Publications Repository - Helmholtz-Zentrum Dresden-Rossendorf

Aim:

Three-dimensional multicellular tumor spheroids (MCTS) of tumor cell lines are a promising model system which reflects the in vivo situation of tumor microregions with increasing accuracy compared with conventional monolayer culture. In this study we quantified the uptake of radiotracers [¹⁸F]FDG and [¹⁸F]FMISO in various types of MCTS at different diameters and after defined times in culture.

Material and Methods:

Human tumor cell lines FaDu, HT-29, MCF-7 and EJ-28 and the murine line B16-F10 were cultured in 96 well plates. Culturing was performed in the presence of 0.24% methylcellulose for 3 to 7 days and with seeding densities of 1,000, 5,000, 10,000 and 30,000 cells per well. Diameters of individual spheroids were assessed and cellular uptake of [¹⁸F]FDG and [¹⁸F]FMISO was recorded after an incubation interval of 2 to 4 hours. MCTS were then harvested, washed onto filters and the individual uptake per spheroid was measured with a gamma counter.

Results:

Between day 3 and day 7, spheroids of a starting concentration of 10,000 cells showed an increase in diameter of 1.4-fold for HT-29, 1.2-fold for FaDu, 1.3-fold for MCF-7 and 1.1-fold for both EJ-28 and B16-F10 cells. In all cell lines, we observed a good correlation between uptake of [¹⁸F]FDG and spheroid diameter and protein content, respectively. With an experimental setting of 10.000 initiated cells and 3 days of culturing, the highest [¹⁸F]FDG uptake was achieved in B16-F10 cell spheroids with a value of 1.46±0.41 percent injected dose per MCTS (%ID/MCTS). In comparison, FaDu uptake was 0.63±0.15%ID/MCTS and 0.38±0.05%ID/MCTS in HT-29. EJ-28 and MCF-7 exhibited less than 0.2%ID/MCTS. In parallel, a different uptake pattern was observed for [¹⁸F]FMISO. Highest uptake was documented in B16-F10 with 0.23±0.11%ID/MCTS, whereas all other cell lines showed an uptake of 0.03%ID/MCTS or less. These data indicate larger areas of hypoxia in the cores of B16-F10 spheroids compared to other cell lines.

Conclusion:

Our data show a spheroid-type specific increase in the uptake of both [18F]FDG and the hypoxia marker [¹⁸F]FMISO as a function of the spheroid diameters which is indicative for an increasing amount of metabolically active cells and an increment of hypoxic areas in growing spheroids. We conclude (i) that radiotracer uptake is a promising approach to monitor the pathophysiological situation in MCTS and (ii) that MCTS are a valuable tool to study the uptake of new radiotracers in a pathophysiological tumor milieu.

Biosystems such as microorganisms, plants, algae’s etc. are influencing for instance the migration of actinides in the environment. It is important to include these processes in the risk assessment of potential high level nuclear waste disposal sites and other affected areas. In general, the overall interaction process of actinides with microbes can be divided into a) direct interaction path ways such as biosorption, bioaccumulation and biotransformation/bioreduction and b) indirect interaction paths such as complexation with released bioligands. The potential of microbes to mobilize actinides by means of the formed bioligands is less investigated.

Our approach is focused on the investigation of selected bioligands having relevant functionalities for a better understanding of the complex actinide interaction processes in biological systems on a molecular level. To achieve this goal a variety of spectroscopic techniques such as time-resolved laser fluorescence spectroscopy (TRLFS) and/or absorption spectroscopy in the ultraviolet-visible-near infrared (UV-vis-NIR) wavelength range will be applied depending on the nature of the actinide element and the bioligand.
The presentation gives an overview about our ongoing research in this area especially the studies about the complexation of uranium with hydroxamic acids.

This work was funded by the BMWA under contract number 02E9985.

The aim of this work is to compare the operation experiences of large grid connected PV systems in the Megawatt class. Two systems with a total power of more than 2000 kWP are located on the roofs of the new Munich Trade Fair Centre, the two others are situated in West Saxonia near Leipzig (5000 kWp ) and Meerane (1000 kWp). In November 1997 the 1016 kWP solar roof on the new Munich Trade Fair was connected to the grid. Since then, until the end of December 2006, more than 8.900 MWh of solar electricity on the AC-side have been fed into the local 20-kV-medium-voltage-grid. The photovoltaic generator consists of 7812 modules, each one showing a nominal power of 130 WP. System voltages up to 600 V DC are applied. The cables on the DC-side show cross-sections up to 600 mm². One central inverter - three 330-kVA-units in master-slave-operation - transforms the DC energy into AC. The neighbour system, which was installed 5 years after the first PV system, shows a nominal power of 1056 kWP. Although equipped with key components such as modules and inverters from the same manufacturers as the first system, it shows some differences coming from the lessons learned from the first system. After some initial problems (over temperature in the inverter rooms, grid fluctuations causing inverter shut downs and damages, faulty isolation measurements, poor designed string fuses) the systems now operates highly reliable and at superior performance. The Saxon systems were put into operation in 2004. In both plants central inverters are used in master-slave operation. The generators of both systems are mounted on ground of former waste sites. It is the purpose of this work to compare the operation of these PV plants. First, a detailed comparison of the yields will be done. Where do the differences come from? Which are the influences of irradiation, modules and their tilt angle, inverters and their operation mode, maintenance etc? In the next step the operation experiences will be compared. Have there been any severe damages? Are there any lessons learned from initial operation? What about the long term behavior of modules, cables, boxes, inverters? As a conclusion recommendations will be given to improve the long term behavior of large PV systems.

Lasers in speciation analysis are used mainly as excitation source for spectroscopic methods.
Laser-induced methods as Laser-induced photoacoustic spectroscopy (LIPAS), Laser-induced thermal lensing spectroscopy (TLS) and laser-induced fluorescence (luminescence) spectroscopy (LIF) as well as the laser-induced time-resolved fluorescence spectroscopy (TRLIF) are common methods for elemental speciation analysis.
The main advantages of these methods are:
Non-invasive methods
Non-destructive
Low detection limits
Especially the last advantage has great importance in actinide chemistry, due to the radioactivity of these elements.
TLS has no great importance in speciation analysis due to the use of an additional probe laser, which has to be aligned with the pump laser beam.
Due to the destruction of species laser ablation combined with spectroscopic methods will not considered in this chapter
The chapter will review the application of both methods (LIPAS and TRLFS) to determine the elemental speciation mainly of lanthanides and actinides in solution. Examples for speciation analysis in solids will be given, here namely focussed to the assignment of some uranium minerals. In the chapter excitation wavelength (spectra) as well as the emission properties will be reviewed.
Additionally shortly the application of TRLFS to determine organic species will be taken into consideration. However, due to the numerous organic species only a short introduction with few examples can be given.

Uranyl complexes with phenylalanine and the analogous ligand phenylpropionate were investigated in aqueous solution by attenuated total reflection (ATR) Fourier transform infrared (FT-IR) spectroscopy. The assignment of the observed bands to vibrational modes was accomplished using spectra of the pure ligands recorded at different pH values and spectra of the 15N labeled analogous compounds of the amino acid. The results presented in this work provide a detailed description of the binding states of the uranyl complexes in solution. A bidentate binding of the carboxylate group to the actinide ion was observed by the characteristic shifts of the carboxylate modes. From the spectra the presence of the protonated amino group in the actinide complex can be derived. Due to these findings, contributions of the amino group to the binding to the uranyl ion in the amino acid complex can be ruled out.

Objectives:

Oxidative stress with resulting oxidation of low-density lipoproteins (LDL) plays a critical role in the atherogenesis. Since hypertension and dyslipidemia are associated with hormonal dysregulation we examined the effect of oxidatively modified LDL on adrenocortical aldosterone and cortisol synthesis.

