Publications Repository - Helmholtz-Zentrum Dresden-Rossendorf

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32314 Publications
Exploratory prospective trial of hypoxia-specific PET imaging during radiochemotherapy in patients with locally advanced head-and-neck cancer
Zips, D.; Zöphel, K.; Abolmaali, N.; Perrin, R.; Abramyuk, A.; Haase, R.; Appold, S.; Steinbach, J.; Kotzerke, J.; Baumann, M.;
Purpose: To explore in a prospective trial the prognostic value of hypoxia imaging before and during radiochemotherapy in patients with locally advanced head and neck cancer.
Patients and methods: Twenty-five patients with stage III/IV head and neck cancer were investigated with [18F]-fluoromisonidazole (FMISO) PET/CT at four time points during radiochemotherapy (baseline, 8–10 Gy, 18–20 Gy,50–60 Gy). FMISO PET/CT image parameters were extracted including maximumtumour-to-background (TBRmax) and thresholded volume at different TBR ratios. CT volume and baseline FDG-PET/CT image parameters were also included. Parameters at all time points were investigated for their prognostic value with the local-progression-free-survival endpoint (LPFS). Significance was evaluated with multivariate Cox (including clinical parameters) and Log-rank tests.
Results: FMISO-image parameters were found to have a strong association with the LPFS endpoint, and were strongest at the week 1 and 2 time points (p = 0.023–0.048 and 0.042–0.061 respectively on multivariate Cox). Parameters measured at baseline were only significant on univariate analysis. None of the clinical parameters, and also FDG- or CT-delineated volumes, were significantly associated with LPFS.
Conclusion: This prospective, exploratory study demonstrated that FMISO-PET/CT imaging during the initial phase of treatment carries strong prognostic value. FMISO-PET/CT imaging at 1 or 2 weeks during treatment could be promising way to select patients that would benefit from hypoxia modification or dose-escalated treatment. A validation study is on-going.
Keywords: [18F]-misonidazole-PET; Head-and-neck cancer; Radiotherapy

Publ.-Id: 18256 - Permalink

Innovative Technologien für Ressourceneffizienz - Strategische Metalle und Mineralien
Dürkoop, A.;
Um die Versorgung mit metallischen Rohstoffen für Deutschland zukünftig nachhaltig zu sichern, hat das BMBF im Jahr 2012 die r3-Fördermaßnahme mit dem Fokus auf strategische Metalle und Mineralien ins Leben gerufen. Die bisher bewilligten r3-Verbundprojekte sowie das koordinierende Helmholtz-Institut Freiberg für Ressourcentechnologie wurden in der Präsentation vorgestellt.
Keywords: Rohstoffeffizienz, Strategische Metalle und Mineralien
  • Invited lecture (Conferences)
    BMBF Branchendialog Nanotechnologien und Neue Materialien für Ressourceneffizienz, 06.12.2012, Berlin, Deutschland

Publ.-Id: 18255 - Permalink

Additional constraints may soften a non-conservative structural system: Buckling and vibration analysis
Lerbet, J.; Kirillov, O.; Aldowaji, M.; Challamel, N.; Nicot, F.; Darve, F.;
The effect of additional kinematic constraints on eigenfrequencies of non conservative systems presenting a non symmetric stiffness matrix is investigated with the use of the second order work criterion. It is shown that there are always additional constraints that may soften structural systems, from both buckling and vibration points of view. The steps for building such constraints are given, consequences on stability are discussed and several illustrating examples are presented.
Keywords: Stability; Vibrations; Non-conservative problems; Constrained systems; Second-order work criterion

Publ.-Id: 18254 - Permalink

Neue Technologien für mehr Rohstoffeffizienz
Dürkoop, A.;
Seit Sommer 2012 forschen bundesweit mehr als 100 Unternehmen, Forschungseinrichtungen und Behörden in der BMBF-Fördermaßnahme r3 „Innovative Technologien für Ressourceneffizienz – Strategische Metalle und Mineralien“ mit dem Ziel, die Effizienz für nicht energetische Rohstoffe nachhaltig zu steigern. Alle bisher gestarteten r3-Verbundprojekte zielen darauf ab, wirtschaftsstrategisch wichtige Metalle wie z.B. Indium, Germanium, Gallium und seltene Erden, aber auch Industrieminerale wie Flussspat zukünftig effizienter zu gewinnen, zu recyceln, aber auch effizienter in Produkten zu verwenden. So werden diese Metalle und Mineralien vor allem für die Herstellung von Hightech-Produkten wie Computern, Mobiltelefonen und Energiesparlampen aber auch für Dauermagnete in Windkraftanlagen benötigt. Zwar werden diese Ressourcen zurzeit nicht in großen Mengen verwendet, sind dafür aber wirtschaftsstrategisch von großer Bedeutung. Dabei sind diese Rohstoffe zunehmend schlechter verfügbar und führen somit zu steigenden Produktionskosten. Da die Versorgungslage für diese strategischen metallischen Rohstoffe unsicher ist, könnte es zu Versorgungsengpässen im Rohstoffimportland Deutschland kommen. Nur mit einer sicheren Rohstoffversorgung können in Deutschland auch zukünftig Hightech-Produkte produziert und entwickelt werden.
Keywords: Strategische Metalle, Rohstoffeffizienz, Recycling
  • GAIA - Ökologische Perspektiven für Wissenschaft und Gesellschaft 22/1(2013), 62-64

Publ.-Id: 18253 - Permalink

Serpent Monte-Carlo Code: An Advanced Tool for Few-Group Cross Section Generation
Fridman, E.;
Serpent is a continuous-energy Monte Carlo (MC) reactor physics code recently developed at VTT Technical Research Centre of Finland(1). Serpent can be used for 2D fuel lattice calculations as well as for 3D full core simulations.Serpent is especially designed to generate homogenized constants for deterministic 3D core analysis. For any region of interest the code automatically calculates homogenized few-group cross sections, group-to-group scattering matrices, diffusion coefficients, assembly discontinuity factors, kinetics parameters, etc.
The capability to generate homogenized few-group constants can be considered as one of the most attractive features of Serpent. Being a MC code, Serpent is capable of handling complex geometries without any major approximations and can be used for producing cross section data for virtually any fuel or reactor type. The demonstration of the Serpent capability to generate few-group cross sections for different reactor systems is the main topic of this paper.
Keywords: Serpent, Monte Carlo, few-group cross section generation
  • atw - International Journal for Nuclear Power 58(2013)3, 156-157

Publ.-Id: 18252 - Permalink

Doping of nanostructure and defect engineering by ion beam implantation and irradiation
Ou, X.;
This talk will give a brief introduction of my recent works on application of ion implantation and ion irradiation on doping of nanostructure and on defect engineering for nanostructure fabrication and nuclear materials.
Doping of vertical Si nanowires (NWs) is demonstrated here by multi energy ion implantation. The doping behavior of the individual Si NWs was investigated by SSRM. A strong surface segregation of the implanted P in Si was found during the subsequent annealing process, and deactivation of the P also was excepted at the NW surface. A diameter dependence of the local resistivity of the NW cross sections RS increases as the NW diameter decreases and this tendency is significantly enhanced as the diameter is below 25 nm.
The resistive switching (RS) of functional oxide thin films has attracted tremendous interest recently due to its promising application as building blocks in non-volatile memory devices. This work reports a low cost and effective approach to tune the resistive switching behavior of BiFeO3 films which have been deposited by pulsed laser deposition and irradiated with low energy Ar+ ions. Due to the preferential sputtering of BiFeO3 films, oxygen vacancies as well as the surface morphology can be tuned by low energy irradiation in a controllable way to enhance the RS performance.
The dual beam facility in Rossendorf is used for the investigation of the radiation damage in yttria-stabilized zirconia (YSZ) created either by simultaneous implantation of Zr+ & He+ or by separate single beam implantation. The results show that the excitation by the additional Zr+ implantation can activate and enhance the out diffusion of the simultaneously implanted helium. The release of helium.from YSZ substrate, instead to be trapped by implantation induced vacancies generated by the heavy Zr+ ions, avoids the formation and growth of He bubbles.
Keywords: doping and defect engineering
  • Lecture (others)
    Lecture given in Beihang University and Perking University, 28.09.2012, Beijing, China

Publ.-Id: 18251 - Permalink

Control of Coulomb-mediated excitonic 2s emission by an external magnetic field
Bhattacharyya, J.; Zybell, S.; Winnerl, S.; Schneebeli, L.; Böttge, C. N.; Breddermann, B.; Kira, M.; Koch, S. W.; Helm, M.; Schneider, H.;
We report on time-resolved photoluminescence (PL) studies of exciton dynamics in undoped GaAs quantum wells in the presence of an external magnetic field. Subsequent to pulsed interband excitation, the photogenerated excitons are manipulated by applying time-delayed THz pulses from the free-electron laser (FEL) FELBE at the Helmholtz-Zentrum Dresden-Rossendorf. Simultaneous time and wavelength resolved spectroscopy using a synchroscan streak camera allows us to investigate the emitted PL with high detection efficiency [1]. If the FEL photon energy is tuned into resonance with the intra-excitonic 1s-2p transition, the PL originating from the 1s exciton is suppressed by the incident THz pulse and subsequently recovers to a value higher than the reference trace. Furthermore, the THz pulse leads to pronounced enhancement of the PL intensity at the energy of the excitonic 2s and 2p states. Since radiative recombination is dipole forbidden for the 2p state, this PL contribution is attributed to 2s emission [2], thus confirming earlier theoretical predictions of efficient Coulomb scattering between the nearly degenerate 2s and 2p states which allows for rapid 2p-2s population transfer [3].
In this presentation, we demonstrate the efficient manipulation of the 2p-2s scattering efficiency via an external magnetic field, which tunes the 2s and 2p exciton energies from resonant to non-resonant since these energies change differently with magnetic field. This leads to efficient suppression of the THz induced 2s PL signal upon increasing the magnetic field from 0 T to 2.5 T. These results demonstrate that the underlying Coulomb-mediated 2p-2s scattering process can be magnetically controlled. Our experiments confirm theoretical calculations which will also be discussed.
Keywords: semiconductor quantum well, exciton, time-resolved photoluminescence, free-electron laser, intra-excitonic transition
  • Poster
    International Workshop on Optical Terahertz Science and Technology 2013, 01.-05.04.2013, Kyoto, Japan

Publ.-Id: 18250 - Permalink

Colloidal Stability of Carbon Nanotubes - A Matter of Modification
Schymura, S.; Weiß, S.; Zänker, H.; Franke, K.;
The implications of a carbon nanotube (CNT) release into the environment are majorly influenced by the colloidal stability of the CNTs in surface or ground waters. Main factors for this stability are the degree of oxidation of the CNTs and the presence of natural organic matter (NOM) such as fulvic or humic acids. Pristine CNTs show very low dispersion stability in water and quickly aggregate and sediment.
However covalent and/or non-covalent modification of the CNTs through, for example, natural oxidation processes or adsorption of NOM can considerably alter their colloidal stability, thereby affecting the fate of the CNTs upon release. For this study samples of different types of CNTs, multi wall as well as single wall CNTs, were modified covalently by a microwave assisted oxidative treatment and non-covalently by dispersion in the presence of fulvic acid. The colloidal stability of the so modified CNTs was investigated using dynamic light scattering methods to follow the aggregation and sedimentation of the CNTs as well as establishing the ζ potential of the modified CNTs in waters of different ionic strength.
The colloidal stability of the modified CNTs in distilled and low ionic strength water or in the presence of fulvic acid can exceed months. This has implications for their transport behavior upon release into the environment. A transport of CNTs in surface and ground waters can be expected under certain conditions.
Keywords: carbon nanotubes, colloidal stability, modification
  • Poster
    NanoNature Clustertreffen 2013, 14.-15.01.2013, Frankfurt a. Main, Deutschland

Publ.-Id: 18249 - Permalink

Radiolabelling of silver and titania nanoparticles as a tool for sensitive detection of nanoparticle release from surface coatings
Hildebrand, H.; Franke, K.; Gibson, N.; Cydzik, I.; Simonelli, F.; Bulgheroni, A.; Holzwarth, U.; Bilz, E.; Freyer, A.;
Engineered nanoparticles (NPs) such as silver and titania are widely used in consumer products e.g. as functional additives in surface coatings. Due to aging or abrasion of these nanocomposites, particle release becomes likely and further transport e.g. in environmental systems could be assumed. For conventional nanocomposites, accurate and sensitive detection and quantification of NP release is still a challenge due to the fact that released fractions might be small but nevertheless significant. The application of radiotracers provides the excellent option of “visibility”, traceability and quantification of NPs in complex media. Therefore, different radiolabelling strategies for engineered nanopowders (TiO2 P 25, Evonic Industries, dp = 21 nm; Ag0, Sigma Aldrich, dp < 100 nm) were established using a diffusive introduction of 110mAg radionuclides (t1/2 = 250 d) into Ag0-NPs (Hildebrand & Franke, 2012) and 44Ti radionuclides (t1/2 = 63 a) into TiO2-NPs through a low-temperature annealing procedure. Another radiolabelling strategy is the direct activation of Ag0 and TiO2 nanopowders that was done via proton irradiation using a Scanditronix MC40 cyclotron (Abbas et al. 2010, Holzwarth et al. 2012).
Both methods were tested with respect to radiolabelling yield, achievable activity concentration, pH-dependent stability of the radiolabelling and the influence on NP properties. Results obtained show an appropriate selection of radiolabelling methods suitable for different experimental conditions for NP release studies.

Abbas K, Cydzik I, Del Torchio R, Farina M, Forti E, Gibson N, Holzwarth U, Simonelli F, Kreyling W (2010) J Nanopart Res 12:2435–2443.
Holzwarth U, Bulgheroni A, Gibson N, Kozempel J, Cotogno G, Abbas K, Simonelli F, Cydzik I (2012) J Nanopart Res 14:880.
Hildebrand H and Franke K (2012) J Nanopart Res 14:1142.
  • Poster
    3. Clustertreffen NanoCare / NanoNature, 14.-15.01.2013, Frankfurt am Main, Deutschland

Publ.-Id: 18248 - Permalink

ELBE SRF Gun Testing Status
Kneisel, P.; Arnold, A.; Murcek, P.; Teichert, J.; Michel, P.; Lu, P.; Vennekate, H.; Xiang, R.; Kamps, T.; Will, I.;
A status report on the fabrication, treatment, and testing of the new SRF gun cavities is given.
Keywords: niobium cavity, photo injector, superconducting radio-frequency
  • Lecture (Conference)
    TESLA Technology Collaboration (TTC) Meeting, 05.-08.11.2012, Newport News, USA

Publ.-Id: 18247 - Permalink

Beam size and intensity diagnostics for a SRF photoelectron injector
Barday, R.; Anders, W.; Hoffmann, F.; Jankowiak, A.; Kamps, T.; Knobloch, J.; Kugeler, O.; Kuske, P.; Matveenko, A.; Neumann, A.; Quast, T.; Rudolph, J.; Schenk, M.; Schubert, S.; Siewert, F.; Völker, J.; Teichert, J.; Smedley, J.; Sekutowicz, J.;
A high brightness photoelectron injector must be developed as a part of the BERLinPro ERL program. The injector is designed to produce an electron beam with 100mA average current and a normalized emittance of 1mm mrad. The project is realised in stages. First experience is gained with a fully superconducting RF gun with a Pb cathode, work ongoing, followed by a normal conducting CsK2Sb cathode capable of generating high current beams. In the first stage we have measured the fundamental beam parameters bunch charge, beam energy and energy spread with a special focus on the measurement of the transverse beam profiles. We also discuss our plans for the beam characterization at high currents.
Keywords: electron accelerator, photo injector, Pb cathode, CsK2Sb, superconducting radio-frequency, beam parameter, high current
  • Poster
    IBIC12, International Beam Instrumentation Conference, 01.-04.10.2012, Tsukuba, Japan
  • Open Access LogoContribution to proceedings
    IBIC12, International Beam Instrumentation Conference, 01.-04.10.2012, Tsukuba, Japan: JACoW

Publ.-Id: 18246 - Permalink

Generation of SFR few-group constants using the Monte Carlo code Serpent
Fridman, E.; Rachamin, R.; Shwageraus, E.;
In this study, the Serpent Monte Carlo code was used as a tool for preparation of homogenized few-group cross sections for the 3D full core analysis of Sodium cooled Fast Reactors (SFR). Few-group group constants for two reference SFR cores were generated by Serpent and then employed by nodal diffusion code DYN3D in full core calculations. The DYN3D results were verified against the references full core Serpent Monte Carlo solutions. A good agreement between the reference Monte Carlo and nodal diffusion results was observed demonstrating the feasibility of using Serpent for generation of few-group constants for the deterministic SFR analysis.
Keywords: Serpent, DYN3D, Monte Carlo, few-group cross section generation, SFR
  • Contribution to proceedings
    Mathematics & Computation 2013, 05.-09.05.2013, Sun Valley, ID, USA
  • Lecture (Conference)
    Mathematics & Computation 2013, 05.-09.05.2013, Sun Valley, ID, USA

Publ.-Id: 18245 - Permalink

Operational Experience with the Nb/Pb Photoelectron Gun
Völker, J.; Kamps, T.; Anders, W.; Barday, R.; Jankowiak, A.; Knobloch, J.; Kugeler, O.; Matveenko, A. N.; Neumann, A.; Quast, T.; Rudolph, J.; Schubert, S.; Volkov, V.; Smedley, J.; Sekutowicz, J.; Teichert, J.; Kneisel, P.; Nietubyc, R.; Will, I.;
The superconducting radio-frequency (SRF) photoinjector concept combines the advantages of photo-assisted production of high brightness, short electron pulses and high gradient, low-loss continuous wave (CW) operation of a SRF cavity. A SRF photoinjector is under development by a collaboration between HZB, DESY, JLAB, BNL and NCBJ. The aim of the project is to understand and optimize the beam performance of a Nb SRF gun cavity coated with a small metallic superconducting Pb cathode film on the cavity backplane.
Keywords: electron source, photo cathode, superconduction radio-frequency, niobium cavity, Pb cathode
  • Poster
    IPAC2012 - International Particle Accelerator Conference 2012, 20.-25.05.2012, New Orleans, USA
  • Open Access LogoContribution to proceedings
    IPAC2012 - International Particle Accelerator Conference 2012, 20.-25.05.2012, New Orleans, USA
    Proceedings of IPAC2012, 978-3-95450-115-1, TUPPD051

Publ.-Id: 18244 - Permalink

Comparison of Serpent and HELIOS-2 as applied for the PWR few-group cross section generation
Fridman, E.; Leppänen, J.; Wemple, C.;
This paper discusses recent modifications to the Serpent Monte Carlo code methodology and related to the calculation of few-group diffusion coefficients and reflector discontinuity factors. The new methods were assessed in the following manner. First, few-group homogenized cross sections calculated by Serpent for a reference PWR core were compared with those generated by commercial deterministic lattice transport code HELIOS-2. Second, Serpent and HELIOS-2 few-group cross section sets were later employed by nodal diffusion code DYN3D for the modeling of the reference PWR core. Finally, the nodal diffusion results obtained using the both cross section sets were compared with the full core Serpent Monte Carlo solution. The test calculations show that Serpent can calculate the parameters required for nodal analyses similar to conventional deterministic lattice codes.
Keywords: Serpent, HELIOS, Monte Carlo, few-group cross section generation, PWR
  • Contribution to proceedings
    International Conference on Mathematics and computational Methods Applied to Nuclear Science and Engineering - M&C 2013, 05.-09.05.2013, Sun Valley, ID, USA
    Proceedings of M&C 2013

Publ.-Id: 18243 - Permalink

Ab intio description of thermoelectric properties based on the Boltzmann theory
Hinsche, N. F.; Hölzer, M.; Ernst, A.; Mertig, I.; Zahn, P.;
Thermoelectric properties are calculated within a quasi-classical transport theory based on the Boltzmann equation.
We consider Bi2Te3 as bulk material and in multilayered structures. Directional anisotropies of the transport coefficients and changes caused by the layered structure with respect to the bulk materials are discussed in detail.
Keywords: Thermoelectric transport, Bi2Te3, multilayers, power factor, figure of merit, strain, directional anisotropy
  • Book chapter
    Eibl, Nielsch, Peranio, Völklein: Thermoelectric Bi2Te3 Nanomaterials, Weinheim: Wiley-VCH, 2015, 978-3-527-33489-6, 187-221

Publ.-Id: 18242 - Permalink

Investigations into the synthesis, radiofluorination and conjugation of a new [18F]fluorocyclobutyl prosthetic group and its in vitro stability using a tyrosine model system
Franck, D.; Kniess, T.; Steinbach, J.; Zitzmann-Kolbe, S.; Friebe, M.; Dinkelborg, L. M.; Graham, K.;
The [18F]fluorocyclobutyl group has the potential to be a metabolically stable prosthetic group for PET tracers. The synthesis of the radiolabeling precursor cis-cyclobutane-1,3-diyl bis(toluene-4-sulfonate) 8 was obtained from epibromohydrin in 7 steps (2% overall yield). The radiolabeling of this precursor 8 and its conjugation to L-tyrosine as a model system was successfully achieved to give the new nonnatural amino acid 3-[18F]fluorocyclobutyl-L-tyrosine (L-3-[18F]FCBT) [18F]17 in 8% decay-corrected yield from the non-carrier-added [18F]fluoride. L-3-[18F]FCBT was investigated in vitro in different cancer cell lines to determine the uptake and stability. The tracer [18F]17 showed a time dependent uptake into different
tumor cell lines (A549, NCI-H460, DU145) with the best uptake of 5.8% injected dose per 5 105 cells after 30 min in human lung carcinoma cells A549. The stability of L-3-[18F]FCBT in human and rat plasma and the stability of the non-radioactive L-3-FCBT in rat hepatocytes were both found to be excellent. These results show that the non-natural amino acid L-3-[18F]FCBT is a promising metabolically stable radiotracer for positron emission tomography.
Keywords: Cyclobutyl; Stability; Metabolism; Fluorine-18; Positron emission tomography (PET)

