Publications Repository - Helmholtz-Zentrum Dresden-Rossendorf

Precession has long been discussed as a complementary energy source for homogeneous dynamo action. To that end, DRESDYN, a large scale, precession driven dynamo experiment, is currently in advanced planning stage at Helmholtz-Zentrum Dresden-Rossendorf. DRESDYN will consist of a variable axis, precessing cylinder of approximately 2m diameter filled with liquid sodium.

Preliminary studies using a 1:6 scale water experiment are currently performed, focussing on laminar-turbulent transition characteristics. A sudden jump in the motor's mesured electrical power suggests transition to occur at a precession rate of $\Gamma = 0.06$. We also conduct Direct Numerical Simulations, although, for the time being, limited to a Reynolds number Re = O(6000), which is ten times smaller than in the water experiment.

At the conference, we will introduce the planned setup of DRESDYN and show first experimental and numerical results for the 1:6 water model.

Mixing of liquid metals is an important issue in many industrial applications. In metallurgy, gas-bubbles are injected into furnaces, ladles or similar melt containing transfer vessels in order to homogenize the melt and their physical and chemical parameters. We present two experimental studies where a mixing enhancement in a gas-stirred ladle is achieved by the use of AC magnetic fields.

This paper is concerned with a liquid metal flow driven by a rotating magnetic field inside a stationary cylinder. We consider especially the secondary meridional flow during the time when the fluid spins up from rest.
Therefore, we filled a Perspex cylinder with the aspect ratio A=H0/D0=2 with the eutectic alloy GaInSn, which is liquid at room temperature. The filled cylinder is placed concentrically in the magnetic induction system PERM at the Helmholtz-Zentrum Dresden-Rossendorf. The PERM stirrer is equipped with six coils, arranged as pole pairs in order to create a rotating magnetic field with field strength up to 17 mT. The magnetic field frequency was fixed to 50 Hz. The developing flow is investigated experimentally and by direct numerical simulations. The fluid velocities are measured non-intrusively using the ultrasound Doppler velocimetry.
Evolving instabilities in the form of Taylor–Görtler vortices have been observed just above the instability threshold (Ta > 1.5*Tacr). They evolve from local spots near midplane that quickly spread around the whole circumference of the cylinder to form closed rings. Subsequently, the central TG-vortex ring is advected by the secondary flow towards the top or bottom of the vessel. In some cases, the central vortex pair is observed to remain stable at half height of the vessel for a long time. The rotational symmetry may survive over a distinct time even if a first Taylor–Görtler vortex pair has been formed as closed rings along the cylinder perimeter. The transition to a three dimensional flow in the side layers results from the advection or a precession and splitting of the Taylor–Görtler vortex rings. The predictable behaviour of the Taylor–Görtler vortices disappears with increasing magnetic field strength. The numerical simulations agree very well with the flow measurements.

Transparent metal-semiconductor field-effect transistors (MESFETs) with a ZnCoO channel have been fabricated by pulsed laser deposition on c-plane sapphire substrates at a temperature of 550 degrees C. The paramagnetic properties have been confirmed by magnetotransport measurements on undepleted ZnCoO films without Schottky gate contacts.
The Au/AgxO Schottky gate contacts were processed by optical lithography and metallization. Below 50 K, the MESFET characteristics are persistently changed from a low resistance state (LRS) to high resistance state by an external magnetic field. The MESFET can be switched back into the LRS only by heating it up to room temperature.

Lorentz force-based flow control in materials with low electrical conductivity has a long history back to the first half of the 19th century. This review will focus on developments during the last two decades, collecting results from numerical simulations and laboratory experiments. Typically, the actuators consist of permanent magnets and electrodes flush-mounted with the surface, generating Lorentz forces in the fluid layers adjacent to the wall. We will discuss the application of Lorentz forces to reduce friction drag in turbulent boundary layers and to delay boundary layer transition. The control of separated flows and shear layers is another key aspect of the review. Energetic efficiency, one of the main criteria for flow control, and its relation to typical operating conditions will be analyzed as well. Lorentz forces can be successfully used to control a broad range of flow phenomena and are a versatile tool for basic fluid dynamics research. However their current applicability in large scale systems is hampered by the low electrical to mechanical efficiency intrinsic to actuators based on the magnetic fields delivered by today’s permanent magnets.

We discuss how to derive a force or a force density from a measured velocity field. The first part focuses on the integral force a fluid exerts on a body, e.g. lift and drag on an airfoil. Obtaining the correct pressure is crucial; however, it cannot be measured within the flow non-intrusively. Using numerical and experimental test cases, we compare the accuracy achievable with three methods: pressure reconstruction from velocity fields via (1) the differential momentum equation, or (2) the Poisson equation, furthermore, (3) Noca’s momentum equation [Noca, JFS 13(5), 1999], which does not require pressure explicitly. The latter gives the best results for the lift, whereas the first or second approach should be used for the drag. The second part deals with obtaining the distribution of a body force density generated by an actuator. Using a stream function ansatz, we obtain a Laplace equation that allows us to compute the solenoidal part of the force distribution; however, the irrotational part is lost. Furthermore, the wall pressure must be known. We validate this approach using numerical data from a wall jet flow in a rectangular box, driven by a fictitious, solenoidal body force. Reconstructing the force distribution yields an error of less than 10−2 for most of the domain.

Quality assurance of natural raw materials (e.g. ores) with beam-based microanalytical methods requires a proper set of homogeneous, matrix-matched reference materials (RMs) doped with trace elements relevant to resource technology applications. Natural minerals usually exhibit chemical heterogeneity at μg/g sampling masses and are unsuitable as RMs for in-situ chemical microanalysis. On the other hand, available synthetic RMs (e.g. glasses, pressed pellets) fail to satisfy matrix-match criterion.
A novel strategy has been established to obtaining such RMs through the synthesis of multi trace element doped phases that would be subsequently tested for chemical and structural homogeneity with both microscopic and spectroscopic spatially-resolved microanalytical methods.
A dark brown tantalite crystal from the melt of composition Fe_0.6Mn_0.4Ta₂O₆ has been grown by the conventional Czochralski method (melting point of about 1600°C) with the use of an Ir crucible and a protective atmosphere consisting of 85% Ar, 10% CO₂ and 5% CO. The growth rate of 1 mm/h and rotation rate of 10 rpm were applied. The boule was 17 mm in diameter and 30 mm in length (Fig. 1). Standard mineralogical thin sections were prepared for chemical analysis.
Back-scatter Electrons imaging (BSE) was implemented to check for the presence of impurities and other phases within the crystal. Electron Probe Microanalysis (EPMA) and Particle Induced X-ray Emission (PIXE) were used to determine the composition and homogeneity of the crystal. Compositional maps were prepared for each element for each method. As shown in Fig. 2 both BSE-EPMA and PIXE consistently proved stoichiometric composition of the crystal what is in agreement with stoichiometric composition of the melt. EPMA and PIXE compositional maps showed homogenous lateral distribution of all constituents of the crystal (Fig. 3).
The obtained tantalite phase turned out to be homogenous and stable. A matrix of the same stoichiometry will be used in further experiments – synthesis of tantalite crystals doped with different sets of technological trace elements - Sc, Ti; Y, Zr, W; La, Ce, Nd – each at concentration of 0.01 wt%.
Fig. 2
Mg wt% Ca wt% Fe wt% Mn wt% Ta wt% O wt% Total
EPMA 0.000048 0.00013 5.94 4.29 70.38 18.51 99.13
PIXE b.d. b.d. 6.44 4.08 70.98 18.50 100.00
b.d.= below limit of detection
Fig. 1 Tantalite boule
Fig. 3 PIXE Fe-Kα intensity distribution map

Quality assurance of natural raw materials (e.g. ores) requires thorough studies on concentration and spatial distribution patterns of technologically relevant trace elements within the mineral matrix at the microscale. Obtaining such a goal is yet only possible with the use of beam-based microanalytical methods and a proper set of homogeneous, matrix-matched reference materials (RMs) doped with trace elements relevant to resource technology.
Natural minerals usually exhibit chemical heterogeneity at μg/g sampling masses and are unsuitable as RMs for in-situ chemical microanalysis. On the other hand, available synthetic RMs (e.g. glasses, pressed pellets) fail to satisfy matrix-match criterion.
A collaboration involving several German scientific institutions centered around TU Bergakademie Freiberg proposed a novel strategy for obtaining such RMs through the synthesis of multi trace element doped mineral matrices subsequently tested for chemical and structural homogeneity with both microscopic and spectroscopic (RMs-dependent and absolute) microanalytical methods.
Three mineral matrices vital to resource technology applications – pyrite, tantalite and feldspar – have been synthesized using flux method, Czochralski method and alkoxide-based sol-gel synthesis, respectively and doped with various sets of technologically important trace elements at the concentration range found in corresponding natural minerals. Their spatial chemical micro-homogeneity has been investigated using light and electron microscopy as well as RMs–dependent (EPMA, LA-ICP-MS) and absolute (PIXE, PIGE) analytical methods.
Quantitative and qualitative elemental spatial distribution maps have been obtained for major and trace elements for each matrix. Homogeneity of the matrices was evaluated using petrologically sensitive statistical analysis.
Established homogeneity testing protocol will be employed in the next stages of the project.

The surface reactions of U(VI) on γ-Al2O3 were comprehensively investigated by a combined approach of in situ vibrational spectroscopy and X-ray absorption spectroscopy. The focus was set to micromolar U(VI) concentrations and a variety of sorption parameters which are relevant to most environmental scenarios, such as pH, ionic strength, different aluminum oxides, and solid-to-liquid ratios. Time-resolved IR spectroscopic sorption experiments at the alumina-water interface evidence the formation of three different species as a function of surface loading: a monomeric carbonate surface complex, an oligomeric surface complex, and a surface precipitate. EXAFS experiments of batch sorption samples different in their U(VI) surface loading, provided consistent results. Aluminum oxides and oxyhydroxides represent an essential structural component of many minerals and play a decisive role in regulating the mobility of contaminants in rocks and soils. Thus, the results presented in this study are of interest for the assessment of water contamination characterized by near neutral solutions. Additionally, the molecular-scale knowledge of the sorption reactions occurring at the water-alumina interface substantiates basic thermodynamic ideas of the formation and transition of surface complexes from sorption of monomers and oligomers to surface precipitation.

The radioactive isotope selenium-79 is a long-lived fission product found in nuclear waste. Due to its half-life of 327,000 years, it is expected to be one of the important isotopes contributing to the potential radiation dose of nuclear waste underground repositories. High level and long-lived radioactive waste increases the temperature in the vicinity of the waste disposal site for at least 10,000 years. Thus, it is important to understand to what extent this temperature increase influences the aqueous speciation of the selenium itself and, hence, its sorption behaviour onto mineral phases.
With respect to the redox properties of selenium with its four main oxidation states (-II, ±0, +IV, +VI), the speciation may become quite complex depending on the prevailing environmental conditions.
The spin ½ nucleus of the inactive isotope Se-77 is well suited to be directly observed by NMR spectroscopy. This method provides a valuable tool for the discrimination of oxidation and protonation states of selenium compounds because of the high structural sensitivity of the selenium nucleus to its electronic environment. Thus, changes in speciation due to elevated temperatures or interactions with metal ions can be investigated.
The spectra clearly demonstrate that the aqueous speciation of Se(VI) is not changed within the investigated temperature range (20 °C – 60 °C). However, the interaction of selenium oxyanions with Ca2+ and Mg2+ can be tracked by changes in the selenium chemical shifts. These findings serve as reference data for further investigations addressing the mobility and the sorption behaviour in the presence of ubiquitous metal ions.

A lot of the physical and the numerical modeling of Czochralski crystal growth is done on the generic Rayleigh-B´enard system. To better approximate the conditions in a Czochralski puller, the influences of a rounded crucible bottom, deviations of the thermal boundary conditions from the generic case, crucible and/or crystal rotation, and the influence of magnetic fields are often studied separately. The present contribution reviews some of these topics while concentrating on studies of the flow and related temperature fluctuations in systems where a rotating magnetic field (RMF) was applied.
The three-dimensional convective patterns and the resulting temperature fluctuations will be discussed both for the mere buoyant case and for the application of an RMF. It is shown that a system between a Rayleigh-Benard and a more realistic configuration, which is still cylindrical but whose surface is partially covered by a crystal model, behaves much the same as a Rayleigh-Benard system. An RMF can be used to damp the temperature fluctuations. Secondly, a more Czochralski-like system is examined. It turns out that the RMF does not provide the desired damping of the temperature fluctutions in the parameter range considered.

Numerical schemes for magnetized rotating flows often attempt to solve the induction equation directly. Due to numerical difficulties, this approach is limited to magnetic Prandtl numbers larger than 0.01, i.e., four orders of magnitude above the values typical for liquid metals. This makes a direct comparison of numerical results with liquid metal experiments difficult. Here we present an alternative approach based on a finite volume scheme for the Navier-Stokes and the Poisson equation describing the electric potential combined with a magnetic field calculation via Biot-Savart’s law. Using this integro-differential formulation, it is possible to circumvent the magnetic Prandtl number limitation mentioned above. First, we will discuss the implementation of this method in the framework of the open source library OpenFOAM. Second, calculations of the Tayler instability (TI), a kink-type current-driven instability, will be presented and compared to the data from a recent liquid metal TI experiment (Seilmayer et al., 2012). The computations faithfully reproduce the experimentally findings. Then, we will elaborate on further details of the TI in liquid metals, as the influence of the aspect ratio on the critical current, transient helical states, and possible implications for large-scale liquid metal batteries.

