Publications Repository - Helmholtz-Zentrum Dresden-Rossendorf

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

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

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

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

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

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

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

Objectives: Lysyl oxidase (LOX, EC 1.4.3.13) and its family members LOX-like 1-4 are copper-dependent matrixmodifying enzymes [1]. The expression of LOX is elevated in many human cancers, including breast cancer and correlates with tissue hypoxia. The enzyme plays a critical role in breast cancer metastasis [2]. The goal of the current study was to target LOX with fluorescent and radiolabeled oligopeptides to visualize LOX in preclinical models of breast cancer.
Methods: mRNA expression of all 5 LOX family members was analyzed by gene expression microarray analysis on samples from 176 breast cancer patients. The peptidic substrate GGGDPKGGGGG was selected to target LOX [3]. The peptide was labeled with either FITC for confocal microscopy experiments or with the positron emitter fluorine-18 for molecular imaging in vivo using positron emission tomography (PET) (Figure 1). The preclinical breast cancer models utilized were the murine breast cancer cell line EMT-6 and xenografts of MCF-7 and MDAMB-231.
Results: Immunofluorescence with a LOX-specific antibody confirmed that LOX protein expression is enhanced in hypoxic EMT-6 cells. FITC-labeled oligopeptide binds to several cell compartments of EMT6 cells under hypoxic conditions. After injection of ¹⁸F-labeled oligopeptide, radioactivity uptake was visible in all three breast cancer models in vivo with SUV_5min values of: 0.70±0.07 (n=3) in EMT-6, 0.57±0.01 (n=3) in MCF-7 and 0.68 (n=2) in MDA-MB-231. The following continuous washout of radioactivity led to SUV_60min values of: 0.18±0.03 (n=3) in EMT-6, 0.14±0.02 (n=3) in MCF-7 and 0.13 (n=2) in MDA-MB-231. Tumor uptake was reduced by pre-dosing with the irreversible LOX inhibitor BAPN 4 h and 24 h prior to injection of the radiotracer.
Conclusions: These data support further investigations towards the development of LOX-binding peptides as molecular probes for imaging of LOX expression in breast cancer.
Acknowledgements: The access to the Alberta Cancer Foundation-supported CBCF Tumor Bank is well appreciated.
References
[1] Payne SL, et al (2007) J. Cell. Biochem.101, 1338-54.
[2] Erler JT, et al (2006) Nature 440, 1222-6.
[3] Nagan N and Kagan HM (1994) J. Biol. Chem. 269, 22366-71.

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

Objectives: Ephrins and its Eph receptors are dysregulated in several human tumor entities including malignant melanoma. In this regard, the EphB4/ephrinB2 system seems to play a major role in melanoma angiogenesis [1].
Thus,we developed a fluorine-18-containing peptide [2] extracellularly binding to EphB4 and a small ¹⁸F-labeled molecule which intracellularly binds to the EphB4 kinase domain with high affinity [3] in the past. However, the results showed low binding/uptake in A375^EphB4 melanoma cells in vitro and in vivo. Therfore, a “second generation” lead structure based on bis-anilinopyrimidines (IC₅₀ = 1.3 nM) [4] was chosen for novel EphB4-targeted radioligands.
Methods: The lead compound is based on two substructures (part A and B) which were synthesized independently. Two positions of the original inhibitor for the best position of the radiolabel were figured out using docking studies. Based on this, references 2 and 4 as well as precursors 1 and 3 were obtained. In order to introduce [¹⁸F]fluoride by ring opening, precursors 1 and 3 were prepared as azetidinium mesylates and lead to high RCYs.
The radiolabeling was done in anhydrous acetonitrile for 30 min at 100°C. Afterwards, the EOE protecting group, which is mandatory for the successful introduction, was cleaved under acidic conditions. The subsequent purification should be easy done by cartridges due to the ionic nature of the precursors [5].
Results: Interestingly, radiofluorination of the first precursor 1 did not lead to the desired tracer [¹⁸F]2. The delocalization of the positive charge over both aromatic rings might be the reason for this result. On the other hand, radiofluorination of diazaspirononane precursor 3 was successful and gives the desired [¹⁸F]4 in a radiochemical yield of 34% (n.d.c.) and high purity (>95%).
Conclusions: [¹⁸F]4 as novel potential EphB4-targeted radioligand based on the bis-anilinopyrimidine scaffold has been successfully synthesized and radiolabeled. Ongoing work is focused on the alternative preparation of radiotracer [¹⁸F]2 and on the biological evaluation of both radiotracers to be a suitable target for diagnostic applications.
References
[1] Mosch, B. et al. (2010), J. Oncol., DOI: 10.1155/2010/135285,
[2] Pretze, M., et al. (2013) ChemMedChem, 8, 935–945,
[3] Mamat, C., et al. (2012) ChemMedChem, 7, 1991–3002,
[4] Bardelle, C., et al. (2010) Bioorg. Med. Chem. Lett., 20, 6242–6245,
[5] Grosse-Gehling, P., et al. (2011) Radiochim. Acta 99, 365–373