Publ.-Id: 18241 - Permalink

Scientific publishing – writing successful papers
Werniewicz, K.;
Scientific publishing is an important part of every researcher’s life. Not only does it educate but it enhances awareness of and promotes your research achievements. It is one of the critical factors contributing to the establishment and subsequent strengthening of your position within the scientific community.
However, getting your paper successfully published is not a trivial task. Before your manuscript is “Accepted”, it must overcome many obstacles, set by rigorous Editors and Reviewers.
To ensure that you are armed with more in-depth knowledge and a set of tools necessary to pass a tricky and laborious peer-review process, the following lecture provides you with valuable hints on how to meet the expectations of the Editors and Reviewers and turn your paper into a success. Based on my own experience gained as a Managing Editor for the Journal of Alloys and Compounds (Elsevier), the step-by-step manuscript screening process (from submission to final decision) will be presented and discussed in detail.
Outline of seminar:
1. Planning a strategy – before you write
(e.g.: identifying the right audience, Journal’s selection, etc.)
2. Peer-review process (Elsevier)
• Brief introduction (“from submission to final decision” diagram)
• Who is going to assess your work (Technical Check, Managing Editor, Editor and Reviewer)
• Assessment:
- What do the Editors and Reviewers want from you?
- Manuscript’s pre-selection criteria
- Tools used to detect the strengths and weaknesses of your work (e.g.:
CrossCheck – plagiarism detector)
- Copyrights
• Demonstration (I will present selected examples (2 or 3) of the comments, which I have given during my time working at JALCOM, Elsevier)
3. Short summary
Keywords: peer-review process, scientific screening, editor role
  • Invited lecture (Conferences)
    7th HZDR PhD Seminar, 08.-10.10.2012, Schöneck, Germany

Publ.-Id: 18240 - Permalink

Quantification of Al and Ga electrical activation in ZnO films grown by reactive magnetron sputtering
Cornelius, S.; Vinnichenko, M.; Munnik, F.; Möller, W.;
In this work Al doped ZnO (AZO) and Ga doped ZnO (GZO) polycrystalline and epitaxial thin films were grown on fused silica and on c-plane sapphire, respectively, by reactive magnetron sputtering using a wide range of target dopant content cT from 0.7 to 8.7 at%. A special method of discharge operation was used in order to establish a precise control of metal to oxygen content in the films [1]. The film thickness and optical properties were determined using a combination of Spectroscopic Ellipsometry and Spectral Photometry. The results of optical modelling using a Parameterized Semiconductor Model (PSEMI) and a Drude term agree well with optical transmission measurements. The electrical resistivity (ρ), Ne and µ were obtained via Hall-effect measurements in van-der-Pauw geometry. The high quality of optimized polycrystalline films is characterized by ρ<4x10-4 Ωcm and µ>40cm²/Vs (epitaxial films µ>55cm²/Vs ) and a visible transmission of ~90%. Microstructural properties such as macrostrain, crystallite size, microstrain, texture and mosaicity were investigated by X-ray diffraction.
This paper is focused on the systematic study of the effects of Al and Ga dopant incorporation in ZnO on the abovementioned properties and the effective dopant activation rate in dependence of the growth parameters. Therefore the film composition has been quantified by a combination of ion beam analysis techniques. In the case of AZO the Al content was obtained by Rutherford backscattering spectrometry (RBS). However, due to the limited mass resolution Ga and Zn are indistinguishable in the RBS spectrum and only the total metal content of the samples is measured. Recently we were able to quantify also the Ga to Zn ratio by using Particle induced X-ray Emission (PIXE). Both Al and Ga show a pronounced systematic variation of their concentration in the films (cF) with substrate temperature and target dopant content. In general cF > cT due to the preferred desorption of surplus Zn during the film growth. These results explain the typically observed Ne(TS) dependence in AZO and GZO. Furthermore it is deduced that the dopant activation rate is constant with an absolute value of ~35% for AZO and ~50% for GZO below a certain critical cF value. At even higher dopant concentrations the film electrical and structural properties deteriorate strongly, which gives rise to the commonly observed optimum substrate temperature behaviour. In extreme cases this may even lead to insulating films, containing a substantial fraction of secondary phases [2]. Finally, implications for the physical limits of electrical transport in ZnO will be discussed.
Keywords: reactive magnetron sputtering, TCO, zinc oxide, doping, activation, RBS, PIXE
  • Lecture (Conference)
    4th Symposium on Transparent Conductive Materials 2012, 21.-26.10.2012, Chersonissos, Crete, Greece

Publ.-Id: 18239 - Permalink

Process control, performance limits and dopant activation for Al-doped ZnO grown by reactive pulsed magnetron sputtering
Cornelius, S.; Vinnichenko, M.; Munnik, F.; Heller, R.; Kolitsch, A.; Möller, W.;
Al-doped ZnO (AZO) films which combine maximum carrier mobility (mu), moderate free electron densities (Ne) and high surface roughness are of special interest for application as transparent front electrode in thin film solar cells. They posses high optical transmission in the visible and near infrared spectral range and enable a superior light trapping behavior.
Reactive magnetron sputtering using a wide range of Al target concentrations (c_Al) in connection with precise process control is used to grow high quality polycrystalline AZO films exhibiting optimum values of mu>45cm²/Vs and rho<2.3x10-4 Ohm*cm.
The present work is focused on systematic investigations of the influence of process parameters like oxygen partial pressure and substrate temperature (Ts) on AZO film properties. The observed dependence of carrier mobility on Ne in AZO is discussed in the framework of ionized impurity scattering and clustering as well as grain boundary limited transport which predicts a fundamental physical limit of mu.
The c_Al is shown to have a strong impact on the optimum process conditions and also on film structure. Ion-beam analysis confirms an Al enrichment in the films with increasing Ts which correlates with the commonly observed deterioration of electrical properties at high Ts values. In combination with Hall-effect measurements it is possible to estimate the fraction of electrically active Al in the ZnO matrix, which is rarely reported in a quantitative and systematic manner.
Keywords: transparent conductive oxide, reactive magnetron sputtering, zinc oxide, doping, activation
  • Lecture (Conference)
    13th International Conference on Plasma Surface Engineering (PSE 2012), 09.-14.09.2012, Garmisch-Partenkirchen, Deutschland

Publ.-Id: 18238 - Permalink

Understanding and using the current-voltage-pressure relationship in reactive magnetron sputtering for the growth of transparent conductive oxides
Cornelius, S.; Vinnichenko, M.; Möller, W.;
Due to its inherent flexibility reactive magnetron sputtering is a very attractive technique for the fabrication of thin compound films. When operated in the transition mode it is possible to growth stoichiometric materials with high deposition rates using cost-effective metallic targets.
Especially where the film composition plays an important role in achieving desired film properties it is of great interest to be able to reliably control the metal to reactive gas flux to the substrate. This is the case in transparent conductive oxides like ZnO and TiO2, where small changes in the oxygen content of the films have a strong effect on micro structure, optical and electrical properties.
A method using the current-voltage-pressure relationship of the reactive magnetron discharge for this purpose is discussed in this work. It is shown that there are two different groups of reactive discharges which can be classified by the ratio of the secondary electron emission coefficients of the metal and the corresponding oxide.
Each group shows a distinct current-voltage behavior, which demands a certain operation mode in order to stabilize the discharge in in the transition mode. This enables a fine control of oxygen partial pressure resulting in optimized films. Model experiments linking discharge parameters with film properties will be discussed in detail.
Keywords: reactive magnetron sputtering, ZnO, TiO2, TCO, oxide
  • Poster
    13th International Conference on Plasma Surface Engineering (PSE 2012), 09.-14.09.2012, Garmisch-Partenkirchen, Deutschland

Publ.-Id: 18237 - Permalink

Resistive Switching in TiO2
Blaschke, D.; Skorupa, I.; Scheumann, B.; Scholz, A.; Zahn, P.; Gemming, S.; Potzger, K.;
In recent years the resistive switching of binary transition metal oxides like NiO, Nb2O5 and TiO2 has attracted considerable attention for application in nonvolatile memory storage systems.
For our investigations we used a thin rutile TiO2 film, which was prepared by the thermal oxidation of a 100nm thick e-beam evaporated Ti film. The oxidation temperatures were varied from 500∘C to 800∘C at an oxygen partial pressure of 1 atmosphere. We will present the dependence of the crystal structure and the switching behavior on the oxidation temperature as well as an interesting feature on the timedependent evolution of the resistance during the Reset process.
The project is funded by the Initiative and Networking Fund of the Helmholtz Association (VH-VI-422).
Keywords: resistive switching, TiO2, thermal oxidation, oxide films, electric transport
  • Lecture (others)
    Topical Problems in Theoretical Physics, 28.11.2012, Chemnitz, Deutschland

Publ.-Id: 18236 - Permalink

Experimental verification of a 4D MLEM reconstruction algorithm used for in-beam PET measurements in particle therapy
Stützer, K.; Bert, C.; Enghardt, W.; Helmbrecht, S.; Parodi, K.; Priegnitz, M.; Saito, N.; Fiedler, F.;
Abstract. In-beam positron emission tomography (PET) had been proven to be a reliable technique in ion beam radiotherapy for the in situ and non-invasive evaluation of the correct dose deposition in static tumour entities. In the presence of intra-fractional target motion an appropriate time-resolved (4D) reconstruction algorithm has to be used to avoid reconstructed activity distributions suffering from motion-related blurring artefacts and to allow for a dedicated dose monitoring. 4D reconstruction algorithms from diagnostic PET imaging that can properly handle the typically low counting statistics of in-beam PET data have been adapted and optimized for the characteristics of the double-head PET scanner BASTEI installed at GSI Helmholtzzentrum Darmstadt, Germany (GSI). Systematic investigations of the reconstructed images have been performed by means of real measurements from moving radioactive sources and irradiation of moving phantoms. From in-beam PET listmode data sets acquired together with a motion surrogate signal valuable images can be generated for different motion patterns and motion-compensated beam delivery techniques.
Keywords: 4D in-beam PET, ion beam therapy, intra-fractional target motion, dose monitoring

Publ.-Id: 18235 - Permalink

PET-Prozesstomographie von Transportvorgängen in Bohrkernen zur Verbesserung des Prozessverständnisses und zur Verifikation von Modellcodes
Kulenkampff, J.; Gründig, M.; Zakhnini, A.; Lippmann-Pipke, J.;
Positronen-Emissions-Tomographie (PET) wird seit etwa 10 Jahren im HZDR, Forschungsstelle Leipzig, für tomographische Untersuchungen an Bohrkernen eingesetzt. Unikal ist hier die Verfügbarkeit einer hochauflösenden PET-Kamera in einem Radionuklidlabor für geowissenschaftliche Untersuchungen. Durch die Nutzung von Radiotracern können Prozesse in opaken Medien rückwirkungslos und mit höchster Selektivität und Sensitivität (< 1 picoMol/Voxel) bei akzeptablem Auflösungsvermögen (1.3 mm) dargestellt werden. Dabei steht nicht die Strukturinformation, wie bei Ultraschall- oder Röntgentomographie (CT), im Vordergrund, sondern der zeitliche Verlauf der Ausbreitung des Radiotracers unter den Einflüssen von Advektion, Dispersion und chemischer Reaktion. Es hat sich herausgestellt, dass präferentielle Transportpfade vorherrschend sind und deshalb nur ein geringer Anteil des Volumens an den Prozessen beteiligt ist. Dies erklärt, warum die Übertragbarkeit auf die makroskopische Skala von petrophysikalischen Parametern, die an kleinen Proben gewonnen werden, oder von physiko-chemischen Parametern aus Batch-Experimenten mit Suspensionen, oftmals versagt.
Im Vergleich zur üblichen Anwendung der PET zur molekularen Bildgebung in biologischem Gewebe besitzen Gesteine eine hohe Dichte. Dadurch wird der Einfluss von Compton-Streuung und Massenschwächung der Annihilationsphotonen signifikant und durch übliche Korrekturalgorithmen nur unzulänglich berücksichtigt, so dass bei der Bildrekonstruktion Artefakte entstehen können. Zur Korrektur dieser Effekte werden Monte-Carlo-Simulationen eingesetzt, die alle kernphysikalischen Prozesse berücksichtigen, vom Zerfall des Positrons über die relevanten Streuprozesse bis zur Detektion der Annihilationsstrahlung und anderer Gammaquanten in der Kamera. Prinzipiell erlaubt dieses Verfahren auch die Inversion der gemessenen Daten, wobei Schwächungs- und Streuparameter aus CT-Bildern abgeleitet werden können.
Als Ergebnis von Transportuntersuchungen in Bohrkernen mit zeitlich aufgelösten PET-Aufnahmen stehen zeitabhängige 3D-Datensätze der quantitativen Tracerverteilung zur Verfügung. Diese dienen einerseits der Ableitung effektiver Transportparameter (Geschwindigkeitsverteilung, Volumen, innere Oberfläche, Kinetik), andererseits geben sie Aufschluss über die real im Gestein ablaufenden Prozesse und können somit den Aufbau numerischer Transportmodelle parametrisieren und Transportcodes kalibrieren und durch direkten Vergleich verifizieren.
  • Lecture (Conference)
    73. Jahrestagung der Deutschen Geophysikalischen Gesellschaft, 04.-07.03.2013, Leipzig, Deutschland

Publ.-Id: 18234 - Permalink

On the feasibility of 4D offline PET-based treatment verification in ion beam therapy
Kurz, C.; Bauer, J.; Unholtz, D.; Richter, D.; Kaderka, R.; Bert, C.; Laube, K.; Parodi, K.;
Aim: Due to the accessible sharp dose gradients, ion beam therapy is prone to uncertainties introduced by organ motion. Hence, in-vivo treatment verification is highly desirable. At the Heidelberg Ion-Beam Therapy Center, this is realised by comparing the irradiation-induced β+-activity within the patient, measured by a commercial full-ring PET/CT scanner installed next to the treatment site, with a corresponding Monte-Carlo (MC) simulation based on the treatment plan. While 3D PET-based treatment verification is used in clinical practice, the feasibility of 4D PET-based treatment monitoring, accounting for tumour motion during the irradiation and the subsequent PET, still needs to be demonstrated.

Methods: PMMA phantoms of different geometries have been irradiated under stationary and moving conditions using a dedicated motion platform. Target movement has been monitored by a pressure sensor motion surrogate, enabling a 4D analysis of the ion beam delivery and the post-irradiation PET. Similarly, 4D datasets of the irradiation and the subsequent PET scans of patients with moving tumours have been collected. The acquired PET images were compared to activity distributions calculated within a dedicated 4D MC simulation framework.

Results: It could be shown that, in the case of moving phantoms, motion induced blurring in the acquired offline PET data can significantly be reduced by a gated 4D PET reconstruction, yielding results comparable to static reference measurements and thus enable the verification of the actual beam delivery.
The analysis of measured irradiation-induced activities within patients is however limited by the very low counting statistics, hindering a reliable verification of the applied treatment.

Conclusion: First moving-phantom studies showed the feasibility of 4D offline PET-based treatment verification. For clinical cases the method is currently limited by the low level of the measured activity.

Acknowledgement: FP7 EU project ENVISION
Keywords: target motion, particle therapy, 4D PET
  • Lecture (Conference)
    52nd Annual Conference of the Particle Therapy Co-Operative Group - PTCOG 52, 02.-08.06.2013, Essen, Deutschland

Publ.-Id: 18233 - Permalink

Low Background Digital Coincidence Spectrometer – A Tool for Investigation of Positron Annihilation in Flight
Čížek, M. V.; Lukáč, F.; Melikhova, O.; Procházka, I.; Anwand, W.; Butterling, M.; Wagner, A.; Brauer, G.;
A digital spectrometer for low background gamma ray spectroscopy equipped with two high purity Ge detectors and a 12-bit two channel digitizer was employed for the investigation of positron annihilation-in-flight. Measurements were performed for positrons emitted by 68Ge/68Ga and 22Na radioisotopes and annihilated in Cu and Mg targets. The contribution of the two-quantum positron annihilation-in-flight was clearly resolved in coincidence two-dimensional gamma ray energy spectra. The contribution of positrons annihilated in flight has a hyperbolic shape described well by the relativistic theory.
Keywords: Digital Spectrometer, Doppler Shift, Positron Annihilation in Flight
  • Book chapter
    B.N. Ganguly, G. Brauer: Near Surface Depth Profiling by Mono-energetic Positrons, Switzerland: Trans Tech Publisher, 2012, 978-3-03785-524-9, 53-73
    DOI: 10.4028/


Publ.-Id: 18232 - Permalink

Ziegler-Bottema dissipation-induced instability and related topics
Kirillov, O.;
Exactly 60 years ago Ziegler [1] observed (I) that viscous dissipation can move pure imaginary eigenvalues of a Lyapunov stable time-reversible non-conservative mechanical system (Ziegler’s pendulum loaded by a follower force) to the right half of the complex plane and (II) that the threshold of asymptotic stability generically does not converge to the threshold of the Lyapunov stability of the non-damped system when dissipation coefficient tends to zero. In 1956 Bottema [2] related the structurally unstable situation (II) to the Whitney umbrella singularity [3] of the stability boundary. I will show the examples of Hamiltonian, reversible and PT -symmetric systems of physics and mechanics with the similar effects of dissipation-induced instabilities and non-commuting limits of vanishing dissipation. I will discuss the relation of these effects to the multiple non-derogatory eigenvalues occurring both on the stability boundary and inside the domain of asymptotic stability, show the connection to the spectral abscissa minimization [4] and in the Hamiltonian case will demonstrate that a suitable combination of damping and nonconservative positional forces can destabilize the eigenvalues with both positive and negative Krein (symplectic) signature of the unperturbed system [5-7].
1. H. Ziegler, Die Stabilit¨atskriterien der Elastomechanik, Ing.-Arch. 20, 49-56 (1952).
2. O. Bottema, The Routh-Hurwitz condition for the biquadratic equation, Indagationes Mathematicae, 18, 403-406 (1956).
3. W. F. Langford, Hopf Meets Hamilton Under Whitney’s Umbrella, in IUTAM Symposium on Nonlinear Stochastic Dynamics. Proceedings of the IUTAM Symposium, Monticello, IL, USA, Augsut
2630, 2002, Solid Mech. Appl. 110, edited by S.N. Namachchivaya et al. (Kluwer, Dordrecht, 2003), pp. 157-165.
4. J. V. Burke, A. S. Lewis and M. L. Overton, Optimal Stability and Eigenvalue Multiplicity, Foundations of Computational Mathematics 1, 205-225 (2001).
5. O. N. Kirillov, Gyroscopic stabilization in the presence of nonconservative forces, Dokl. Math. 76(2), 780-785 (2007).
6. O. N. Kirillov and F. Verhulst, Paradoxes of dissipation-induced destabilization or who opened Whitney’s umbrella? Z. Angew. Math. Mech., 90(6), 462-488 (2010).
7. O. N. Kirillov, Stabilizing and destabilizing perturbations of PT -symmetric indefinitely damped systems. Phil. Trans. R. Soc. A (2013).
Keywords: Dissipation-induced instabilities, Krein signature, negative energy modes, spectral abscissa
  • Invited lecture (Conferences)
    Spectral Analysis, Stability and Bifurcation in Modern Nonlinear Physical Systems (12w5073), 04.-09.11.2012, Banff, Canada

Publ.-Id: 18231 - Permalink

On the WKB threshold of magnetorotational instability in axial and helical magnetic fields
Kirillov, O.; Stefani, F.;
The magnetorotational instability (MRI) triggers turbulence and enables outward transport of angular momentum in hydrodynamically stable rotating shear flows, e.g., in accretion disks. What laws of differential rotation are susceptible to the destabilization by axial, azimuthal, or helical magnetic field? How the standard, helical and azimuthal versions of MRI are related to each other? The answer to these questions, which is vital for astrophysical and experimental applications, inevitably leads to the study of spectral and geometrical singularities on the instability threshold. These singularities provide a connection between seemingly discontinuous stability criteria and thus explain several paradoxes in the theory of MRI that were poorly understood since the 1950s. On the other hand, the singular geometry of the instability threshold is a powerful tool for parametric optimization that predicts, e.g., how close to the Kepler or solid body rotation profiles the instability threshold can be moved by varying the magnetic field configuration, velocity, and material properties of the liquid. Using the local WKB approximation we study the thresholds of standard and helical MRI for axi- and non-axisymmetric perturbations, their extrema and the links between them in the fully viscous and resistive setting. We discuss the connection between standard and helical MRI via a spectral exceptional point as well as the behavior of the helical MRI threshold both in the inductionless approximation when the magnetic Prandtl number (Pm) tends to zero and in case when it is small but finite. We demonstrate that the Liu limit for the Rossby number at the onset of HMRI slightly increases when Pm is not vanishing and find its ultimate value.
1. O.N. Kirillov, F. Stefani, On the relation of standard and helical magnetorotational instability. The Astrophysical Journal, 712, 52-68, (2010).
2. O.N. Kirillov, F. Stefani, Paradoxes of magnetorotational instability and their geometrical resolution. Physical Review E, 84, 036304 (2011).
3. O.N. Kirillov, D.E. Pelinovsky, G. Schneider, Paradoxical transitions to instabilities in hydromagnetic Couette-Taylor flows, Physical Review E, 84, 065301(R), (2011).
4. O.N. Kirillov, F. Stefani, Standard and helical magnetorotational instability: How singularities create paradoxical phenomena in MHD. Acta Applicandae Mathematicae, in Press, (2012),
DOI: 10.1007/s10440-012-9689-z
Keywords: Standard and helical magnetorotational instability, Couette-Taylor flow, accretion disk, WKB
  • Poster
    IAU XVIII General Assembly, 20.-31.08.2012, Beijing, China