Alternating magnetic fields provide a comfortable means for non-intrusive flow control in conductive fluids. However, despite a long history of applications in metallurgy and crystal growth, detailed investigation of the practically important transitional and turbulent flow regimes has become possible only in the last dozen years. The present review gives an overview of this topic with focus on recent experimental and numerical studies of the flow driven by rotating and traveling magnetic fields. We discuss the three-dimensional, instantaneous flow structure as well as the resulting average transport properties for a broad range of parameters, including the superposition of both field types. In addition to the ideal case, the effect of a misalignment of the field with respect to the container axis will be considered, too.

Verfahrenstechnische Prozesse sind zumeist mit mehrphasigen Stoffströmungen verbunden. Die Analyse und Vermessung solcher Mehrphasenströmungen ebenso wie räumlicher Verteilungen von Prozessparametern erfordern fortgeschrittene Mess- und Bildgebungsverfahren. Im Fokus des Interesses stehen dabei vor allem tomographische Bildgebungsverfahren, die heute bereits in der Medizin und in der zerstörungsfreien Prüfung verbreitet sind. Diese müssen allerdings an die oft vielfältigen Anwendungsbedingungen in der Verfahrenstechnik angepasst werden. Typische Probleme sind die optische und akustische Intransparenz von Stoffgemischen, hohe Betriebsdrücke, Temperaturen und aggressive Medien in Prozessanlagen und prozessnahen Versuchsständen sowie die bei vielen bekannten Messverfahren oft zu geringe zeitliche Auflösung bei der Untersuchung transienter Vorgänge. Der Beitrag gibt einen Überblick über neuere Entwicklungen im Bereich der Bildgebungsverfahren für Mehrphasenströmungen und erläutert deren Grundprinzipien und Anwendung.

The pp -> ppK+K- reaction was measured below the phi threshold at a beam energy of 2.568 GeV using the COSY-ANKE magnetic spectrometer. By assuming that the four-body phase space is distorted only by the product of two-body final state interactions, fits to a variety of one-dimensional distributions permit the evaluation of differential and total cross sections. The shapes of the distributions in the Kp and Kpp invariant masses are reproduced only if the K-p interaction is even stronger than that found at higher energy. The cusp effect in the K+K- distribution at the K0K0bar threshold is much more clear and some evidence is also found for coupling between the K-p and K0bar n channels. However, the energy dependence of the total cross section cannot be reproduced by considering only a simple product of such pair-wise final state interactions.

Auf der Grundlage eines methodisch konstruktiven Vorgehens wird die Suche nach Prinziplösungen für die Umsetzung eines Experimentaufbaus zum Studium der Magneto-Rotationsinstabilität und der Tayler-Instabilität beschrieben. Einer Kurzvorstellung des Zieles dieser Arbeit und des Experimentes folgt eine Übersicht artverwandter Experimente in der Magnetohydrodynamik. Der Fokus ist dabei auf Gestaltung und Funktion gerichtet. Ein Überblick zu den physikalischen Grundlagen und fluiddynamischen Phänomenen schließt sich an, bevor detailliert auf die angewandte Konstruktionsmethodik eingegangen wird. Anhand der Anforderungen zum Aufbau des Experimentes wird eine zweckdienliche Abstraktion zur technischen Hauptaufgabe durchgeführt. Schrittweise werden dadurch Flussbilder und darauf aufbauend Funktionsstrukturen abgeleitet. Ausgehend davon werden danach einzelne Funktionsgruppen näher betrachtet und Lösungskonzepte entwickelt. Mittels eines Vergleichs der Konzepte wird eine Vorzugsvariante gefunden. Eine Darstellung der Prinziplösung liegt als Ergebnis vor und bietet für den nachfolgenden Entwurfs- und Ausarbeitungsprozess die Basis.

Objective
Pheochromocytoma (PHEO) is a rare but potentially lethal neuroendocrine tumor arising from catecholamine producing chromaffin cells. Available treatment strategies are limited and, if the tumor has metastasized, not very effective. The abundant expression of peptide hormone receptors on endocrine tumor cells allows specific targeting by highly effective anti-tumor peptide analogs. The present study focuses on the preclinical evaluation of potential therapies in the treatment of pheochromocytoma targeting peptide hormone receptors.

Design and method
Our in vitro evaluation of peptide hormone receptor expression on the mouse pheochromocytoma (MPC) cell line and a more malignant mouse tumor tissue-derived (MTT) cell line was based on RT-PCR and immunohistological analysis. Based on these data, we evaluated the effects of cytotoxic peptide hormone analogs on cell viability, apoptosis and necrosis on MPC and MTT cells. For in vivo studies, we established a subcutaneous mouse model of MPC-derived PHEO and multimodal tumor imaging using PET, MRI, and CT, fluorescence and bioluminescence.

Results and conclusions
Our data reveal significant anti-tumor effects mediated by the cytotoxic peptide hormone analogs AN-162 and AN-238 targeting somatostatin receptor 2 (sst2), by the antagonist Cetrorelix and the cytotoxic analog AN-152 targeting luteinizing hormone-releasing hormone receptor (LHRH-R) as well as by the antagonist MIA-602 targeting growth hormone-releasing hormone receptors (GHRH-R) on MPC cells. Similar anti-tumor effects were evidenced for AN-152 and MIA-602 also on the more aggressive MTT cells. Using our newly established mouse model, we were able to visualize the growth of MPC cell-derived subcutaneous pheochromocytomas in vivo by multimodal molecular imaging including SSTR2 PET. Additionally, ex vivo tumor characterization demonstrated unaltered peptide hormone receptor expression during in vivo tumor growth in mice.
Our current investigation provides strong evidence for a possible future treatment of malignant pheochromocytoma using targeted peptide hormone receptor therapy.

Objective
Pheochromocytoma (PHEO) is a rare but potentially lethal neuroendocrine tumor arising from catecholamine producing chromaffin cells of the adrenal medulla. Especially for malignant pheochromoytoma the available treatment strategies are not very effective. Peptide hormone receptors are abundantly expressed on endocrine tumor cells and can be specifically targeted by highly effective anti-tumor peptide analogs. Our actual study focuses on the preclinical evaluation of potential peptide hormone receptor therapies for the treatment of pheochromocytoma.

Design and method
In our in vitro studies we evaluated peptide hormone receptor expression on a neuroendocrine tumors relevant mouse pheochromocytoma (MPC) cell line and a thereof established more malignant mouse tumor tissue-derived (MTT) cell line based on RT-PCR and immunohistological analysis. We also measured the effects of cytotoxic peptide hormone analogs on cell viability, apoptosis and necrosis on MPC and MTT cells. Furthermore, for our in vivo studies we established a subcutaneous mouse model of PHEO for optimization of multimodal tumor imaging using PET, MRI, and CT, fluorescence and bioluminescence imaging.

Results and conclusions
We could demonstrate significant anti-tumor effects mediated by the cytotoxic peptide hormone analogs AN-162 and AN-238 targeting somatostatin receptor 2 (sst2), by the antagonist Cetrorelix and cytotoxic analog AN-152 targeting luteinizing hormone-releasing hormone receptor (LHRH-R) as well as by the antagonist MIA-602 targeting growth hormone-releasing hormone receptors (GHRH-R) on MPC cells. Furthermore, similar anti-tumor effects were evidenced also for AN-152 and MIA-602 on more aggressive MTT cells. In our mouse model we were able to visualize tumor growth of MPC cell-derived subcutaneous pheochromocytomas in vivo by fluorescence imaging. Ex vivo tumor characterization demonstrated that peptide hormone receptors are still expressed during tumor growth in mice.
Our current investigation provides strong evidence for the usefulness of targeted peptide hormone receptor therapy for a possible future treatment of malignant pheochromocytoma.

Pheochromocytoma is a rare but potentially lethal chromaffin cell tumor. The prognosis for malignant pheochromocytoma is particularly poor and there are currently no effective treatments. Interestingly, peptide hormone receptors are frequently overexpressed on endocrine tumor cells and can be specifically targeted by highly effective anti-tumor peptide analogs. Our actual study focuses on two endocrinologically relevant mouse pheochromocytoma cell lines, one more malignant and one more benign one as well as on mouse models of pheochromocytoma, which our group currently establishes.
First, we could demonstrate significant anti-tumor effects mediated by cytotoxic somatostatin analogs AN-162 and AN-238, by LHRH antagonist Cetrorelix and cytotoxic LHRH analog AN-152 as well as by GHRH antagonist MIA-602 targeting their respective receptors on mouse pheochromocytoma cells (MPC). Furthermore, similar anti-tumor effects were evidenced also for AN-152 and MIA-602 on more aggressive tumor tissue-derived (MTT) cells.
Second, we established a subcutaneous mouse model of pheochromocytoma for optimization of parametric tumor imaging in vivo. Tumor volume, morphology, metabolic activity and peptide receptors are evaluated using PET/MR and PET/CT imaging as well as fluorescence and bioluminescence imaging after injection of mCherry or luciferase transduced MPC cell lines. Furthermore, we are establishing an intravenous mouse model of pheochromocytoma to test the most effective peptide analogs in vivo. Ex vivo characterization of mouse pheochromocytomas demonstrated that peptide hormone receptors are still expressed during tumor growth in mice.
Altogether, our current investigation provides further evidence for the usefulness of targeted peptide hormone receptor therapy as a potential new option for future treatment of malignant pheochromocytoma

As a continuation of our previous work, we present new results regarding the interaction of slow highly charged ions with HOPG. Lateral atomic force microscopy measurements with calibrated cantilevers were performed to investigate in more detail the locally enhanced friction at ion impact sites, which has been reported earlier. For very high charge states, apart from ever-present changes in frictional and electronic properties, we find evidence for true topographic surface modifications (hillocks). In complementary studies, we have investigated these structures regarding their conductivity by employing high-resolution conductive atomic force microscopy. In addition, we demonstrate the possibility to etch ion-induced surface structures by thermal annealing.

Significant isospin effects are observed by the HADES collaboration in inclusive dilepton production channels in the pp and quasi free np experiments at 1.25 GeV kinetic beam energy. Triggered by this observation, analyses of several exclusive channels within either dilepton or pion production have been started to shed more light on the possible explanations. Furthermore, the exclusive p⁺p⁻ production in np and pp collisions provide tests for a consistent description of double pion production in different isospin states, which is necessary to understand contributions of the double Δ(1232) and N^*(1440) production. This is also important in the context of the recent results from the WASA collaboration on the ABC effect with reference to a d* dibaryon resonance in isospin 0 channel.

Introduction
The epidermal growth factor receptor (EGFR) plays a critical role in epithelial tumors and, therefore, is a promising target for both tumor imaging and therapy. In order to develop novel EGFR-targeted radiotracers/radiotherapeutics the present work aims at synthesis of structurally modified recombinant EGF. One strategy implies incorporation of azidohomoalanine instead of methionine using supplementation-based incorporation by E. coli. Consequently, the biomolecule can be labeled site-selectively by Click reaction (Huisgen 1,3-dipolar cycloaddition) with fluorescence and radiolabeled building blocks, respectively.

Method and Results
The EGF gene motif was successfully ligated into vectors containing either a GST-tag or His6-tag. Resulting plasmids were transformed into methionine-auxotrophic E. coli (B834(DE3)pLysS), protein synthesis under addition of azidohomoalanine and protein purification were established. Purification of the GST fusion protein only resulted in the unmodified protein, but not in the azido-functionalized protein. In contrast, purification of His6-tagged azido-functionalized EGF was successfully established. This could be demonstrated by reaction with various alkynylated fluorescent dyes. Moreover, the modified EGF was radiolabeled with 1-(but-3-inyl)-4-(3-[18F]fluoropropyl)piperazine ([18F]BFP) as the alkyne with a radiochemical yield of about 0.5 % using Click reaction. First cell binding studies of [18F]BFP-labeled EGF demonstrated cellular association in EGFR-overexpressing A431 human epidermoid carcinoma cells. Cellular uptake amounted to about 25 % of injected dose/mg protein after 1 hour at 37°C.

Conclusion
Ongoing work focuses on the optimization of site-selective radiolabeling of EGF by Click reaction with higher radiochemical yield and specific activity. Afterwards, the radiolabeled protein will be radiopharmacologically tested concerning its properties as potential radiotracer.