Objectives: The overexpression of various Eph receptors in tumors provokes the recent interest in highly affine inhibitors as attractive leads for the development of new targeted radioligands to image cancer [1]. Selective Ephtyrosine
kinase inhibitors based on the purinedione skeleton have been explored in the past as potential probes for imaging of EphB4 [2] and a SNEW peptide for EphB2 [3]. However up to now, there is still no optimal radiotracer
available. Herein, we report the synthesis, radiofluorination and biological evaluation of two novel purinedione derivatives as potential multi Eph inhibitor radioligands.
Methods: Based on known positions for affinity-related interactions of the lead structure with the receptor [4] two positions are favorable for the labeling with fluorine-18. Two precursors 1 and 3 as well as their reference compounds 2 and 4 were prepared. The radiolabeling was done in dry ACN at 100°C for 30 min. First cell association studies were performed using various Eph expressing melanoma cells (A375^wt/mock, A375^EphB4,
A375^EphB6, A375^EphB4) and Eph-negative controls (HL-60).
Results: After labeling, both tracers [¹⁸F]2 and [¹⁸F]4 were obtained in 10 – 15 % RCY (n.d.c.) after HPLC separation (RCP: > 95%). Cell experiments in vitro revealed a substantial cell association of both [¹⁸F]2 and [¹⁸F]4 ranging from 40 to 50 %ID/mg protein at 120 min in all cell lines used. The lack of any significant difference between wild type, recombinant and control cells is indicative for cell association of, as expected, low selectivity, but also of low specificity. The latter is consistent with the observation that preincubation with 100 μM of nonradioactive compound did not result in substantial inhibition of cell association.
Conclusions: [¹⁸F]2 and [¹⁸F]4 were synthesized successfully and first in vitro experiments were accomplished showing substantial cell association for both tracers in various melanoma cells. However, the cell experiments revealed data on specificity of purinedione derivatives that are contradictory to data from literature [4]. These observations will be elucidated in ongoing studies.
Acknowledgements
References
[1] Mosch, B. et al. (2010), J. Oncol., DOI: 10.1155/2010/135285;
[2] Mamat, C. et al. (2012), ChemMedChem, 7, 1991–2003;
[3] Pretze, M., et al. (2013) ChemMedChem, 8, 935–945; [4] Lafleur, K. et al.
(2009) J. Med. Chem., 52, 6433–6446.