Methods:

LDL obtained from healthy volunteers by very fast ultracentrifugation was oxidized in vitro by sodium hypochlorite resulting in molar oxidant to LDL ratios of 272:1 (oxLDL-272, minimally oxidized LDL), 543:1 (oxLDL-543, mildly oxidized LDL), and 2716:1 (oxLDL-2716, heavily oxidized LDL). Human NCI-H295R adrenocortical cells were cultured in DMEM/F12. Cell proteins were separated by SDS-PAGE (10%) and immunoblotted with a polyclonal antibody against pERK 1/2 (1:1000). Aldosterone was measured by RIA and cortisol release was determined by competitive luminometric assay.

Results:

Incubation of adrenocortical cells with 10 to 100µg/mL native LDL (natLDL) or oxidized LDL (oxLDL) for 24h stimulated aldosterone release dose-dependently up to 3-fold. Subsequent stimulation of NCI-H295R cells with angiotensin II induced an additional aldosterone secretion up to 2.9-fold in LDL-pretreated samples. Similar effects were observed for cortisol release. Compared to natLDL, oxLDL induced a smaller hormone release. The ability of oxLDL to induce hormone release decreased with increasing degree of LDL oxidation. NatLDL and oxLDL induced ERK phosphorylation with a maximum at 5min poststimulation. Blocking ERK activation with U0126, the inhibitor of ERK upstream kinase MEK, markedly reduced aldosterone release.

Conclusion:

Oxidative modification of LDL decreases adrenocortical aldosterone and cortisol release. The ERK signalling cascade is critically involved in LDL-induced hormone release.

Im Vortrag werden sowohl die sehr frühen Vorstellungen zur Entstehung des Erdmagnetfeldes als auch die moderne Theorie des Geodynamos vorgestellt. Es folgt eine kritische Diskussion der Dynamoexperimente in Riga, Karlsruhe und Cadarache sowie des PROMISE-Experiments zum Nachweis der Magnetorotationsinstabilität.

Im Vortrag werden sowohl die frühen Vorstellungen zur Entstehung des Erdmagnetfeldes vorgestellt als auch die moderne Dynamotheorie, die ganz massgeblich von Professor Fritz Krause in den 60er Jahren des 20. Jahrhunderts entwickelt worden war. Es folgt eine Diskussion der Experimente zum Nachweis des alpha-Effektes sowie der Dynamoexperimente in Riga, Karlsruhe und Cadarache.

Der Vortrag spannt einen Bogen von den sehr frühen Vorstellungen zur Entstehung des Erdmagnetfeldes
bis hin zur modernen Theorie des Geodynamos. Die Dynamoexperimente in Riga, Karlsruhe und Cadarache sowie das PROMISE-Experiment zum Nachweis der Magnetorotationsinstabilität werden vorgestellt.

I will describe a large source dedicated to research, the Dresden IR & THz free-electron laser, and a compact, scalable emitter, which is a photoconductive antenna with an interdigitated electrode structure.

For the estimation of the expected annual energy yield and the month-by-month check of a PV system’s performance, methods based on irradiance maps published by weather services, both general or dedicated to solar energy application, are in use. Examples for this type of information for Germany are the annual and monthly radiation maps as published by the German Weather Service DWD, the data bank of hourly irradiance data with continuous spatial coverage prepared by the University of Oldenburg, and the radiation data products of the Climate Monitoring Satellite Application Facility CMSAF assembled by a consortium of European Weather Services.
To assess the validity of these data sets for the aforementioned tasks, a case study for a region covering the German federal state of Saxony is performed using data for the year 2005. For this region a set of ground-measured irradiance data from meteorological stations operated by the German Weather Service DWD is available. The comparison of hourly information on radiation sums is on one hand performed by the monthly analysis of the bias and the RMS-error for the Oldenburg data bank of hourly values versus the ground station data. For an additional inter-comparison of the different data sources, the annual maps presenting the estimates of the irradiance sums for 2005 are analyzed, giving information of data accuracy with respect to the spatial structure of the irradiance field.
The assessment of the end use accuracy of the irradiance data is made by investigating a set of monthly energy yield data of grid-connected PV systems. This is done via the estimation of the energy yield using a PV system simulation applying the irradiance data generated at the University of Oldenburg.

Ausgehend vom derzeitigen Nutzungsstand wird das vorhandene Wasserkraftpotenzial in Duetschland bewertet. Eine zusätzliche und maximal mögliche jährliche Stromgewinnung durch Neubau, Erweiterung und Erneuerung von Anlagen, wird von den Ländern derzeit mit etwa 2,4 TWh angenommen. Damit würde sich eine Stromgewinnung von insgesamt gut 22 TWh ergeben.
Die Verfasser halten Zuwächse von etwa 1 TWh pro Jahrzehnt für möglich. Im Jahr 2015 könnte demnach etwa 21 TWh Wasserkraftstrom zur Verfügung stehen. Das setzt auskömmliche wirtschaftliche Rahmenbedingungen für die Anlagenbetreiber voraus. Allerdings steht das Umweltrecht/Wasserhaushaltsgesetz dem Bau von Anlagen an bisher nicht genutzten Standorten schwerwiegend entgegen.
Das gesamte technisch nutzbare Potenzial regenerativer Wasserkräfte beziffern die Verfasser auf etwa 25,5 TWh. Die derzeitige Nutzung dieses Potenzials erfolgt demnach zu etwa 78%.

Die Stromgewinnung aus regenerativer Wasserkraft erfolgt in Deutschland wesentlich aus Laufwasser- und Speicherkraftwerken. Derzeit beträgt deren Leistung etwa 3.960 MW, davon Speicherkraftwerke 350 MW. Die Stromgewinnung aus diesen Anlagen einschließlich der aus natürlichen Zuflüssen in "Pumpspeicher-Kraftwerken mit natürlichem Zufluss" (etwa 0,6 TWh/a) beträgt - Stand 2005 - als Wert des Regelarbeitsvermögens, gleichbedeutend dem Wert der Erzeugung im Regeljahr, etwa 20 TWh. Die Leistung aller Pumpspeicher-Kraftwerke wird bei der Beurteilung der Möglichkeiten der Nutzung regenerativer Wasserkräfte nicht berücksichtigt.
In den zurückliegenden drei Jahrzehnten ist ein durchschnittlicher Anstieg der Stromerzeugung aus regenerativer Wasserkraft von etwa 1 TWh pro Jahrzehnt erkenntlich.

The Greifswald NPP was operated between 1973 and 1990. The units are of Russian WWER-440-230 type. Now trepans from the RPV were gained to investigate the post mortem properties of the material.
The paper describes the results of weld metal originating from the critical weld of the RPV of unit 1. The RPV of this unit was annealed after 14 years of operation, followed by two additional years of operation.
The neutron dosimetry was based on fluence calculations as well as retrospective Nb dosimetry. Both approaches are shortly described. A decrease of 60% through the thickness of the RPV was found by both methods.
The ongoing material test results comprise Charpy-V, tensile and fracture toughness parameters. The main interest is focussed on the comparison of assessment codes applied in Russia and other European countries where WWER-440 reactors are operated. An additional aspect is the comparison of results determined on sub-size Charpy specimens after the annealing procedure. The RPV of Greifswald Unit 1 is uncladded. After the annealing templates of weld metal were taken from the inner RPV wall. The toughness of the weld metal was measured with sub size Charpy specimens.

The document provides an internally compltete set of guidelines for a range of single phase applications of CFD to NRS problems. However, it is not meant to be comprehensive. The document should provide direct guidance on the key considerarions in known single phase applications, as nodalization, model selection and validation, and general directions for resolving renmaining details. It is intended to serve as a template for further applicationb specific BPG documents.