Publ.-Id: 18230 - Permalink

Cannabinoid receptor density is increased in a newborn piglet but not an adult rat model of traumatic brain injury
Donat, C. K.; Gaber, K.; Fischer, F.; Walter, B.; Deuther-Conrad, W.; Bauer, R.; Meixensberger, J.; Brust, P.;
Traumatic brain injury (TBI) is a leading cause of death and disability in the paediatric age group and also among adults with lifelong impairments and concomitant socioeconomic consequences. There is evidence from animal experiments and patient studies that cannabinoid signalling is involved in TBI either by modulating neuroinflammation or for neuroprotective pathways. However, almost no data exist on changes of cannabinoid receptors (CBR) after TBI. The present study was performed to investigate CBR in two different animal models of TBI. The identification of disease-related targets within the cannabinoid system is a precondition for potential molecular imaging of TBI patients with Positron-Emission-Tomography (PET), e.g. for monitoring of neuroprotective pharmacotherapy.
Thirteen female newborn piglets (post-TBI survival time: 6 h) underwent moderate fluid percussion (FP) injury (n = 7) or sham operation (n = 6) with an impact pressure of 3.8 ± 0.3 atmospheres. Furthermore, male Sprague-Dawley rats were randomized into four groups (post-TBI survival time: 6, 24, and 72 h), anaesthetized and subjected to sham injury/craniotomy (control, n = 3-5) or mild-to-moderate controlled cortical impact injury (CCI) (n = 5, 2 mm depth at 4 m/sec). From brains of both species, cryostat sections were cut (rat 12 µm, pig 20 µm) and density of CB1/2R ([3H]CP-55,940) and CB1R ([3H]SR141716A) was assessed with in vitro autoradiography. If appropriate, CB1- and CB2-specific ligands SR141716A and SR144528, respectively, were applied for receptor blockade.
In the newborn piglet model, we found a statistically significant overall increase of [3H]CP-55,940 binding in the brains of injured animals (15 of 24 investigated brain regions, including cerebral cortex, hippocampus, thalamus hypothalamus and midbrain; max: +140%, mean: +47%). No significant increases in [3H]SR141716A binding were observed.
In contrast, in adult rats, no statistically significant changes in CBR density were detected, although in few brain regions increases as well as decreases of up to 30% of [3H]CP-55,940 binding were found.
In conclusion, the expression density of CBR is significantly altered after experimental TBI in newborn piglets. Because CB1R show no significant alterations after injury, it is very likely, that the increases are of CB2R origin, probably due to activated microglia.
In a mild-to-moderate adult rat model, no statistically significant changes in CBR density are found, which can either be attributed to species differences in e.g. brain morphology, or differences in the severity of the employed models.
Data from newborn pigs indicate involvement of a cannabinoid mechanism in paediatric TBI. The identification of the underlying mechanisms, supported for instance by molecular imaging with PET, could help to detect clinically relevant neuroreceptor changes after TBI and provide valuable insights which may prove helpful in the development of cannabinoid-based neuroprotectants.
  • Lecture (Conference)
    BRAIN’13 and BRAINPET’13, 20.-23.05.2013, Shanghai, China

Publ.-Id: 18229 - Permalink

Target Characterization of Large Area Minor Actinide Layers for Fast Neutron Induced Fission Cross Section Experiments at nELBE
Kögler, T.; Beyer, R.; Eberhardt, K.; Hannaske, R.; Junghans, A. R.; Massarczyk, R.; Schwengner, R.; Vascon, A.; Wagner, A.;
The development of Accelerator Driven Systems (ADS) requires accurate nuclear data. Especially neutron induced fission cross sections of Plutonium and minor actinides in part show high uncertainties in the fast energy range. For 242Pu current uncertainties are of around 21 %, the target uncertainties in the order of 7 %. Sensitivity studies ( [1], [2]) show that the total uncertainty has to be reduced below 5 %, to enable reliable neutron physical simulations.
This challenging task will be performed at the neutron time-of-flight facility of the new German National Center for High Power Radiation Sources at HZDR, Dresden. Improved experimental conditions (low scattering environment) and beam power, paired with the right spectral shape of the nELBE neutron source will provide excellent conditions to achieve this aim. A parallel plate ionization chamber with it’s approximately 100 % intrinsic detection efficiency will measure fission fragments from thin minor actinide layers (areal density: 580 and 220 µg/cm2; total mass: 200 mg of 235U and 75 mg of 242Pu). These very homogeneous targets are produced by the institute of radiochemistry of the University of Mainz. To handle the high specific alpha activity of the Pu targets, a combination of fast preamplifiers and digital signal processing has been developed to suppress pile-up effects.
It is planned to determine the homogeneity of the minor actinide targets by two different methods. Due to their high specific activity the number of fissionable Pu atoms per unit area will be determined by a spatially resolved alpha spectroscopy. The required setup was optimized using Geant 4 simulations. Results of this simulations and first experimental approaches will be presented. For the uranium targets it is planned to determine the homogeneity in a fission chamber with a collimated neutron beam at PTB Braunschweig. Physical properties (distance between anodes and cathodes, counting gas etc.) of the chamber have also been optimized using the Geant 4 framework.
The work is embedded in the TRAKULA project (BMBF 02NUK13A, supported by the Federal Ministry for Education and Research of Germany.

[1] OECD/NEA, „Nuclear Data High Priority Request List,“ 2011. [Online]. Available:
[2] Working Party on International Evaluation Co-operation of the NEA Nuclear Science Committee, „Uncertainty and Target Accuracy Assesment for Innovative Systems Using Recent Covariance Data Evaluations,“ 2008. [Online]. Available:
Keywords: fast neutron induced fission, target characterization
  • Poster
    International Conference on Nuclear Data for Science & Technology 2013, 04.-08.03.2013, New York, USA
  • Nuclear Data Sheets 119(2014), 404-406
    DOI: 10.1016/j.nds.2014.08.113

Publ.-Id: 18228 - Permalink

Dark current measurements at the ELBE SRF gun
Xiang, R.; Teichert, J.; Lu, P.; Arnold, A.; Murcek, P.; Vennekate, H.;
We present the dark current measurement and analysis at the ELBE SRF gun, and the assumption of dark current in the new SRF gun cavity.
Keywords: Dark current, SRF gun
  • Invited lecture (Conferences)
    Unwanted Beam Workshop 2012, 17.-18.12.2012, Berlin, Germany

Publ.-Id: 18227 - Permalink

photocathodes for Rossendorf SRF gun
Xiang, R.; Arnold, A.; Murcek, P.; Teichert, J.;
Rossendorf SRF gun is an electron source based on superconducting RF technology but use normal conducting photocathode. Cs2Te is chosen as the standard photocathode. A vacuum transport system with UHV is built to move the cathodes from cathode lab to ELBE accelerator hall. Up to now 34 Cs2Te photocathodes have been prepared in our cathode laboratory and eight of them have been operated in the SRF gun. Quantum efficiency of 1% and life time of months satisfy the gun operation. On the other hand, the SRF gun is a good test bench for various cathodes. Metal cathodes, such as Cu and Pb-coated-Nb, and semiconductors, as GaN and GaAs, were ever tested in it.
Now the activities in our cathode laboratory are guided to new photocathode materials with high Q.E. for high current electron sources. Cs3Sb and GaN(Cs) photocathodes have been tested as new candidates, and the design of a preparation system for GaAs(Cs, O) is ongoing. The first GaAs photocathode is planned in one year.
Keywords: SRF gun, photocathode, Quantum efficiency
  • Lecture (Conference)
    Photocathode Physics for Photoinjectors, 08.-10.10.2012, Cornell University, USA

Publ.-Id: 18226 - Permalink

In-beam SPECT based in-vivo Dosimetry: From Treatment Planning to Measured Dose.
Müller, A.; Fiedler, F.; Georg, D.; Hopfgartner, J.; Enghardt, W. :.;
no abstract available
Keywords: in vivo dose monitoring, in-beam SPECT

Publ.-Id: 18225 - Permalink

Automated Detection of Ion Beam Modifications in in-beam PET Images
Kuess, P.; Birkfellner, W.; Helmbrecht, S.; Fiedler, F.; Enghardt, W.; Georg, D. :.;
no abstract available
Keywords: PT PET, ion beam therapy

Publ.-Id: 18224 - Permalink

Validation of Interface Capturing and Tracking Techniques with different Surface Tension Treatments against a Taylor Bubble Benchmark Problem
Marschall, H.; Boden, S.; Lehrenfeld, C.; Falconi Delgado, C. J.; Hampel, U.; Reusken, A.; Wörner, M.; Bothe, D.;
The validation and verification of models and numerical methods for interfacial two-phase flow simulation is still a challenge and standards have not yet been established. Mostly comparing with analytical solutions, many validation studies so far have considered simple or simplified two-phase flow scenarios. While this is mandatory for method development, complementary, validation against more complex test-cases is essential, in order to prove the method's final scope of capabilities. However, one reason for the absence of such two-phase flow benchmark studies is the lack of freely accessible, detailed and high-quality experimental data.
The Priority Program SPP 1506 Transport Processes at Fluidic Interfaces by the German Research Foundation DFG proposes a benchmark problem for validation of interfacial two-phase flow solvers by means of specifically designed experiments for Taylor Bubble Flow. The benchmark experiments aim at providing detailed and local data as a basis for validation. This contribution demonstrates its use by assessing and approving the reliability and accuracy of the solvers used by several research groups within the priority program. Special emphasis is set upon different approaches to surface tension calculation both for interface capturing and interface tracking methods. Data and material of the presented benchmark can be freely downloaded from the website of SPP
1506 (
Keywords: validation, surface tension treatment, two-phase flow, Taylor bubble, benchmark problem

Publ.-Id: 18223 - Permalink

Image Based In‐vivo Dosimetry: From PT‐PET to In‐ Beam SPECT
Fiedler, F.;
no abstract available
Keywords: PT PET, in-beam SPECT, in-vivo dose monitoring, ion beam therapy, proton beam therapy
  • Lecture (Conference)
    Micro- Mini- and Nano- Dosimetry & International Prostate Cancer Treatment Workshop, 06.-09.12.2012, Wollongong, Australia

Publ.-Id: 18222 - Permalink

Position-Resolved Positron Annihilation Lifetime Spectroscopy
Fiedler, F.; Anwand, W.; Butterling, M.; Cowan, T. E.; Enghardt, W.; Fritz, F.; Heidel, K.; Kempe, M.; Steudtner, T.; Wagner, A.;
A method allowing for position-resolved positron lifetime spectroscopy studies in large volume samples will be presented. This technique was developed at the superconducting linear accelerator ELBE (Electron linac with high brilliance and low emittance) at the Helmholtz-Zentrum Dresden-Rossendorf, Germany. A beam of continuous 16 MeV electron bunches of about 5 ps temporal width and a repetition frequency of 26 MHz was used to generate bremsstrahlung preserving the sharp timing of the electron beam. Positrons produced in the target via pair production feature a sharp time stamp for lifetime studies. They decelerate quickly and annihilate in microscopic defects. This allows for high timing resolution and high signal to background ratios due to the coincident detection of two annihilation photons. Two commercially available Lutetium Oxyorthosilicate scintillator (LSO) detectors were employed to detect the annihilation photons. These LSO detectors are already clinically used in the SIEMENS Biograph PET Scanner. Each detector consists of a crystal matrix with 13 13 pixels and a total size of 52 mm 52 mm 20 mm. The total energy resolution was measured to be 5.1% (RMS) and the timing resolution is 225 ps (RMS). Experiments resulting in position resolved lifetime measurements will be presented.
Keywords: position-resolved positron life time spectroscopy, non-destructive material analysis
  • Lecture (Conference)
    IEEE Nuclear Science Symposium and Medical Imaging Conference - NSS MIC 2012, 29.10.-03.11.2012, Anaheim, USA

Publ.-Id: 18221 - Permalink

Techniques for Image Based in-vivo Dosimetry: from Particle Therapy PET to in-beam Prompt Gamma Imaging
Fiedler, F.; Golnik, C.; Helmbrecht, S.; Kormoll, T.; Kunath, D.; Laube, K.; Müller, A.; Priegnitz, M.; Rohling, H.; Schöne, S.; Enghardt, W.;
Radiation therapy is an important treatment modality in cancer therapy. New radiation species, like protons and light ions have the potential to increase tumor conformality of irradiation and to decrease normal tissue dose. Such high precision radiotherapy treatment requires efficient quality assurance techniques. Therefore, a dose monitoring system is highly desirable. Between 1997 and 2008, the in-beam Positron Emission Tomography (PET) method was used at the GSI Helmholtzzentrum fr Schwerionenforschung, Darmstadt, Germany, for monitoring the dose delivered by 12C beams. The spatial distribution of positron emitters generated via nuclear interactions is measured during and shortly after the irradiation. By means of a comparison between measured and simulated activity distribution conclusions on the accuracy of the dose deposition can be drawn. Different modalities of PET, i.e. measuring during the irradiation versus taking data after the treatment have been compared. Recent investigation and limits of the PET method used for in-vivo dose monitoring at ion beams will be presented and discussed. Due to inherent physical restrictions of this method, a direct quantification of the delivered dose is not feasible. Therefore, another approach based on dose monitoring by detection of prompt gamma rays is currently under investigation. In contrast to PET this method relies on the detection of prompt gamma rays between 0 and 10 MeV emitted almost instantaneously during the therapeutic irradiation. To measure these photons a Compton camera design was evaluated with respect to the special requirements and conditions that arise from this application. Different concepts were compared by means of simulation. The complete chain from simulation based on the treatment plan to the iterative reconstruction of the data was developed and is now under optimization. First measurements have been successfully performed with radioactive sources and ion beams.
Keywords: PT PET, dose monitoring, ion beam therapy, proton therapy
  • Lecture (Conference)
    IEEE Nuclear Science Symposium and Medical Imaging Conference - NSS MIC 2012, Hadron Therapy Workshop, 29.10.-03.11.2012, Anaheim, USA

Publ.-Id: 18220 - Permalink

Status of the Development of a Single Gamma-Ray Imaging System for in-vivo Dosimetry at Particle Beams
Fiedler, F.; Golnik, C.; Kormoll, T.; Mueller, A.; Rohling, H.; Schöne, S.; Enghardt, W.;
Ion beams offer advantages over conventional treatment modalities, such as photons. Because of the way ions deposit their energy on their path through tissue they allow for an increased dose deposition in the tumor volume and reduce the collateral damage to the surrounding healthy tissue. However, small changes in the irradiated volume will lead to a misalignment of the deposited dose maximum and the tumor. Therefore, a dose monitoring system is highly desirable. Positron Emission Tomography (PET) was clinically applied for example between 1997 and 2008 at the GSI Helmholtzzentrum fr Schwerionenforschung, Darmstadt, Germany, for monitoring the dose delivered by 12C beams. Due to inherent limitations of this method, a direct quantification of the delivered dose is not feasible. Therefore, another approach currently under investigation monitors the dose by means of the detection of prompt gamma-rays. A Compton camera may be a feasible technical solution for such a monitoring system. A first prototype for imaging radioactive sources has been developed. Results of simulations used for the optimization of the detector configuration will be presented as well as an approach for the reconstruction.
Keywords: ion beam therapy, proton beam therapy, in-vivo dose monitoring, Compton camera, gamma ray detection
  • Lecture (Conference)
    IEEE Nuclear Science Symposium and Medical Imaging Conference - NSS MIC 2012, 29.10.-03.11.2012, Anaheim, USA

Publ.-Id: 18219 - Permalink

Dependence of simulated positron emitter yields in ion beam cancer therapy on modeling nuclear fragmentation
Lühr, A.; Priegnitz, M.; Fiedler, F.; Sobolevsky, N.; Bassler, N.;
In ion beam cancer therapy, range verification in patients using positron emission tomography (PET) requires the comparison of measured with simulated positron emitter yields. We found that 1) changes in modeling nuclear interactions strongly affected the positron emitter yields and that 2) Monte Carlo simulations with SHIELD-HIT10A reasonably matched the most abundant PET isotopes 11C and 15O. We observed an ion-energy (i.e., depth) dependence of the agreement between SHIELD-HIT10A and measurement. Improved modeling requires more accurate measurements of cross section values.
Keywords: ion beam therapy, PT PET, Simulation of positron emitter yields, Shield Hit

Publ.-Id: 18218 - Permalink

Imaging of Point Sources with a Compton Camera for in-vivo Dose Monitoring of Ion Beam Irradiation
Kormoll, T.; Fiedler, F.; Golnik, C.; Heidel, K.; Kempe, M.; Schoene, S.; Sobiella, M.; Zuber, K.; Enghardt, W.;
no abstract available
Keywords: in vivo dosimetry, Compton camera, proton therapy, gamma detection
  • Open Access LogoAbstract in refereed journal
    Radiotherapy and Oncology 102(2012)1, S41-S42
    DOI: 10.1016/S0167-8140(12)70078-6
  • Lecture (Conference)
    ICTR-PHE 2012, 27.02.-04.03.2012, Geneva, Switzerland

Publ.-Id: 18217 - Permalink

Np(V/VI) redox chemistry in cementitious systems: XAFS investigations on the speciation under anoxic and oxidizing conditions
Gaona, X.; Wieland, E.; Tits, J.; Scheinost, A. C.; Dähn, R.;
The use of cementitious materials is foreseen to immobilize long–lived intermediate level wastes that may contain significant amounts of 237Np. Predicting the release of Np from a cement–based repository requires an adequate understanding of its interaction with the main sorbing components of cement. Although Np(IV) will prevail under repository conditions after depletion of oxygen, Np(V) is expected to control the chemistry of neptunium in the early stage after repository closure as well as in the presence of oxidizing waste forms (i.e. high content of NO3–). Moreover, little is known on the stability of Np(VI) under hyperalkaline conditions, resulting in a rather ill–defined Np(V/VI) redox chemistry in cementitious environments.
Evaluation of XANES data from Np(V)–doped calcium silicate hydrates (C–S–H phases) and hardened cement paste (HCP) under anoxic and under oxidizing conditions (provided by 510–3M NaClO) clearly indicated the predominance Np(V) and Np(VI), respectively. Two different neptunyl moieties were also observed by EXAFS, with significantly shorter Np–Oax and Np–Oeq obtained for samples with NaClO (1.79–1.85 Å and 2.24–2.25 Å) compared to samples under anoxic conditions (1.88–1.89 Å and 2.39 Å), thus confirming the oxidation of Np(V) to Np(VI) in the presence of NaClO. The strong EXAFS features resulting from the neptunyl–oxygen coordination hamper the signal of atoms beyond their coordination sphere in Np(V/VI)–doped C–S–H and HCP samples. Nevertheless, Np–Oeq distances as well as evaluation of the Si–shells provided some evidence for an incorporation mechanism taking place in the C–S–H structure. In contrast to Np(V), the molecular environment of Np(VI) in C–S–H phases depends not only on the Ca:Si ratio of these phases but also on the pH of the solution, likely reflecting the differences between the hydrolysis scheme of both Np redox states under these pH conditions.
EXAFS data confirmed the predominance of aqueous Np(VI) species (as NpVIO2(OH)42–) in hyperalkaline and oxidizing tetramethylammonium hydroxide (TMA–OH) solutions. Under anoxic conditions and in the presence of CO32– (as impurity of TMA–OH), the predominance of a mixed Np(V)–OH–CO3 species was indicated by EXAFS. These Np(V/VI) aqueous species are not considered in the current NEA thermodynamic selection and therefore deserve further attention.
Keywords: Neptunium(V/VI), EXAFS, cement, C–S–H, uptake mechanism, anoxic/oxidizing conditions

Publ.-Id: 18216 - Permalink

Identification of multiple putative S-layer genes partly expressed by Lysinibacillus sphaericus JG-B53
Lederer, F.; Weinert, U.; Günther, T.; Raff, J.; Weiß, S.; Pollmann, K.;
Lysinibacillus sphaericus JG-B53 was isolated from the uranium mining waste pile Haberland near Johanngeorgenstadt, Germany. Previous studies have shown that many bacteria that have been isolated from these heavy metal contaminated environments possess surface layer proteins (S-layers) which enable the bacteria to survive by binding metals with high affinity. Conversely, essential trace elements are able to cross the filter layer and reach the interior of the cell. This is especially true of the S-layer of Lysinibacillus sphaericus JG-B53 which is therefore of high interest for both environmental studies and technical applications. Particularly the latter due to the high amounts isolatable from biomass and the outstanding recrystallisation and metal binding properties.
In this study, S-layer protein gene sequences encoded in the genome of L. sphaericus JG-B53 were identified using next generation sequencing (NGS) technology followed by bioinformatic analyses. The genome of L. sphaericus JG-B53 encodes at least 8 putative S-layer protein genes with distinct differences. Using mRNA analyses the expression of the putative S-layer protein genes was studied. The functional S-layer protein B53 Slp1 was identified as dominantly expressed S-layer protein in Lysinibacillus sphaericus JG-B53 by mRNA studies, SDS PAGE and N-terminal sequencing. B53 Slp1 is characterised by square lattice symmetry and a molecular weight of 116 kDa.
The S-layer protein B53 Slp1 shows a high similarity to the functional S-layer protein of Lysinibacillus sphaericus JG-A12, being isolated from the same uranium mining waste pile Haberland described by previous research. These similarities indicate horizontal gene transfer and DNA rearrangements between these bacteria. The presence of multiple S-layer gene copies may enable the bacterial strains to quickly adapt to changing environments.
Keywords: S-layer, Lysinibacillus sphaericus, next generation sequencing, horizontal gene transfer, DNA rearrangement

Publ.-Id: 18214 - Permalink

Influence of annealing conditions on the formation of regular lattices of voids and Ge quantum dots in an amorphous alumina matrix
Pinto, S. R. C.; Buljan, M.; Marques, L.; Martin-Sanchez, J.; Conde, O.; Chahboun, A.; Ramos, A. R.; Barradas, N. P.; Alves, E.; Bernstorff, S.; Grenzer, J.; Muecklich, A.; Ramos, M. M. D.; Gomes, M. J. M.;
In this work, the influence of air pressure during the annealing of Ge quantum dot (QD) lattices embedded in an amorphous Al2O3 matrix on the structural, morphological and compositional properties of the film is studied. The formation of a regularly ordered void lattice after performing a thermal annealing process is explored. Our results show that both the Ge desorption from the film and the regular ordering of the QDs are very sensitive to the annealing parameters. The conditions for the formation of a void lattice, a crystalline Ge QD lattice and a disordered QD lattice are presented. The observed effects are explained in terms of oxygen interaction with the Ge present in the film.