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

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

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

Objectives: The decay properties of both nuclear isomers, like convenient half life ^197mHg (T_1/2 = 23.8 h, Eγ 133.98 keV, 33.5%) and 197Hg (T1/2 = 64.14 h, Eγ 77.4 keV, 18.7%), low energy gamma radiations for imaging and numerous Auger- and conversion electrons useful for therapy combined with unique chemical and physical properties of mercury and its compounds represent the motivation for this project. The no carrier added (NCA) radionuclide ^197(m)Hg is accessible in sufficient quantity and quality for radiopharmaceutical research by irradiation of gold with protons using a cyclotron [1]. As the following logical step after examination of the production feasibility, the search for a suitable labeling tool was intensified.
Methods: Three different approaches to prepare a stable labeling unit at NCA level with ^197(m)Hg were studied. The reactivity of the mercury(II) ions towards sulfur containing ligands (a), solvomercuration of alkenes (b) and electrophilic aromatic substitution (c) were investigated in this context. Prepared characteristic representatives of all three groups are shown in Figure 1.
Results: For all studied reactions the desired ^197(m)Hg labeled compounds were detected. The mercury thiolate complexe (a) and the product of solvomercuration (b) show low stability in the presence of competing thiol ligands and therefore the suitability for radiopharmaceutical applications is not given. In contrast, diphenylmercury (c) as the simplest representative for symmetric diarylmercury compounds shows high stability against competing
ligands.
Conclusions: As a basis for the development of a convenient labeling method different kinds of mercury compounds were prepared and characterized at NCA level. After nuclide production this was the required succeeding part of the evaluation of the cyclotron-based NCA ^197(m)Hg regarding their suitability for diagnostics and therapy of tumors. First promising results of investigations concerning the development of mercury compounds stable in vivo will be reported.

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

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

Objectives: High metabolic stability, low immunogenicity and negligible specificity for naturally binding partners are predominant characteristics of L-configured oligonucleotides. These advantages predestine this substance class
for its use in pretargeted radioimmunotherapy as in vivo recognition system between a tumor-specific antibody and a radiolabeled chelate. We evaluated this new pretargeting system consisting of ⁶⁴Cu labeled NOTA-L-DNA-10kDa-PEG and c-L-DNA modified Cetuximab (C225) in vitro and in vivo.
Methods: C225 was functionalized with NOTA, maleimide moieties and thiol-bearing c-L-DNA. Competition studies were carried out against ⁶⁴Cu labeled standard NOTA₃-C225 in FaDu and A431-cell lysates. In vitro pretargeting studies were done in intact FaDu and A431 cells. PET and biodistribution studies were performed both in FaDu and A431 tumor bearing mice by intravenous injection of 4 nmol NOTA₃-C225-(c-L-DNA)_1,5 and 1 nmol [⁶⁴Cu]Cu-NOTA-L-DNA-10kDa-PEG 24 h later.
Results: We synthesized two Cetuximab derivatives with 1.5 and respective 5 c-L-DNA molecules per antibody. Competition assays showed that affinities are not affected as a result of conjugation with NOTA and c-L-DNA.
PET studies injecting only [⁶⁴Cu]Cu-NOTA₃-C225-(c-L-DNA)_1.5 revealed that a pretargeting interval of 24 h is the best compromise between tumor accumulation, blood background as well as liver uptake. Biodistribution in pretargeted A431 tumor mice is characterized by decreased tumor uptake (see figure). Internalization of antibody within waiting period is the obvious reason and could be confirmed by cellular uptake studies. After 24 h over 2/3 of surface bound antibody was internalized.
Conclusions: The present pretargeting concept shows high potential for further preclinical studies. Use of a noninternalizing antibody is necessary to enhance both tumor uptake and tumor to background ratios.

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

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

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

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

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

References

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

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

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

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

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

Using a generic model of a pressurized water reactor, we have defined a set of severe accident-like reactor states depicting various degrees of coolant level decrease and core degradation. We then computed the gamma radiation distribution which would occur outside the reactor pressure vessel in each of the previously defined states using stationary Monte Carlo simulations. This is done in an effort to understand if it is possible to detect the occurrence of certain phenomena from outside the RPV and to eventually develop a system for state detection.

This paper investigates the feasibility of a once-through thorium fuel cycle for the novel reactor-design concept named the pressure tube light water reactor with variable moderator control (PTVM LWR). The PTVM LWR operates in a “breed & burn” mode, which makes it an attractive system for utilizing thorium fuel in a once-through mode. The “breed & burn” mode can emphasize the in-situ generation as well as incineration of 233U, which are the basic foundations of the once-through thorium fuel cycle. The PTVM LWR concept makes use of a seed-blanket geometry, whereby the core is divided into separated regions of thorium-based fuel channel assemblies (blanket) and low-enriched uranium (LEU) based fuel channel assemblies (seed). A novel fuel in-core management scheme based on two separate fuel flow routes (i.e., seed route and blanket route) is proposed and analyzed. Neutronic performance analysis indicates that the proposed novel fuel in-core management scheme has the potential to utilize both LEU- and thorium- based fuel in an efficient manner. The once-through thorium cycle, presented and discussed in this paper, provide interesting research leads and can serve as a bridge between current LEU-based fuel cycles and a thorium fuel cycle based on recycling of 233U.

