 2012). The characteristic coronas around the Permian mona- zites are lacking. Permian monazites occur mainly in a zone with fibrolitic sillimanite and andalusite in the vicinity of the pegmatites.

The Oetztal-Stubai basement to the W of the Tauern Window is characterised by a Cretaceous metamor- phic overprint. Permian pegmatites have not yet been reported. The monazite Th-U-Pb EMP ages in the Sellrain area and in the central Oetztal valley (Umhau- sen, Sölden) in the northern vicinity of the Cretaceous metamorphic zone are mostly Carboniferous. They are interpreted to be related to a Variscan amphibolite- to-eclogite-facies garnet crystallisation (Rode et al. 2012). Recent investigations in the Stubai valley re- vealed garnet metapelites with exclusively Permian monazites. These monazites are often surrounded and partly replaced by coronas of apatite and allanite. The mineral-chemical properties and the special character of the dating method allow the conclusion that the Permian monazites represent a distinct crystallisation event at low pressures, apparently in an occasional association to the pegmatites.


Krenn, E., Schulz, B. & Finger, F. (2012): Three generations of monazite in Austroalpine basement rocks to the south of the Tauern Window – evidences for Variscan, Permian and Alpine metamorphism. – Swiss Journal of Geosci- ences, 105, DOI 10.1007/s00015-012-0104-6.

Montel, J.-M., Foret, S., Veschambre, M., Nicollet, C. & Provost, A. (1996): A fast, reliable, inexpensive in-situ dating technique: Electron microprobe ages on monazite. – Chem. Geol., 131: 37-53.

Rode, S., Rösel, D. & Schulz, B. (2012): Constraints on the Variscan P-T evolution by EMP Th-U-Pb monazite dat- ing in the polymetamorphic Austroalpine Oetztal-Stubai basement (Eastern Alps). – Z. Dt. Ges. Geowiss. 163: 43- 67; Stuttgart.

Schuster, R., Scharbert, S., Abart, R. & Frank, W. (2001): Permo-Triassic extension and related HT/LP metamor- phism in the Austroalpine - Southalpine realm. – Mitt. Ges. Geol. Bergbaustud. Österr., 45: 111-141; Wien.

  • Poster
    GeoFrankfurt 2014, 21.-24.09.2014, Frankfurt/Main, Deutschland

Publ.-Id: 22077

Numerical Simulation of the Copper Slag Cleaning Process

Yang, H.; Wolters, J.; Pischke, P.; Solters, H.; Fröhlich, J.; Eckert, S.

Slags from smelting of copper still contains up to 20 % of copper inclusions, which can to some extend be recovered by a special cleaning process. The long-term goal of the authors is to use numerical MHD to simulate the complex slag cleaning process in detail and to optimize it. The paper presents preliminary results on simplified test cases and configurations.
It turned out when simulating the copper droplets in the slag by a discrete phase model, the pure stochastic parcel collision algorithm in FLUENT failed to provide mesh-independent and precise results for inter-droplets collisions and coalescence. Therefore, a new hybrid collision algorithm and the updated coalescence regimes were implemented in FLUENT. Several benchmark tests were reported in order to demonstrate the significant differences between the two algorithms and the main advantages of the new hybrid algorithm for simulations on the slag cleaning process.

Keywords: EM stirring; collision model; copper slag cleaning; MHD

  • Poster
    8th International Conference on Electromagnetic Processing of Materials (EPM), 12.-16.10.2015, Cannes, France
  • Contribution to proceedings
    8th International Conference on Electromagnetic Processing of Materials (EPM), 12.-16.10.2015, Cannes, France, 978-2-9553861-0-1, 255-258

Publ.-Id: 22076

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