Publ.-Id: 18213 - Permalink

Helmholtz-Beamline at XFEL
Grenzer, J.;
Helmholtz-Beamline at XFEL
  • Lecture (Conference)
    Institute Seminar - Weinböhla 2012 Institute of Ion Beam Physics and Materials Research, 04.-05.06.2012, Weinböhla, Deutschland

Publ.-Id: 18212 - Permalink

Materialforschung „zu Hause‘‘ und am Synchrotron: Röntgenuntersuchungen an nano-kristallinen dünnen Filmen
Grenzer, J.;
  • Invited lecture (Conferences)
    Bruker XRD Anwendertreffen, 09.-10.10.2012, Lüneburg, Deutschland

Publ.-Id: 18211 - Permalink

In-situ X-ray Scattering & Diffraction: Studying the Formation of Nanostructure
Grenzer, J.;
Nowadays, the development of new materials is often associated with specific properties of functionalized nanostructures. X-ray investigations are a very important tool to find the link between the functional (magnetism, luminescence) and the corresponding structural properties (size, orientation etc.) that are generating this function and to explain the underlying physical processes. This knowledge makes it possible to design new materials with specific properties.
Modern synchrotron sources give us the possibility to study the nanostructure during deposition. A sputtering chamber mounted on a six-circle goniometer allows an insight into the growth of nanostructures using different scattering and diffraction methods. We report on an in-situ X-ray investigation of a self-assembled growth of Ge nanocrystals embedded in a dielectric matrix forming a BCC-like super structure. A single some 100nm thick Ge+Al2 O3 layer using magnetron sputtering was deposited at an elevated substrate temperature. The self-assembly during growth or subsequent annealing results in the formation of a well ordered three-dimensional BCC-like quantum dot lattice within the whole deposited volume. The parameters of the formed super structure can be directly influenced by changing the deposition parameters. The self-ordering of the quantum dots is explained by diffusion mediated nucleation and surface morphology effects.
  • Invited lecture (Conferences)
    Gemeinsames Festkörperphysik-Seminar, Institut für Theoretische Physik, Universität Bremen, 18.12.2012, Bremen, Deutschland

Publ.-Id: 18210 - Permalink

Preclinical dose assessment of (S)-(-)- [18F]fluspidine and (R)-(+)-[18F]fluspidine, new PET tracers for imaging of σ1 receptors.
Kranz, M.; Sattler, B.; Deuther-Conrad, W.; Fischer, S.; Hiller, A.; Donat, C. K.; Wünsch, B.; Steinbach, J.; Sabri, O.; Brust, P.;
Objectives : [18F]fluspidine (FPD) is a new σ1 receptor radioligand for imaging of cancer and neuropsychiatric diseases which consists of two enantiomers of different kinetics and affinity. Biodistribution, organ doses (ODs) and effective dose (ED) of (S)-(-)-FPD# (Ki=2.3nM) and (R)-(+)-FPD## (Ki=0,52nM) were determined in mice to assess the radiation risk to humans.

Methods : 28#/22## female CD1 mice (29.8±2.2g#/29.3±1.9g##) were injected with 0.35±0.08MBq# and 0.39±0.05MBq## FPD into tail vein. At 5, 15, 30, 45, 60, 90, 120, 180 and 240 min. p.i. they were sacrificed and organ masses and activity determined. The fractions of activity were displayed as %ID. Time and mass were scaled to human magnitude. Using OLINDA/EXM, the cumulated activity in source organs and ODs were calculated.

Results : For (S)-(-)-FPD the adrenals received the highest OD [µSv/MBq] (36.0), followed by the kidneys (35.6). The highest contribution to ED (ICRP103, [µSv/MBq]) was by lungs (3.7) and upper large intestine (2.0). For (R)-(+)-FPD the lungs receive the highest OD (45.5), followed by the kidneys (27.6). The highest contribution to ED was by lungs (5.5) followed by ovaries (2.0). The estimated ED is 16.7#/18.4##. Considering 40% underestimation in preclinical dosimetry [1] for 300MBq of FPD i.v. the expected ED to humans is 8.4# and 9.2## [mSv].

Conclusions : Considerable differences in ODs were observed between the enantiomers. However, the putative ED to humans is within the range of what is caused by other 18F-labeled compounds. The results support the further development of the radioligands as a clinical tool for brain and cancer PET-imaging.

[1] Sattler B, …, Sabri O. Incorporation dosimetry of F-18-Flubatine - Comparison of animal model data with first-in-man results J. Nucl. Med. 2012; 53(suppl): 1503.

Research Support: The trial is funded by the german research organization (AO599719)
  • Lecture (Conference)
    SNMMI 2013 Annual Meeting, 08.-11.06.2013, Vancouver, Canada

Publ.-Id: 18209 - Permalink

Preclinical Incorporation Dosimetry of (+)-[18F]Flubatine
Sattler, B.; Kranz, M.; Patt, M.; Donat, C. K.; Deuther-Conrad, W.; Fischer, S.; Smits, R.; Hoepping, A.; Brust, P.; Sabri, O.;
Objectives : (+)-[18F]flubatine is the mirror image isomer of (-)-[18F]flubatine, which is successfully used for neuroimaging of alpha4beta2 nAChRs in human. To assess the radiation risk by this new radioligand, biodistribution, organ doses (OD) and the effective dose (ED) were determined in piglets.

Methods : Whole body dosimetry was performed in 3 female piglets (age: 43±1.2d, weight: 14±1.0kg). The animals were anesthetized and sequentially PET-imaged up to 5h post i.v. injection of 183.5±9.0MBq on a SIEMENS Biograph16 PET/CT-system on 7 bed positions (BP) per frame, 1.5 to 6 min/BP, CT-attenuation correction (AC) and iterative reconstruction. All relevant organs were defined by volumes of interest. Exponential curves were fitted to the time-activity-data (%ID/g, and %ID/organ). Time- and mass-scales were adapted to the human order of magnitude. The ODs were calculated using the adult male model with
OLINDA. The ED was calculated using tissue weighting factors as published in the ICRP103.

Results : The highest OD [µSv/MBq] was received by urinary bladder (71.7±26.3) and kidneys (45.1±6.5). The highest contribution to ED [µSv/MBq] was by urinary bladder (2.9±1.1) and lungs (1.7±0.02). The estimated ED to humans is 14.3±0.3.

Conclusions : Considering 40% underestimation of the ED to humans by preclinical dosimetry [1], the expected ED to humans after 300MBq i.v. is 7.2 mSv, which is about the ED by (-)-[18F]flubatine (6.8 mSv/300MBq) and well within the range of what other F-18-labeled compounds cause to humans. This risk assessment encourages to transfer (+)-[18F]flubatine from preclinical to clinical study phases and to further develop as a clinical tool for PET imaging of the brain.

[1] Sattler B, …, Sabri O. Incorporation dosimetry of F-18-Flubatine - Comparison of animal model data with first-in-man results. J. Nucl. Med. 2012; 53(suppl): 1503.

Research Support: The trial is partly co-funded by Strahlenschutzseminar in Thüringen e.V. and by Helmholtz Validation Fonds.
  • Lecture (Conference)
    SNMMI 2013 Annual Meeting, 08.-11.06.2013, Vancouver, Canada
  • Poster
    EANM 2013, 19.-23.10.2013, Lyon, Frankreich
  • Abstract in refereed journal
    European Journal of Nuclear Medicine and Molecular Imaging 40(2013)2, S289-S289

Publ.-Id: 18208 - Permalink

First results of the one-step one-pot radiosynthesis of the selective alpha7 nicotinic receptor radioligand [18F]NS10743 using a microwave-based automated system
Teodoro, R.; Fischer, S.; Hiller, A.; Wenzel, B.; Deuther-Conrad, W.; Peters, D.; Brust, P.;
Objectives: Alpha7 nicotinic acetylcholine receptors (α7 nAChRs) play an important role in many neuropsychiatric diseases and various types of cancer [1]. [18F]NS10743, a promising and highly competetive α7 nAChR radioligand [1], has been successfully radiolabeled with high specific activity and radiochemical purity using a manual single-mode microwave device [2]. However, the palladium-catalyzed reduction of the remaining aromatic nitro-precursor (NS10796) to amine raises pharmaceutical restrictions and impedes the development of an automated radiosynthesis system. Here we report first results of a modified Discover CEM® microwave-based automated radiosynthesis of [18F]NS10743, which is followed by a direct RP-HPLC separation of the product from the respective nitro precursor.
Methods: The reference compound NS10743 and the corresponding nitro-precursor NS10796 were separated by different analytical RP-HPLC conditions (Multospher 120 RP 18 AQ, ReproSil-Pur 120 CN, Lichrospher 60 RP Select B, ReproSil Gold 120 C18) using (26-95%) ACN with 10 mM NH4OAc in water. F-18 microwave-assisted nucleophilic substitution of the nitro-precursor (3.0-4.0 mg) was conducted using Kryptofix® 2.2.2 (K222) as phase transfer catalyst. Reaction variables such as solvent system, reaction temperature, and time as well as microwave settings such as synthesis mode, applied power and cooling cycles were systematically optimized. Labelling yields were calculated based on radio-TLC and used to estimate the reproducibility of the microwave-based automated reactor. Semi-preparative RP-HPLC columns were chosen based on previous analytical tests, the desired product [18F]NS10743 separated from the precursor, purified with a Sep-Pak C18 cartridge and eluted with MeOH. Radiochemical purity was determined by radio-TLC and analytical radio-HPLC.

Figure. Analytical RP-HPLC separation of NS10743 from the corresponding nitro-precursor NS10796 using Reprosil-Pur 120 CN column (left) and one-step one-pot radiosynthesis of [18F]NS10743 (right).
Results: Optimal separation of NS10743 from the nitro-precursor NS10796 was obtained using the RP-HPLC Reprosil-Pur CN column and the related semi-preparative column using 26% ACN with 10 mM NH4OAc in water. NS10743 was eluted in front of NS10796 at low flow rates of 0.8 and 1.2 mL/min in analytical and semi-preparative RP-HPLC systems, respectively. Radiofluorination of NS10743 was successfully achieved using power cycling synthesis mode with 24 cooling cycles in DMF (140-158 °C) at a microwave radiation of 75 W for 15 min (Figure). Labelling efficiencies of ≥54% and radiochemical purity of ≥99% were achieved under these conditions, rendering a moderate-to-good reproducibility of the microwave cavity.
Conclusions: We achieved a promising one-step one-pot radiosynthetic route for the radioligand [18F]NS10743, avoiding the palladium-catalyzed reduction step. The microwave-based automated system module showed a moderate-to-good reproducibility, which encourages the further coupling with the automated system.
Acknowledgements: The work was financially supported by DFG (DE 1165/2-1).
References: [1] Brust P, Deuther-Conrad W(2012) Neuroimage Clinical Applications (Bright P., ed.) InTech - Open Access Publisher, 533-558. [2] Deuther-Conrad W, et al. (2011) Eur J Nucl Med Mol Imaging, 38, 1541–49.
  • Poster
    The 20th International Symposium on Radiopharmaceutical Sciences - ISRS2013, 12.-17.05.2013, Jeju, South Korea
  • Abstract in refereed journal
    Journal of Labelled Compounds and Radiopharmaceuticals 56(2013), S120-S120

Publ.-Id: 18207 - Permalink

Organic synthesis, radiofluorination and first biological evaluation of N-aryl-oxadiazolyl-propionamides as potential radioligands for PET imaging of cannabinoid CB2 receptors
Moldovan, R.; Teodoro, R.; Lueg, C.; Fischer, S.; Hiller, A.; Donat, C.; Deuther-Conrad, W.; Günther, R.; Ludwig, F.-A.; Wünsch, B.; Brust, P.;
Objectives: The cannabinoid receptor type 1 (CB1) has been intensively investigated but much less is known about the role and distribution of the cannabinoid receptor type 2 (CB2) in the central nervous system. Recently, we reported the synthesis and radiofluorination of a novel N-aryl-oxadiazolyl-propionamide for non-invasive imaging of CB2 with PET. However, the radiolabelling yields were unsatisfactory [1]. Thus, medicinal chemistry approaches were taken to develop fluorinated CB2 derivatives of 1 without compromising biological activity or selectivity. Radiofluorination and first biological evaluation were performed for the most promising CB2-selective ligands.

Methods: The reference compounds 2 (X2 = -19F) and 3 (Y2 = -19F) were achieved via a modified synthetic procedure [2] from the respective benzoic acid, succinic anhydride and N-alkyl-3-amino-carbazole. SAR studies were performed by varying both N-carbazole and amide-oxadiazole chain lengths. In addition to this, the substitution pattern of the aromatic region has been investigated. Distribution coefficients (LogD, pH = 7.2) were experimentally determined for 2 and 3 using a RP-HPLC method. Aliphatic [X1 = LG, Y1 = -H (LG = leaving group)] and aromatic (X1 = -H, Y1 = -LG) radiofluorinations of 1 were performed in AcCN using Kryptofix® 222 (K222) as phase transfer catalyst (PTC). The reaction conditions were optimized by varying the amount of PTC and precursor 1 (X1 or Y1 = -LG). For in vitro and in vivo studies, 18F-2 in isotonic saline solution containing 5% EtOH, was used. Rat spleen slices were incubated with 18F-2 in absence and presence of CB1/2-specific ligands. Ex vivo autoradiographs were obtained from brain and spleen of CD-1 mice after i.v. injection of 30 MBq of 18F-2.

Figure 1. Radiofluorination of N-aryl-oxadiazolyl-propionamide precursors 1; Ki = inhibition constant

Results: The N-ethyltosylate-carbazole 1 (X1 = -OTs, Y1 = -F) was the best choice for aliphatic radiofluorination. Although several LG were implemented (compound 1, X1 = H, Y1 = -LG), aromatic radiofluorination was only successfully achieved using the ammonium salt 1 (Y1 = Me3N+I) as precursor. Under optimized conditions, similar radiolabelling efficiencies (>50%), high radiochemical purities (>97%) and specific activities >250 GBq/µmol were obtained for 18F-2 and 18F-3. Increasing amounts of K222 lead to a decrease of the labelling efficiencies for 18F-2. LogD values of 3.8 and 4.4 for 2 and 3, respectively, suggest a good blood-brain barrier penetration. Autoradiography of spleen slices showed high inhibition of 18F-2 binding (≥–74%) by the CB1/CB2-specific CP55,940 and by CB2-specific ligands (JTE 907, GP1a, SR144528). Notably, no inhibition by the CB1-specific SR141716A was observed indicating highly selective CB2 binding of 18F-2. Ex vivo autoradiographs at 30 min p.i. showed heterogeneous radiotracer distribution in spleen (%ID/g = 6.96), comparable to the in vitro distribution of [3H]CP55,940, and low uptake and homogenous radiotracer distribution in brain (%ID/g = 1.49).

Conclusions: Fluorinated derivatives of 1 have been synthesized and the compounds with the best pharmacological properties were further investigated. Direct nucleophilic 18F-substitutions successfully delivered highly selective CB2 radioligands 18F-2 and 18F-3. Biological evaluation of 18F-2 suggests specific CB2 binding in vivo, which makes the compound a promising candidate for further evaluation.
Acknowledgements: This work has been supported by the DFG (project BR 1360/12-1).
References: [1] Rühl T, et al. (2012), Org Med Chem Lett, 2:32 [2] Cheng Y, et al. (2008), J Med Chem, 51, 5019-5034.
  • Lecture (Conference)
    The 20th International Symposium on Radiopharmaceutical Sciences - ISRS2013, 12.-17.05.2013, Jeju, South Korea
  • Abstract in refereed journal
    Journal of Labelled Compounds and Radiopharmaceuticals 56(2013)1, S1-S1

Publ.-Id: 18206 - Permalink

Development of new PET radioligands for α7 nicotinic acetylcholine receptors: A highly challenging task
Rötering, S.; Fischer, S.; Hiller, A.; Wenzel, B.; Scheunemann, M.; Donat, C. K.; Peters, D.; Steinbach, J.; Deuther-Conrad, W.; Brust, P.;
Objectives: The particular properties of intracellular signalling triggered by activation of neuronal and non-neuronal α7 nicotinic acetylcholine receptors (nAChR) establishes the involvement α7 nAChR in a host of pathological conditions including brain and cancer diseases. Recent approaches to clinically use the potential of α7 nAChR as diagnostic target by quantitative imaging by PET interfere with insufficient characteristics of the available radiotracers. From a series of highly affine and α7 nAChR-specific oxadiazolyl-diazabicyclononanes we have chosen fluoro-phenyl- and N-fluoroethyl-indole-substituted ligands for radio-labelling and comparative preclinical investigation of the respective radiotracers [18F]NS10743 [1] and [18F]NS14490.

Methods: [18F]NS14490 was synthesized by both a two-step labelling process starting from the indole NS14540 via [18F]fluoroethyltosylate 1 as well as a one-step nucleophilic substitution of a tosylate precursor 2 using K[18F]F-Kryptofix 222-carbonate complex (Fig.1). Stability and partition coefficient (shake-flask method) at pH 7.2 as well as in vitro affinity towards α7 nAChR were analyzed. The specific in vitro binding of [18F]NS14490 assessed by autoradiography of mice and pig brain was compared with [125I]α-bungarotoxin as reference. Biodistribution of [18F]NS14490 was investigated in female CD-1 mice at 5, 15, 30, and 60 min p.i. Radiotracer metabolism in vivo was studied by radio HPLC analysis of mice plasma, brain, and urine samples (30 and 60 min p.i.). Target specific binding of [18F]NS14490 in brain was shown by pre-administration of specific α7 nAChR ligands SSR180711 and NS6740 (10 mg/kg i.p., 10 min before [18F]NS14490). A preliminary dynamic PET study was performed in one female piglet.

Results: [18F]NS14490 was obtained by two-step and one-step radiosyntheses with labelling yields of ~7% and ~70%, respectively. The product of the further used one-step procedure was obtained with 36 ± 3% RCY at As ~150 GBq/µmol and a radiochemical purity of >98% within ~2.5 hours (n=13). [18F]NS14490 was stable for at least 120 min in both TRIS buffer and PBS. LogDoctanol/PBS of 1.11 ± 0.02 (n=12) and logDcyclohexane/PBS = -2.05 ± 0.03 (n=3) were determined. The α7 nAChR binding affinity of NS14490 (Ki=2.5 nM) is considerably higher than assessed for NS10743 (Ki=11.6 nM [1]). The distribution of [18F]NS14490 binding in mice and pig brain matches the expression of α7 nAChR in these species. Compared to [18F]NS10743, a much lower fraction of [18F]NS14490 passed the blood-brain barrier (BBB) in mice (SUV 1.76 [2] vs. 0.05 at 5 min p.i.). Notably, pre-administration of NS6740 significantly reduced brain uptake of [18F]NS14490 in mice (-30% at 60 min p.i.; p-value <0.005), and the maximum SUV of [18F]NS14490 in pig brain (~0.6) was about tenfold higher than in mice. [18F]NS14490 is metabolically more stable than [18F]NS10743 [2] with 55% vs. 40% of total activity in plasma accounting for the respective parent radiotracer at 60 min p.i. , and the chromatographic analysis of brain samples revealed that none of the radiometabolites of [18F]NS14490 detected in plasma crossed the BBB.