Repair of DNA breaks by single-strand annealing (SSA) is a major mechanism for the maintenance of genomic integrity. SSA is promoted by proteins (SSAPs) like eukaryotic RAD52 and lambda phage Redß that use a short single-stranded region to find sequence identity and initiate homologous recombination. However, it is unclear how SSAPs detect homology and catalyze annealing. Using single-molecule experiments, we provide evidence that homology is recognized by Redß monomers that weakly hold single DNA strands together. Once annealing begins, dimerization of Redß clamps the double-stranded region and nucleates nucleoprotein filament growth. In this manner, DNA clamping ensures and secures a successful search for DNA sequence homology. The clamp is characterized by a structural change of Redß and a remarkable stability against force up to 200 pN. Our findings not only present a detailed explanation for SSAP action but also identify the DNA clamp as a very stable, non-covalent, DNA-protein interaction.

Numerical simulations of a liquid metal flow and corresponding velocity measurements using a dual plane, two-component ultrasound array Doppler velocimeter were carried out in a rectangular cavity with an aspect ratio of unity. The liquid metal (GaInSn) was suddenly exposed to an azimuthal body force generated by a rotating magnetic field (RMF). The measurements show a similar flow structure compared to the case of the RMF-driven flow in a cylindrical container, in particular the so-called initial adjustment phase followed by an inertial phase which is dominated by inertial oscillations of the secondary flow. The transition from the steady double vortex structure of the secondary flow to an oscillating regime was detected at a magnetic Taylor number of T a > 3 × 10^5.

This paper summarises the proceedings and discussions at the third annual workshop held in Tubingen, Germany, dedicated to the advancement of the technical, scientific and clinical applications of combined PET/MRI systems in humans. Two days of basic scientific and technical instructions with "hands-on" tutorials were followed by 3 days of invited presentations from active researchers in this and associated fields augmented by round-table discussions and dialogue boards with specific themes. These included the use of PET/MRI in paediatric oncology and in adult neurology, oncology and cardiology, the development of multi-parametric analyses, and efforts to standardise PET/MRI examinations to allow pooling of data for evaluating the technology. A poll taken on the final day demonstrated that over 50 % of those present felt that while PET/MRI technology underwent an inevitable slump after its much-anticipated initial launch, it was now entering a period of slow, progressive development, with new key applications emerging. In particular, researchers are focusing on exploiting the complementary nature of the physiological (PET) and biochemical (MRI/MRS) data within the morphological framework (MRI) that these devices can provide. Much of the discussion was summed up on the final day when one speaker commented on the state of PET/MRI: "the real work has just started".