There is currently a great interest in the application of nanoparticles for molecular imaging. This results in the development of both, organic and inorganic nanoparticles functionalized in a way that radionuclides, targeting ligands, and different biopolymers can be attached in order to provide an imaging signal. Ultrasmall superparamagnetic iron oxide (Fe3O4) nanoparticles (USPIOs) are one of the most widely studied nanomaterials. USPIOs possess unique magnetic properties that make them attractive candidates as advanced biomedical materials (1).
Furthermore, the biocompatibility of USPIOs makes them suitable to be used as multifunctional agents. They can serve as contrast agents for clinical use in magnetic resonance imaging (MRI), positron emission tomography (PET) and optical imaging (OI) (2).
This work aims at the development of new nanotracers based on USPIOs coated with a biodegradable polymer that are also decorated with agents for radiochemical and/or fluorescence imaging and Epidermal Growth Factor Receptor-specific ligands as targeting units (3).
The production of hydrophobic USPIOs has been achieved using thermal decomposition and monodisperse nanocrystals within a size of 4-5 nm were observed with Transmission electron microscopy (TEM) (4). The main limitation of using USPIOs for in vivo applications is their instability in water. Different biocompatible polymers such as polyvinylalcohol and polyacrylic acid have been tested for the hydrophilic coating of the iron oxide core to make them stable in aqueous solution (5). After an intensive physicochemical characterization including studies of their stability in water and several buffers, carboxymethyl polyvinyl alcohol (CMPVA) was chosen as the most suitable coating agent for the surface modification of USPIOs (6). The stability of the CMPVA-coated USPIOs was studied using Dynamic Light Scattering (DLS, Zetasizer/ Malvern).
Our first goal was to engineer and functionalize the surface of the hydrophilic USPIOs. This included the attachment of a fluorescent label to the shell. This enabled the USPIOs to be suitable for fluorescence imaging. Furthermore, preliminary radiolabeling studies (64Cu) have been undertaken using USPIOs decorated with functional copper chelating agents, such as NOTA. Radio-HPLC and Radio-TLC have been applied to get information about the labelling efficiency and stability of the 64Cu-labeled USPIOs.
From our point of view, the generated nanoparticles possess promising features as novel imaging agents for in vivo cancer diagnostics.

1. Barreto, J.A., et al. Advanced Materials, 23(12): p. H18-H40, 2011.
2. Laurent, S., et al., Chemical Reviews, 108(6): p. 2064-211, 2008.
3. Li, Z., et al., The FASEB Journal, 19(14): p. 1978-1985, 2005..
4. Park, J., et al., Nat Mater, 3(12): p. 891-895, 2004.
5. Zhang, F., et al., Small, 7(22): p. 3113-3127, 2011.
6. Liong, M., et al., Advanced Materials, 22(45): p. 5168-5172, 2010.

kein Abstract verfügbar

A novel program package has been developed which allows for the simultaneous treatment of atomistic kinetics in collision cascades caused by energetic ion impacts and thermally activated relaxation and diffusion. In this 3D program named TRIDER (TRansport of Ions in matter with DEfect R}elaxation) the collision cascades treated in the framework of the Binary Collision Approximation has been combined with kinetic lattice Monte-Carlo simulations of the atomistic relaxation and diffusion. TRIDER simulations allow a more realistic description of ion-induced surface patterning because subsurface defect kinetics can be included in the simulations, which is demonstrated for low-energy Ar+ ion irradiation of silicon. The deeper understanding of ion beam mixing of bimetal interfaces can also be achieved: it is shown that the conventional Gaussian mixing profile is changed substantially for immiscible metals due to precipitation and for chemically active metals due to formation of intermetallics of different stoichiometry.

kein Abstract verfügbar

The production of strongly magnetized laser plasmas, of interest for laboratory astrophysics and inertial confinement fusion studies, is presented. This is achieved by coupling a 16 kV pulse-power system. This is achieved by coupling a 16 kV pulse-power system, which generates a magnetic field by means of a split coil, with the ELFIE laser facility at Ecole Polytechnique. In order to influence the plasma dynamics in a significant manner, the system can generate, repetitively and without debris, high amplitude magnetic fields (40 T) in a manner compatible with a high-energy laser environment. A description of the system and preliminary results demonstrating the possibility to magnetically collimate plasma jets are given.

Following our recent letter [1] on inclusive e+e− pair production in proton induced reactions at Ekin = 3.5 GeV on the nucleus Nb, we present here in addition the transverse and rapidity distributions for various e+e− invariant mass bins and compare them to reference data measured in p+p reactions.

Fe(II)-bearing phases are naturally occuring in most anoxic aquifers, and form also at the surface of corroding steel containers under typical nuclear waste repository conditions. Due to their ability to reduce metal and metalloid contaminants, they are expected to play a key role for the migration behaviour of a wide range of radionuclides, including actinides and fission products. Using X-ray absorption spectroscopy as main tool, we have studied reaction end products, mechanisms and kinetics of redox processes at a range of water/mineral interfaces, including magnetite, green rust, mackinawite, chukanovite, and Fe2+-sorbed clays, but also in more redox-inert systems like cement.
Our results show that the electron transport within mineral structures and at the surface is controlling the extent and the kinetics of multi-electron redox reactions.

Magnetite, which forms under anoxic conditions on the surface of corroding steel containers, is able to reduce a range of elements, including radionuclides of high relevance in the context of nuclear waste disposal, e.g. Se, Tc, U, Np, Pu [1]. Aqueous Pu(V) is rapidly reduced by nanoparticulate magnetite to Pu(III), which then forms stable, tridentate sorption complexes on the {111} faces of magnetite [2]. Trivalent lanthanides have been shown to substitute for Fe(III) in magnetite, although their ionic radii are about 1.4 times larger than that of Fe(III) (1.15-1.17 vs. 0.79 Å in six-fold coordination) [3]. To investigate if such an incorporation is also possible for Pu(III) with a similar ionic radius as the lanthanides, we conducted coprecipitation experiments with two Pu loadings of 1000 and 3500 ppm. UV-VIS spectroscopy showed an immediate reduction of Pu(V) to Pu(III) in the initial Fe(II)/Fe(III) chloride solution. After formation of the black magnetite precipitate, Pu(III) concentration in solution was below 10-9 M. X-ray Absorption Near-Edge Structure (XANES) spectroscopy confirmed the trivalent oxidation state of solid phase-associated Pu. Extended X-ray Absorption Fine-Structure (EXAFS) spectroscopy was then used to investigate the molecular structure of incorporated Pu(III) in the fresh precipitate as well as after Fe(II)-induced aging [4]. The EXAFS spectra revealed two different spectral components. The first component represents the tridentate Pu(III) sorption complex also observed during sorption experiments. The second component represents Pu(III) in a highly distorted magnetite Oh site. The proportion of the incorporated Pu(III) decreased from about 75% to 40% with Fe(II)-induced aging, while the proportion of sorbed Pu(III) increased correspondingly. Our results suggest, therefore, that Pu can be incorporated by magnetite, but will convert to sorbed species on the long time scales relevant for nuclear waste disposal.

[1] Scheinost et al. (2008) J. Contam. Hydrol. 102, 228-245. [2] Kirsch et al. (2011), Environ. Sci. Technol. 45, 7267–7274. [3] Moon et al. (2007) Extremophiles 11, 859-867. [4] Boland et al. (2011) Environ. Sci. Technol. 45, 1327-1333.

For the redox-reactive fission products and actinides Se, Tc, U, and Np, it is assumed that the strongly reducing conditions in deep underground, anoxic nuclear waste repositories will reduce their mobility, since their lower-oxidation states commonly form solids of very low solubility. This is not necessarily the case for Pu, where the hexa- and pentavalent aquo-complexes prevalent at higher pe are replaced at lower pe by a tetravalent solid of low solubility, PuO2, but also by a trivalent aquocomplex at lower pH (Fig. 1) [1, 2]. Since the predominance field of Pu(III)aq overlaps with that obtained for the Fe(II)/Fe(III) redox couple as aqueous species or in equilibrium with Fe(II)-bearing minerals [3], one should assume that Pu(III) exists under anoxic nuclear waste conditions, where Fe(II) sources are provided by corroding steel containers and Fe(II)-bearing clays used as confinement, as well as by geogenic minerals. Although some studies have previously reported on trivalent lanthanides, little is known on the retention mechanisms of the trivalent Pu aquo complex by minerals, with implications for the safety case of nuclear waste repositories.

Melanoma is the most malignant type of all skin neoplasms. Although current clinical, morphologic, pathologic, and biochemical methods provide insights into disease behavior and outcome, melanoma is still an unpredictable disease. Once in an advanced stage, it remains a fatal neoplasm with scarce therapeutic options. Therefore, significant efforts still need to be made in finding suitable biomarkers that could aid or improve its early diagnosis, its correct staging, the discrimination of other pathological conditions as well as indicate patients’ prognosis or the most appropriate therapeutic regimes. On the other hand, well-defined diagnostic markers are necessary to avoid the apparent overdiagnosis of melanoma.

Cu(I)-mediated [3+2]cycloaddition between azides and alkynes has evolved into a valuable bioconjugation tool in radiopharmaceutical chemistry. We have developed a simple, convenient and reliable radiosynthesis of 4-[¹⁸F]fluoro-N-methyl-N-(propyl-2-yn-1-yl)benzenesulfonamide ([¹⁸F]FSA) as a novel aromatic sulfonamide-based click chemistry building block. [¹⁸F]F-SA could be prepared in a remotely controlled synthesis unit in 32 ± 5 % decay-corrected radiochemical yield in a total synthesis time of 80 min. The determined lipophilicity of [¹⁸F]F-SA (logP = 1.7) allows handling of the radiotracer in aqueous solutions. The versatility of [¹⁸F]F-SA as click chemistry building blockwas demonstrated by the labeling of a model peptide (phosphopeptide), protein (HSA), and oligonucleotide (L-RNA). The obtained radiochemical yields were 77 % (phosphopeptide), 55–60 %(HSA), and 25 %(L-RNA), respectively. Despite the recent emergence of a multitude of highly innovative novel bioconjugation methods for ¹⁸F labeling of biopolymers, Cu(I)-mediated click chemistry with [¹⁸F]F-SA represents a reliable, robust and efficient radiolabeling technique for peptides, proteins, and oligonucleotides with the short-lived positron emitter ¹⁸F.

Complexation of [UO2]2+ with Cl−, Br−, and I− in N,N-dimethylformamide (DMF) was studied by UV-vis absorption spectroscopy and extended X-ray absorption fine structure (EXAFS) to clearly differentiate halide coordination strengths to [UO2]2+. In the Cl− system, it was clarified that the Cl− coordination to [UO2]2+ in DMF proceeds almost quantitatively. The coordination number of Cl− increases up to 4 with increasing its total concentration, i.e., the limiting complex is [UO2Cl4]2−. Logarithmic gross stability constants of [UO2Clx]2−x (x = 1-4) were evaluated as log 1 = 9.67, log 2 = 15.49, log 3 = 19.89, and log 4 = 24.63 from UV-vis titration experiment. The EXAFS results well demonstrated not only the Cl− coordination, but also the DMF solvation in the equatorial plane of [UO2]2+. The similar experiments were also performed for the Br− and I− systems. As a result, the Br− coordination to [UO2]2+ stops at the second step, i.e., only [UO2Br]+ and UO2Br2 were observed. The molecular structure of each occurring species was confirmed by EXAFS. The evaluated log x of [UO2Brx]2−x (x = 1, 2) are 3.45 and 5.42, respectively. The much smaller log x than those of [UO2Clx]2−x indicates that Br− is much weaker ligand to [UO2]2+ than Cl−. The EXAFS experiments revealed that the presence of I− in the test solution does not modify any coordination structure around [UO2]2+. Thus, I− does not form any stable [UO2]2+ complexes in DMF. Consequently, the stability of the halido complexes of [UO2]2+ in DMF is exactly in line with the hardness order of halides. This trend clearly manifests the hardness of [UO2]2+.

Cerium(III) and cerium(IV) form both formate complexes. However, their species in aqueous solution and the solid-state structures are surprisingly different. The species in aqueous solutions were investigated with Ce K-edge EXAFS spectroscopy. Ce(III) formate shows only mononuclear complexes, which is in agreement with the predicted mononuclear species of Ce(HCOO)2+ and Ce(HCOO)2+. In contrast, Ce(IV) formate forms in aqueous solution a stable hexanuclear complex of [Ce6(μ3-O)4(μ3-OH)4(HCOO)x(NO3)y]12-x-y. The structural differences reflect the different influence of hydrolysis, which is weak for Ce(III) and strong for Ce(IV). Hydrolysis of Ce(IV) ions causes initial polymerization while complexation through HCOO- results in 12 chelate rings stabilizing the hexanuclear Ce(IV) complex.
Crystals were grown from the above mentioned solutions. Two crystal structures of Ce(IV) formate were determined. Both form a hexanuclear complex with a [Ce6(µ3-O)4(µ3-OH)4]12+ core in aqueous HNO3 / HCOOH solution. The pH titration with NaOH resulted in a structure with the composition [Ce6(µ3-O)4(µ3-OH)4(HCOO)10(NO3)2(H2O)3] (H2O)9.5, while the pH adjustment with NH3 resulted in [Ce6(µ3-O)4(µ3-OH)4(HCOO)10(NO3)4] (NO3)3(NH3)3(H2O)5. Furthermore, the crystal structure of Ce(III) formate, Ce(HCOO)3, was determined. The coordination polyhedron is a tricapped trigonal prism which is formed exclusively by nine HCOO- ligands. The hexanuclear Ce(IV) formate species from aqueous solution is widely preserved in the crystal structure, whereas the mononuclear solution species of Ce(III) formate undergoes a polymerization during the crystallization process.