The thermal stability of an antisite pair in cubic silicon carbide (3C-SiC) is studied using ab initio
molecular dynamics within the framework of density functional theory. The lifetime of the antisite
pair configuration is calculated for temperatures between 1800 and 2250 K, and the effective
activation energy for antisite pair recombination is determined to be 2.52 eV. The recombination
energy path and static energy barrier are also calculated using the nudged elastic band method along
with the dimer method to accurately locate the transition states. The consistency of the results
suggests that the antisite pair cannot be correlated with the DI photoluminescence center, as
proposed previously by theoretical interpretations. An extended exchange mechanism is found for
the antisite pair recombination.

We present a brief review of brane-world models — models in which our observable Universe with its standard matter fields is assumed as localized on a domain wall (three-brane) in a higher dimensional surrounding (bulk) spacetime. Models of this type arise naturally in M-theory and have been intensively studied during the last years. We pay particular attention to the covariant projection approach, the Cardassian scenario, to induced gravity models, self-tuning models and the Ekpyrotic scenario. A brief discussion is given of their basic properties and their connection with conventional FRW cosmology.

Single crystalline diamond samples of type IIa were implanted with boron and CVD diamond samples with fluorine or iron ions. Defect rich surface layers extending to a depth of about 300 nm for boron and 1 μm for fluorine and iron were produced by multiple energy implantation. The ion concentrations at the implanted regions were between 30 and 600 ppm for iron and fluorine and 0.5 to 1.5 at.% for boron. In all samples the magnetic properties were dominated by the diamagnetism of pure diamond. The main influence of iron and fluorine implantation on the magnetic properties of diamond is the creation of paramagnetic centres induced by disorder. Whereas diamond implanted with boron at a temperature of 900 °C does not show detectable paramagnetism. After subtraction of the linear background all implanted samples show small ferromagnetic-like loops. Although these signals are clearly above the detection limit and appear to be caused by ferromagnetism, we show that the measured loops are mainly caused by a SQUID artefact. We did not find any evidence for the existence of superconductivity in boron-doped diamond samples prepared under the used conditions.

Concentration variations observed at circular electrodes with their axis parallel to a magnetic and normal to the gravitational field have previously been attributed elsewhere to the concentration gradient force only. The present paper aims to show that Lorentz force driven convection is a more likely explanation.

Magnetic fields influence the motion of liquid metals, but the melt motion modifies magnetic field distributions as well. Eventually, melt motions are able to create a magnetic field, known as the dynamo effect.
We present various laboratory experiments demonstrating this interaction between the flow and magnetic fields.

A non-Hermitian complex symmetric 2×2 matrix toy model is used to study projective Hilbert space structures in the vicinity of exceptional points (EPs). The bi-orthogonal eigenvectors of a diagonalizable matrix are Puiseux-expanded in terms of the root vectors at the EP. It is shown that the apparent contradiction between the two incompatible normalization conditions with finite and singular behavior in the EP-limit can be resolved by projectively extending the original Hilbert space. The complementary normalization conditions correspond then to two different affine charts of this enlarged projective Hilbert space. Geometric phase and phase jump behavior are analyzed and the usefulness of the phase rigidity as measure for the distance to EP configurations is demonstrated. The EP-related quantum brachistochrone problem of PT-symmetrically extended Quantum Mechanics is discussed. Finally, aspects of a smooth globally defined line bundle structure over spectral Riemann surfaces are sketched.

The talk is partially based on arXiv:0704.1291v2 [math-ph] and includes newer findings going beyond this e-print.

Hydrogen behavior in monocrystalline diamonds with different concentrations and types of nitrogen defects was studied using Nuclear Reaction and micro-Elastic Recoil Detection Analyses and Thermal Desorption Spectroscopy. Diamonds were studied in as-received state, after HPHT treatment and after hydrogenation in molecular hydrogen. A considerable amount of hydrogen was found to be bonded to diamond surfaces. Kinetics of surface hydrogen desorption is similar to what was reported for plasma-hydrogenated diamonds. The solubility of hydrogen in type IIa diamonds is very low. The efficiency of hydrogen traps in diamond bulk varies with the dominant type of nitrogen-related defects. The cross-section of traps decreases in row Ib > IaA > IaB diamonds, though binding energy in type IaB crystals may be higher, than in type IaA. Dislocations may promote hydrogen diffusion. A marked dependency of the hydrogen content and diffusivity between diamond growth sectors were observed for some samples. The total hydrogen content is higher in octahedral sectors.

The structural state (i.e., order-disorder) of minerals and other solids analyzed in an electron microprobe or scanning electron microscope may notably affect the back-scattering of incident beam electrons. Structural heterogeneity, as it is commonly observed in radiation-damaged minerals, may thus contribute to signal intensity variations in back-scattered electron (BSE) images. Such structural BSE effects are easily overlooked because they may be insignificant in cases of minerals with high internal Z contrast. Correspondingly, it has generally been assumed that BSE images of single-crystals of minerals are mainly controlled by the sample’s chemical heterogeneity. However, structural heterogeneity cannot be neglected in the discussion of BSE images; this is especially the case if crystals only show minor Z variations.
We show with two examples that radiation damage (i.e., gradual to complete destruction of the crystal lattice) results in a significant increase of the back-scatter coefficient. The phenomenon is assigned to lowered penetration depths of electrons and thus related to electron channelling contrast. The BSE of natural zircon crystals is in most cases predominantly controlled by radiation damage. Annealing studies revealed that after structural reconstitution, the BSE intensity is notably decreased and much more uniform, in spite of the same chemical heterogeneity (especially concentrations of Hf and U) as before the treatment. As an even more unambiguous example we present observations on irradiation-damaged silicon. Damage up to complete amorphization was produced upon implantation of Si ions. Consequently there are no chemical variations and no Z contrast in this case. Examples show that the degree of structural damage needs to be considered in the discussion and interpretation of BSE images of radiation-damaged minerals.

We have studied irradiation damage in a single-crystal silicon wafer prepared parallel to (100) by micro-Raman spectroscopy. Surficial structural damage in areas ~150 µm in size was produced by irradiation with a microbeam loaded with 600 keV Si⁺ ions at a 3MV Tandetron accelerator, Rossendorf (GRAMBOLE et al., 2007). Several implantations were done with a uniform fluence of 5 × 10¹⁴ cm^-2, however, at different temperatures to produce areas with different degrees of damage. Full amorphisation was reached at implantation temperatures below 140 °C (NASDALA et al., 2007). Monte Carlo simulations using the SRIM code (ZIEGLER et al., 1985) predict that trajectory lengths of implanted ions are below 1 µm. This still exceeds the low penetration depth of light in silicon and, with that, the depth probed by Raman spectroscopy. Spectra obtained from partially amorphised areas virtually consist of an overlap of the two Raman spectra of amorphous and crystalline silicon, i.e., the LO=TO band of crystalline silicon at ~ 521 cm^-1 shows only minor band broadening and shift when compared to the spectrum of the unirradiated host wafer. This indicates that the majority of the structural damage is located in amorphous clusters whereas the remnant crystalline silicon fraction shows only low levels of point defects as caused by atomic displacements.

References
GRAMBOLE, D., HERRMANN, F., HEERA, V. & MEIJER, J. (2007): Nucl. Instr. Meth. Phys. Res. B (in press).
NASDALA, L., GRAMBOLE, D., KRONZ, A. & TRULLENQUE, G. (2007): Am. Mineral. (accepted).
ZIEGLER, J. F., BIERSACK, J. P. & LITTMARK. U. (1985): The Stopping and Range of Ions in Solids.
Pergamon, New York.