Conclusion: Radiofluorination of the novel oxadiazolyl-diazabicyclononane analogue NS14490 was achieved and optimized. [18F]NS14490 was obtained with high RCY and As. Although biodistribution data indicate lower brain uptake of [18F]NS14490 in comparison to [18F]NS10743 in mice, the tenfold higher SUV in pig as well as the target specific binding shown by blocking studies in mice prompt us to continue with the preclinical evaluation of [18F]NS14490.

Acknowledgements: The work was financially supported by DFG (DE 1165/2-1). We would like to thank Jonni Heberg, Tove Thomsen, and Gitte Friberg for technical assistance.
References: [1] Deuther-Conrad, W, et al (2009) Eur J Nucl Med Mol Imaging, 36, 791-800.
  • Lecture (Conference)
    The 20th International Symposium on Radiopharmaceutical Sciences - ISRS2013, 12.-17.05.2013, Jeju, South Korea
  • Abstract in refereed journal
    Journal of Labelled Compounds and Radiopharmaceuticals 56(2013), S34

Publ.-Id: 18205 - Permalink

Discovery of enantioselective suitability of (R)-(+)- and (S)-(-)-[18F]fluspidine for σ1 receptor imaging
Deuther-Conrad, W.; Maisonial, A.; Patt, M.; Stittsworth, S.; Becker, G.; Habermann, B.; Holl, K.; Schepmann, D.; Funke, U.; Donat, C. K.; Fischer, S.; Hiller, A.; Wenzel, B.; Steinbach, J.; Wünsch, B.; Lever, S.; Hesse, S.; Sabri, O.; Brust, P.;
Objectives: It is widely accepted that σ1 receptors represent a novel biological target for the possible pharmacological treatment of cancer and several brain diseases, e.g. depression and neurodegeneration. From a series of σ1-specific racemic 18F-fluoroalkylated spirocyclic piperidines1-3 we have chosen the superior [18F]fluspidine [1] for detailed investigation of the (R)-(+)- and (S)-(–)-enantiomers (Ki: 0.52 nM; 2.3 nM) to identify their individual potential for disease-related imaging studies in humans.

Methods: The racemic tosylate precursor of [1] was enantioseparated by semi-preparative chiral HPLC on immobilized cellulose-tris-(3,5-dimethylphenyl)-carbamate as stationary phase. Automated radiosynthesis of (R)- and (S)-[1] was accomplished by nucleophilic substitution using K[18F]F-Kryptofix 222-carbonate complex (Figure 1) and organ distribution studies were performed in CD-1 mice to obtain organ-specific time activity data (%ID/g). Brain pharmacokinetics of the two enantiomers was confirmed by dynamic PET studies in pigs. Additionally, the highly selective σ1 receptor agonist SA4503 was used in blocking studies to assess target specificity. SUV values were calculated for 24 MR-defined brain regions. Using a metabolite-corrected plasma input function compartment modelling was applied to estimate the distribution volume of both enantiomers.

Figure 2. PET time-activity curves for (S)- and (R)-[1] in pig brain (baseline and blocking conditions)

Results: Enantiomerically pure (R)- and (S)-tosylate precursors were obtained with high enantiomeric excess of >98 % and >96 %, respectively. (R)- and (S)-[1] were synthesized within ~70 min with RCY of 35-45% (EOS), RCP of >99%, and As of 650 and 870 GBq/µmol, respectively. In mice, both radiotracers readily passed the blood-brain barrier. However, large differences in brain pharmacokinetics of the two enantiomers were found with continuous increase of brain uptake of (R)-[1] (3.57 %ID/g at 5’, 6.01% ID/g at 240’ p.i.) in comparison to (S)-[1] with higher initial brain uptake (4.35 %ID/g at 5’ p.i.) and rapid clearance (1.04% ID/g at 240’ p.i.). Dynamic PET studies in pigs confirmed these enantiomer-related differences in brain uptake kinetics. Under baseline conditions, the initial uptake of (S)-[1] in brain was higher than that of (R)-[1] (e.g. SUVmax, Cerebellum ~3.4 vs. ~2.9). Clearance of (S)-[1] from brain was fast (SUVCerebellum ~1.1 at 95-120’ p.i.) whereas the uptake of (R)-[1] remained close to the initial level (SUVCerebellum ~2.5 at 95-120’ p.i.). In comparison to baseline data, application of σ1 specific SA4503 reduced the uptake of (S)- and (R)-[1] in the target region cerebellum by initially 40% and 15% (SUVmax ~2.0 and ~2.5, respectively) and at later measurement periods significantly by ~80% (SUV ~0.2 and ~0.6 at 95-120’ p.i., respectively). Washout kinetics and SUV values determined under blocking conditions indicate both target specificity of the binding as well as minor nonspecific binding of the two radiotracers.

Conclusions: We successfully developed and validated an automated synthesis of the two enantiomers of [1]. The pharmacokinetics of (S)-[1] as investigated in two different animal models suggests that this radiotracer is most suitable for upcoming studies of depression-related changes in receptor expression in human brain. The irreversible-like binding behaviour of (R)-[1] may have advantages for tumor imaging.
Acknowledgements: Supported by DFG (STE 601/10-2, WU 176/7-2) and NIH (T32 EB004822).
References: [1] Fischer S, et al (2011) Eur J Nucl Med Mol Imaging, 38, 540-551. [2] Maisonial A, et al (2011) ChemMedChem, 6, 1401-1410. [3] Maisonial A, et al (2012) Bioorg Med Chem, 20, 257-269
  • Lecture (Conference)
    The 20th International Symposium on Radiopharmaceutical Sciences - ISRS2013, 12.-17.05.2013, Jeju, South Korea
  • Abstract in refereed journal
    Journal of Labelled Compounds and Radiopharmaceuticals 56(2013)1, S55-S55

Publ.-Id: 18204 - Permalink

Development of transport solutions for DYN3D. Current status.
Litskevich, D.; Merk, B.;
An outline of current status of development of transport solutions for pin-power reconstruction in DYN3D is presented. Presently, an advanced method of current coupling collision probability with flux expansion in zones is being developed and tested for cylindrical geometry. Results of test calculations for cylindrical cell shows very good agreement with the results obtained with Monte Carlo method. This very convincing results encourage the development of a two dimensional solver and the implementation of this advanced pin power calculation method into DYN3D as further steps.
Keywords: DYN3D, first flight collision probability, transport solution
  • Open Access LogoContribution to proceedings
    Annual Meeting on Nuclear Technology (Jahrestagung Kerntechnik), 14.-16.05.2013, Berlin, Deutschland
    Proceedings of the Annual Meeting on Nuclear Technology
  • Lecture (Conference)
    Annual Meeting on Nuclear Technology (Jahrestagung Kerntechnik), 14.-16.05.2013, Berlin, Deutschland

Publ.-Id: 18203 - Permalink

Steady state analysis of SFR cores using DYN3D-Serpent codes sequence
Rachamin, R.; Fridman, E.;
The advanced multi-group nodal diffusion code DYN3D is currently being extended to the analysis of Sodium-cooled Fast Reactor (SFR) cores. Thermo-physical properties of sodium (such as thermal conductivity, density, viscosity, etc.) were included into the thermal-hydraulics module database. The development of thermo-mechanical model (to account for the core thermal expansion effects) is planned for the near future. The main objective of this study is to demonstrate the feasibility of using DYN3D for the modeling of SFR cores. For this purpose, a 2D model of the mixed oxide fuel (MOX) European Sodium Fast Reactor (ESFR) core was considered. 2D full core depletion calculations were performed using Serpent-DYN3D code sequence and the results were compared with those obtained from a 2D full core Monte Carlo solution. Very good agreement between the codes was observed for the core integral parameters and power distribution at beginning of life (BOL) and end of life (EOL).
Keywords: Sodium-cooled Fast Reactor (SFR), DYN3D, Serpent, few-group cross section generation
  • Open Access LogoContribution to proceedings
    Annual Meeting on Nuclear Technology (Jahrestagung Kerntechnik), 14.-16.05.2013, Berlin, Deutschland
    Proceedings of the Annual Meeting on Nuclear Technology
  • Lecture (Conference)
    Annual Meeting on Nuclear Technology (Jahrestagung Kerntechnik), 14.-16.05.2013, Berlin, Deutschland

Publ.-Id: 18202 - Permalink

Structure-affinity relationship study of novel vesamicol analogs as basis for the development of a selective PET-Ligand for the vesicular acetylcholine transporter
Wenzel, B.; Barthel, C.; Sorger, D.; Stüwe, R.; Wondrousch, D.; Schweiger, S.; Jäckel, P.; Deuther-Conrad, W.; Steinbach, J.; Schüürmann, G.; Sabri, O.; Brust, P.;
Objectives: The vesicular acetylcholine transporter (VAChT) is a transmembrane protein located in presynaptic vesicles of cholinergic neurons and is discussed to be an interesting target for PET imaging of neurodegenerative disorders. Previous developments of VAChT radiotracers are based on vesamicol (trans-2-(4-phenylpiperidino)cyclohexanol) and are focused on structural modifications in order to keep the high affinity of vesamicol to VAChT and to lower the affinity to σ1 and σ2 receptors, two off-targets which are also addressed by vesamicol. The moderate selectivity of several VAChT-ligands is one of the limiting factors for a successful application as radiotracer. Based on numerous literature data and our own intensive synthetic work in this field, we observed that structural modifications based on single-target structure affinity considerations are rarely successful. Therefore, we synthesized different series of systematically modified vesamicol analogs as basis for the development of a 3D-QSAR model, which will consider for the first time the affinity to VAChT as well as to the σ1 and σ2 receptors.

Methods: Nucleophilic ring opening of an epoxide precursor with a secondary amine was used to synthesize a large number of vesamicol derivatives. By varying the epoxide precursor, structural modifications in ring A of the vesamicol skeleton were realized (left part of the figure). Due to the selection of different amines, the rings B and C were sterically or electronically modified (right part of the figure). The binding affinities to VAChT were determined with competitive binding experiments using preparations of PC12 cells stably transfected with ratVAChT cDNA and (-)-[3H]vesamicol. To determine the binding affinity to the sigma receptors, rat cortex membranes and (+)-[3H]pentazocin for σ1 and rat liver membranes and [3H]DTG for σ2 receptors were used.

Results: So far we synthesized 55 derivatives belonging to the four classes of vesamicols, F-benzoylvesamicols, benzovesamicols and azavesamicols (Fig.) and determined their binding affinity to VAChT, σ1 and σ2 receptors. A few of them such as benzovesamicol or FBT are already known and were used as reference compounds. Interestingly, the VAChT binding data obtained by our test system differ to some extent from the values reported in literature. Therefore, VAChT binding data of selected vesamicol derivatives obtained either with PC12 cells or membranes of pig and/or rat brain are compared and differences of Ki values are discussed. The use of preparations obtained by freezing and thawing of PC12 cells stably transfected with ratVAChT cDNA and (-)-[3H]vesamicol was found to be the most practicable and reliable method. As a preliminary trend we could observe that modifications in ring B and C led to a loss of VAChT affinity, whereas modifications in ring A partly increased VAChT affinity, which was however often accompanied by an increase in σ12 receptor affinity.

Figure. Vesamicol as chemical lead and derived new analogs

Conclusion: Based on our previous results, we have to conclude that VAChT affinity suitable for PET imaging correlates often with significant off-target affinity to the σ1 and σ2 receptors.
Acknowledgment: Supported by DFG (WE 2927/4-1).
  • Poster
    The 20th International Symposium on Radiopharmaceutical Sciences - ISRS2013, 12.-17.05.2013, Jeju, South Korea
  • Abstract in refereed journal
    Journal of Labelled Compounds and Radiopharmaceuticals 56(2013), S265-S265

Publ.-Id: 18201 - Permalink

Separation of the optical antipodes of the novel σ1 receptor ligand [18F]fluspidine using chiral HPLC
Wenzel, B.; Maisonial, A.; Holl, K.; Fischer, S.; Hiller, A.; Funke, U.; Steinbach, J.; Wünsch, B.; Brust, P.;
Objectives: (±)-[18F]Fluspidine represents a novel ligand with high binding affinity and selectivity toward σ1 receptors [1,2]. With the aim to identify the individual potential of the two enantiomers of (±)-[18F]fluspidine for particular disease-related imaging studies, this racemate as well as its tosylate precursor needed to be enantioseparated. Therefore, we performed an extensive chiral HPLC study with different chiral stationary phases (CSPs) and eluent modes.

Methods: The use of the immobilized polysaccharide type column Chiralpak IA (Chiral Technologies Europe, Daicel) offered the possibility to study various solvents, which are not common for HPLC. We used mixtures of several alkenes with ethers, esters, alcohols and chlorinated solvents as NP mode eluents. ACN and MeOH as organic modifier mixed with aqueous TEA/AcOH or NH4OAc as buffers were used in RP mode. Working with this column type in the polar ionic mode by using 100% ACN or MeOH with TEA/AcOH was possible as well. Furthermore, we studied the enantioselectivity on different coated polysaccharide phases (cellulose and amylose based), a Pirkle-type CSP (with pi-acceptor-donor character) and a glycopeptide CSP (teicoplanin derived; Dr. Maisch, Germany). The identification of the enantiomers was carried out with a chiral detector (OR 2090, JASCO) and is based on the measurement of optical rotation.

Results: The tosylate precursor could be best enantioseparated with the Chiralpak IA column using 90% n-hexane/THF/0.1% DEA. At a flow rate of 1mL/min the (–)-enantiomer eluted with tR=13.9 min in front of the (+)-enantiomer with tR=32.4 min. This remarkable separation is appropriate for a semi-preparative separation of the precursor compound to provide enantiomerically pure precursor compounds for the radiosynthesis of (S)-(–)-[18F]fluspidine and (R)-(+)-[18F]fluspidine. In contrast to the results obtained with the tosylate, the corresponding fluoro compound fluspidine could not be enantioseparated with the Chiralpak IA column. Also most of the other columns investigated were not successful. Exclusively, the Reprosil-Chiral OM column (comparable to Chiralcel OD) was appropriate to separate the fluspidine enantiomers sufficiently in NP mode using 97% n-hexane/isopropanol/0.1% DEA (Figure). This method was transferred to the automated radiosynthetic procedure to analyze the enantiomeric purity of (S)-(–)-[18F]fluspidine and (R)-(+)-[18F]fluspidine, which was higher than 97%.

Figure. Analytical enantioseparation of (±)-fluspidine (left) and verification of (R)-(+)-[18F]fluspidine after radiosynthesis (right) on Reprosil-Chiral OM with 97% n-hexane/isopropanol/0.1% DEA

Conclusion: We successfully developed two chiral HPLC methods for enantioseparation of fluspidine and its tosylate precursor. Furthermore, we have repeatedly shown, that it is not predictable which chiral phase will be suitable to separate the enantiomers of a compound even if the derivatives are structurally related.

Acknowledgment: Supported by DFG (STE 601/10-2, WU 176/7-2).
References: [1] Fischer S, et al (2011) Eur J Nucl Med Mol Imaging, 38, 540-551. [2] Maisonial A, et al (2012) Bioorg Med Chem, 20, 257-269.
  • Poster
    The 20th International Symposium on Radiopharmaceutical Sciences - ISRS2013, 12.-17.05.2013, Jeju, South Korea
  • Abstract in refereed journal
    Journal of Labelled Compounds and Radiopharmaceuticals 56(2013)1, S259-S259

Publ.-Id: 18200 - Permalink

Imaging of α7 nicotinic acetylcholine receptors (α7nAChRs): A challenge for PET radiotracer development.
Brust, P.; Fischer, S.; Rötering, S.; Scheunemann, M.; Hiller, A.; Wenzel, B.; Donat, C. K.; Peters, D.; Steinbach, J.; Deuther-Conrad, W.;
Objectives: Pre- and postsynaptic modulation of different neurotransmitter systems and further non-neuronal mediators connect α7nAChRs to brain development, learning and memory, sleep, pain perception, reward, drug dependency and various neuropsychiatric diseases. Recent approaches to use α7 nAChR as target for neuroimaging interfere with insufficiencies of the available radiotracers connected to a rather low receptor density in brain1. From a series of highly affine and α7nAChR-specific oxadiazolyl-diazabicyclononanes we have chosen fluoro-phenyl- and N-fluoroethyl-indole-substituted ligands for radiolabelling and comparative preclinical investigation of the respective radiotracers [18F]NS107432 and [18F]NS14490.

Methods: [18F]NS14490 was synthesized by one-step nucleophilic substitution of an unlabelled tosylate precursor (Fig.). Stability against defluorination and partition coefficient (shake-flask method, pH 7.2) and in vitro affinity towards α7nAChR and other nAChR were investigated. [18F]NS14490 receptor autoradiography of mice (Fig.) and pig brain was compared with [125I]bungarotoxin as reference. In female CD-1 mice biodistribution (5´, 15´, 30´, 60´ p.i.) was investigated, and [18F]NS14490 metabolism was studied by radio-HPLC (plasma, brain, urine; 30´, 60´ p.i.). Target specific binding of [18F]NS14490 was demonstrated by pre-administration (10´ before radioligand) of highly specific α7nAChR ligands (SSR180711, NS6740; 10 mg/kg). A preliminary dynamic PET study was performed in female pig (Fig.).

Results: [18F]NS14490 was obtained within 2-2.5h with RCY of 36%±3% (n=13), RCP >98%, and As ~150 GBq/µmol. It was stable for >2h in TRIS-buffer and PBS. LogDoctanol/PBS of 1.11±0.02 (n=12) and logDcyclohexane/PBS of -2.05±0.03 (n=3) were determined. The α7 binding affinity of NS14490 (2.5 nM) is considerably higher than assessed for NS10743 (11.6 nM2). [18F]NS14490 binding in mice and pig brain matches the expression of α7nAChR in these species. No receptor-free reference region was identified. Almost similar striatum-to-cerebellum ratios (~1.3) were obtained in pig autoradiography and dynamic PET studies with [18F]NS14490 and [18F]NS107432. However, compared to [18F]NS10743, a much lower fraction of [18F]NS14490 passed the blood-brain barrier (BBB) in mice (SUV 1.22 vs. 0.05 at 5´ p.i.). Notably, pre-administration of NS6740 significantly reduced the brain uptake of [18F]NS14490 in mice (30% at 60´ p.i.; p< 0.005) and the maximum SUV of [18F]NS14490 in pig brain (~0.6) was an order of magnitude higher than in mice. [18F]NS14490 is metabolically more stable than [18F]NS107432 with 55% vs. 40% of total activity in plasma accounting for parent compound at 60´ p.i. Chromatographic analysis of brain samples revealed that no radiometabolites of [18F]NS14490 crossed the BBB.

Conclusion: Radiofluorination of the novel oxadiazolyl-diazabicyclononane analogue NS14490 was achieved and optimized. [18F]NS14490 was obtained with high RCY, RCP and As. Although biodistribution data indicate lower brain uptake of [18F]NS14490 in comparison to [18F]NS10743 in mice, the more than ten-fold higher SUV in pig and the target specific binding shown by blocking studies in mice prompt us to continue with the preclinical evaluation of [18F]NS14490.
Acknowledgements: Supported by DFG (DE1165/2-1).