Tetravalent actinides form strong complexes with carboxyl containing ligands. Such complexes play an important role in technological processes as well as biological and environmental systems. The aqueous chemistry of such complexes is therefore of wide interest. So far, most of the thermodynamic data of actinide(IV) carboxylates are estimated assuming mononuclear solution species (see for example [1]). We applied comprehensive spectroscopic studies (EXAFS, UV-Vis-NIR spectroscopy and X-ray diffraction) to estimate the complex structure of actinide(IV) carboxylates with different actinides (Th4+, U4+ and Np4+) and carboxylates (RCOO–; R = H, CH3, CHR’NH2; R’ = H, CH3, CH2SH) in aqueous solution and solid state [2-4]. These studies show clearly that in all of the investigated systems hexanuclear complexes appear, which become predominant with increasing metal and ligand concentration as well as increasing pH, and comprise finally often close to 100% of the species distribution. The aim of our studies was to investigate the complex structure, stability constants, and the mechanism of complex formation.

Herein, we present simple and rapid colorimetric and UV/VIS spectroscopic methods for detecting anionic arsenic (V) complexes in aqueous media. The methods exploit the aggregation of S-layer-functionalized spherical gold nanoparticles of sizes between 20 and 50 nm in the presence of arsenic species. The gold nanoparticles were functionalized with oligomers of the S-layer protein of Lysinibacillus sphaericus JG-A12. The aggregation of the nanoparticles results in a color change from burgundy-red for widely dispersed nanoparticles to blue for aggregated nanoparticles. A detailed signal analysis was achieved by measuring the shift of the particle plasmon resonance signal with UV/VIS spectroscopy. To further improve signal sensitivity, the influence of larger nanoparticles was tested. In the case of 50 nm gold nanoparticles, a concentration of the anionic arsenic (V) complex lower than 24 ppb was detectable.

Background
Assessment of dual time point (DTP) positron emission tomography was carried out with the aim of a quantitative determination of Km, the metabolic uptake rate of [18F]fluorodeoxyglucose as a measure of glucose consumption.

Methods
Starting from the Patlak equation, it is shown that Km?mt/ca0 + Vr/?a, where mt is the secant slope of the tissue response function between the dual time point measurements centered at t=t0. ca0=ca(t0) denotes arterial tracer concentration, Vr is an estimate of the Patlak intercept, and ?a is the time constant of the ca(t) decrease. We compared the theoretical predictions with the observed relation between Ks=mt/ca0 and km in a group of nine patients with liver metastases of colorectal cancer for which dynamic scans were available, and Km was derived from conventional Patlak analysis. derived from conventional Patlak analysis. Twenty- two lesion regions of interest (ROIs) were evaluated. ca(t) was determined from a three-dimensional ROI in the aorta. Furthermore, the correlation between Km and late standard uptake value (SUV) as well as retention index was investigated. Additionally, feasibility of the approach was demonstrated in a whole-body investigation.

Results
Patlak analysis yielded a mean Vr of Vr = 0.53?0.08 ml/ml. The patient averaged ?a was 99?23 min. Linear regression between Patlak-derived Km and DTP-derived Ks according to Ks = b ? Km + a yielded b = 0.98 ? 0.05 and a = -0.0054 ? 0.0013 ml/min/ml (r = 0.98) in full accordance with the theoretical predictions b = 1 and a ? -Vr=?a Ks exhibits better correlation with Km than late SUV and retention index, respectively. K(c)s = Ks + Vr=?a is proposed as a quantitative estimator of Km which is independent of patient weight, scan time, and scanner calibration.

Conclusion
Quantification of Km from dual time point measurements compatible with clinical routine is feasible. The proposed approach eliminates the issues of static SUV and conventional DTP imaging regarding influence of chosen scanning times and inter-study variability of the input function. Ks and K(c)s exhibit improved stability and better correlation with the true Km. These properties might prove especially relevant in the context of radiation treatment planning and therapy response control.

Pheochromocytoma is a rare but potentially lethal chromaffin cell tumor with currently no effective treatment. Peptide hormone receptors are frequently overexpressed on endocrine tumor cells and can be specifically targeted by various anti-tumor peptide analogs. The present study carried out on mouse pheochromocytoma cells (MPCs) and a more aggressive mouse tumor tissue-derived (MTT) cell line revealed that these cells are characterized by pronounced expression of the somatostatin receptor 2 (sst2), growth hormone-releasing hormone (GHRH) receptor and the luteinizing hormone-releasing hormone (LHRH) receptor. We further demonstrated significant anti-tumor effects mediated by cytotoxic somatostatin analogs, AN-162 and AN-238, by LHRH antagonist, Cetrorelix, by the cytotoxic LHRH analog, AN-152, and by recently developed GHRH antagonist, MIA-602, on MPC and for AN-152 and MIA-602 on MTT cells. Studies of novel anti-tumor compounds on these mouse cell lines serve as an important basis for mouse models of metastatic pheochromocytoma, which we are currently establishing.

In January 2012 the 10 kW CW klystrons (CPI VKL7811St) used to operate the superconducting cavities of ELBE since 2001 have been replaced by pairs of 10 kW solid state amplifiers (SSPA) providing 20 kW RF power per cavity. The paper reviews the procedures and the problems during commissioning the new RF system.

In January 2012 the 10 kW CW klystrons (CPI VKL7811St) used to operate the superconducting cavities of ELBE since 2001 have been replaced by pairs of 10 kW solid state amplifiers (SSPA) providing 20 kW RF power per cavity. The paper gives an overview on the activities and the problems during high power CW operation.

With the expansion of the radiation source ELBE, a centre for high power radiation sources is being built until 2014 at the Helmholtz Zentrum Dresden Rossendorf. One part of this program is to double the beam current of the ELBE LINAC. In January 2012 the 10 kW CW klystrons, used to operate the superconducting cavities of ELBE since 2001, had been replaced by a pair of 10 kW solid state amplifiers. The paper gives an overview on the activities around this project and the first experience with the new RF-system.

We report on pairs of diverging/converging spin vortices in Co/Rh/Ni81Fe19 trilayer disks. The lateral magnetization distribution of these effective spin merons is imaged directly by means of element-selective x-ray microscopy. By this method, both the divergence and circulation states of the individual layers are identified as antisymmetric. Reversal measurements on corresponding continuous films reveal that biquadratic interlayer exchange coupling is the origin for the formation of effective meron pairs. Furthermore, their three-dimensional magnetization structure is determined by micromagnetic simulations. Interestingly, the magnetic induction follows a kind of flux-closing torus. This toroidal topology enforces a symmetry break, which ties the core polarities to the divergence configuration.

In January 2012 the 10 kW CW klystrons (CPI VKL7811St) used to operate the superconducting cavities of ELBE since 2001 have been replaced by pairs of 10 kW solid state amplifiers (SSPA) providing 20 kW RF power per cavity. The paper gives an overview on the activities and the problems during high power CW operation.

The study of Ni-Ti shape memory alloy films is of great technological interest for applications in the field of microengineering. They can work as sensors and actuators at the same time. However, there are still important issues unresolved like formation of film crystallographic orientation and its control. Films exhibiting the two-way shape memory effect are also required.
A two-magnetron sputter deposition chamber mounted into the six-circle diffractometer of the Rossendorf Beamline at the European Synchrotron Radiation Facility was used for the processing of Ni-Ti films. The in-situ x-ray diffraction studies enabled to identify the different steps of the structural evolution during film growth.
Deposition conditions leading to Ni-Ti films mainly containing grains with (100) or (110) planes of the B2 phase parallel to the film surface were successfully defined. This is an important achievement since texture has a strong influence on the extent of the strain recovery. The deposition of films with a “two-way” actuation (films with a combination of superelasticity and shape memory characteristics) was also achieved. It will allow the development of smaller devices since no consideration has to be paid to a resetting spring.

no abstract available

Flashing evaporation of water inside a vertical pipe under four different system pressures is investigated by mono-dispersed CFD simulations. Phase change is assumed to be caused only by thermal heat transfer. The available thermal energy decreases rapidly with the increase of pressure level. Under low-pressure conditions, the maximum steam volume fraction is over-predicted, while an overestimation is observed in high-pressure cases. The possible explanation for the deviation is that bubble growth during the evaporation is especially significant in low-pressure cases, which reduces the evaporation rate but is not considered in the simulation. Furthermore, as the system pressure increases the contribution of nucleation to the total steam generation rate becomes large, which is confirmed by the experimental data. In addition, the effect of pressure on the critical bubble diameter that succeeds in starting flashing as well as the nucleation mechanism is discussed.

The linear dispersion for electrons in graphene leads to a non-equidistant Landau-level (LL) spectrum. This enables one to investigate single Landau-level transitions by resonant pump-probe experiments. So far, however, only the quasi-continuum of high-index LL states has been studied in near-infrared pump-probe experiments. Here we report on terahertz pump-probe measurements at a fixed photon energy of 14 meV, where the free-electron laser FELBE at Dresden-Rossendorf served as radiation source. The magnetic field was varied between 0 T and 7 T. For these measurements we used a sample with 50 layers of graphene, which were epitaxially grown on the C-face of silicon carbide. While the interface layers are highly doped, the major part of the layers is quasi neutral with a Fermi energy in the range of ~10 meV.
At a magnetic field of 0.165 T the photon energy of 14 meV becomes resonant with the inter-LL transition LL-1(0) -> LL0(1). The amplitude of the pump-probe signal is increased by roughly a factor of 4 compared to zero field. Only the quasi neutral layers contribute to this signal, since the first LL is fully occupied for the interface layers with a higher doping. Surprisingly a decreased relaxation time is observed on resonance. We will discuss how the contribution of the LL-1 -> LL0 and LL0 -> LL1 and Auger-type processes lead to a unique relaxation scenario. At higher magnetic fields higher intraband LL transitions can be tuned into resonance (LLn -> LLn+1, n=1,2,3,…). The observed pump-probe signals then stem from these transitions in the interface layers, where the elevated Fermi energy ensures that the ground state LL is populated. With increasing magnetic field both amplitude and decay time constants vary non-monotonically. In the magnetic field region around 3 T negative pump-probe signals occur. The main features observed in the experiments are explained by a model for the electron temperature after optical excitation, which describes the absorption in the layers via the Kubo formalism and takes into account the doping level of the interface layers. The doping levels agree well with values previously obtained from pump-probe experiments without magnetic field.

In this work we study the THz transmission of a 40 nm wide undoped In0.1Ga0.9As quantum well (QW) under optical excitation. Carriers are photoexcited by a near-infrared (NIR) fs pulse and probed in the frequency range from 0.1 to 3 THz by electro-optic sampling using the modified setup of Ref. [1]. The THz pulse is focused on a side facet of the QW sample such that the THz electric field is mostly polarized perpendicular to the QW layer. Fig. 1a depicts the THz field transients for modulated (signal) and un-modulated (reference) NIR excitation. The presence of the carriers which were photoinjected several ps prior to the THz pulse creates a large amount of THz signatures in the QW. Our present goal is to disentangle the various possible contributions to the THz signal: electron intersubband, heavy-hole intersubband, 1s-2p intraexciton and free-carrier absorption. In addition we search for a Fano-like behavior, similar as has been observed in narrower QWs in the mid infrared [2], which is supposed to arise from the interplay between the intersubband absorption and the purely reactive ponderomotive contribution. The different phase of the associated dielectric functions results in a (non-quantum like) interference between these two polarizations, which is only visible in the differential transmission but not in the absorption. We will also report experiments where we use wavelength tuning of the near-infrared pulse using an optical parametric amplifier in order to selectively pump optically either into the barrier or into the QW. Polarization resolved measurements are underway which should help us to reveal the various contributions.
[1] M. Wagner et. al. , Appl. Phys. Lett. 99, 131109 (2011).
[2] D. Golde, M. Wagner et. al., PRL 102, 127403 (2009).

Presentation of my scientific CV, laser-electron theory at HZDR and the work on PIConGPU.

Presentation of recent feature enhancements and physical Validations of PIConGPU. We presented laser dispersion test, radiation tests and thermal plasma tests, added new numerical shemes for the PIC cycle and performed HPC simulations for the recent laser-electron experiment at draco, performed by A. Irman et al.

Contribution to the Annual Report 2012 of EPP/IPFN at Instituto Superior Técnico (Lisboa).

The transverse spin correlations Ax,x and Ay,y have been measured in the ~d~p ! pspec{pp}sπ−reaction at COSY-ANKE at 353 MeV per nucleon. Here {pp}s denotes a proton-proton pair with low excitation energy, which is dominantly in the 1S0 state. By measuring three protons in the final state it was possible to extract events where there was a spectator proton pspec so that the reaction could be interpreted in terms of quasi-free ~n ~p ! {pp}sπ−. The proton analyzing power in this reaction was also deduced from this data set by averaging over the polarization of the deuteron beam. The values of A^p _y were shown to be consistent with a refined analysis of our earlier results obtained with a polarized proton incident on a deuterium target. Taking these data in combination with our earlier measurements of the differential cross sections and analyzing powers in the ~pp ! {pp}s π0 reaction, a more robust partial wave decomposition was achieved. Three different acceptable solutions were found and the only way of resolving this ambiguity without further theoretical input would be through a measurement of the mixed spin-correlation parameter Ax,z.

Final talk about the results of the cooperation/internship at Instituto Superior Técnico (IST) in 2012/13.
A new method for charged beam loading in particle-in-cell simulations was presented. Furthermore, side-topics like the creation of a Raspberry Pi (ARM) cluster, the development of a dependency analyser for fortran modules for parallel builds, a GPU vs CPU benchmark, the development of a transversal resolution criteria for gaussian laser beams and a Thrust-Fortran binding were presented.