The deformation of Ge-nancrystals embedded in SiO2 during high energy ion irradiation has been investigated. For this purpose 200 nm thermally grown SiO2 was covered with a 5 nm Ge layer and a 100 nm SiO2 top layer by sputter deposition. Subsequent thermal annealing at 950 °C for 300s transformed the embedded continuous Ge layer through spinodal dewetting into Ge nanocrystals with a mean diameter of 20 nm. Afterwards, the Ge nanocrystals buried in SiO2 were irradiated at room temperature with 38 MeV I7+ ions in the dose range (1-4)x1015 cm-2. The ion current density was 40 nA/cm2. Cross-section TEM investigation of the irradiated samples showed that under given irradiation conditions the spherical Ge nanocrystal were shaped mainly into oblate-like Ge particles, which are in the amorphous state. As a result of the investigations we conclude that Ge nanoparticles embedded in SiO2 show the same form transformation behaviour under ion irradiation as irradiated amorphous silica colloides, namely, an expansion perpendicular to the ion beam direction and a contraction parallel to the ion beam direction. Mechanisms of the observed ion beam induced anisotropic deformation of Ge nanoparticles are discussed.

In the introduction of the talk the Rossendorf FIB tool and the application possibilities in nanofabrication will be described.
The main part of the contribution is focused on cobalt FIB ion beam synthesis of CoSi2 nanowires with feature dimensions of about 20-50 nm in diameter and wire lengths of some µm. Using the Rossendorf FIB equipped with a CANION 31Mplus FIB column (Orsay Physics) a focusing of the Co++ ion beam down to a spot diameter of 30-50 nm was achieved. The ion energy was chosen to be 60 keV corresponding to a mean ion penetration depth of Rp = 53 nm. For the study of the conventional ion beam synthesis of CoSi2 nanowires (phase separation through precipitation and wire ripening during thermal treatment) and their decay into chains of nanoparticles due to nanowire instabilities the samples were implanted with high doses (1x1016-2x1017 cm-2) and at 420 °C sample temperature. Additionally, the scan direction of the FIB relative to the crystal directions was varied (normal FIB scan-direction was parallel to the [110]-direction on the Si surface). Small misalignment of the FIB trace relative to the [110] orientations leads to the decay of the CoSi2 nanowires into chains of more or less prolonged CoSi2 nanoparticles. Samples implanted at lower ion doses (1014-1016 cm-2) and at room temperature were used to investigate the influence of locally FIB induced irradiation defects on the CoSi2 nanowire growth. In this case, nanowires were again formed during thermal treatment by reacting of cobalt from a thin evaporated layer on the sample back side with defects induced by Co+ ion implantation with the FIB. The nanowires here are self-aligned along the in-plane [110] silicon crystal directions in (001)- and (111)-Si. In contrast to conventional ion beam synthesis of CoSi2 nanowires by high dose FIB implantation along a narrow trace defect-induced and self-aligned nanowire growth seems to be more stable.
Finally, in the outlook some examples of FIB based fabrication of nanostructures for different applications (e.g. 3D-nanostructures) will be discussed.

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Fluorescent Pseudomonas species secrete pyoverdin-type siderophores with a high potential to dissolve, bind, and thus transport uranium in the environment. The formation of complexes of UO22+ with pyoverdins released by the groundwater bacterium Pseudomonas fluorescens (CCUG 32456) isolated at a depth of 70 m depth in the Äspö Hard Rock Laboratory, Sweden, was studied. Mass spectrometry indicated that the cells produce a pyoverdinmixture with four main components: pyoverdin with a succinamide side chain, pyoverdin with a succinic acid side chain, ferribactin with a succinamide side chain, and ferribactin with a glutamic acid side chain. Three pK values could be determined from the pH-dependent changes in the absorption spectra of the pyoverdin mixture: log ß012 = 22.67 ± 0.15 (pK1 = 4.40), log ß013 = 29.15 ± 0.05 (pK2 = 6.48), and log ß014 = 33.55 ± 0.05 (pK3 = 10.47). The fluorescence properties of the pyoverdin mixture were pH dependent. The emission maximum changed from 448 nm at pH = 2.1 to 466 nm in the pH3.88.9 range. At pH > 4 a mono-exponential fluorescence decay dominates with a decay time of 5865 ± 640 ps. A drastic change in the intrinsic fluorescence properties, e.g., static fluorescence quenching, occurred due to the complex formation with UO22+. Species containing UO22+ of the type MpLqHr were identified from the dependencies observed in the ultraviolet visible and time-resolved laser-induced fluorescence spectroscopy spectra at pyoverdin concentrations below 0.1 mM. The following average formation constants were determined: log β112 = 30.00 ± 0.64 and log β111 = 26.00 ± 0.85 at ionic strength I = 0.1 M (NaClO4). The determined stability constants can be used directly in safety calculations of the mobilizing effect of released pyoverdins on uranium, in uranium-contaminated environments such as mine waste disposal sites.

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In this work, we investigate the strain and defect state of silicon implanted with nitrogen by plasma immersion ion implantation, with doses between 4.5 1016 and 8.7 1016 cm 2. For this purpose, we have used Auger electron spectroscopy, x-ray reflectivity, and high-resolution x-ray diffraction. Auger spectra showed that nitrogen concentration profiles broaden and shift deeper into the substrate as the dose increases. High oxygen concentration in the first 20 nm suggested the presence of an amorphous oxide layer at the sample surface, which was confirmed by x-ray reflectivity measurements. Reciprocal space maps revealed a tensile strain perpendicular to the surface, while no in-plane strain was detected. Since no significant diffuse scattering was found, randomly distributed point defects must be predominant in the strained region compared to large displacement field defects such as clusters and dislocations. 2 scans around (004) Bragg reflection were fitted using dynamical theory of x-ray diffraction. The strain profiles obtained from the best fits correlated well with nitrogen concentration depth profiles, signaling interstitial nitrogen as the main source of strain.

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A pure magnetic patterning by means of ion irradiation which relies on a local modification of the magnetic anisotropy of a magnetic multilayer structure has been first demonstrated in 1998. Since then also other magnetic properties like the interlayer exchange coupling, the exchange bias effect, the magnetic damping behavior and the saturation magnetization to name a few have also been demonstrated to be affected by ion irradiation or ion implantation. Consequently, all these effects can be used if combined with a masking technique or employing direct focused ion beam writing for a magnetic patterning and thus an imprinting of an artificial magnetic domain structure, which subsequently modifies the integral magnetization reversal behavior or the magnetization dynamics of the film investigated. The present review will summarize how ion irradiation and implantation can affect the magnetic properties by means of structural modifications. The main part will cover the present status with respect to the pure magnetic patterning of micro- and nanostructures.

In-situ x-ray diffraction (XRD) was employed to study the effect of the deliberate change of the ratio Ti/Ni during the deposition of Ni-Ti films. Thus, graded films were deposited exhibiting distinctive composition and crystalline structure along the growth direction. The as-sputtered films were ex-situ characterized by Auger Electron Spectroscopy (AES), Cross-sectional Transmission Electron Microscopy (XTEM), and Electrical Resistivity (ER) measurements (during thermal cycling). In this paper results are presented concerning a film with a Ti-rich composition in the central part and near-equiatomic composition in the extremities, following 4 distinct deposition periods (different Ti target powers). During the initial deposition step (near-equiatomic composition) the Ni-Ti B2 phase starts by stacking onto (h00) planes on the naturally oxidized Si(100) substrate due to the presence of the native Si oxide (2-3 nm). The increase of the power of the Ti target in the second and third steps induced the precipitation of Ti₂Ni. When stopping the Ti co-sputtering, Ti₂Ni “dissolves” and, thus, plays the role of a reservoir for the formation of B2 phase now preferentially stacking onto (110) with the system approaching again the equiatomic composition. The ex-situ study of the interface’s morphology has shown the presence of NiSi₂ silicides (A-NiSi₂ and B-NiSi₂), Ti₄Ni₄Si₇, Ti₂Ni and a non-identified phase constituted by Ni, Ti and Si, most likely amorphous. During thermal cycling, electrical resistivity measurements revealed phase transitions associated with the B2, R-phase and B19’ phases. This type of studies allow the identification of intermediate states during deposition and annealing, and the correlation with the final structure of the film, being useful for the optimisation of the deposition parameters in order to fabricate films with a two-way reversible actuation.