References: 1Brust P, Peters D, Deuther-Conrad W (2012) Curr Drug Targets 13, 594-601.
2Deuther-Conrad W et al. (2009) Eur J Nucl Med Molec Imaging, 36, 791-800.
  • Poster
    BrainPET2013, 20.-23.05.2013, Shanghai, China

Publ.-Id: 18199 - Permalink

Neuroimaging of Alzheimer´s disease (AD) with Positron Emission Tomography (PET)
Brust, P.; Barthel, H.; Sabri, O.;
PET is a well-established neuroimaging method in identifying AD. An ideal PET biomarker for AD should allow a reliable estimation of disease risk and rate of disease progression long before first symptoms are clinically diagnosed. The main pathologic processes of AD, deposition of β-amyloid, hyperphosphorylated tau protein, degeneration of cholinergic and other neurons, precede clinical symptoms by years providing potential targets for the identification of individuals at risk for AD.
In the last few years, several PET tracers targeting β-amyloid in AD have been developed, such as [11C]PIB, [18F]florbetaben, [18F]florbetapir, [18F]flutemetamol. The suitability of these PET radiopharmaceuticals to differentiate AD patients and patients with mild cognitive impairment (MCI) from control subjects has been demonstrated. However β-amyloid deposition has been found in about 20% of normal elderly subjects. Therefore other potential neuroimaging biomarkers, for instance based on radiopharmaceuticals for the cholinergic system may be of interest.
Loss of nicotinic acetylcholine receptors (nAChRs) is a major contributor to the cognitive deterioration in AD. The α4β2-nAChR subtype is thought to be the most severely reduced in the onset of AD. Using 2-[18F]F-A85380 PET we showed a significant decline in α4β2-nAChRs in early AD which correlated significantly with the loss of cognitive function. Because this tracer is not suitable as a biomarker in a routine clinical set-up for early AD-diagnosis we developed the new radiotracer (-)-[-[18F]flubatine with faster kinetics, significantly improved brain uptake and better image quality.
Our further attempts for development of PET biomarkers include the α7nAChR and σ1 receptors as targets, as both are suggested to be involved in early AD. [18F]NS10743 and [11C]NS14492 are radioligands which show high brain uptake, regional distribution and dose-dependent blockade in accordance with α7nAChR expression pattern in animal PET studies and are promising for in vivo mapping and quantitative imaging of α7nAChR in AD. For PET imaging of σ1 receptors a series of fluoroalkyl substituted spirocyclic piperidines was developed and (S)-[-[18F]fluspidine has been selected as the most promising for molecular imaging in human.
Taken together, there is optimism that it might be possible in future to improve early neuroimaging diagnosis of AD as a multifactorial disorder by a multi-tracer PET imaging strategy, with important implications for early preventive/therapeutic interventions.
  • Invited lecture (Conferences)
    24th Biannual Meeting of the International Society for Neurochemistry, 20.-24.04.2013, Cancun, Mexico
  • Abstract in refereed journal
    Journal of Neurochemistry 125(2013)Suppl.s1, 41-41

Publ.-Id: 18198 - Permalink

Intraexcitonic Autler-Townes effect in semiconductor quantum wells
Teich, M.; Wagner, M.; Stehr, D.; Helm, H.; Schneider, M.; Chatterjee, S.; Klettke, A. C.; Koch, S. W.; Kira, M.; Gibbs, H. M.; Khitrova, G.;
A fundamental problem in light-matter interaction is the coupling of an intense, monochromatic electromagnetic wave with a quantum mechanical two-level system. One effect related to this is the Autler-Townes or AC Stark effect. Originally observed and described in molecular spectroscopy the effect refers to a splitting of an energy level that is resonantly coupled via intense radiation to an adjacent level, i.e. the states get ”dressed” by the light-matter interaction. We investigate this effect using a free-electron laser (FEL) driven intra-excitonic transition between the heavy-hole 1s and 2p states in a semiconductor multiple quantum well. We have observed distinct intensity- and wavelength dependent Rabi sidebands of the 1s exciton line in the terahertz (THz) regime when the FEL was tuned around the 1s-2p transition [1]. Temperature-dependent measurements have been done and a clear Rabi-sideband behavior is observable up to 200 K where the thermal energy already exceeds the exciton binding energy by a factor of 1.7 [2]. A threefold NIR transmission change at 200 K on picosecond timescales could be promising for optical modulators with Peltier-cooling. We also present measurements at higher THz fields exploring the regime beyond the rotating-wave approximation (RWA), where the Rabi energy is comparable to the transition energy. Theoretical calculations support the understanding of the underlying processes especially for the high-field measurements.
[1] M. Wagner, H. Schneider, D. Stehr, S. Winnerl, A. M. Andrews, S. Schartner, G. Strasser, and M. Helm, Phys. Rev. Lett. 105, 167401 (2010)
[2] M. Wagner, M. Teich, M. Helm, and D. Stehr, Appl. Phys. Lett. 100, 051109 (2012)
Keywords: quantum well free-electron laser (FEL) intra-excitonic transition Autler-Townes AC Stark effect
  • Poster
    NOEKS11 - Nonlinear Optics and Excitation Kinetics in Semiconductors, 23.-27.09.2012, Stuttgart, Deutschland

Publ.-Id: 18197 - Permalink

Intraexcitonic coherent nonlinear optics in quantum wells
Teich, M.; Wagner, M.; Stehr, D.; Schneider, H.; Helm, M.; Chatterjee, S.; Klettke, A.; Koch, S. W.; Gibbs, H.; Khitrova, G.;
A fundamental problem in light-matter interaction is the coupling of an intense, monochromatic electromagnetic wave with a quantum mechanical two-level system. One effect related to this is the Autler-Townes or AC Stark effect. Originally observed and described in molecular spectroscopy the effect refers to a splitting of an energy level that is resonantly coupled via intense radiation to an adjacent level, i.e. the states get ”dressed” by the light-matter interaction. We investigate this effect using a free-electron laser (FEL) driven intra-excitonic transition between the heavy-hole 1s and 2p states in a semiconductor multiple quantum well. We have observed distinct intensity- and wavelength dependent Rabi sidebands of the 1s exciton line when the FEL was tuned around the 1s-2p transition [1]. We also present measurements at higher electric fields exploring the regime beyond the rotating-wave approximation (RWA), where the Rabi energy is comparable to the transition energy. Theoretical calculations support the understanding of the underlying processes, which is especially interesting for the regime beyond the RWA. Also temperature-dependent measurements have been done and a clear Rabi-sideband behavior is observable up to 200 K where the thermal energy already exceeds the exciton binding energy by a factor of 1.7 [2]. A threefold NIR transmission change at 200 K on picosecond timescales could be promising for optical modulators with Peltier-cooling.
[1] M. Wagner, H. Schneider, D. Stehr, S. Winnerl, A. M. Andrews, S. Schartner, G. Strasser, and M. Helm, Phys. Rev. Lett. 105, 167401 (2010)
[2] M. Wagner, M. Teich, M. Helm, and D. Stehr, Appl. Phys. Lett. 100, 051109 (2012)
Keywords: Intraexcitonic coherent nonlinear optics quantum wells Autler-Townes AC Stark effect free-electron laser (FEL)
  • Poster
    International Conference on Superattices, Nanostructures and Nanodevices - ICSNN 2012, 22.-27.07.2012, Dresden, Deutschland

Publ.-Id: 18196 - Permalink

Fine Structure of the Giant M1 Resonance in 90Zr
Rusev, G.; Tsoneva, N.; Dönau, F.; Frauendorf, S.; Schwengner, R.; Tonchev, A. P.; Adekola, A. S.; Hammond, S. L.; Kelley, J. H.; Kwan, E.; Lenske, H.; Tornow, W.; Wagner, A.;
The M1 excitations in the nuclide 90Zr have been studied in a photon-scattering experiment with monoenergetic and linearly polarized beams from 7 to 11 MeV. More than 40 Ji^pi = 1+ states have been identified from observed ground-state transitions, revealing the fine structure of the giant M1 resonance with a centroid energy of 9 MeV and a sum strength of 4.17(56) mu_N^2 . The result for the total M1 strength and its fragmentation are discussed in the framework of the three-phonon quasiparticle-phonon model.
Keywords: Nuclear structure, magnetic dipole strength, giant resonance, photon scattering, monoenergetic polarized gamma rays, shell model, quasiparticle-phonon model.

Publ.-Id: 18195 - Permalink

Resistance of brain glucose metabolism to thiopental-induced CNS depression in newborn piglets
Bernd, W.; Eiselt, M.; Cumming, P.; Xiong, G.; Hinz, R.; Uthe, S.; Brust, P.; Bauer, R.;
The transition from mild sedation to deep anaesthesia is marked by the phenomenon of burst suppression (BS). FDG-PET studies show that the cerebral metabolic rate for glu-cose (CMRglc) declines dramatically with onset of BS in the adult brain. Global CMRglc increases substantially in the post-natal period and achieves its maximum in preadoles-cence. However, the impact of post-natal brain development on the vulnerability of CMR-glc to the onset of BS has not been documented.
Therefore, cerebral blood flow and metabolism were measured using a variant of the Kety-Schmidt method, in conjunction with quantitative regional estimation of brain glucose uptake by FDG-PET in groups of neonate and juvenile pigs, under a condition of light sedation or after induction of deep anaesthesia with thiopental. Quantification of simultaneous ECoG recordings was used to establish the correlation between anaesthesia-related changes in brain electrical activity and the observed cerebrometabolic changes.
In the condition of light sedation the magnitude of CMRglc was approximately 20% higher in the older pigs, with the greatest developmental increase evident in the cerebral cortex and basal ganglia (P < 0.05). Onset of BS was associated with 20-40% declines in CMR-glc.
Subtraction of the mean parametric maps for CMRglc showed the absolute reductions in CMRglc evoked by thiopental anaesthesia to be two-fold greater in the preadolescent pigs than in the neonates (P < 0.05). Thus, the lesser suppression of brain energy demand of neonate brain during deep anaesthesia represents a reduced part of thiopental suppressing brain metabolism in neonates.
Keywords: cerebral glucose consumption; swine; positron emission tomography; coloured microspheres; brain maturation

Publ.-Id: 18194 - Permalink

Velocity measurements in the liquid metal flow driven by a two-phase inductor
Pedcenko, A.; Bojarevics, A.; Priede, J.; Gerbeth, G.; Herrmann, R.;
We present the results of velocity measurements obtained by ultrasonic Doppler velocimetry and local potential probes in the flow of GaInSn eutectic melt driven by a two phase inductor in a cylindrical container. This type of flow is expected in a recent modification to the floating zone technique for the growth of small-diameter single intermetallic compound crystals. We show that the flow structure can be changed from the typical two toroidal vortices to a single vortex by increasing the phase shift between the currents in the two coils from 0 to 90 degrees. The latter configuration is thought to be favourable for the growth of single crystals. The flow is also computed numerically and a reasonable agreement with the experimental results is found. The obtained results may be useful for the design of combined two-phase electromagnetic stirrers and induction heaters for metal or semiconductor melts.
Keywords: -

Publ.-Id: 18193 - Permalink

Local modification of magnetic anisotropy and ion milling of Co/Pt multilayers using a He+ ion beam microscope
Fowley, C.; Diao, Z.; Faulkner, C. C.; Kally, J.; Ackland, K.; Behan, G.; Zhang, H. Z.; Deac, A. M.; Coey, J. M. D.;
We use a focused helium ion beam microscope to controllably remove material from Pt-capped thin film multilayers with perpendicular magnetic anisotropy. The dose range required to remove several nm of the cap layer is the same as that required to induce a spin reorientation transition. Milling depth for Pt is found to scale with the logarithm of ion dose, with very high removal yields of hundreds of atoms per He ion at low doses. While the deposited energy is of order of previous broadbeam helium irradiations, the current density impacting on the surface of the sample is several tens of A/cm2, orders of magnitude higher. Patterning of the platinum capping layer with 20 nm resolution is demonstrated.
Keywords: Magnetic anisotropy, Magnetic multilayers, Sputtering by atom, molecule, and ion impact, Hall effect in thin films, Ion beam lithography

Publ.-Id: 18191 - Permalink

Effect of an in-plane field on microwave dynamics in point contact spin valve structures combining inplane and out-of-plane magnetic layers
Fowley, C.; Sluka, V.; Bernert, K.; Gan, H.; Fassbender, J.ORC; Rippard, W. H.; Pufall, M. R.; Russek, S. E.; Deac, A. M.
Point contact spin transfer devices combining out-of-plane and in-plane magnetized layers are promising candidates for spin transfer oscillators, in that they can achieve high-power and close to zero field operation [1][2]. We present recent experimental results on spin transfer torque oscillators combining both out-of-plane (CoFe/Pd) and in-plane (CoFe) magnetized layers. The device structure is such that the in-plane layer is lithographically patterned (to serve as a nanopillar/point contact) whereas the out-ofplane layer is extended. We find that, unlike previously reported point-contact devices where both ferromagnetic layers were extended [2], microwave oscillations are excited at zero applied field. We investigate how the high frequency dynamics are affected as a function of in-plane applied magnetic fields. As the in-plane field is increased, the current frequency dependence changes from negative (red-shift) to positive (blue-shift) slope. This occurs as the magnetisation direction of the out-of-plane layer nears its anisotropy field which is determined from MR curves. High frequency oscillations persist beyond the anisotropy field of the out-of-plane magnetised layer.
In order to gain insight to the observed response of the system, we calculated current-field phase diagrams for both layers by numerical integration of the LLG equation, taking into account the Slonczewski spin Transfer torque including the spin transfer asymmetry characterized by the coefficient λ [3]. According to These calculations, dynamics in the in-plane layer are only expected when the initial magnetisation is aligned antiparallel to the applied field, while oscillations of the out-of-plane layer are not expected with an in-plane applied field above the anisotropy field. Since the observed microwave spectra seem not to be adequately explained by individual layer dynamics it may be necessary to account for dynamics of both layers simultaneously.

A.M.D. and C.F. acknowledge financial support from the Swiss National Foundation Ambizione grant (PZ00P2_131808).
[1] Houssameddine, D. et al., Nature Mat. 6, 447 (2007).
[2] Rippard, W.H., et al., Phys. Rev. B. 81, 014426 (2010).
[3] Slonczewski, J.C., J. Magn. Magn. Mater. 247, 324 (2002).
Keywords: Spin transfer torque, Spin transfer oscillators, Spin valves, Giant magnetoresistance
  • Poster
    12th Joint MMM/Intermag Conference, 14.-18.01.2013, Chicago, IL, USA

Publ.-Id: 18190 - Permalink

Guidelines for Thermodynamic Sorption Modelling in the Context of Radioactive Waste Disposal
Payne, T. E.; Brendler, V.; Ochs, M.; Baeyens, B.; Brown, P. L.; Davis, J. A.; Ekberg, C.; Kulik, D. A.; Lützenkirchen, J.; Missana, T.; Tachi, Y.; van Loon, L. R.; Altmann, S.;
Thermodynamic sorption models (TSMs) offer the potential to improve the incorporation of sorption in environmental modelling of contaminant migration. One specific application is safety cases for radioactive waste repositories, in which radionuclide sorption on mineral surfaces is usually described using distribution coefficients (Kd values). TSMs can be utilised to provide a scientific basis for the range of Kd values included in the repository safety case, and for assessing the response of Kd to changes in chemical conditions. The development of a TSM involves a series of decisions on model features such as numbers and types of surface sites, sorption reactions and electrostatic correction factors. There has been a lack of consensus on the best ways to develop such models, and on the methods of determination of associated parameter values. The present paper therefore presents recommendations on a number of aspects of model development, which are applicable both to radioactive waste disposal and broader environmental applications.
The TSM should be calibrated using a comprehensive sorption data set for the contaminant of interest, showing the impact of major geochemical parameters including pH, ionic strength, contaminant concentration, the effect of ligands, and major competing ions. Complex natural materials should be thoroughly characterised in terms of mineralogy, surface area, cation exchange capacity, and presence of impurities. During the application of numerical optimisation programs to simulate sorption data, it is often preferable that the TSM should be fitted to the experimentally determined Kd parameter, rather than to the frequently used percentage sorbed. Two different modelling approaches, the component additivity and generalised composite, can be used for modelling sorption data for complex materials such as soils. Both approaches may be coupled to the same critically reviewed aqueous thermodynamic data sets, and may incorporate the same, or similar, surface reactions and surface species. The quality of the final sorption model can be assessed against the following characteristics: an appropriate level of complexity, documented and traceable decisions, internal consistency, limitations on the number of adjustable parameter values, an adequate fit to a comprehensive calibration data set, and capability of simulating independent data sets. Key recommendations for the process of TSM development include: definition of modelling objectives, identification of major decision points, a clear decision making rationale with reference to experimental or theoretical evidence, utilisation of a suitable consultative and iterative model development process, testing to the maximum practicable extent, and thorough documentation of key decisions. These recommendations are consistent with international benchmarks for environmental modelling.
Keywords: Sorption; modelling; radioactive waste; repository; distribution coefficient

Publ.-Id: 18189 - Permalink

Investigation of Uranium Binding Forms in Some German Mineral Waters
Osman, A. A. A.; Geipel, G.; Bernhard, G.; Worch, E.;
Cryogenic time-resolved laser-induced fluorescence spectroscopy (cryo-TRLFS) was successfully used to identify uranium binding forms in some German mineral waters of extremely low uranium concentrations (< 2.0 µg/L). The measurements were performed at low temperature of 153 K. The spectroscopic data showed a prevalence of aquatic species Ca2UO2(CO3)3 in all investigated waters, while other uranyl–carbonate complexes, viz, UO2CO3(aq) and UO2(CO3)22- only existed as minor species. The pH value, alkalinity (CO32-), and the main water inorganic constituents, specifically Ca2+ concentrations, showed a clear influence on uranium speciation. Thermodynamic calculations of the main uranium binding form in the investigated waters indicated a good agreement with spectroscopy.
Keywords: Mineral waters, uranium, cryo-TRLFS, binding forms, thermodynamic modeling

Publ.-Id: 18188 - Permalink

Uptake of Se(IV) oxyanions onto maghemite
Jordan, N.; Ritter, A.; Scheinost, A. C.; Foerstendorf, H.; Heim, K.; Weiß, S.;
Summary about interaction of Se(IV) with maghemite
  • Lecture (Conference)
    Status Seminar 2012 "Nuclear Safety Research – From Reactors to Disposal", 11.-12.12.2012, Dresden, Germany

Publ.-Id: 18186 - Permalink

Recent and future experiments on dynamo action, magnetorotational instability, and Tayler instability
Stefani, F.; Albrecht, T.; Galindo, V.; Gerbeth, G.; Giesecke, A.; Gellert, M.; Gundrum, T.; Kaplan, E.; Kirillov, O.; Nore, C.; Rüdiger, G.; Seilmayer, M.; Weber, N.; Weier, T.;
Precession has long been discussed as a complementary energy source for homogeneous dynamo action. Here we describe the present status of the preparations - theoretical predictions, velocimetry of a scale model water experiment, and engineering/construction concerns - for a liquid sodium precession experiment. Furthermore, we report recent experimental and theoretical results on the magnetorotational (MRI) and Tayler (TI) instabilities, and discuss plans for a large-scale liquid sodium experiment to study the combination of MRI and TI.
  • Open Access LogoAbstract in refereed journal
    Geophysical Research Abstracts 15(2013), EGU2013-6743

Publ.-Id: 18185 - Permalink

Neue Messtechniken für Flüssigmetallströmungen
Buchenau, D.; Eckert, S.; Gerbeth, G.; Gundrum, T.; Stefani, F.; Wondrak, T.;
Heiße Schmelzen werden in vielen Technologien eingesetzt, beginnend beim traditionellen Stahlguss über die Elektrolyse von Aluminium bis hin zur Züchtung von Silizium-Einkristallen. In der Optimierung dieser sehr energieintensiven Prozesse liegt ein volkswirtschaftlich relevantes Einsparpotenzial. Grundlage einer optimalen Prozessführung ist aber stets die Kenntnis der relevanten physikalischen Parameter der Schmelze, zu denen neben Temperatur, Druck und Lage der Phasengrenzen häufig auch das Geschwindigkeitsfeld gehört. Ein typisches Beispiel hierfür ist der Strangguss von Stahl, dessen finale Qualität ganz wesentlich von der Strömungsstruktur in der Kokille abhängt. Die online-Bestimmung dieser Strömung während des Gießprozesses würde die Möglichkeit einer aktiven Strömungskontrolle eröffnen, mit deren Hilfe deutlich höhere Gießgeschwindigkeiten erreicht werden könnten. In diesem Beitrag werden verschiedene Messprinzipien und ihre Anwendung für Flüssigmetallströmungen besprochen. Das erste Verfahren, die Ultraschall-Doppler-Velozimetrie (UDV), beruht auf der Bestimmung der Doppler-Frequenz-Verschiebung bei der Rückstreuung an bewegten Streuteilchen. Das zweite Verfahren nutzt den Faradayschen Induktionseffekt in bewegten elektrischen Leitern unter dem Einfluss eines äußeren Magnetfeldes. Auf dieser Basis wurden mehrerer kontaktlose Messverfahren entwickelt, so z.B. zur Bestimmung von Durchflüssen in Rohrströmungen, aber auch zur tomographischen Rekonstruktion vollständiger zwei- oder dreidimensionaler Geschwindigkeitsfelder.
  • Elektrowärme International 2012(2012)4, 79-82

Publ.-Id: 18184 - Permalink

A simple visual score of heterogeneity of FDG uptake as prognostic marker in sarcoma patients
Steffen, I. G.; Apostolova, I.; Schrapler, A.; Hofheinz, F.; Buchert, R.; Brenner, W.;
Spatial heterogeneity of FDG uptake in the tumor is a promising predictor of patient outcome in various tumor entities. Different definitions have been proposed for spatial heterogeneity of tracer uptake and mathematical approaches range from simple to very sophisticated algorithms. Here we propose a simple score for visual assessment of both heterogeneity (VSHETER) and shape irregularity (VSIRREG) of FDG uptake in the primary tumor. The prognostic value of these new scores was evaluated in sarcoma patients with F18‐FDG‐PET for initial staging.
In total 56 sarcoma patients (30 m, median age 15 y, range 2‐61 y) were included retrospectively. Histological subtypes were 22 Ewing sarcomas (EWS), 17 osteosarcomas (OS) and 17 sarcomas with various subtypes (VS). Primary tumors were visually analyzed for maximum tracer uptake relative to the liver uptake (5‐score), size (3‐score), heterogeneity of FDG uptake (3‐score), irregularity of the shape of FDG uptake (3‐score) and central necrosis (yes/no). The presence or absence of metastases was also taken into account (yes/no). The metabolic tumor volume (MTV) was measured using the semi‐automatic ROVER 3D segmentation tool which is based on thresholding at the volume‐reproducible intensity threshold after subtraction of the local background. Cox proportional hazards models and corresponding hazard ratios (HR) were used to analyze the predictive value of the visual scores as well as SUVmax and MTV for overall survival (OAS) and progression free survival (PFS).
40 patients (17 EWS, 15 OS, 8 VS) survived till the end of the follow‐up with OAS times ranging from 9.1 to 97.8 months (median 46.5 months). OAS of non‐survivors ranged from 2.7 to 49.6 months (median 17.1 months). A significant association with sarcoma subtype was observed for SUVmax (p<0.01), VSHETER (p=0.05) and central necrosis (p<0.01). Multivariate cox proportional hazard analysis revealed VSHETER (HR=2.4, p=0.01) and tumor subtype (VS vs EWS, HR=4.9, p<0.01) as significant predictors of PFS whereas there was no significant association of PFS with VSIRREG, central necrosis, presence of metastatses, SUVmax or MTV. OAS was associated with the presence of metastases (HR=5.1, p=0.01), VSHETER (HR=2.6, p=0.04) and tumor subtype (VS vs EWS, HR=3.2, p=0.05). Conclusion A simple visual 3‐score for heterogeneity of FDG uptake in the primary tumor provides additional power for the prognosis of sarcoma patients based on F18‐FDG‐PET. Simple visual scores are easily implemented in the routine clinical workflow.
  • Poster
    Annual Congress of the European Association of Nuclear Medicine (EANM), 27.-31.10.2012, Milan, Italy
  • Abstract in refereed journal
    European Journal of Nuclear Medicine and Molecular Imaging 39(2012), S476

Publ.-Id: 18183 - Permalink

Template-based approach for detecting motor task activation-related hyperperfusion in pulsed ASL data
Petr, J.; Ferré, J.-C.; Raoult, H.; Bannier, E.; Gauvrit, J.-Y.; Barillot, C.;
Arterial spin labeling (ASL) permits the non-invasive measurement of quantitative values of cerebral blood flow (CBF) and is thus well adapted to study inter- and intra-subject perfusion variations whether at rest or during an fMRI task. In this study, a template approach to detect brain activation as a CBF difference between resting and activated groups was compared with a standard generalized linear model (GLM) analysis. A basal perfusion template of PICORE-Q2TIPS ASL images acquired at 3T from a group of 25 healthy subjects (mean Age 31.6±8.3 years) was created. The second group of 12 healthy subjects (mean age 28.6±2.7 years) performed a block-design motor task. The template was compared with the mean activated image of the second group both at the individual and at the group level to extract activation maps. The results obtained using a GLM analysis of the whole sequence were used as ground truth for comparison. The influences of spatial normalization using DARTEL registration and of correction of partial volume effects (PVE) in the construction of the template were assessed.
Results showed that a basal perfusion template can detect activation-related hyperperfusion in motor areas. The true positive ratio was increased by 2.5% using PVE-correction and by 3.2% using PVE-correction with DARTEL registration. On average, the group comparison presented a 2.2% higher true positive ratio than the one-to-many comparison.