PIConGPU is a highly-scalable implementation of the fully relativistic electromagnetic particle-in-cell algorithm for GPGPUs. It allows for fast simulations of laser plasma interaction and astrophysical plasmas.
We present several physics validation results, allowing reliable checks during development stages of the code. Furthermore, we show applications in astrophysical scenarios and in laser wakefield acceleration experiments for next generation electron accelerators.

Dissipative solitons have been reported in a wide range of nonlinear systems, but the observation of their magnetic analog has been experimentally challenging. Using spin transfer torque underneath a nanocontact on a magnetic thin film with perpendicular magnetic anisotropy (PMA), we have observed the generation of dissipative magnetic droplet solitons and report on their rich dynamical properties. Micromagnetic simulations identify a wide range of automodulation frequencies, including droplet oscillatory motion, droplet "spinning," and droplet "breather" states. The droplet can be controlled by using both current and magnetic fields and is expected to have applications in spintronics, magnonics, and PMA-based domain-wall devices.

We introduce a parametric family for random convex polytopes in Rd which allows for an easy generation of samples for further use, e. g., as random particles in materials modelling and simulation. The basic idea consists in weighting the Poisson cell, which is the typical cell of the stationary and isotropic Poisson hyperplane tessellation, by suitable geometric characteristics. Since this approach results in an exponential family, parameters can be efficiently estimated by maximum likelihood. This work has been motivated by the desire for a flexible model for random convex particles as can be found in many composite materials such as concrete or refractory castables.

With the observation of superconductivity at ambient pressure conditions in B doped Si in 2006 [1] and Ga doped Ge [2] the group-IV semiconductors become of interest for future information processing technologies like quantum computing.
To achieve the high doping levels needed for superconductivity non-equilibrium doping techniques like gas immersion laser doping or ion implantation and short term annealing are needed. Only the latter one is fully compatible to standard microelectronic technology. In a new approach we implanted a Ga concentration up to 11 at.% through a 30 nm SiO₂ cover layer into commercial Si and Ge wafers [3-6]. During annealing a thin superconducting Ga-rich nanolayer is formed at the SiO₂/semiconductor interface. These layers show promising superconducting properties (T_C = 7 K, B_C < 8 T, j_C < 50 kA/cm2).
Detailed microstructural investigations by means of XTEM and RBS/C will be discussed. Recent results show the adjustability of the superconducting properties. We are able to produce superconducting microstructures having a width of 3 µm and used the FIB to implement a Josephson junction as key element for a prospective SQUID.
[1] E. Bustarret et al., Nature 444 (2006) 465
[2] T. Herrmannsdörfer et al., Phys, Rev. Lett. 102 (2009) 217003
[3] R. Skrotzki et al., Appl. Phys. Lett. 97 (2010) 192505
[4] J. Fiedler et al., Phys. Rev. B 83 (2011) 214504
[5] J. Fiedler et al., Phys. Rev. B 85 (2012) 134530
[6] V. Heera et al., Appl. Phys. Lett. 100 (2012) 262602

The former salt mine (1908-1964) Asse II, Germany is a final disposal site of radioactive waste. It is composed of salt rocks, which are approximately 250 million years old. A number of salt sumps exist in the Asse II, which were so far not microbiologically characterized. In this study, cultivation-independent methods, e.g. pyrosequencing, were applied to identify the microbial diversity in these unique salt sump habitats.
In this study, a total of 3.168 sequences, divided in 314 operational taxonomic units (OTUs), representing bacterial and archaeal groups from the underground Asse II salt mine. The class halobacteria (Euryarchaeota) predominates the archaeal community, representing 99.5% of all sequences. The least abundant sequences were represented by Thermoprotei (Crenarchaeota) and Methanobacteria (Euryarchaeota).
In addition, halophilic bacteria have been detected in the salt sumps of the underground Asse II mine. A total of 8 phyla of bacteria were identified by 16S rRNA sequence analyzes. The dominating phylum are Firmicutes (e.g. Bacilli, Halocella, Filifactor, Veillonella) with ~51% of all detected bacterial sequences, followed by Proteobacteria (Marinobacter, Hyphomicrobium, Methylophilus, Pseudomonas, Sphingomonas) with ~19%.
This study identified for the first time extreme halophilic bacteria and archaea in the underground salt sumps of the Asse II environment. For generating a final disposal site, not only geological, chemical or physical, but also microbiological aspects are important to consider.

All-optical switching (AOS) in ferrimagnetic Fe100−x Tbx alloys is presented. AOS is witnessed below, above, and in samples without a magnetic compensation point. It is found that AOS is associated with laser heating up to the Curie temperature and intimately linked to a low remanent sample magnetization. Above a threshold magnetization of 220 emu cm−3 helicity dependent AOS is replaced by pure thermal demagnetization.

In the coming years supercomputers will have millions of compute cores.
It is estimated that the computing power will grow by a factor of 1000 in the coming years while the memory will only grow by a factor of 10.
This means that at optimum codes can be 100 times faster than before.
I will show that such codes exist today and both allow and require online visualization and interaction with the user.
Based on the example of particle-mesh methods I will present the most important techniques on how to write optimum codes.

The release of engineered titanium dioxide nanoparticles in the environment is nowadays continuously increasing due to their wide range of industrial applications. Their potential toxicity effects became of major concern and several assessment studies in natural waters were already undertaken. However, no consensus arised about the environmental factors influencing their hazardous impact, but rather contrary conclusions were drawn. In this study, the acute toxicity of commercial TiO2 nanoparticles suspensions at different concentrations on microcrustacean (Daphnia magna), marine rotifers (Brachionus plicatilis) and marine microalgae (Phaeodactylum tricornutum) under environmental conditions, in synthetic fresh and marine water, was investigated. Factors driving TiO2 adverse effects on aquatic environment, such as allotropic form, primary particle size, surface area, particle concentration and agglomerate size were studied. A thorough characterization of both surface and bulk properties of nano-sized TiO2 particles was therefore performed. Our results showed that Daphnia magna test is the most sensitive test for assessing toxicity of TiO2 samples on aquatic organisms. For anatase samples, toxicity towards aquatic organisms depends (i) on the primary particle size and the extent of agglomeration (mass median diameter d50), and consequently on surface reactivity (total surface site concentration, specific surface area, pHIEP) (ii) on the presence of rutile impurities in the sample.
Toxicity results of rutile and anatase samples of comparable primary particle size (sub micrometric range) are of same order of magnitude and remained less toxic than nanometric particles. Rutile agglomeration was found to be higher than anatase agglomeration, toxicity results obtained for rutile could be attribute to the shape of particles, or it could be due to the presence of BaTiO3 impurities.
This work emphasized the importance of studying the effects of different bulk and surface parameters of engineered TiO2 nanoparticles to understand their reactivity towards micro-organisms under environmental conditions.

Intraband excitation of optically injected carriers using strong mid-infrared or THz pulses provides interesting opportunities to study carrier and exciton dynamics in semiconductor quantum wells (QW). In particular, owing to the odd parity of the dipole operator, such intraband excitation transfers excitons located in radiative states into dark (or interband-forbidden) states as long as the symmetry of the QW ensures parity conservation. This property yields spectroscopic access to specific dark states, giving rise to resonant enhancement of intraband absorption as well as suppression of the photoluminescence (PL), and allows us to investigate associated dynamical processes.
We will report on time-resolved PL studies, where we investigate the dynamics of excitons and electron-hole plasma subsequent to pulsed irradiation using the free-electron laser (FEL) at the Helmholtz-Zentrum Dresden-Rossendorf. The FEL is tuned into resonance with, respectively, intraexcitonic and intersubband transitions. Specifically, Figs. 1(a)-(b) demonstrate the effect of FEL excitation of radiative excitons in resonance with the 1s-2p transition, located at 9 meV for 8.2 nm wide high-quality QWs (sample 1). Besides quenching and recovery of the 1s PL, the salient feature in Fig. 1(b) is the appearance of PL originating from the 2s exciton. As direct excitation from 1s into 2s is dipole forbidden, the latter has to be the consequence of rapid scattering from the 2p into the 2s state, which nicely confirms earlier theoretical predictions. This 2s PL is specific for resonant 1s-2p excitation and just seen in high-quality quantum wells. Figs. 1(c) and (d) show PL transients for FEL excitation at 173 meV, in resonance with the electron intersubband transition for 6 nm wide GaAs QWs (sample 2). Typically, the PL recovery after the FEL pulse obeys the same time constant as the initial PL formation after NIR excitation, and its value after recovery exceeds the reference value since the population transferred into nonradiative states eventually returns into the radiative ones, such that the time-integrated PL emission is conserved.

After the German reunification the Wismut GmbH, formerly the 3rd largest U producer of the world, started to remediate the legacies of their U mining activities. As part of the remediation strategy the pit body was flooded to induce reductive processes. Although flooding of the mines Pöhla and Schlema-Alberoda was already finished about ten years ago, the mine water still contains elevated concentrations of toxic metals such as U, As and Ra. Thus, expensive and long-lasting monitoring and waste water treatment is required. Since microorganisms can influence the toxicity of metals directly or indirectly, one alternative approach is to use them for bioremediation. Here, the diversity of the indigenous microbial community of the mine water from Pöhla and Schlema-Alberoda is reported. Bacteria as well as Archaea were analyzed by state-of-the-art pyrosequencing of the 16S rRNA gene. Mine water samples were either filtrated or harvested from a flow cell. For the filtrated Pöhla mine water, the Pöhla flow cell, the filtrated Schlema mine water, and the Schlema flow cell 485, 697, 325 and 527 sequences, respectively, were divided into 98, 189, 188 and 89 operational taxonomical units (OTUs), respectively, belonging mainly to Bacteria. The bacterial sequences from the Pöhla mine were classified into Proteobacteria, Verrumicrobia, Bacteriodetes, WS3, Chloroflexi, Firmicutes, Acidobacteria, SR1, Actinobacteria, Spirochaetes and OD1. For the Schlema mine Proteobacteria, Acidobacteria, WS3, Bacteriodetes, Chloroflexi, SR1, Chlorobi, TM7 and Acinobacteria were found. The dominant bacterial phylum in all samples are the Proteobacteria. Higher bacterial diversities were observed in flow cells in comparison with filtrated waters. A dataset of 15786, 17872, 11404, 7780 sequences revealed 639, 643, 769 and 455 OTUs, respectively, mainly for Archaea of the filtrated Pöhla mine water, the Pöhla flow cell, the filtrated Schlema mine water and the Schlema flow cell, respectively. The archaeal sequences of the Pöhla as well as the Schlema mine water belong to the class of Methanobacteria, Thermoprotei, Methanomicrobia, Thermoplasmata and Halobacteria.

We use terahertz pulses to induce resonant transitions between the eigenstates of optically generated exciton populations in a high-quality semiconductor quantum well sample. Monitoring the excitonic photoluminescence, we observe transient quenching of the 1s exciton emission, which we attribute to the terahertz-induced 1s-to-2p excitation. Simultaneously, a pronounced enhancement of the 2s exciton emission is observed, despite the 1s-to-2s transition being dipole forbidden. A microscopic many-body theory explains the experimental observations as a Coulomb-scattering mixing of the 2s and 2p states, yielding an effective terahertz transition between the 1s and 2s populations.

In this comparative study, the surface speciation of uranium(VI) on ferrihydrite (Fh) and maghemite (Mh) were investigated by vibrational spectroscopy. The experimental setup allows the monitoring of the surface processes at the water-solid interface in real time with a time resolution in the subminute time range. The performance of the experiments under inert gas atmosphere and under ambient conditions provides further insight into the molecular events of the binary and ternary sorption systems, respectively.
The spectra clearly demonstrate a characteristic surface speciation in dependence of the solid phase. On Fh, the formation of ternary inner sphere complexes are observed as it was derived earlier [1]. In addtion, the time-resolved spectra reveal the change of the surface speciation of atmospherically derived carbonate upon U(VI) sorption [2].
From the sorption experiments on Mh, outer sphere complexation of the uranyl ion can be derived. In ambient atmosphere, contributions of carbonate ions to the U(VI) surface speciation on Mh can not be ruled out.

[1] Ulrich et al. (2006) Geochim. Cosmochim. Acta 70, 5469-5487. [2] Foerstendorf et al. (2012) J. Colloid Interface Sci. 377, 299-306.

In the present study we investigated the reduction of SeO32− by Azospirillum brasilense. The formation of fairly soluble Se(0) nano-particles during this process might be of interest for both bioremediation of Se-contaminated sites and for nanobiotechnology. After A.brasilense being exposed to Se(IV), the bacterial growth continued subsequent to a prolonged lag-phase. After a cultivation time of 3 days, a clearly reddish staining of the sample was observed and a bright red precipitate occurred, indicating the formation of Se(0) nano-particles. The SEM-EDX spectra derived from the nano-spheres indicated that they mainly consist of selenium. In addition, only 10 % of the initial Se(IV) concentrations was recoverd in culture media by means of HG-AAS, indicating a Se(IV) removal from the media. The isolated and resuspended Se(0) nanoparticles showed a long time stability of some hours, which is sufficient for the PCS and the zeta potential measurements. In contrast, Se(0) chemically formed by reduction with hydroxylamine solution produced amorphous aggregates with a rapid sedimentation behavior. The PCS measurement and the SEM imaging of the Se(0) particles showed a particle size distribution between 100 and 300 nm with an averaged particle diameter of 200 nm. The isoelectric point of Se(0) particles was found at pH 2.8 ± 0.2. The preference of forming Se(0) particles with a negative charge agree very well with the literature [1].