This paper describes the analytical work done by modelling and evaluating a thermal shock in a WWER-440 reactor pressure vessel due to an emergency case. An axial oriented semielliptical underclad/surface crack is assumed to be located in the core weld line. Threedimensional finite element models are used to compute the global transient temperature and stress-strain fields. By using a three-dimensional submodel, which includes the crack, the local crack stress-strain field is obtained. With a subsequent postprocessing using the j-integral technique the stress intensity factors KI along the crack front are obtained. The results for the underclad and surface crack are provided and compared, together with a critical discussion of the VERLIFE code.

The synthesis and application of 4-[¹⁸F]fluorobenzaldehyde-O-(2-{2-[2-(pyrol-2,5-dion-1-yl)ethoxy]ethoxy}ethyl)oxim ([¹⁸F]FBOM) as a novel prosthetic group for ¹⁸F labelling of SH-group bearing biomacromolecules is described.
The aminooxy-functionalised labelling precursor for the radiosynthesis of [¹⁸F]FBOM was synthesised in a four-step synthesis sequence with a total yield of 14%. [¹⁸F]FBOM could be obtained in a condensation reaction between the labelling precursor and [¹⁸F]fluorobenzaldehyde through formation of an oxim. The radiochemical yield ranged between 14 and 19% (decay-corrected). In a typical experiment, starting from 6.5 GBq of [¹⁸F]fluoride 730MBq of [¹⁸F]FBOM could be obtained within 80 minutes (including HPLC purification). The specific activity was determined to be 51 GBq/µmol. The lipophilicity of [¹⁸F]FBOM was determined to be logP = 0.84. The use of [¹⁸F]FBOM as SH-reactive group prosthetic group was demonstrated by the reaction with glutathion, low densitiy lipoproteins (LDL) and modified neurotensin derivatives. [¹⁸F]FBOM can easily be synthesised, and [¹⁸F]FBOM represents an interesting novel prosthetic group for the labelling of SH-group containing biomacromolecules with ¹⁸F under mild conditions.

Development of novel materials and structures for drug delivery systems is currently a very active field of research. Recently the drug-eluting stents were designed to deliver a drug locally from a surface layer to reduce restenosis. Noble gas ion implantation into metals can be used to form nanoscale cavities or sponge like structures. These nanostructures have unique characteristics which offer potential for medical applications such as metal-based drug-eluting stents.
Investigations of the influence of implantation parameters on the surface morphology and cavity characteristics (e.g. size, distribution, and degree of interconnection) have to date been rather limited.
In the present work we have studied the formation of nanostructures on stainless steel surfaces by plasma immersion ion implantation (PIII) using different gases (helium or argon), ion energies (between 5 – 35 keV) and ion fluences (> 1e18 at/cm2). The surface topography and structure of the modified materials have been analyzed by scanning electron microscopy and atomic force microscopy. The phase and element compositions have been examined by grazing incidence X-ray diffraction analysis (GIXRD), X-ray photoelectron spectroscopy, and elastic recoil detection analysis.
Varying the ion energy, fluences, and substrate temperature has been found to produce either void or sponge like structures on the nano- (~10 nm) to micro-scale (~1 µm). Apart from the austenite iron peaks, the GIXRD patterns of the implanted samples display weak peaks of ferrite (bcc iron) as well as oxide phases.

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The present study describes an approach for the scale-bridging modeling of ferroic materials as functional elements in micro- and nanoelectronic devices. Ferroic materials are characterized by temperature-dependent complex ordering phenomena of the internal magnetic, electronic, and structural degrees of freedom with several involved length and time scales. Hence, the modelling of such compounds is not straightforward, but relies on a combination of electronic-structure-based methods like ab-initio and density-functional schemes with classical particle-based approaches given by Monte-Carlo simulations with Ising, lattice-gas, or Heisenberg Hamiltonians, which incorporate material-specific parameters both from theory and experiment. The interplay of those methods is demonstrated for device concepts based on electroceramic materials like ferroelectrics and multiferroics, whose functionality is closely related with their propensity towards structural and magnetic polymorphism.

In the present case, such scale-bridging techniques are employed to aid the development of an organic field effect transistor on a ferroelectric substrate generated by the self-assembly of field-sensitive molecules on the surfaces of ferroic oxides. Electronic-structure-based methods yield the microscopic properties of the oxide, the surface, the molecules, and the respective interactions. They are combined with classical particle-based methods on a scale-hopping basis. This combination allows to study the morphology evolution during the self-assembly of larger adsorbate arrays on the (defective) oxide surface and to investigate the interplay of low-temperature magnetic ordering phenomena with the ferroelectric functionality at higher temperatures in multiferroic oxides like the hexagonal manganites. The combination of density-functional data with classical continuum modelling also yielded a model Hamiltonian for the quick determination of the properties of a gate structure based on bio-functionalized carbon nanotubes.

Metallschmelzen in industriellen Prozessen unterliegen in der Regel verschiedenen Arten von Strömungen. Diese Strömungen haben einen entscheidenden Einfluss auf den Wärme- und Stofftransport, und damit zumeist auch auf die Effizienz des Prozesses oder die Qualität des Endproduktes. Zukünftige Anstrengungen im Hinblick auf eine Optimierung derartiger Anlagen oder Technologien müssen aus diesem Grund eine wirksame Strömungskontrolle berücksichtigen.
Elektromagnetische Felder eröffnen aufgrund des kontaktlosen Zugangs und der einfachen Regelbarkeit eine attraktive Möglichkeit zur Strömungskontrolle. Eine gezielte Einflussnahme setzt aber ein umfangreiches Wissen über das Strömungsfeld und die Wechselwirkung mit den elektromagnetischen Kraftfeldern voraus. Neben numerischen Simulationen sind Modellexperimente mit sogenannten „kalten“ Schmelzen, d.h. mit Flüssigmetallen mit einem Schmelzpunkt < 300°C, ein unverzichtbares Mittel, um die Strömungsvorgänge besser zu verstehen und geeignete Maßnahmen zur Strömungskontrolle zu ergreifen.
Im Vortrag werden an ausgewählten Beispielen mit Bezügen zu industriellen Anwendungen die Möglichkeiten einer elektromagnetischen Strömungskontrolle erläutert. In diesem Zusammenhang wird auf die wechselseitige Abhängigkeit von numerischen Berechnungen und Modellexperimenten mit „kalten“ Modellschmelzen hingewiesen. Es werden neue Entwicklungen auf dem Gebiet Messtechnik für Flüssigmetalle vorgestellt, die einen wirkungsvollen Einsatz der Modellexperimente erst ermöglichen.

For bare metal stents the in-stent restenosis was a serious problem for about 25 - 35% of the patients and this spurred the medical device companies to come up with a solution. Drug-eluting stents are designed to deliver a drug locally from a polymeric coating to reduce tissue in growth and reduce restenosis to less then 8% of the treated patients. Development of novel materials and structures for drug delivery systems is still very actual topic.
In the present work plasma immersion ion implantation (PIII) using helium or argon plasmas has been employed for the nanostructures formation on metal surfaces with a view to their applications for metal-based drug-eluting stents. A multi-layer pore system on stent surfaces in the range from nanoscale to microscale sizes is desired for drug loading and controlling the rate of elution of therapeutic agents.
Recently we have investigate the formation of nanostructures on stainless steel surfaces by PIII at different gases (He, Ar), ion energies (between 5 – 35 keV) and ion fluences (> 1e18 at/cm2). The surface topography and structure of the implanted materials were analysed by scanning electron microscopy and atomic force microscopy. The phase and element compositions were examined by grazing incidence X-ray diffraction analysis, auger electron spectroscopy, and elastic recoil detection analysis.
Variety of nanostructures as well as their characteristics (e.g. size, distribution, degree of interconnection) can be controlled by varying the implantation parameters. The results of these studies have demonstrated that PIII is a promising technique for the surface topography modification of stainless steel for cardiovascular application.