Publ.-Id: 18182 - Permalink

Speciation of bioaccumulated uranium(VI) by Euglena mutabilis cells obtained by laser fluorescence spectroscopy
Brockmann, S.; Arnold, T.; Bernhard, G.;
Euglena mutabilis cells were used to study the influence of eukaryotic microorganisms on the migration behavior of uranium in acid mine drainage (AMD) environments. Batch sorption experiments at pH 3 and 4 were performed in Na2SO4 background solutions to mimic AMD conditions and in NaClO4 background solutions for comparison, respectively. It was found that axenic cultures of Euglena mutabilis were able to bioaccumulate more than 94 % of uranium from a 1×10­5 mol/L uranium solution. Laser induced fluorescence spectroscopy, used to identify the speciation of uranium, indicated that the bioaccumulated uranium species forming in Euglena cells or on euglenid pellicles were related to carboxylic groups and/or organophosphate groups.
In similar experiments using sterile filtrated AMD waters, obtained from a former uranium mine, reduced uranium immobilization rates for Euglena mutabilis cells were observed. However, the identified uranium speciation in both experiments was identical. The reduced rates were attributed to the competition by other cations for available sorption sites on or in the Euglena cells. The results showed that Euglena mutabilis or components of it are able to immobilize aqueous uranium and thus may be used in future as promising agent for immobilizing uranium in low pH waste water environments.
Keywords: Euglena mutabilis, uranium, bioaccumulation, Laser-induced fluorescence spectroscopy (LIFS), AMD, speciation

Publ.-Id: 18181 - Permalink

Modelling, simulation and experiments on boiling processes in pressurized water reactors
Krepper, E.; Rzehak, R.; Hampel, U.; Schneider, C.; Frank, T.; Fröhlich, J.; Hurtado, A.; Koch, E.; Koch, M.; Otic, I.; Sattelmayer, T.;
A collaborative project funded by the Federal Ministry of Education and Research (BMBF) in the framework of the R&D program "Energie 2020+" by four Universities, two Research Centres and ANSYS is coordinated by Helmholtz-Zentrum Dresden-Rossendorf (HZDR). The project is directed towards the development and validation of CFD models of boiling processes in PWR in the range from subcooled nucleate boiling up to the critical heat flux. The work is oriented towards basic research and focused on model development, simulation and experiments on different scales. An important objective is the education and maintaining of competence in nuclear technology.
Keywords: CFD, model development, model validation, small scale experiments, large scale experiments, modern measurement technique
  • Contribution to proceedings
    The 15th International Topical Meeting on Nuclear Reactor Thermalhydraulics, NURETH15, 12.-15.05.2013, Pisa, Italy
  • Lecture (Conference)
    The 15th International Topical Meeting on Nuclear Reactor Thermalhydraulics, NURETH15, 12.-15.05.2013, Pisa, Italy

Publ.-Id: 18180 - Permalink

Visualization of cyclooxygenase-2 using a 2,3-diarylsubstituted indole-based inhibitor and confocal laser induced cryofluorescence microscopy at 20 K in melanoma cells in vitro
Tondera, C.; Laube, M.; Wimmer, C.; Kniess, T.; Mosch, B.; Großmann, K.; Pietzsch, J.;
This study aimed at visualization of cyclooxygenase-2 (COX-2) protein expression in melanoma cells by confocal laser induced cryofluorescence microscopy using 4-(3-(4-methoxyphenyl)-1H-indol-2-yl)benzene-sulfonamide (C1) representative for a novel class of autofluorescent 2,3-diarylsubstituted indole-based selective COX-2 inhibitors. COX-2 expression was measured in human melanoma cell lines A2058 and MelJuso by immunocytochemistry and immunoblotting. Cellular uptake experiments using varying C1 concentrations down to 0.1 nM (with/without molar excess of celecoxib as control) were performed at 37°C. Cryofluorescence microscopy was conducted at 20 K. COX-2 protein expression was successfully visualized by C1 in A2058 cells. COX-2-negative MelJuso cells showed no specific accumulation of C1. Control experiments using celecoxib and, additionally, implemented fluorescence spectroscopy confirmed specificity of both cellular uptake and intracellular association of C1. Cryofluorescence microscopy in combination with spectroscopy allowed for visualization of COX-2 protein expression in melanoma cells in vitro using a selective COX-2 inhibitor at very low concentrations.

Publ.-Id: 18179 - Permalink

Radionuclide binding to Cetuximab - a promising approach for the treatment of Squamous Cells/Radionuklidbindung an Cetuximab – ein vielversprechender Ansatz für die Behandlung von Plattenepithelkarzinomzellen
Eke, I.; Förster, C.; Ingargiola, M.; Kunz-Schughart, L.; Baumann, M.; Runge, R.; Kotzerke, J.; Heldt, J.-M.; Steinbach, J.; Cordes, N.;
Zielgerichtete Therapiestrategien gegen den epidermalen Wachstumsfaktorrezeptor (EGFR) mittels Cetuximab verbessern in Kombination mit Bestrahlung das Überleben und die lokale Tumorkontrolle bei Patienten mit Plattenepithelkarzinomen (SCC) des Kopf/Hals-Bereiches. Trotz dieses Behandlungserfolgs machen auftretende Tumorresistenzen eine weitere Optimierung dieser Therapie notwendig. In unserer Studie untersuchten wir das Überleben von SCC Zellen nach Behandlung mit einem Konjugat aus Cetuximab und dem Radionuklid Yttrium-90 ([90Y]Y-CHX-A´´-DTPA-Cetuximab).
In vier verschiedene humane SCC Zelllinien (FaDu, SAS, UTSCC14, A431) wurden EGFR-Hemmung und nachgeschalteter Signalmoleküle mittels Western blot und die Bindung von Cetuximab an EGFR durch Fluorochrom-markiertes Cetuximab analysiert. Das Überleben nach Behandlung mit 90Y, [90Y]Y-CHX-A´´-DTPA-Cetuximab (beide ca. 5–15 MBq äquivalent zu 2–6 Gy), Cetuximab-DTPA oder Cetuximab alleine oder in Kombination mit externer Bestrahlung (Röntgenstrahlen; 200 kV, 20 mA, 1.3 Gy/min; 2–6 Gy) wurde im Koloniebildungstest bestimmt. Zusätzlich wurden Adhäsions- und gammaH2AX-Foci-Assays durchgeführt.
Obwohl Cetuximab-Behandlung zu einer Hemmung von EGFR und nachgeschalteten Signalmolekülen führte, zeigte keine der verwendeten Zelllinien eine Strahlensensibilisierung. Fluorochrom-markiertes Cetuximab blieb zellmembranständig ohne Hinweise auf Internalisierung oder Abbau. 90Y]Y-CHX-A´´-DTPA-Cetuximab verringerte das klonogene Überleben signifikant stärker und in Abhängigkeit der EGFR-Expression als alleiniges 90Y. Zellen, die mit 90Y plus externe Bestrahlung behandelt wurden, überlebten deutlich besser als Zellen nach [90Y]Y-CHX-A´´-DTPA-Cetuximab plus externe Bestrahlung. Das klonogene Überleben konnte mit strahleninduzierten gammaH2AX-Foci korreliert werden. Ein Einfluss von Cetuximab auf die Zelladhäsion war nicht zu verzeichnen.
Unsere Daten zeigen, dass eine Verbindung aus Cetuximab und einem Radionuklid das Überleben von SCC Zellen deutlich stärker reduziert als das unkonjugierte Radionuklid oder externe Bestrahlung. Weitere In-vitro- und In-vivo-Studien sind nötig, um zu untersuchen, inwieweit derartige Konjugate in Therapiestrategien im Rahmen einer Strahlentherapie eingebunden werden können.
  • Poster
    DEGRO 2012 18. Jahreskongress der Deutschen Gesellschaft für Radioonkologie , 07.-10.06.2012, Wiesbaden, D
  • Abstract in refereed journal
    Strahlentherapie und Onkologie 188(2012), 121

Publ.-Id: 18178 - Permalink

Effect of He+ irradiation on Fe–Cr alloys: Mössbauer-effect study
Dubiel, S. M.; Cieslak, J.; Reuther, H.;
Effect of He ions irradiation on three model Fe100−xCrx alloys (x = 5.8, 10.75 and 15.15) was investigated with the conversion electron Mössbauer spectroscopy. The study of the alloys irradiated with 25 keV ions revealed that the strongest effect occured in the Fe84.85Cr15.15 sample where an inversion of a short-range-order (SRO) parameter was found.

Publ.-Id: 18177 - Permalink

Flow cytometric cell-based assay to preselect antibody constructs for radionuclide conjugation
Ingargiola, M.; Dittfeld, C.; Runge, R.; Zenker, M.; Heldt, J.-M.; Steinbach, J.; Cordes, N.; Baumann, M.; Kotzerke, J.; Kunz-Schughart, L.;
Radiolabeled antibodies (Abs) are an attractive tool for targeting and delivering particle emitters for therapy or imaging applications. The labeling of Abs with metal radionuclides requires chelating agents and can cause loss of binding to their ligands. The aim of the present approach was to design an easy-handling flow cytometric cell-based assay to evaluate Ab-binding capacity of conjugates of the therapeutic Ab Cetuximab and to verify the most promising candidate in a competitive radioactive binding experiment. The final setup for flow cytometric assessment of cellular binding capacities of epidermal growth factor receptor (EGFR)/ErbB1-directed Ab conjugates is based on (a) the selection of a robust cell line model (b) the definition of nonsaturated staining concentrations for the unconjugated reference Ab Cetuximab plus implementation of a reasonable isotype control, and (c) the calculation of relative Ab affinities based on the flow cytometric data. Two (FaDu, SAS) out of the three cell lines with different total and cell surface expression levels of EGFR turned out to be adequate models but the application of one cell line was sufficient to estimate reduced binding capacities of conjugates relative to Cetuximab. Only 1/11 conjugate Abs exhibited a fluorescence signal comparable to unconjugated Cetuximab and was applied for radiolabeling with Yttrium-90. Unaltered binding affinity of this conjugate was proven in a competitive radioactive Ab-binding study. We conclude that the flow cytometric assay is reliable and that the relative binding capacity of Cetuximab is neither affected by covalent modification with CHX-A″-DTPA (N-[(R)-2-Amino-3-(p-isothiocyanato-phenyl) propyl]-trans-(S,S)-cyclohexane-1,2-diamine-N,N,N′,N″,N″-pentaacetic acid) with a final chelator-to-Ab ratio of 5 nor by subsequent radiolabeling. [90Y]Y-CHX-A″-DTPA-Cetuximab thus qualifies for preclinical treatment testing as a prerequisite for therapeutic application.
Keywords: EGFR/ErbB1; cell-based assay; antibody binding; radionuclide; chelators; flow cytometry; 2-D cell culture; competitive binding

Publ.-Id: 18176 - Permalink

Electronic Griffiths Phase in the Te-Doped Semiconductor FeSb2
Hu, R.; Wang, K.; Ryu, H.; Lei, H.; Choi, E. S.; Uhlarz, M.; Wosnitza, J.; Petrovic, C.;
We report on the emergence of an electronic Griffiths phase in the doped semiconductor FeSb2, predicted for disordered insulators with random localized moments in the vicinity of a metal-insulator transition. Magnetic, transport, and thermodynamic measurements of Fe(Sb1-xTex)2 single crystals show signatures of disorder-induced non-Fermi liquid behavior and a Wilson ratio expected for strong electronic correlations. The electronic Griffiths phase states are found on the metallic boundary between the insulating state (x = 0) and a long-range albeit weak magnetic order (x ≥ 0.075).

Publ.-Id: 18175 - Permalink

Towards Fluid Flow Estimation from Tomographic Images
Korn, N.;
  • Lecture (others)
    KOMPOST2012, 13.12.2012, Rossendorf, Deutschland

Publ.-Id: 18174 - Permalink

Fabrication of nanostructure arrays by ion beam irradiation
Ou, X.; Kögler, R.; Facsko, S.;
Periodic semiconductor nanostructure arrays have the potential for nano-electronic and nano-optoelectronic application. The broad ion beam erosion is a simple and potentially mass productive technique to fabricate the nanostructure patterns on semiconductor surface as it avoids conventional lithographic steps.[1] The present work reports the fabrication of horizontal silicon nanowire arrays on insulator by Xe+ ion beam erosion of Si-on-insulator substrate. [3] A periodic ripple surface pattern of the Si surface is created by irradiation with Xe+ ions and the transfer of this pattern to the oxide interface as shown in figure 1a. This procedure results in an array of disconnected parallel ordered Si nanowires. A more recent achievement concerns nanopattern of single crystal Ge substrate which is based on a “negative epitaxy”. Vacancies created during ion beam sputtering will diffuse and rearrange according to the crystallographic anisotropy of the substrate which results in orientation-dependent pattern formation of the Ge surface.
Figure 1 (a) Schematic of Si NWs array fabricated by Xe+ beam irradiation on Si-on-insulator substrate. (b)Atomic Froce Miroscopy (AFM) images showing the nanostructure and pattern fabricated on Ge (100) and Ge (111) surface based on “negative epitaxy” process. The scale is 100 nm
[1] S. Facsko et al. Science 285, (1999) 1551.
[2] C. S. Madi et al. Physical Review Letters, 106, (2011) 066101.
[3] X. Ou et al. AIP Advances, 1, (2011) 042174.
Keywords: Irradiation, nanostructure
  • Lecture (others)
    Lecture at University of Konstanz, 12.-15.11.2012, Konstanz, Germany

Publ.-Id: 18173 - Permalink

Fluid Dynamics Research at HZDR
Hampel, U.;
The presentation gives an overview over current research topics, methods and results in research at the Institute of Fluid Dynamics at HZDR. The talk covers both research topics in nuclear reactor safety and efficient processes and described among other the development and application of advanced two-phase flow measurement techniques and computation afluid dynamics tools.
Keywords: fluid dynamics, multiphase flow, CFD
  • Invited lecture (Conferences)
    HIF Seminar Series, 07.01.2013, Freiberg, Germany

Publ.-Id: 18172 - Permalink

Tailoring the properties of semiconductor nanowiresfor thermoelectric applicationsby means of metal-assisted chemical etching
Geyer, N.; Tonkikh, A. A.; Ou, X.; Kögler, R.; Skorupa, W.; Werner, P.; Keywords: metal-assisted etching, semiconductor nanowires, silicon, thermoelectrics
  • Lecture (Conference)
    31th International and 10th European Conference on Thermoelectrics, 09.-12.07.2012, Aalborg, Denmark

Publ.-Id: 18171 - Permalink

AMS of 36Cl with the VERA 3 MV tandem accelerator
Martschini, M.; Andersson, P.; Forstner, O.; Golser, R.; Hanstorp, D.; Lindahl, A. O.; Kutschera, W.; Pavetich, S.; Priller, A.; Rohlén, J.; Steier, P.; Suter, M.; Wallner, A.;
Recent progress with compact ionization chambers has opened new possibilities for isobar suppression in accelerator mass spectrometry (AMS). Separation of 36Cl (t1/2 = 0.30 Ma) at natural isotopic levels from its stable isobar 36S became feasible at particle energies of 24 MeV, which are also accessible for mediumsized tandem accelerators with 3 MV terminal voltage like VERA (Vienna Environmental Research Accelerator). Investigations with an ionization chamber revealed how physics favors isobar separation even at energies below the maximum of the Bragg curve. The strong energy focusing effect at high energy losses reduces energy straggling significantly and isobar separation steadily increases up to almost full energy loss. With an optimized detection setup, sulfur suppression factors of 2 × 104 have been achieved.
Refraining from the additional use of degrader foils has the benefit of high transmission to the detector (~16%), but requires a low sulfur output from the ion source. Therefore several backing materials have been screened for sulfur content. The dependence of the sulfur output on the AgCl sample size has been investigated as well.
Precision and accuracy have been thoroughly assessed over the last two years. Since drifts in the spectra are efficiently corrected by monitoring the position of the 36S peak, the reproducibility for high ratio samples (36Cl/Cl > 10-12) is better than 2%. Our blank value of 36Cl/Cl ≈ (5 ± 5) × 10-16 is competitive to other labs. 36Cl has become a routine AMS-isotope at VERA.
Recently we also explored novel techniques for additional sulfur suppression already in the ion source. While results with a small gas reaction cell in front of the sputter target were discouraging, a decrease in the sulfur/chlorine ratio by one order of magnitude was achieved by directing 300mW continuous wave laser beam at 445 nm towards the cathode in the ion source.
Keywords: AMS, 36Cl, Isobar separation, Energy loss straggling, Cesium sputter ion source

Publ.-Id: 18170 - Permalink

Extraktionsuntersuchungen von umweltrelevanten Radionukliden mit modifizierten Calix[4]arenen
Poetsch, M.; Mansel, A.; Schnorr, R.; Haupt, S.; Kersting, B.;
Im Rahmen eines vom BMBF geförderten Projektes beschäftigt sich die Abteilung „Reaktiver Transport“ des HZDR in Wechselwirkungsstudien mit der Komplexbildung und dem Transportverhalten von d- und f-Elementen mit makrozyklischen Chelatliganden.
Als kurzlebige Analoga für langlebige, umweltrelevante Radionuklide kommen in den Studien 56Co, 64Cu, 65Zn und 85Sr zum Einsatz. Diese werden am hauseigenen Zyklotron hergestellt. Die makrozyklischen Liganden basieren auf funktionalisierten Calix[4]arenen.
Das Komplexierungsverhalten der Calix[4]arene bezüglich der genannten Radionuklide wurde in Extraktionsstudien in flüssig-flüssig Systemen untersucht. Dabei lag der Fokus auf den Reaktionsbedingungen, unter denen eine erfolgreiche Extraktion realisierbar war. Die Extraktionswirkung der Calix[4]arene wurde mit Hilfe der Radiotracertechnik verfolgt.
Unter alkalischen Bedingungen konnten für zwei spezielle Calix[4]arene Extraktionsausbeuten von >90 % erreicht werden. Die entstandenen Komplexe wurden hinsichtlich ihres Bindungsverhaltens spektroskopisch untersucht. Weiterhin konnten Aussagen zur Reversibilität der Reaktionen getroffen werden.
Basierend auf den Reaktionsbedingungen konnten die Extraktionsversuche der Calix[4]arene bezüglich der erwähnten Radionuklide erfolgreich auf reale Wasserproben mit komplexeren Matrizes übertragen werden.
  • Lecture (Conference)
    Anakon 2013, 04.-07.03.2013, Essen, Deutschland