[1] Dhanjal & Cameotra (2010) Microb. Cell Fact. 9,1-11.

One major process controlling the mobility and bioavailability of selenium, a long-lived fission product found in nuclear waste, is the adsorption onto mineral surfaces of both the engineered and geological barrier. In this context, it is important to understand to what extent this sorption is influenced particularly by characteristic parameters as expected in deep underground repositories for high level and long-lived radioactive waste. These parameters include inter alia the presence of different background salts which are important with regard to salt domes as potential repositories.
In the present study, a combination of macroscopic sorption experiments, electrophoretic mobility and in-situ ATR FT-IR spectroscopy measurements was used to study the interaction of selenate with aged γ-Al2O3 in the presence of NaCl and MgCl2. From in-situ ATR FT-IR spectra, a change in the symmetry of the aqueous tetrahedral selenate anion can be derived evidencing the formation of a surface complex on γ-Al2O3. From batch experiments, we observe a dependence of selenate sorption on the ionic strength and composition of the electrolyte. Additionally, the sorption generally decreases with increasing pH. However, in the presence of 0.1 M MgCl2, the sorption increased again at a pH above 9.5.
The isoelectric point (pHIEP) of γ-Al2O3 is located at pH 9.6 for low NaCl background electrolyte concentration (I = 0.1 M). The increase of ionic strength (up to I = 1 M) results in a decrease of the zeta potential for both the acidic and alkaline pH range. However, in the alkaline range the decrease of the zeta potential is more pronounced. Additionally, we observe that the pHIEP is shifted to more alkaline values and finally no charge reversal is observed. In the presence 0.1 M MgCl2, the surface charge of γ-Al2O3 is positive throughout the studied pH range (3-11). Above pH 10, a sharp potential decrease occurs due to Mg(OH)2 precipitation. The impact of the varied parameters on the sorption of selenate in the alkaline pH range will be verified in detail.

The retention behavior of the crystalline rock diorite from the Äspö Hard Rock Laboratory (HRL, Sweden) towards the redox-sensitive actinides U and Np was studied by means of batch sorption experiments. The influence of various parameters, such as grain size (0.063 – 0.2 mm, 0.5 – 1 mm, 1 – 2 mm), temperature (25 and 10°C), atmosphere and sorption time (5 to 108 days) was studied using a synthetic Äspö groundwater (pH 7.8, I = 0.178 M) as background electrolyte. For U(VI), sorption isotherms were recorded (5x10⁻⁹ M to 7x10⁻⁵ M). Distribution coefficients, K_d values, were determined.

There is no abstract.

The free-electron laser (FEL) facility FELBE in Dresden provides unique opportunities to advance our knowledge on the interaction of intense mid-infrared and terahertz fields with materials and devices. Its nearly transform-limited ps pulses, which can also be combined with synchronous ps or fs pulses from near-infared tabletop lasers, represent a versatile radiation source for novel experiments, which is also available to external users. This talk reviews some of our recent experimental studies, which are also representative for advanced measurement techniques at FELBE.
In high-quality semiconductor quantum wells, time-resolved photoluminescence allows us to investigate the dynamics of excitons, i.e. two-dimensional, hydrogen-like electron-hole quasiatoms. In particular, applying time-delayed FEL pulses tuned to the intra-excitonic 1s-2p transition (at 9 meV for an 8 nm wide GaAs/AlGaAs quantum well), we have studied the population transfer between the 2p and 2s exciton states. Moreover, strong terahertz pumping in resonance with the 1s-2p transition results in a characteristic splitting (Rabi splitting) of the 1s exciton state, which is a manifestation of the intra-excitonic Autler-Townes effect [1].
In semiconductor quantum dots, resonant excitation between s, p and d sublevels in these zero-dimensional atom-like nanostructures is shown to produce an absorption contrast in aperture-less scattering scanning near-field optical microscopy (s-SNOM). This effect allows us to obtain functional s-SNOM images with deep sub-wavelength resolution, where far-infrared absorption by single electrons produces sufficient contrast to map individual quantum dots [2].
In graphene, FEL-based pump-probe spectroscopy has shown evidence of different relaxation times for excitation energies above and below those of the optical phonons, as well as a transition from induced transmission (bleaching) to induced absorption if the photon energy becomes smaller than twice the Fermi energy [3]. In particular, the latter observation is indicative for interesting potential applications of this two-dimensional semiconductor material, e.g. as an electro-optical modulator.
[1] J. Wagner et al., Phys. Rev. Lett. 105, 167401 (2010)
[2] R. Jacob et al., Nano Lett. 12, 4336–4340 (2012))
[3] S. Winnerl et al., Phys. Rev. Lett. 107, 237401 (2011)

There is no abstract.

High conversion Light Water Reactor concepts typically rely on heterogeneous core configuration, where fissile zones are interspersed with fertile blanket zones in order to achieve high conversion ratio. Such a heterogeneous structure renders the modeling of these cores impossible using conventional reactor analysis methods. It was recently suggested to overcome such difficulties, in particular, for the case of axially heterogeneous reduced moderation BWRs, by introducing additional set of discontinuity factors in the axial direction at the interfaces between fissile and fertile fuel assembly zones. However, none of the existing nodal diffusion core simulators have the capability of accounting for discontinuity of homogeneous nodal fluxes in the axial direction since the fuel composition of conventional LWRs is much more axially uniform. In this work, we modified nodal diffusion code DYN3D by introducing such capability. The new version of the code was tested on a series of reduced moderation BWR cases with Th-U233 and U-Pu-TRU fuel. The library of few-group homogenized cross sections and the data required for calculation of discontinuity factors were generated using Monte Carlo transport code Serpent. The results obtained with the modified version of DYN3D were compared with the reference Monte Carlo solutions and were found to be in a good agreement. The current analysis demonstrated that high conversion LWRs can in principle be modeled using existing nodal diffusion core simulators.

An innovative light water reactor constructed as a multitude of modular, horizontal fuel channels has been proposed. The basic novelty of the proposed design is an implementation of the “breed & burn” mode of operation by a dynamic variation of the moderator content in the core. This paper describes the novel reactor core design and explores the physical principles underlying its operation. Initially, a single fuel channel assembly was analyzed in order to evaluate the impact of the moderator variation on the reactivity and “breed & burn” processes. At the second stage, a full core model was analyzed, demonstrating a possibility of a realistic fuel management scheme with on-power moderator addition. The BGCore Monte-Carlo based depletion code was used for the analyses. It has been shown that the proposed design has a potential to increase the fuel utilization, attain negative reactivity coefficients and reduce the excess core reactivity during the power operation. The physical observations, presented and discussed in this paper, provide an interesting research lines for future investigation and continuous design developments.

The compact neutron-time-of-flight facility nELBE at the superconducting electron accelerator ELBE of Helmholtz-Zentrum Dresden-Rossendorf is currently being rebuilt. As the neutron radiator consists of a liquid-lead circuit no moderated neutrons are produced and also the background from capture gamma-rays is very small. The useful neutron spectrum extends from some tens of keV to about 10 MeV. nELBE is intended to deliver cross section data of fast neutron nuclear interactions e.g. for the transmutation of nuclear waste and an improvement of neutron physical simulations of innovative nuclear systems. The new experimental hall will allow measurements of angular distributions in neutron scattering. Inelastic neutron scattering, e.g. on 56Fe, has been studied with a double time-of-flight setup and with photon detectors to measure the gamma-rays produced in the process. The neutron total cross sections of Au and Ta were determined in a transmission experiment.

The world’s first permanent nuclear-waste repository for high-level waste (HLW) will be the underground rock characterization facility tunnel ONKALO, situated near the nuclear power plants of Olkiluoto, approximately 300 km northwest of Helsinki (Finland). Geological mapping showed that the bedrock of the tunnel is mainly composed of veined gneisses with a migmatic appearance, which are interspersed by numerous fractures. Massive 5–10-mm thick biofilms (microbial communities) are observed attached to the tunnel walls where groundwater is seeping from bedrock fractures feeding the biofilm. Groundwater and biofilm samples were taken during the EURATOM collaborative project ReCosy for laboratory experiments in flow cells, where uranium(VI) was added to the circulating groundwater with a final uranium concentration (4.25×10–5 M), which was expected from a damaged and leaking waste canister in the far-field of a nuclear-waste repository. The aim of our studies was to simulate the fate and behaviour of uranium(VI) in the presence of microorganisms using different methods to find evidence of the possibility of uranium retention.

In our experiments, aqueous uranium percolated the biofilm and induced interaction between biofilm microorganisms and uranium(VI), forming an intracellular U-phosphate mineral similar to autunite (Ca[UO2]2[PO4]2 • 2-6H2O or meta-autunite Ca[UO2]2[PO4]2 • 10-12H2O) as determined by means of EF-TEM/EELS. The potential toxicity of uranyl was consequently avoided by the uranium forming these strong complexes with phosphate in the cytoplasm of these microorganisms. Inorganic phosphate (H2PO4–) was released from the cellular polyphosphate as a cells’ response to the heavy metal stress. In contrast, aqueous uranium carbonate species, likely calcium uranyl carbonates species (Ca2UO2[CO3]3), were formed using the large available amount of carbonate in the uranium-contaminated circulating groundwater. The results of the laser-induced fluorescence spectroscopy studies performed at 283 K are in excellent agreement with the thermodynamic calculations of the theoretical predominance fields of the uranium species formed in the uranium-contaminated circulating groundwater. These complexes consequently influence the speciation of uranium, contributing to the transport and migration of uranium(VI).

Our studies aimed to improve our understanding of the mechanisms by which biofilms respond to the exposure to radionuclide with respect to safety assessments in the far-field of nuclear-waste repositories. In this environment, microorganisms must be considered, along with minerals, as an important factor influencing radionuclide transport.

With PIConGPU, new physics phenomena previously not accessible within laser plasma simulations can be studied, which will help us optimize laser-driven radiation sources. Presents results on laser wakefield acceleration of electrons simulated on the Oakridge TITAN system and discuss in detail which techniques help us to get the most out of these clusters. Finally showing how to add fault-tolerance and load-balancing to a large hybridh CPU-GPU code such as PIConGPU to achieve optimum performance.

We present the algorithmic building blocks of PIConGPU, one of the fastest implementations of the particle-in-cell algortihm on GPU clusters. PIConGPU is a highly-scalable, 3D3V electromagnetic PIC code that is used in laser plasma and astrophysical plasma simulations.

To allow simulation of nanosecond scale plasma processes, we are developing a 3D fully relativistic fluid code with LTE (local thermal equilibrium) closure. This code is intended to be able to take output from PIC simulations as its initial state, to allow self-consistent simulation of processes acting over multiple time and density scales. In this code, both electrons and ions are treated as inertial fluids. Local fluid pressure is tied to the energy density using the Maxwell-Jüttner distribution, allowing investigation of the effect of local temperatures on, for example, the expanding sheath in TNSA (target normal sheath acceleration) experiments.

Plasma heating and ionization are important processes during the interaction of high power ultra-short laser pulses with solid density targets. In order to understand the relevant physics, particle-in-cell simulations including collisions and ionization were run to study ion heating dynamics in buried layer targets illuminated by high-intensity, ultra-short laser pulses. Our results show that bulk ions can be heated to above 1keV temperature. When studying the ionization dynamics strong filaments have been observed which depend on preplasma on the target front side, laser pulse duration and intensity. In order to study the evolution of ionization and ion bulk heating in experiment, ultra-bright X-ray free electron lasers - such as the European XFEL - are a very promising and strong tool to resolve the spatial and temporal scales of these processes inside the solid target.

High-precision measurements of the hyperfine splitting values on Li- and H-like bismuth ions, combined with precise atomic structure calculations allow us to test QED-effects in the regime of the strongest magnetic fields that are available in the laboratory. Performing laser spectroscopy at the experimental storage ring (ESR) at GSI Darmstadt, we have now succeeded in measuring the hyperfine splitting in Li-like bismuth. Probing this transition has not been easy because of its extremely low fluorescence rate. Details about this challenging experiment will be given and the achieved experimental accuracy will be presented.

We present new results on broadband laser cooling of stored relativistic C3+ ion beams at the ESR in Darmstadt. For the first time we could show laser cooling of bunched relativistic ion beams using a UV-laser which could scan over a very large range and thus cool all the ions in the ‘bucket’. This scheme is much more versatile than a previous scheme, where the bunching frequency was scanned relative to a fixed laser frequency. We have also demonstrated that this cooling scheme works without pre-electron cooling, which is a prerequisite for its general application to future storage rings and synchrotrons, such as the HESR and the SIS100 at FAIR. We also present results from in vacuo VUV-fluorescence detectors, which have proven to be very effective.