New oxorhenium complexes with 3-methylazapentane-1,5-dithiolate (SNMeS) and thiol functionalized monodentate tetrahydroquinolyl and tetrahydroisoquinolyl derivatives have been synthesized by simultaneous reaction of [PPh₃]₂[Re(O)Cl₃] with tridentate HSNMeSH and the corresponding N-heterocycle containing thiol. The characterization of complexes involved elemental analysis, IR, ¹H and ¹³C NMR spectroscopy and X-ray crystallographic analysis. The nature of the heterocycle in monodentate ligand, even situated at the distance of two methylene group length, has been found to have a significant influence on the molecular conformation. Metal complexes were found to be active in psychotropic in vivo and cytotoxicity in vitro screening.

Als neuartige Markierungsmethode in der ¹⁸F-Chemie wurde die Suzuki-Kupplung von 4-[¹⁸F]Fluoriodbenzol mit verschiedenen Organoborverbindungen entwickelt. Anhand der Modellreaktion von p-Tolylboronsäure mit 4-[¹⁸F]Fluoriodbenzol wurde der Einfluss verschiedener Palladiumkomplexe, Basen und Lösungsmittel auf die Reaktion untersucht. Mittels der so optimierten Reaktionsbedingungen wurden verschiedene funktionelle Gruppen tragende ¹⁸F-markierte Biphenyle synthetisiert. Die Reaktion zeigte eine hohe Kompatibilität gegenüber vielen funktionellen Gruppen. Die radiochemischen Ausbeuten erreichten bis zu 95% (bezogen auf 4-[¹⁸F]Fluoriodbenzol) innerhalb von 5 Minuten.

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System L amino acid transport is increased in various types of cancer. The new positron emission tomography (PET) tracer 3-O-methyl-6-¹⁸F-fluoro-L-DOPA (OMFD) is mainly accumulated via the system L and could serve to image cancer in vivo. However the differentiation between tumor and inflammatory reaction in tissues is often complicated. Therefore, we studied in vitro the accumulation mechanisms of OMFD in model systems of human tumors and inflammation, respectively. It is suggested that the high uptake of amino acid tracers is primarily caused by the higher transporter expression in tumors when compared to other tissues, e.g., inflammatory cells.
As previously shown, the subtype L-type amino acid transporter 1 (LAT1) is playing a key role of L amino acid transport in tumor cells. The functional LAT1 is a heterodimeric complex comprising a single membrane-spanning catalytic light chain protein (hLAT1) and the heavy chain of 4F2 antigen (h4F2hc), which are covalently linked via a disulfide bond.
For molecular characterization of L-type amino acid transporters focusing on the hLAT1-h4F2hc subtype quantitative RT-PCR was performed using the two different human tumor cell lines FaDu (squamous cell carcinoma) and HT-29 (colorectal adenocarcinoma). In comparison, phorbol ester stimulated THP-1 cells (a human monocyte/macrophage cell line) representing inflammatory cells were used. In vitro uptake assays were performed with HT-29, FaDu and THP-1 cells with OMFD under physiological amino acid concentrations.
OMFD demonstrated a saturable and sodium- and energy-independent accumulation in vitro in the different tumor cell lines, suggesting its uptake to be mediated mainly by sodium-independent LAT1. However, OMFD showed a significantly higher uptake in tumor cells when compared to inflammatory cells.
Our data demonstrate that OMFD could be a promising PET tracer for imaging of specific amino acid transport via LAT1 in tumors and, furthermore, for possible differentiation of tumorigenic from inflammatory processes. In conclusion, the identification and characterization of tumor specific amino acid transporters like LAT1 will be a helpful tool for diagnosis and therapy monitoring.

Accumulation of excess abdominal visceral fat has been shown to play a crucial role in the development of cardiovascular disease and obesity-related disorders like diabetes mellitus, hyperlipidemia, and hypertension.
In the last years, rodent models have gained an important role in the investigation of adipose tissue (AT) biology and disorder. In this line, non-invasive differentiation and characterization of various AT deposits in the living animal is a current challenge. MRS at high magnetic field strength is a potential tool to learn more about the pathophysiological role of lipids in vivo.

The aim of the present study was to derive the spin-spin relaxation times T2 of 9 different proton resonances occurring in lipid spectra in vivo. With these values the correction factors M₀/M_TE (with the magnetization M_TE = M₀ x exp(-TE/T2), TE = echo time) for the peak integrals of the 9 different peaks can be calculated for specific TE. These correction factors can then be used to correct in vivo PRESS spectra to derive the true values for saturation and unsaturation of the triacylglycerols in lipids.

Localized MR spectra were generated in male Wistar rats with a 7 Tesla small animal scanner with a 30 cm bore (BioSpec 70/30, Bruker BioSpin MRI GmbH, Ettlingen, Germany) equipped with a mini imaging gradient coil system (gradient strength 400 mT/m) and a ¹H transmit-receive quatrature coil with 72 mm inner diameter.

We used a localized PRESS sequence with a repetition time of 1.8 s and a series of different TE (TE = 12 – 50 ms) to calculate T2. We determined T2 for 9 different peaks (in the range from 0.9 – 5.35 ppm) by fitting the monoexponential model function M_TE to the measured signal intensities at the different TE.

As results we got values for the spin-spin relaxation times T2 in the range from 24.7 ms to 57.4 ms. These values result in correction factors M₀/M_TE in the range from 2.25 to 1.42 for the 9 different peak integrals arising in lipid spectra derived with localized PRESS spectroscopy with TE = 20 ms.

We have measured 9 different T2-relaxation times of the protons of lipids in rats in vivo. These values have been used to correct localized PRESS spectra measured in vivo to obtain the true values for saturation and unsaturation of the fatty acids of AT deposits in experimental animal models. Prospectively, this method is also applicable in human studies using clinical MRS.

There is increasing interest in targeting peptide receptors and their ligands for tumor diagnostics and therapy since there is evidence that some of these receptors are overexpressed in tumors compared to normal tissues. Among these receptors playing a key role in tumor progression is the neurotensin receptor (NTR) family. The present study investigated both mRNA and protein expression of NTR in human adeno- (HT-29) and squamous (FaDu) cell carcinoma cell lines and in corresponding mouse xenograft models. mRNA analysis revealed a higher expression of NTR3 compared to NTR1 and NTR2. Protein analysis revealed enhanced signals for NTR1 followed by NTR2 both in tumor cells and xenografts. In contrast, no NTR3 protein expression was detected. Autoradiography with [³H]neurotensin showed higher receptor binding activity on HT-29 compared to FaDu.

Ziel/Aim:

Spiegelbildliche Oligonukleotide sind chemisch synthetisierte Desoxyribonukleinsäuren bzw. Ribonukleinsäuren, mit einer nicht natürlich vorkommenden L-Konfiguration der Ribose. Diese Modifizierung der Nukleinsäurestruktur führt zu einer besonders hohen Stabilität gegenüber dem enzymatischen Abbau in biologischen Medien (1). Zur Markierung von L Oligonukleotiden mit dem Positronen emittierenden Radiometall Y-86-Yttrium (t1/2 = 14,7 h) muss das Molekül mit einem Chelator funktionalisiert sein. Der Einfluss unterschiedlicher Y-86-Chelatstrukturen auf die pharmakologischen Eigenschaften von Y-86-Chelat-L Nukleinsäuren wurde am Beispiel eines L RNA 12mers 1 (Sequenz: 5’ Aminohexyl UGA CUG ACU GAC-3’, MW 3975) untersucht. Dazu wurde die L RNA 1 über zwei verschiedene Chelatoren mit 86Y(III) radiomarkiert und die Bioverteilung in Ratten untersucht.