Publ.-Id: 18169 - Permalink

Stand der CFD-Modellierung von Siedevorgängen am Beispiel des NUPEC-Heisskanaltests (PSBT)
Rzehak, R.; Krepper, E.;
Die NUPEC “PWR Subchannel and Bundle Tests” (PSBT) waren zur Untersuchung kritischer Wärmestromphänomene in Brennelementbündeln und zur Validierung von Heißkanalcodes ausgelegt. Einige der Tests sind zur Validierung von CFD-Wandsiedemodellen geeignet. Der Vortrag präsentiert CFD-Analysen der Gasgehaltsverteilung unter Verwendung des CFD-Codes ANSYS CFX-12.1. Zunächst werden die wichtigsten Aspekte des implementierten Modells und Unsicherheiten der Modellparameter herausgestellt. Es kann gezeigt werden, dass die gemessenen querschnittsgemittelten Messwerte mit einem Satz im Rahmen der Mo-dellunsicherheiten kalibrierter Modellparameter reproduziert werden kann. Für die Reproduktion der Verteilungsmuster des Dampfgehaltes im Kanalquerschnitt muss die Modellierung der Turbulenz beachtet werden. Nur ein Turbulenzmodell, das die turbulenten Sekundärströ-mungen auflösen kann, ist in der Lage, die beobachteten Verteilungsmuster zu reproduzieren.
Keywords: CFD, two fluid model, wall boiling, PSBT, turbulence
  • Lecture (Conference)
    Aktuelle Themen der Reaktorsicherheitsforschung in Deutschland: "Kondensationsinduzierte Druckstöße" und "Sieden in DWR", 11.-12.10.2012, Rossendorf, Deutschland

Publ.-Id: 18168 - Permalink

Sorption von U(VI) und Np(V) an Äspö-Granit unter anaeroben und aeroben Bedingungen
Gürtler, S.;
Eine Anforderung an das Wirtsgestein eines möglichen Endlagers für radioaktive Abfälle in tiefen geologischen Formationen ist dessen Funktion als geologische Barriere zur Herabsetzung der Mobilität von im Störfall freigesetzten Actiniden.
Zur Untersuchung des Rückhaltevermögens von Granit gegenüber Actiniden wurde in der Diplomarbeit die Sorption von U(VI) und Np(V) an Granit aus dem Untertagelabor in Äspö (Äspö Hard Rock Laboratory, Äspö HRL, Schweden) untersucht. Die Wechselwirkungen wurden in Batch-Sorptionsversuchen im Labor simuliert und beschrieben. Um den endlagerspezifischen Bedingungen und der geplanten Einlagerung von wärmeentwickelnden, hochradioaktiven Abfällen gerecht zu werden, wurde dabei der Einfluss der Korngrößen des Granits, der Einfluss der Ionenstärke des Hintergrundelektrolyten und der Einfluss der Temperatur unter anaeroben und aeroben Bedingungen ermittelt. Die Konzentration von U(VI) und Np(V) in der wässrigen Phase wird mittels Flüssigszintillation bestimmt. Der Oxidationszustand der Actinide wird durch Flüssig-Flüssig-Extraktion mit 2-Thenoyltrifluoroaceton in Xylol ermittelt. Durch Schwingungsspektroskopie (ATR FT-IR) wurde die Speziation der Oberflächenkomplexe bestimmt.
Keywords: Uran(VI), Neptunium(V), Sorption, Granit
  • Diploma thesis
    Hochschule Fresenius, University of Applied Sciences, Zwickau, 2012
    73 Seiten

Publ.-Id: 18167 - Permalink

The Composition and Depositional Environments of Mesoarchean Iron Formations of the West Rand Group of the Witwatersrand Supergroup, South Africa
Smith, A. J. B.; Beukes, N. J.; Gutzmer, J.;
This paper documents the sedimentological setting, mineralogy, and geochemistry of several iron formation units interbedded with siliciclastic strata of the Mesoarchean Witwatersrand Supergroup, well known for its world-class conglomerate-hosted Au-U deposits. Four major iron formation beds, with associated magnetic mudstones, are present in two distinctly different lithostratigraphic associations, namely shale- and diamictite-associated iron formation. The shale association is represented by the Water Tower and Contorted Bed iron formations in the Parktown Formation of the Hospital Hill Subgroup in the lower part of the succession and the diamictite association by the Promise and Silverfield iron formations in the overlying Government Subgroup. The iron formation units have been subjected to lower greenschist facies metamorphism. Oxide (magnetite and limited hematite), carbonate, and silicate facies iron formations are recognized. The iron formations typically overlie major transgressive flooding surfaces in the succession and, in turn, form the base of progradational coarsening-upward increments of sedimentation comprising magnetic mudstone, nonmagnetic shale, and interbedded siltstone-quartzite. The upward transition from iron formation into magnetic mudstone is accompanied by a change in mineralogical composition from hematite-magnetite iron formation at the base in the most distal setting through magnetite-siderite- and siderite-facies iron formation in the transition zone to magnetic mudstone. The siderite with associated ankerite displays highly depleted 13C values, suggesting crystallization via iron respiration in presence of organic carbon. The iron formations display positive post-Archean Australian shale-normalized Eu and Y anomalies with depletion in light rare-earth elements relative to heavy rare-earth elements, indicating precipitation from marine water with a high-temperature hydrothermal component. Integration of sedimentological, petrographic, and geochemical results indicates that the shale-associated iron formation was deposited during the peak of transgression, when reduced iron-rich hydrothermal waters entered the Witwatersrand Basin over a limited vertical extent due to neutral buoyancy, with the top of the plume occurring below the photic zone. It is suggested that chemolithoautotrophic iron-oxidizing bacteria, which would have been able to exploit the difference in chemistry between the iron-enriched plume water and ambient ocean water to fuel metabolic activity in the presence of limited free molecular oxygen, were responsible for precipitation of initial ferric iron oxyhydroxides. The vertical facies associations in the iron formations most likely developed in response to the limited vertical extent of the hydrothermal plume, with (from distal to proximal) hematite preserved where the base of the plume was not in contact with the basin floor, magnetite where the plume water was in contact with bottom sediment, iron-rich carbonates where organic carbon input was high, iron-rich alumosilicates where siliciclastic input became significant in more proximal settings, and iron-poor sediment above the top of the plume. Diamictite-associated iron formations in the Witwatersrand are inferred to have been deposited in a fashion similar to the shale-associated iron formations, with the exception that major transgressions and hydrothermal plume invasion were preceded by glacial ice cover. The climate warming and increased volcanic activity required could have been related to increased tectonic activity inferred for the Witwatersrand Supergroup during deposition of the glacially associated iron formations.
Keywords: no keywords

Publ.-Id: 18166 - Permalink

CFD analysis of a void distribution benchmark of the NUPEC PSBT tests - model calibration and influence of turbulence modelling
Krepper, E.; Rzehak, R.;
The NUPEC “PWR Subchannel and Bundle Tests” (PSBT) were designed to investigate critical heat flux phenomena in rod bundles and yield data to validate hot channel codes. Some of the tests are suitable for validating a CFD wall boiling model. The paper presents CFD calculations of the void distribution tests of the PSBT benchmark using ANSYS CFX. First, relevant aspects of the implemented wall boiling model are reviewed highlighting the uncertainties in several model parameters. It is then shown that the measured cross sectionally averaged values can be reproduced well with a single set of calibrated model parameters for different tests cases. For the reproduction of patterns of void distribution cross sections attention has to be focussed on the modelling of turbulence in the narrow channel. Only a turbulence model with the capability to resolve turbulent secondary flows is able to reproduce at least qualitatively the observed void distribution patterns. Furthermore the influence of bubble forces on the calculated void distribution is investigated.
Keywords: CFD, two fluid model, wall boiling, PSBT, turbulence
  • Contribution to proceedings
    The 15th International Topical Meeting on Nuclear Reactor Thermalhydraulics, NURETH15, 12.-15.05.2013, Pisa, Italy
  • Lecture (Conference)
    The 15th International Topical Meeting on Nuclear Reactor Thermalhydraulics, NURETH15, 12.-15.05.2013, Pisa, Italy

Publ.-Id: 18165 - Permalink

CFD model of wall boiling considering the bubble size distribution
Krepper, E.; Rzehak, R.; Lifante, C.; Frank, T.;
New developments in the framework of a common project simulating subcooled boiling are described. The computational model used combines the Euler / Euler two-phase flow description with heat flux partitioning. Main achievements were a comprehensive study of the boiling process itself and a better description of the interfacial area by coupling of wall boiling with a population balance model. The paper presents validations and shows the capabilities of the model extensions. A careful calibration of correlations used in the wall boiling model is necessary to obtain agreement with the measured data. For the demonstration, DEBORA tests were used. During these tests radial profiles for gas volume fraction, gas velocity, liquid temperature and bubble size were measured.
Keywords: CFD, two fluid model, wall boiling, populatioon balance, MUSIG, DEBORA experiments
  • Contribution to proceedings
    The 15th International Topical Meeting on Nuclear Reactor Thermalhydraulics, NURETH15, 12.-15.05.2013, Pisa, Italy
  • Lecture (Conference)
    The 15th International Topical Meeting on Nuclear Reactor Thermalhydraulics, NURETH15, 12.-15.05.2013, Pisa, Italy

Publ.-Id: 18164 - Permalink

Verbundprogramm Modellierung, Simulation und Experimente zu Siedevorgängen in DWR
Krepper, E.;
Der Vortrag fasst den Wissensgewinn und das Fazit des Projektverbundes zusammen
Keywords: CFD, model development, model validation, experiments
  • Invited lecture (Conferences)
    Aktuelle Themen der Reaktorsicherheitsforschung in Deutschland: "Kondensationsinduzierte Druckstöße" und "Sieden in DWR", 11.-12.10.2012, Rossendorf, Deutschland

Publ.-Id: 18163 - Permalink

Modellierung, Simulation und Experimente zu Siedevorgängen in DWR – Relevanz für die Kerntechnik
Krepper, E.;
Die Simulation des kritischen Wärmestromes spielt eine wichtige Rolle bei der sicheren und effektiven Auslegung von Anlagen zur Energieerzeugung. CFD-Modelle sind hierfür sehr gut geeignet, da sie es prinzipiell ermöglichen, Strömungsvorgänge unabhängig von der konkreten Geometrie in einem weiten Bereich der thermohydraulischen Parameter zu simulieren.
Ein im Rahmen des Förderprogramms "Energie 2020+" durch das Bundesministerium für Bildung und Forschung geförderten Verbundprojektes, in dem 4 Universitäten, 2 Forschungszentren sowie der Codeentwickler ANSYS zusammenarbeiten, wird durch das HZDR koordiniert. Das Projekt ist auf die Entwicklung und Validierung von CFD-Modellen für Siedevorgänge in Druckwasserreaktoren vom unterkühlten Sieden bis hin zum kritischen Wärmestrom gerichtet. Das Projekt ist auf die Grundlagenforschung orientiert und richtet sich auf die Modellentwicklung sowie die Durchführung von Experimenteten in verschiedenen Größenordnungen. Ein wichtiges Ziel ist die Ausbildung aund Aufrechterhaltung der Kompetenz in der Kerntechnik.
Keywords: boiling, critical heat flux, CFD, two fluid model, experiments
  • Invited lecture (Conferences)
    Aktuelle Themen der Reaktorsicherheitsforschung in Deutschland: Kondensationsinduzierte Druckstöße und Sieden in DWR, 11.-12.10.2012, Rossendorf, Deutschland

Publ.-Id: 18162 - Permalink

Modelling, simulation and experiments on boiling processes in pressurized water reactors
Krepper, E.;
A collaborative project funded by the Federal Ministry of Education and Research (BMBF) in the framework of the R&D program "Energie 2020+" by four Universities, two Research Centres and ANSYS is coordinated by Helmholtz-Zentrum Dresden-Rossendorf (HZDR). The project is directed towards the development and validation of CFD models of boiling processes in PWR in the range from subcooled nucleate boiling up to the critical heat flux. The work is oriented towards basic research and focused on model development, simulation and experiments on different scales. An important objective is the education and maintaining of competence in nuclear technology.
Keywords: CFD, wall boiling, models, experiments
  • Kerntechnik 78(2013)1, 35-37

Publ.-Id: 18161 - Permalink

CFD analysis of a void distribution benchmark in a rod bundle
Krepper, E.; Rzehak, R.;
The NUPEC “PWR Subchannel and Bundle Tests” (PSBT) were designed to investigate criti-cal heat flux phenomena in rod bundles and yield data to validate hot channel codes. Some of the tests are suitable for validating a CFD wall boiling model. The paper presents CFD calcu-lations of the void distribution tests of the PSBT benchmark using ANSYS CFX-12.1. First, relevant aspects of the implemented wall boiling model are reviewed highlighting the uncer-tainties in several model parameters. It is then shown that the measured cross sectionally av-eraged values can be reproduced well with a single set of calibrated model parameters for different tests cases. For the reproduction of patterns of void distribution cross sections atten-tion has to be focussed on the modelling of turbulence in the narrow channel. Only a turbu-lence model with the capability to resolve turbulent secondary flows is able to reproduce at least qualitatively the observed void distribution patterns.
Keywords: CFD, two-fluid model, wall boiling, model validation, PSBT, rod bundle
  • Kerntechnik 78(2013)1, 38-42

Publ.-Id: 18160 - Permalink

CFD-modelling of subcooled boiling
Krepper, E.; Rzehak, R.; Lifante, C.; Frank, T.;
In this paper new developments in the framework of a common project simulating subcooled boiling are described. The computational model used combines the Euler / Euler two-phase flow description with heat flux partitioning. Main achievements were a comprehensive study of the boiling process itself and a better description of the interfacial area by coupling of wall boiling with a population balance model. The model extensions are validated and the present capabilities of CFD for wall boiling are investigated.
Keywords: CFD, two fluid model, wall boiling, population balance model, DEBORA tests
  • Kerntechnik 78(2013)1, 43-49

Publ.-Id: 18159 - Permalink

Simulation und Messung der Hochfrequenzeigenschaften einer supraleitenden Photo-Elektronenquelle
Arnold, A.;
Der Erfolg zukünftiger Synchrotronstrahlungsquellen und Hochleistungs-IR-FELs wird eng mit der Entwicklung einer geeigneten Elektronenquelle verbunden sein. Einen vielversprechenden Ansatz, die dafür erforderliche Brillanz und den hohen mittleren Strom zu erzeugen, stellt der supraleitende Hochfrequenz-Photoinjektor (SRF-Gun) dar. Im Rahmen dieser Arbeit konnte die bislang einzige, an einem Elektronen-Linearbeschleuniger betriebene Quelle dieses Typs erfolgreich in Betrieb genommen sowie wesentliche Eigenschaften theoretisch und praktisch untersucht werden.

The success of future synchrotron radiation sources and high power IR free-electron lasers (FELs) largely depends on the development of an appropriate electron source. At the moment, the superconducting radio frequency photoinjector (SRF gun) seems to be a promising approach to achieve the required brightness and the high average current at the same time. Within the present thesis a SRF gun was brought into operation and essential characteristics were investigated. At the time of printing, it was the only source equipped with all components and operated at a linear accelerator.
Keywords: superconducting radio frequency photo gun; SRF gun; electron injector; electron source; radiation source ELBE; supraleitender Hochfrequenz-Photoinjektor; Elektronenquelle; Strahlungsquelle ELBE
  • Doctoral thesis
    Fakultät für Informatik und Elektrotechnik der Universität Rostock, 2012
    293 Seiten


Publ.-Id: 18158 - Permalink

Incorporation dosimetry of F-18-Flubatine – Comparison of animal model data with first-in-man results
Sattler, B.; Kranz, M.; Patt, M.; Donat, C.; Deuther-Conrad, W.; Hoepping, A.; Sattler, T.; Brust, P.; Steinbach, J.; Sabri, O.;
Objectives: (-HF-18]-Flubatine (former NCFHEB) is a new tracer for neuroimaging of !l4ß2 nAChRs with PET. To assess the radiation risk, its biodistribution, organ doses (00) and effective dose (EO) were determined in pigs and compared to earlier results in mice and humans [SNM20J J No. 1454, 1459J.
Methods: For whole body dosimetry, 5 female piglets (age: 44±3.0d, weight: 13.7±1.7kg) were narcotized (20 mglkg Ketamine, 2mglkg Azaperone; 1.5% Isoflurane in 70% N20/30% 02) and sequentially imaged up to 5h post i.v. injection of 186.6±7.4MBq F1ubatine on a PET/CT-system with 7 bed positions (BP) per frame, J .5-6min/BP, CT-attenuation correction and iterative reconstruction. All relevant organs were defined by volumes of interest. Exponential curves were fitted to the time-activitydata (%ID/g, and %IO/organ). Time and mass were adapted to the human scale. The OOs were calculated using the adult male model with OLINOA. The EO was calculated using tissue weighting factors as published in the ICRPI03.
Results: The highest 00 was received by the urinary bladder (49.0± 19.4j.1SvIMBq*) and the kidneys (39.9±6. J *). The highest contribution to the EO was by the urinary bladder (2.0±0.7*) and the stornach (1.5±0.3*). The EO to humans after i.v. injection of(-)-Flubatine is 14.6±3.2*.
Conclusions: As true for other PET-Tracers, preclinical dosimetry potentially underestimates the EO to humans. The EO by F1ubatine yielded from pig-(this study) and mice-(14.2j.1SvIMBq) studies compared to human dosimetry (22.6±0.68j.1Sv/MBq) show that animal dosimetry underestimates the potential radiation exposure to humans by 35-37%. This fact needs to be considered in the assessment ofthe EO to humans prior early phase clinical trials.
Research Support: The study was supported by Strahlenschutzseminar in Thüringen e. V
  • Abstract in refereed journal
    Journal of Nuclear Medicine 53(2012)1, 1503

Publ.-Id: 18157 - Permalink

Hydrodynamic studies in slurry bubble columns: An experimental and numerical study
Rabha, S.; Schubert, M.; Hampel, U.;
To overcome the current difficulties in designing a slurry bubble column reactor with respect to the effect of particle properties, the influence of solid concentration (Cs) on the hydrodynamics of a slurry bubble column was studied experimentally using ultrafast electron beam X-ray tomography. Experiments were carried out for dP = 100 µm at Cs = 0 – 0.36 at superficial gas velocity UG = 0.02 – 0.05 m/s in a slurry bubble column of diameter DT = 0.07 m. The real time gas flow structure, average bubble diameter and average gas hold-up as a function of UG and Cs have been reported. Corresponding three-phase simulations were also performed using the Euler-Euler multi-fluid model implemented in CFX 14. The bubble size distribution was calculated using the MUSIG model. The predicted gas hold-up and bubble size distribution also show dependence on UG and Cs and agree quite well with the measurements.
Keywords: Slurry bubble column, three-phase flow, solid concentration, ultrafast electron beam X-ray tomography, Euler-Euler modeling

Publ.-Id: 18156 - Permalink

Ferromagnetic Behavior of Fe+ Implanted Si(100) Semiconductor
Yilgin, R.; Yurtisigi, M.; Parabas, A.; Turksoy, M.; Ozdemir, M.; Aktas, B.; Kolitsch, A.;
Fe ions have been implanted into Si (100) single crystals using ion implantation technique. The Fe ions have been accelerated to 45 keV with a dose of 5x10(17) ion/cm(2) at room temperature. The ions have been sent to the substrate's surface at normal incidence. The temperature dependence of magnetization measurement was explored at the temperature range of 10-300 K. The implanted Si substrate was studied with Ferromagnetic Resonance (FMR) technique and Vibrating Sample Magnetometer (VSM). The FMR spectra were recorded by applying external magnetic field in different experimental geometries. FMR spectra were analyzed and the magnetic properties, which are the g-factor, effective magnetization and uniaxial anisotropy parameter, were estimated by simulation of the experimental data. The sample showed two-fold magnetic anisotropic symmetry. By fitting the Si-2p region obtained through XPS measurements it is observed that Fe and Fe compounds are present in the material.

Publ.-Id: 18155 - Permalink

Intrinsic flow behaviour in a slurry bubble column: A comprehensive study on the effect of particle properties
Rabha, S.; Schubert, M.; Hampel, U.;
There is a strong controversy in the literature on the effect of particle properties which limit reliable design of slurry bubble columns. Thus, the influence of particle size (dP) and solid concentration (Cs) on the hydrodynamics of a slurry bubble column was studied experimentally using ultrafast electron beam X-ray tomography. Experiments were carried out for dP = 50 - 150 µm at Cs = 0 – 0.20 and superficial gas velocity UG = 0.02 – 0.05 m/s in a slurry bubble column of diameter DT = 0.07 m. The real time gas flow structure, average bubble diameter and averaged gas hold-up were found to be independent of dP and Cs at small particle size and low solid concentration. However, at large dP and high Cs, strong dependency on dP and Cs was observed. Corresponding three-phase simulations were also performed using the Euler-Euler multi-fluid model implemented in CFX 14. The bubble size distribution was calculated using the MUSIG model. The predicted gas hold-up and bubble size distribution also shows dependence on dP and agreed quite well with the measurements and previous studies
Keywords: Slurry bubble column, three-phase flow, gas hold-up, ultrafast electron beam X-ray tomography, Euler-Euler modeling, MUSIG model

Publ.-Id: 18154 - Permalink

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