Methods: Fifteen patients (f, 6; m, 9; median age, 59 years; range, 32 to 72 years) with 28 liver metastases were included retrospectively. FDG-PET/CT imaging (median activity, 237 MBq; range, 231 to 252 MBq; median uptake, 61 min; range, 55 to 67 min) was performed on a Siemens Biograph mCT 64 followed by image reconstruction using 3D-ordered subset expectation maximization (3D-OSEM) or 3D-OSEM with PSF modeling - both with and without TOF information. Differences in SUVmax were analyzed using the Friedman test and Wilcoxon test for paired non-parametric data. The correlation of inter-method differences with the lesions’ TBR was studied using Spearman’s rank correlation coefficient (rho). Differences between lesions with low (<4.8) and high (>4.8) TBR were analyzed using the Mann-Whitney U test (TBR measured with 3D-OSEM; binarized by its median).
Background: The maximum standardized uptake value (SUVmax) is a common clinical parameter for quantification in F18-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT), but it is influenced by image reconstruction. The aim of this study was to analyze the association of SUVmax deviations related to point spread function (PSF) and time-of-flight (TOF) reconstruction with tumor-to-background ratios (TBR) in colorectal liver metastases (CRLM).
Results: There was a significant correlation of the lesions’ TBR with relative SUVmax differences related to PSF (PSF + TOF vs. 3D-OSEM + TOF, rho = 0.61; PSF vs. 3D-OSEM, rho = 0.52) or TOF (PSF + TOF vs. PSF, rho = −0.58; 3D-OSEM + TOF vs. 3D-OSEM, rho = −0.61). Accordingly, PSF algorithms only showed higher SUVmax than non-PSF algorithms in lesions with a high TBR (median differences at low/high TBR, +2.6%/+9.1% [PSF + TOF vs. 3D-OSEM + TOF]; +0.7%/+6.4% [PSF vs. 3D-OSEM]). TOF integration also led to higher SUVmax but mainly at low TBR (low/high TBR, +10.4%/+1.8% [PSF + TOF vs. PSF]; +8.6%/−0.1% [3D-OSEM + TOF vs. 3D-OSEM]).
Conclusions: Both PSF and TOF reconstruction resulted in a substantial alteration of SUVmax in CRLM. TOF provided the highest SUVmax increase in low-contrast lesions while - vice versa - PSF showed the most relevant increase in high-contrast lesions. Thus, one should be aware that quantitative analyses of lesions with varying TBR, e.g., in radiotherapy or follow-up studies, may be mainly affected by either PSF or TOF reconstruction, respectively.

The DREsden Accelerator Mass Spectrometry facility (DREAMS) is in routine operation since autumn 2011 [1, Figure 1].

Figure 1. DREAMS incl. planned Time-of-Flight (ToF) and SIMS connection for TEAMS/Super-SIMS.

Here, long-lived so-called cosmogenic radionuclides such as ¹⁰Be, ²⁶Al, ³⁶Cl, ⁴¹Ca and ¹²⁹I can be quantified at the 10^-14 (radionuclide/stable nuclide) level. Applications are performed within interdisciplinary cooperations with users from universities and research centres. Hence, research is focussed on topics from e.g. astrophysics [2], climate, cosmochemistry [3,4], geomorphology [5-7], hydrogeology and nuclear decommissioning [8].

To keep DREAMS a state-of-the-art facility in-house research such as the development of a low cross-contamination and memory-effect ion source [9], a high-current ion source and expansion to stable nuclides with (Super-Secondary Ion Mass Spectrometry (SIMS)) or without spatial resolution (Trace Element AMS = TEAMS) is performed. This kind of technology development is partially based on our own research interests, but also driven by the steadily increasing demands of our users.

Quality assurance incl. the use of primary or traceable standards and dedicated AMS chemistry labs accessible for users make DREAMS especially attractive for experienced cosmogenic nuclide researchers but even more for newcomers. Thus, training on the job e.g. in the chemistry labs is an essential tool of our “mission” to widen the fields of AMS applications and user communities.

Ackn.: Operators, S. Akhmadaliev, S. Enamorado Baez & A. Renno for help; DFG/DAAD for funding.

[1] S. Akhmadaliev et al., Nucl. Instr. Meth. Phys. Res. B 2013, 294, 5. [2] J. Feige et al., EPJ Web of Conferences 2013, 63, 03003. [3] U. Ott et al., Meteorit. Planet. Sci. 2014, 49, 1365. [4] J. Llorca, et al., Meteorit. Planet. Sci. 2013, 48, 493. [5] M.C. Fuchs et al., Earth Surf. Dynam. Discuss. 2015, 3, 83. [6] K. Hahne et al., System Erde. GFZ-Journal 2013, 3 (2), 44. [7] R. Zech et al., Palaeogeography, Palaeoclimatology, Palaeoecology 2013, 369, 253. [8] D. Hampe et al., J. Radioanal. Nucl. Chem. 2013, 296, 617. [9] S. Pavetich et al., Nucl. Instr. Meth. Phys. Res. B 2014, 329, 22.