We present new results on laser cooling of relativistic C3+ ion beams at the Experimental Storage Ring at GSI. For the first time we could show laser cooling of bunched relativistic ion beams using fast scanning of the frequency of the cooling laser over a range larger than the momentum acceptance of the bucket. Unlike previously employed cooling schemes where the bucket frequency was scanned relatively to a fixed laser frequency, scanning of the laser frequency can be readily applied to future high energy storage rings such as HESR or SIS 100 at FAIR.

PIConGPU can handle large-scale simulations of laser plasma and astrophysical plasma dynamics on GPU clusters with thousands of GPUs. High data throughput allows to conduct large parameter surveys but makes it necessary to rethink data analysis and look for new ways of analyzing large simulation data sets. The speedup seen on GPUs enables scientists to add physical effects to their code that up until recently have been too computationally demanding. We present recent results obtained with PIConGPU, discuss scaling behaviour, the most important building blocks of the code and new physics modules recently added. In addition we give an outlook on data analysis, resiliance and load balancing with PIConGPU.

Aim:

Nicotinic α4β2* acetylcholine receptors (nAChR) are an important target for diagnostic neuroimaging because of their involvement in Alzheimer's disease, Parkinson's disease, tobacco and alcohol addiction. 2-[¹⁸F]FA-85380 (2-FA) has been used extensively for PET imaging of α4β2* receptors but is limited as biomarker by its unfavourable slow kinetic. The newly developed radiotracer (-)-[¹⁸F]-Flubatine (Flubatine) shows a significantly improved brain uptake, receptor affinity and selectivity (1). Here we estimated the compartmental parameters of both tracers by full kinetic modeling and compared them.

Materials and methods:

After intravenous administration of ~370 MBq radiotracer PET brain imaging was performed in 20 healthy controls with Flubatine (age 70.6±4.6, scan duration 90 min) and in 7 healthy controls with 2-FA (age 60.7±9.0, scan duration 420 min) using an ECAT EXACT HR+ system. PET frames were motion corrected with SPM2 and kinetic modeling using a 1-tissue compartment model (1TCM) with arterial input-function was applied to the volume of interest (VOI) based tissue time-activity curves (TACs) generated for 29 brain regions (anatomically defined via MRI co-registration). The model-based receptor parameter used was the total distribution volume V_T (ml/cm³), tracer uptake was measured by K₁ (ml/cm³/min) and tracer tissue clearance by k₂ (1/min).

Results:

For both tracers TACs of all 29 brain regions could be described appropriately with the 1TCM and all kinetic parameters could be reliably estimated from the PET data. Regional V_T increased as expected with regional nAChR density. Parameters of Flubatine in characteristic regions with very low, medium and high receptor density were: Corpus callosum (K₁= 0.18±0.04, k₂= 0.032±0.004, V_T= 5.68±1.01), Frontal cortex (K₁= 0.37±0.04, k₂= 0.040±0.003, V_T= 9.18±0.59), Thalamus (K₁= 0.48±0.06, k₂= 0.020±0.003, V_T= 25.03±3.33). The respective parameters of 2-FA were: Corpus callosum (K₁= 0.063±0.009, k₂= 0.014±0.003, V_T= 4.45±0.65), Frontal cortex (K₁= 0.099±0.013, k₂= 0.018±0.001, V_T= 5.42±0.56), Thalamus (K₁= 0.13±0.019, k₂= 0.010±0.001, V_T= 13.06±2.62).

Conclusions:

Flubatine is superior to 2-FA in tracer uptake velocity (characterized by K₁), velocity of washout (characterized by k₂) and in the amount of measured specific binding (characterized by V_T-target - V_T-reference). It shows a threefold higher uptake rate constant K₁ and a twofold higher washout rate constant k₂, providing the rational for much shorter scan durations in case of Flubatine. These results are in good agreement with our former findings in an animal (pig) model (1).

Reference:

1. P. Brust, ..O. Sabri: In vivo measurement of nicotinic acetylcholine receptors with [¹⁸F]Norchloro-Fluoro-Homoepibatidine (Flubatine). Synapse 2008;62:205-218.

We present recent results on TNSA, simulations and laser cooling of ion beams

Ziel/Aim:

Our aim was to port our previously developed high resolution 3D list-mode image reconstruction for the HR+ PET to the Philips Ingenuity TF PET/MR system. Porting to a different scanner usually requires a major rewrite to account for system specific aspects. Instead, a general interface was designed and implemented in our reconstruction to allow simultaneous support of multiple scanners and to facilitate future adoption to further scanner types. We report on application of this strategy for implementing our reconstruction on the Philips PET/MR.

Methodik/Methods:

We implemented a generalized interface using abstract classes which completely removes scanner dependency from the reconstruction algorithm and allows runtime switching between scanners. The reconstruction obtains system specific information
such as geometry parameters and data formats directly via an abstract interface using internal formats. The port to the Philips PET/MR was performed accordingly and evaluated: i) quantitative accuracy and spatial resolution in phantoms, ii) visual evaluation of patient studies, iii) runtime performance evaluation.

Ergebnisse/Results:

The use of an abstract interface influences the runtime performance of the reconstruction only minimal. The ported reconstruction shows substantial improvements in comparison to the vendor provided software. In phantoms we obtain improved resolution and a high level of quantitative accuracy. Visual inspection of phantom and patient data reveals an improved level of detail rendering.

Schlussfolgerungen/Conclusions:

The implementation of an abstract interface simplifies porting of the software to other scanners. For the Philips PET/MR we observed improved resolution and overall image quality compared to the vendor provided software. Support of Time-of-Flight information is currently implemented and already shows further improvements of image quality at reduced reconstruction times.

Ziel/Aim:

Members of the Eph receptor tyrosine kinase family play an essential role in the pathogenesis of cancer and, therefore, are promising candidates for molecular imaging purposes, e.g. by PET. In this regard, radiochemical access to 11C-radiotracers derived from potent inhibitors (IC₅₀ = 1.3 nM, calcd. logP = 3.42) targeting EphB4 kinase domain and bearing the indazolylpyrazole structural motif was developed.

Methodik/Methods:

The evaluation of a protecting group strategy based on the ethoxyethyl moiety (EOE) was necessary for the regioselective labeling with [¹¹C]CH₃I due to three secondary amino groups of the precursor. The labeling was accomplished in a remotely controlled synthesis module in three steps. The first step involved the preparation of [¹¹C]CH₃I from [¹¹C]CH₄, the second step comprehended the radiolabeling of the protected precursor and the final step included the cleavage of the protecting group.

Ergebnisse/Results:

The synthesis of the reference as well as the precursor was done starting from EOE protected indazole. Subsequent reaction with 2,4-diochloropyrimidine give the first substructure. For the preparation of the precursor, the first substructure was treated with 3,5-di(morpholino)aniline under Buchwald-Hartwig conditions. For the preparation of the reference, the first substructure was first methylated and then treated with 3,5-di(morpholino)aniline. The radiolabeling was done starting with ~ 1-1.5 GBq [¹¹C]CH₃I under basic conditions. After 2 min reaction time 1 M HCl was added and the mixture was maintained for 2 min. Approx. 200 MBq of the desired radiotracer could be obtained within 20 min after EOB (30-35% d.c. yield based on [¹¹C]CH₄).

Schlussfolgerungen/Conclusions:

The two-step radiolabeling of a novel indazolylpyrazole derivative with [¹¹C]CH₃I was successfully demonstrated. First stability tests showed beneficial behaviour ex vivo. Further biological studies for an application as radiotracer for functional tumor imaging are ongoing.

Literatur/References:

Mamat C, Mosch B et al. (2012) ChemMedChem 7:1991-2003.

Ziel/Aim:

The synthesis of fluorine-18 labeled peptides with high affinity towards the EphB2 receptor and the evaluation as radiotracers for PET was described. This receptor is known to be overexpressed in various types of cancer. Thus, a peptide was applied with high affinity to the EphB2 receptor which is strongly constrained of the amino acid key sequence SNEW. Two novel bifunctional and bioorthogonal building blocks were evaluated. The labeling of the peptides was done using the Huisgen click approach.

Methodik/Methods:

Two labeling building blocks based on the piperazine skeleton with either alkyne or azide function were used and an automated module synthesis was evaluated. Further, it was found that the peptide SNEWILPRLPQH show a high affinity to EphB2. Thus, the C-terminus of the peptide was functionalized with alkyne or azide, to retain the high affinity which is constrained of the key sequence SNEW at the N-terminus.

Ergebnisse/Results:

The automated one-step radiosynthesis of two novel building blocks gave the desired piperazine derivatives [¹⁸F]AFP and [¹⁸F]BFP in radiochemical yields of 25-45% (d.c.) within 50 min and a high purity after convenient separation from [¹⁸F]F- and precursor using silica gel cardridges. Radiolabeling of several functionalized SNEW peptides under Click conditions pointed out that [¹⁸F]AFP is only suitable and yielded the radiofluorinated peptide in 10-15 % RCY (d.c.). A by-product was observed when the alkyne building block [¹⁸F]BFP was used due to the competing Glaser coupling. Finally, the peptide was prepared, radiolabeled and purified from the Cu with bispidine on SPPS. This is urgent, otherwise, aggreagtion of the peptide with Cu occur. Finally, the stability of the labeled SNEW peptide was investigated ex vivo showing >80% intact peptide after 1 h. Three more hydrophilic metabolites were observed not determined as [¹⁸F]F-.

Schlussfolgerungen/Conclusions:

With the SNEW peptides highly potent 18F-containing EphB2 inhibitors were found and the labeling on SPPS with [¹⁸F]AFP was successfully established.

With upcoming supercomputer technology, the simulation of laser-driven radiation sources enters the realm of large-scale parameter surveys, interactive simulation and the possibility to add physical effects hitherto impossible to account for.
We present new ideas and techniques to deliver simulations that are closer to experiment and can be better connected to new experimental diagnostics.
We finally show how an integrated experimental and theoretical program is needed to increase the predictive capability of codes and why code validation will be the focus of laser plasma simulations.

Ziel/Aim:

Transglutaminasen und Polyamin-Transporter sind interessante Targets für die funktionelle Bildgebung von Tumoren mittels PET. Zur Adressierung dieser Targets sollen Polyamin-basierte Fluor-18-Tracer Anwendung finden, in denen das Radionuklid über die 4-Fluorbenzoylgruppe (FBz) eingeführt wird. Um die dafür erforderlichen Fluor-19-Analoga zugänglich zu machen, wurde eine Festphasensynthese entwickelt, die die selektive Fluorbenzoylierung an einer Aminogruppe in verschiedenen Polyaminen (u. a. Putrescin, Spermidin, Spermin) ermöglicht. Der etablierte Syntheseweg soll auf die entsprechenden F-18-markierten Analoga übertragen werden.

Methodik/Methods:

Zur selektiven mono-Fluorbenzoylierung wurde das von Wang et al. beschriebene Synthesekonzept angewendet (1). Es beinhaltet den Aufbau des Polyamin-Gerüstes durch Festphasensynthese der entsprechenden Oxopolyamine und deren anschließende Reduktion durch BH₃/THF. Durch Einsatz von Dde und Boc als orthogonale Schutzgruppen und der Möglichkeit, mit 2-Acetyldimedon selektiv primäre Aminogruppen zu schützen, wird die selektive Fluorbenzoylierung verschiedener Aminogruppen ermöglicht.

Ergebnisse/Results:

Durch gezielte Anwendung des genannten Synthesekonzeptes konnten folgende neue Verbindungen in guten bis sehr guten Ausbeuten erhalten werden: N-FBz-Putrescin, N-FBz-Cadaverin, N¹-FBz-3-Oxospermidin, N⁸-FBz-5-Oxospermidin, N¹-FBz-3,8-Dioxospermin, N¹-FBz-Spermidin, N⁴-FBz-Spermidin, N⁸-FBz-Spermidin und N¹-FBz-Spermin. Die Identitäten der Verbindungen wurden NMR-spektroskopisch bestätigt.

Schlussfolgerungen/Conclusions:

Die Festphasensynthese mono-fluorbenzoylierter Polyamine und Oxopolyamine konnte erfolgreich etabliert werden. Durch das Vorliegen der Referenzverbindungen kann nun die Radiosynthese der Fluor-18-Analoga erfolgen, bei denen die 4-Fluorbenzoylgruppe [F-18]SFB-vermittelt angeknüpft wird. Dabei kann vermutlich analog zur Synthese der nichtradioaktiven Verbindungen vorgegangen werden.