Methodik/Methods:

Die Modifizierung des L RNA 12mers 1 mit DOTA erfolgte zum einen über einen reaktiven N Succinimidylester 2 – zu DOTA L RNA 3, zum anderen über ein Isothiocyanatderivat 4 zu DOTA bz L RNA 5. Die über eine Amidbindung 3 und eine Thioharnstoffbindung 5 DOTA-modifizierten L RNAs wurden anschließend mit Y-86 in radiochemischen Ausbeuten von 76 % bzw. 85 % radiomarkiert (2). Die Identität der Verbindungen 3a und 5a wurde mit geträgerten Y-86/Y-Markierungen und Massenspektrometrie nachgewiesen (3a m/z: 4447,0 [M+H]+; 5a m/z: 4611,3 [M+H]+). Die Bioverteilungsstudien wurden für jede Verbindung mit acht männlichen Wistar Ratten durchgeführt (3a: 240 ± 15 g Gewicht; 5a: 150 ± 7.5 g Gewicht).

Ergebnisse/Results:

Die Untersuchung der Bioverteilung der beiden Y-86-markierten L RNAs 3a und 5a zeigte für beide Substanzen eine hohe renale Ausscheidung, wobei aber eine unterschiedliche Retention der radiomarkierten Verbindungen in Nieren und Nebennieren beobachtet wurde. Der Standardized uptake value (SUV) ereichte für 3a in den Nieren einen Wert von 10 ± 2,0 nach 5 min und 6,1 ± 0,53 nach 60 min. Für die Verbindung 5a stieg der SUV in den Nieren von 13 ± 1,6 nach 5 min auf 14 ± 1,1 nach 60 min. Bemerkenswert hohe SUVs (3,5 ± 0,48 und 3,2 ± 0,33) wurden in den Nebennieren nach 60 min für beide Verbindungen beobachtet. Der SUV anderer Organe lag in dieser Untersuchung für 3a und 5a nach 60 min unter 1,0. Nach 12 h Inkubation in Rattenblut bei 37 °C konnte keine Zersetzung von 5a über HPLC-Analyse beobachtet werden.

Schlussfolgerungen/Conclusions:

Die unterschiedliche chemische Anbindung der Y-86-DOTA Chelate an die L-RNA 1 deutet neben den strukturellen Unterschieden der Y-86-Komplexe in 3a und 5a auf eine starke Beeinflussung der Bioverteilung des L Oligonukleotides hin. Die hohe metabolische Stabilität der L RNA verdeutlicht das Potential von L Oligonukleotiden als molekulare Sonden für die PET.

Literatur/References:

(1) Nat Biotechnol 14 (1996), 1112-5
(2) LDDD 3(5) (2006), 330-5

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There is evidence that intrauterine growth restriction (IUGR) is associated with altered dopaminergic function in the immature brain. Compelling evidence exists that in the newborn brain, specific structures are especially vulnerable to O₂ deprivation. The dopaminergic system is shown to be sensitive to O₂ deprivation in the immature brain. However, the respective enzyme activities have not been measured in the living neonatal brain after IUGR under hypercapnic hypoxia (H/H). Therefore, ¹⁸F-labeled 6-fluoro-L-3,4-dihydroxyphenylalanine (FDOPA) together with positron emission tomography was used to estimate the aromatic amino acid decarboxylase activity of the brain of seven normal weight (body weight 2078 +/- 434g) and seven IUGR newborn piglets (body weight 893 +/- 109 g). Two positron emission tomography scans were performed in each piglet. All animals underwent a period of normoxia and moderate H/H. Simultaneously, cerebral blood flow was measured with colored microspheres and cerebral metabolic rate of O₂ was determined. In newborn normal-weight piglets, the rate constant for FDOPA decarboxylation was markedly increased in mesostriatal regions during H/H, whereas brain oxidative metabolism remained unaltered. In contrast, moderate H/H induced in IUGR piglets a marked reduction of clearance rates for FDOPA metabolites (p < 0.05), which was accompanied by a tendency of lowering the rate constant for FDOPA conversion. Furthermore, IUGR piglets maintained cerebral O₂ uptake in the early period of H/H, but during the late period of H/H, a significantly reduced cerebral metabolic rate of O₂ occurred (p < 0.05). Thus, IUGR is accompanied by a missing activation of dopaminergic activity and attenuated brain oxidative metabolism during moderate H/H. This may indicate endogenous brain protection against O₂ deprivation.

Emerging experimental data indicate that the pulmonary blood flow remained directed toward the dorsal regions after turning animals from a supine to a prone position. This finding supported the hypothesis that the distribution of perfusion throughout the lung was not primarily dictated by the gravity but by the fractal behavior of the pulmonary vasculature. However there are only limited data about the spatial distribution of lung perfusion in rats in prone and supine position. The purpose of the study was to quantify the relative perfusion (Q) distribution in rat lungs in both positions using [⁶⁸Ga]Ga-DOTA-microspheres with small-animal PET, -CT, and -MRI to obtain reference data for further investigations on injured rat lungs.

Methods:

Regional pulmonary perfusion was investigated after injection of [⁶⁸Ga]Ga-DOTA-microsphers (20 micrometer diameter) of albumin in both prone and supine positions in normal breathing rats, anesthetized with desflurane. The heart rate was continuously recorded. The right femoral artery and vein were cannulated, arterial blood pressure, blood gases, and pH were measured. The microspheres were intravenously applied. Emission data were collected for 30 min. Before and after the PET measurement the animals were studied with CT to investigate the lungs and to calculate their volumes. Randomly selected animals were studied also with smallanimal MRI. The [⁶⁸Ga]-activity 3D distributions were analyzed from the coregistered volume data reconstructed with 3D OSEM MAP algorithm (resolution in the center of field of view 1.8 mm).

Results:

There were no significant differences of mean Q in the ventral and dorsal elements of normal rat lungs.

Conclusion:

The body position (prone and supine) of normal breathing rats does not influence the mean Q btained with small-animal PET and the lung volumes measured with small-animal CT. The histogram of the regional blood flow in supine position reflects a more heterogeneous blood flow distribution.

[¹⁸F]Fluoroacetate ([¹⁸F]FAC) is discussed as an addition to the well-established PET radiotracer [¹¹C]acetate ([¹¹C]ACE) for the diagnosis and treatment monitoring of low [¹⁸F]FDG accumulating cancer entities. The purpose of this study was to establish a reproducible method of [¹⁸F]FAC synthesis, and to assess the biodistribution and kinetics in rats and tumor bearing mice to evaluate the potential of [¹⁸F]FAC for tumor imaging, and to gain information about the [¹⁸F]FAC accumulation mechanism in human squamous cell carcinoma (FaDu) and adenocarcinoma (HT-29) xenografts.

Results and Discussion:

The optimized radiosynthesis of n.c.a. sodium [¹⁸F]FAC was performed in two steps: (1) Incorporation of fluorine into (methanesulfonyloxy)-acetic acid tert.-butyl ester as the superior labeling precursor in acetonitrile followed by (2) acidic hydrolysis of the resulting [¹⁸F]fluoroacetic acid tert.-butyl ester to afford [¹⁸F]FAC. Several consecutive purification gave sodium [¹⁸F]FAC in very reproducible radiochemical yields in high radiochemical purity (>95%) within 50 min. Arterial blood samples were analyzed and no metabolites of [¹⁸F]FAC were observed up to 60 min p.i. [¹⁸F]FAC was readily accumulated in FaDu and HT-29 tumors (tumor/muscle 1.8+/-0.2 mean+/-SEM, n=6) as shown in small-animal PET studies. [¹⁸F]FAC and [¹¹C]ACE could clearly delineate the tumors and reached a tumor to muscle ratio up to two. Both agents showed a similar biodistribution. The differences were limited to the higher activity accumulation of the [¹¹C]ACE in pancreas, spleen, kidneys, and the slower blood clearance of [¹⁸F]FAC. In some animals dehalogenation was observed.

Conclusion:

The remotely-controlled two step/one pot synthesis of [¹⁸F]FAC represents a robust and reproducible procedure. The differences of biodistribution between [¹⁸F]FAC and [¹¹C]ACE in rats and tumor bearing mice are relatively small. The absence of metabolites in the arterial blood plasma allows using the plasma activity for quantitative kinetic studies without further metabolite analyses.
(Partly supported by the EU project BioCare No. 505785)

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Dedicated small-animal tomographs are nowadays available for the three major modalities PET, MRI, and CT. Utilization of all three techniques for true multimodality imaging requires the solution of several technical problems including reproducible animal positioning, overcoming file format incompatibilities and coregistration of the different image volumes, preferably without application of markers.
Methods: We developed an isolation chamber and adapter for imaging devices, enabling physiologic animal control, reproducible positioning, pathogen barrier, anesthesia, probe application and the use of catheter systems. Furthermore, we developed the necessary software for file format conversions and coregistration of the image volumes.
The basis is the animal holder system, consisting of the fixing adapters and the animal chamber that could be positioned in our three tomographs (microPET P4, SkyScan 1178, and BioScan 70/30 USR).
The animal holder system is temperature-controled. It allows gas anesthesia of the animals and could be used as a closed system. The bed is air heated.
In the different modalities the data are stored in different formats using different image matrix and pixel sizes. In order to analyze the data they are converted to a common data format (Siemens ECAT7) and the pixel sizes are adjusted. Residual differences in the relative positioning of the animals are corrected via coregistration. We implemented a mutual information algorithm using the conjugate gradient maximization method.
Validation studies showed a good coregistration of the images from PET, CT, and MRI. In longitudinal [18F]FDG studies the coregistration allowed to compare the tumor SUVmax data between different studies.
Conclusion: Multimodality imaging of small animal PET, -CT, and MRI allows the direct comparison and quantification of regional PET, CT, and MRI/MRS parameters enabling the characterization of functional and anatomical changes during tumor development and therapy.
The project was partly supported by the EU project BioCare No. 505785.

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Dendritische Liganden eröffnen einen neuen Zugang zu Radiometallpharmaka und zwar insbesondere dann, wenn es gelingt, radioaktive Metallnuklide im Kern topologisch so zu verkapseln, dass sie unter physiologischen Bedingungen kinetisch und thermodynamisch stabil fixiert sind. Eine Modifizierung der Dendrimeroberfläche erlaubt dann die Einstellung definierter Löslichkeits- und selektiver Bindungseigenschaften.
Wir berichten über die Synthese von sternförmigen Liganden mit peripheren Peptideinheiten sowie einem metallbindenden Zentrum. Als Peptid wird das biologisch aktive Neurotensinfragment NT-(8-13) eingeführt.[1] Dieses bindet an den Neurotensin-Rezeptor 1 (NTR-1), der insbesondere an duktalen exokrinen Pankreaskarzinomen stark überexprimiert ist.[2] Als Kernbaustein wird Cyclam (1,4,8,11-Tetraazacyclotetradecan) ausgewählt, das zur stabilen Bindung von diagnostisch und therapeutisch relevanten Radiometallnukliden, wie 64/67Cu, 99mTc und 186/188Re, geeignet ist. Derartige radioaktiv markierte Peptidkonjugate können Bedeutung in der Tumordiagnostik und Tumortherapie erlangen.
Es werden Ligand-Rezeptor-Bindungs-studien an NTR-1-überexprimierenden humanen Adenokarzinom(HT-29)-Zellen präsentiert. Erste Ergebnisse weisen auf eine sehr hohe Affinität des Tetramers I sowie des entsprechenden Kupfer(II)-Komplexes zum Neurotensin-Rezeptor 1 im pico-molaren Bereich hin und ist damit vergleichbar zu einem Tetramer anderer Struktur {3]. Es werden sich Untersuchungen zur Markierung mit 64Cu anschließen, um Aussagen zur metabolischen Stabilität dieses Liganden sowie zur Bioverteilung in vivo zu erhalten.

[1] B.M. Tyler-McMahon et al., Regul. Pept. 2000, 93, 125-136
[2] J. C. Reubi, Endocr. Rev. 2003, 24, 389-427.
[3] C. Hultsch et al., Bioorg. Med. Chem. 2006, 14, 5913-5920

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The reactive gas incorporation into a Ti sputter target has been investigated using laterally resolving ion beam analysis during DC magnetron deposition of TiN in an Ar/N2 atmosphere. At sufficiently low reactive gas flow, the nitrogen incorporation exhibits a pronounced lateral variation, with a lower areal density in the target race track compared to the target centre and edge. The findings are reproduced by model calculations. In the race track, the balance of reactive gas injection and sputter erosion is shifted towards erosion. The injection of nitrogen is dominated by combined molecular adsorption and recoil implantation versus direct ion implantation.

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Hypoxia causes upregulation of vascular endothelial growth factor (VEGF) which is a key regulator in tumor angiogenesis and essential for the proliferation of endothelial cells. Endothelial cells have been described to accumulate radiotracers like ¹⁸F-FDG. However, the contribution of radiotracer uptake by endothelial cells to uptake measured in tumors by positron emission tomography (PET) is still unclear. In this study ¹⁸F-FDG and ¹⁸F-FMISO radiotracer uptake in various tumor and primary endothelial cells cultured at hypoxic conditions was investigated. Experimental hypoxia was confirmed by significant upregulation of VEGF mRNA. In comparison to normoxic conditions, cellular uptake of ¹⁸F-FDG was significantly increased at hypoxic conditions in two of the tumor and all endothelial cells, whereas ¹⁸F-FMISO uptake was only enhanced in tumor cell lines HT-29 and MCF-7. Our data showed a marked influence of experimental hypoxia on the metabolism and gene expression of tumor and endothelial cells in vitro. This indicates an important contribution of endothelial cells to ¹⁸F-FDG radiotracer uptake in tumors and for the visualization of tumors by means of PET.

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Mass-shift of the ρ and ω meson and their mixing in nuclear matter

Tantalum oxide was deposited by radical enhanced atomic layer deposition using tantalum ethoxide and oxygen radicals. The radicals were produced by dissociating oxygen gas in a remote microwave plasma discharge. Argon was used as the carrier and purge gas. The films were deposited at 150 and 250°C on glass, silicon, and platinum substrates. Growth rate of the films was 0.19 nm per cycle with a 0.6 s pulse length for tantalum ethoxide and 3 s for oxygen radicals. The films were amorphous according to X-ray diffraction. The densities measured by X-ray reflectivity were between 7.1 and 7.6 g/cm3 for films grown both at 150 and 250°C. The dielectric constants were 28 and 36 for films grown on platinum electrodes at 150 and 250 °C, respectively. The leakage current densities at 1 MV/cm electric field were less than 1 x 10-8 A/cm2 for both deposition temperatures. The effect of water as an additional oxidant was studied at 250 °C. The water was supplied as a separate pulse either right before or after the tantalum ethoxide pulse.