Literatur/References:

(1) F. Wang, S. Manku, D. G. Hall, Org. Lett. 2000, 2, 1581-1583

Neptunium (Np) is one of the most important components of nuclear waste to consider for the long-term safety assessment of nuclear waste repositories, due to the increasing en-richment, the long half-life and the high toxicity of Np-237. Hence, great attention is attract-ed to its geochemistry [1]. Among the various geochemical reactions, the molecular pro-cesses occurring at the solid-water interface, e.g. sorption onto mineral phases, surface precipitation, and colloid formation strongly affect the migration behavior of the radioactive contaminant in the environment [2]. Thus, various components of geological materials, such as iron oxides and hydroxides play an important role in regulating the mobility of actinides in aquifers, due to their widespread environmental presence, high sorption capacity and tendency to form coatings on mineral surfaces [3]. In recent years, the sorption behavior of Np(V), the most relevant oxidation state under ambient conditions, onto iron oxides was mainly studied by macroscopic experiments [4]. For a better understanding of the molecular events occurring at the mineral’s surfaces, ATR FT-IR spectroscopy is a useful tool for the in-situ identification of surface species [5]. In addition, time-resolved measurements provide kinetic information on the surface reactions.
In this work, Np(V) sorption on hematite is studied under a variety of environmentally rele-vant sorption conditions by in-situ ATR FT-IR spectroscopy [5]. The IR spectra obtained from the subsequent steps of the experiment, that is (1) conditioning, (2) sorption, and (3) flushing, are shown in Fig. 1.
The absence of significant bands below 1000 cm−1 in the conditioning spectrum demon-strates the stability of the stationary hematite film directly prepared on the ATR crystal’s surface. The bands at 1491 and 1356 cm−1 represent the removal of carbonate by rinsing the hematite film, prepared in air with the CO2 free solution. Upon Np(V) sorption, the band observed at 790 cm−1 is assigned to the antisymmetric stretching vibrational mode (ν3) of the neptunyl ion. The IR spectrum obtained from an aqueous solution at 50 µM Np(V), 0.1 M, pH 6 shows the absorption of ν3(NpVO2) at 818 cm−1. The red shift of ν3 to 790 cm−1 upon sorption can be assigned to an inner-sphere monomeric sorption complex, as previ-ously reported for TiO2, SiO2 and ZnO [5]. The band at 1042 cm−1 is most probably due to surface modes of the mineral oxide provoked by the sorption processes and were already observed for interactions with U(VI), Cs(I) and CO32 [5]. In the flushing stage, a weakly bound species is released from the stationary phase, reflected by a negative band at 795 cm−1 in the respective spectra.
Additional experiments were performed at varied values of pH (5.6 – 12) and ionic strength (0.001 – 0.1) (Fig. 2). Upon increasing the pH from 5.6 to 8.6, no shifts of the bands at 1041 and 790 cm−1 are observed. But the intensities of these spectral features are consid-erably increased at higher pH values indicating an enhanced sorption capacity close to the IEP at pH 9.2. At pH > 10, the aqueous Np(V) speciation changes and NpO2OHaq is formed and distinctly changes the sorption behavior. The band of ν3(NpVO2) is shifted to 773 cm−1. The variation of ionic strength between 0.1 and 0.01 does not change the spectral characteristics. The higher intensities observed at 0.0001 M NaCl can be attributed to contributions of an outer-sphere complex which has to be verified by future experiments.
In summary, the IR spectra evidence the formation of Np surface complexes on hematite which can be easily removed to a considerable extent by flushing with blank solution. From this behavior, the simultaneous formation of an inner-sphere species with con-tributions of an outer-sphere complex is suggested.

[1] Kaszuba, J. P. et al. (1999) Environ. Sci. Technol. 33, 4427-4433.
[2] O'Day, P. A. (1999) Reviews of Geophysics 37, 249-274.
[3] Tochiyama, O. et al. (1996) Radiochim. Acta 73, 191-198.
[4] Brendler, V. et al. (2003) Journal of Contaminant Hydrology 61, 281-291.
[5] Müller, K. et al. (2009) Environ. Sci. Technol. 43, 7665-7670.

Ziel/Aim:

Die Revision von gelockerten Hüft-Pfannen kann den Einsatz von impaktierten Knochen-Allografts (CBA) zur Stabilisierung der Pfanne und zum Auffüllen von Knochendefekten erfordern. Können mittels NaF-PET osteometabolische Veränderungen des CBA zu einem frühen Zeitpunkt nach Revision dokumentiert werden?

Methodik/Methods:

18F-NaF-PETs wurde 1 und 6 Wochen nach Revision durchgeführt. 12 Patienten wurden in die Studie (BfS- und Ethik-Votum) eingeschlossen, 9 Patienten absolvierten PET1+2. Die PET wurden an einem ECAT EXACT HR+ (Siemens/ CTI, USA) durchgeführt. Nach einer 4-min. Transmissionsmessung (Ger-68-Stabquellen) begann mit i.v.-Injektion von 240– 300 MBq F18-NaF eine dynamische Emission über 30 min über den Hüften. Auf einem post-op CT wurden Volumes of interest (VOIs) abgegrenzt (CBA, supracetabulär, os pubis) und nach Fusion von CT- und PET-Datensätze auf das PET übertragen. Die quantitative NaF-Aufnahme der VOIs wurde mit einem irreversiblen 2-Kompartment-Modell berechnet. Die Inputfunktion wurde aus der A. iliaca communis der dynamischen PET bestimmt. Der Parameter km (min-1) repräsentiert den Fluorid-influx in den Knochen.

Ergebnisse/Results:

km des supracetabulären Knochen zeigte auf der operierten Seite von PET1 zu PET2 eine nicht signifikante Zunahme (mean (±SD)) von 0,0491 (±0,0249) auf 0,0678 (±0,0367). Das CBA zeigte eine nicht signifikante Zunahme von 0,0384 (±0,0307) auf 0,0549 (±0,0319). In Zusammenschau mit dem CT war diese Zunahme im Randbereich des CBA lokalisiert und konnte nicht sicher von angrenzendem genuinem Knochengewebe, das visuell bei PET2 eine höhere Stoffwechselaktivität aufwies, getrennt werden.

Schlussfolgerungen/Conclusions:

Die NaF-PET 1 und 6 Wochen nach Revision zeigt eine nicht signifikante Zunahme des Knochenstoffwechsels ipsilateral supracetabulär. In dem CBA können beginnende osteometabolische Veränderungen im Randbereich zum genuinen Knochen nicht ausgeschlossen werden, zur sicheren Dokumentation einer stabilen Durchbauung des CBA wäre eine NaF-PET zu einem späteren Zeitpunkt erforderlich.

Ziel/Aim:

Therapy response varies considerably in advanced cervical carcinoma(ACC). Glucose metabolism and microvascular characteristics of the tumor have been evaluated as biomarkers for identification of patients with poor response before or early during treatment. The combination of both biomarkers for detection of tumor regions with a ‘malignant mismatch’(MM), i.e. strongly increased glycolysis at low blood flow levels, might indicate resistance to therapy. The aim of the present study was to test whether ACC show MM that can be detected by the combination of FDG- and O-15-water-PET.

Methodik/Methods:

Twelve women (27-69y) with locally ACC (FIGO IIB-IIIB; grade G2 n=7, G3 n=5) were included prior to chemo-radiation. Regional blood flow was computed voxel-by-voxel from the O-15-water PET using a weighted integral approach and an image-derived arterial input function. FDG uptake was characterized by SUV. The primary tumor was segmented manually in the CT. A tumor voxel was considered to present MM if the perfusion was lower than the median perfusion in the tumor and the SUV was higher than the median SUV. The absolute total MM volume (aMMV) was obtained by multiplying the number of MM voxels with the voxel volume. The relative MM volume (rMMV) was obtained by dividing the aMMV by the tumor volume.

Ergebnisse/Results:

The volumes of the primary tumors ranged from 54 to 225ml. The tumors were quite heterogeneous with respect to both FDG uptake and perfusion. The aMMV ranged from 7.7 to 35.5ml, the rMMV from 7.9 to 26.6%. There was no correlation between rMMV and tumor volume (p=0.517). T-testing revealed a tendency (p=0.083) for an association between aMMV and histological grading, aMMV being higher in the G3 than in the G2 tumors. There was no association between grading and rMMV (p=0.888).

Schlussfolgerungen/Conclusions:

ACC show a metabolism/perfusion MM to a strongly variable extent. The mismatch volume seems to be associated with the tumor grade. Evaluation of the prognostic value requires follow-up data in a larger cohort.

Ziel/Aim:

Hypoxie ist charakteristisch für solide Tumoren und trägt maßgeblich zu einem potenziellen Versagen einer Radiochemotherapie (RCT) bei. Ziel dieser prospektiven Studie war es deshalb, den prognostischen Wert der Hypoxie-Bildgebung vor und unter RCT bei Patienten mit lokal fortgeschrittenen Kopf-Hals-Tumoren (KHT) zu explorieren.

Methodik/Methods:

Fünfundzwanzig Patienten mit histologisch gesicherten, unbehandelten KHT im klinischen Stadium III / IV wurden mit der F-18-Misonidazol- (F-MISO-) PET/CT zu 4 Zeitpunkten der kurativ intendierten RCT (initial, 8-10 Gy, 18-20 Gy und 50-60 Gy) untersucht. Parameter wie die maximale Ziel-Hintergrund-Ratio und das Schwellwert-basierte Tumorvolumen bei verschiedenen Ziel-Hintergrund-Rationes, das Tumorvolumen aus der CT sowie typische Basisparameter der initial und bei 40 Gy durchgeführten FDG-PET/CT wurden zu allen Untersuchungszeitpunkten auf ihren prognostischen Wert hin untersucht. Als Endpunkt diente das lokal Progressions-freie Überleben (LPFS). In einer multivariaten Cox-Analyse (einschließlich klinischer Parameter) und mehreren Log-Rank-Tests erfolgte die Prüfung auf signifikante Unterschiede.

Ergebnisse/Results:

Die Parameter aus der F-MISO-PET zeigten eine Assoziation mit dem LPFS-Endpunkt, am strengsten assoziiert waren die Zeitpunkte bei 10 Gy und 20 Gy unter der RCT (p = 0,023-0,048 und 0,042-0,061 in der multivariaten Cox-Analyse). Parameter aus der initialen F-MISO-PET/CT waren nur in der univariaten Analyse signifikant. Weder klinische Parameter, noch CT- oder FDG-PET-basierte Tumorvolumina zeigten eine signifikante Assoziation mit dem LPFS.

Schlussfolgerungen/Conclusions:

Diese prospektive Explorationsstudie demonstriert die prognostische Bedeutung der F-MISO-PET/CT in der frühen Phase der kurativen RCT. F-MISO-Bilder nach 1 oder 2 Wochen RCT (bei 10 bzw. 20 Gy) sind vielversprechend, wenn es um die Selektion der Patienten geht, die von einer Modifikation der Hypoxie oder von einer Dosis-eskalierten Radiatio profitieren könnten. Eine prospektive Validierungsstudie läuft bereits.

The main purpose of Subproject 2 is to further investigate the Key Safety Aspects identified by the Safety Advisory Group of the RAPHAEL project and to contribute to their resolution. Work package 23 targets to fill the knowledge gaps in dust production, deposition and remobilisation. Experimental and (advanced) analytical methods have been adopted to investigate all aspects of dust behaviour.

Aim
There is evidence that α7nAChRs play an important role in cancer and neurodegenerative diseases. Therefore, quantitative imaging of α7nAChRs using PET represents a new approach for investigation of those diseases.
Due to its high target affinity and selectivity [¹⁸F]NS14490, an oxadiazolyl-diazabicyclononane derivative, is a promising radiotracer for α7nAChRs imaging. Manual radiosynthesis of [¹⁸F]NS14490 and its in vivo evaluation in mice were already reported [1]. The subsequent assessment of its imaging potential by dynamic PET studies in piglets and PET/CT studies in tumor-bearing mice required the transfer of the manual synthesis to an automated synthesis module.

Materials and Methods
For dynamic PET studies, the manual radiosynthesis of [¹⁸F]NS14490 [1] was transferred to an automatic synthesis module (Tracerlab FX-N) including azeotropic drying of [¹⁸F]F- with Kryptofix K222/K₂CO₃ in acetonitrile, direct nucleophilic substitution at the precursor, semipreparative HPLC and solid phase extraction. After evaporation the radiotracer was formulated in phosphate buffered saline containing 5% ethanol.
Dynamic PET studies in piglets (female, 15-18 kg) were performed under control and blocking conditions (n=2 each) with a highly selective α7nAChRs ligand (NS6740; bolus: 3 mg kg-¹ h^-1; infusion: 1 mg kg^-1 h^-1) for 4 hours. The metabolism of [¹⁸F]NS14490 in piglets was analyzed by chromatography of plasma samples.
PET/CT studies were performed in tumor-bearing nude mice under control and blocking conditions with NS6740.

Results and Conclusion
During transfer of radiosynthesis into an automated synthesis module, solid phase extraction was challenging. For desorption of the radiotracer from divinyl/polystyrene cartridge, the elution solvent ethanol/acetic acid used in manual synthesis was replaced by acetonitrile/formic acid resulting in more efficient elution, formerly not accomplished. The radiotracer was achieved within 1.25 hours and radiochemical yields (32%), radiochemical purity (> 90%) and specific activity (> 150 GBq μmol_-1) were comparable to the manual synthesis [1]. Brain uptake of [¹⁸F]NS14490 peaked in piglets at 3 min p.i. and is with a value of SUV_max = 0.504 about tenfold higher than in mice. Blocking by NS6740 decreased the specific uptake in brain by 28% (SUV 240 min p.i. 0.174 vs. 0.125 under baseline and blocking conditions, respectively).The metabolic stability of [¹⁸F]NS14490 in piglets is lower than in mice. At 60 min p.i. intact radiotracer represented 30% of plasma activity in piglets compared to 55% in mice.
Preliminary animal PET/CT studies in tumor-bearing mice provide evidence that [¹⁸F]NS14490 may also be suitable for tumor imaging.
[1] Rötering, S. et al. Bioorg. Med. Chem. 2013