The DREsden Accelerator Mass Spectrometry facility (DREAMS) is in routine operation since autumn 2011 [1, Figure 1].

Figure 1. DREAMS incl. planned Time-of-Flight (ToF) and SIMS connection for TEAMS/Super-SIMS.

Here, long-lived so-called cosmogenic radionuclides such as ¹⁰Be, ²⁶Al, ³⁶Cl, ⁴¹Ca and ¹²⁹I can be quantified at the 10^-14 (radionuclide/stable nuclide) level. Applications are performed within interdisciplinary cooperations with users from universities and research centres. Hence, research is focussed on topics from e.g. astrophysics [2], climate, cosmochemistry [3,4], geomorphology [5-7], hydrogeology and nuclear decommissioning [8].

To keep DREAMS a state-of-the-art facility in-house research such as the development of a low cross-contamination and memory-effect ion source [9], a high-current ion source and expansion to stable nuclides with (Super-Secondary Ion Mass Spectrometry (SIMS)) or without spatial resolution (Trace Element AMS = TEAMS) is performed. This kind of technology development is partially based on our own research interests, but also driven by the steadily increasing demands of our users.

Quality assurance incl. the use of primary or traceable standards and dedicated AMS chemistry labs accessible for users make DREAMS especially attractive for experienced cosmogenic nuclide researchers but even more for newcomers. Thus, training on the job e.g. in the chemistry labs is an essential tool of our “mission” to widen the fields of AMS applications and user communities.

Ackn.: Operators, S. Akhmadaliev, S. Enamorado Baez & A. Renno for help; DFG/DAAD for funding.

[1] S. Akhmadaliev et al., Nucl. Instr. Meth. Phys. Res. B 2013, 294, 5. [2] J. Feige et al., EPJ Web of Conferences 2013, 63, 03003. [3] U. Ott et al., Meteorit. Planet. Sci. 2014, 49, 1365. [4] J. Llorca, et al., Meteorit. Planet. Sci. 2013, 48, 493. [5] M.C. Fuchs et al., Earth Surf. Dynam. Discuss. 2015, 3, 83. [6] K. Hahne et al., System Erde. GFZ-Journal 2013, 3 (2), 44. [7] R. Zech et al., Palaeogeography, Palaeoclimatology, Palaeoecology 2013, 369, 253. [8] D. Hampe et al., J. Radioanal. Nucl. Chem. 2013, 296, 617. [9] S. Pavetich et al., Nucl. Instr. Meth. Phys. Res. B 2014, 329, 22.

For heat and mass transfer processes in two-phase flow systems an understanding of the conditions leading to entrainment of a liquid surface film by a gas flow is of considerable practical importance.

Employing the linear sigma model, the effective masses of quasi-particle excitations are found to exhibit significant variations within the phase diagram, which has a critical point at non-zero chemical potential, where a first-order phase transition sets in.
Soft-photon emission rates in lowest order display, for selected channels, a sensible dependence on the effective masses of the involved excitations and let us argue that they could map out the phase diagram.

Because of the ability to work in opaque fluids and to deliver complete velocity profiles in real time the Ultrasound Doppler Velocimetry (UDV) can be considered as an attractive technique to obtain velocity data from liquid metal flows. This paper presents several examples for UDV measurements in liquid metal two-phase flows. The measuring technique shows the capability to detect both the bubble and the liquid velocity simultaneously. The probability density function of the recorded velocity data was examined to the signals arising from the liquid and the gaseous phase. Multiple reflections of the ultrasonic beam occurring between the gas bubbles at higher gas flow rates may complicate a precise discrimination between both phase velocities. An iterative threshold method was applied to obtain accurate velocity profiles by identifying and excluding artifacts in the signal. Nevertheless, the signal quality deteriorates significantly with increasing gas flow rate.
Bubble-driven flows play a prominent role in many industrial facilities and processes. In metallurgical applications gas bubbles are injected into furnaces, ladles or similar melt containing transfer vessels in order to homogenize the melt and their physical and chemical properties. On the other hand, uncontrolled entrainment of cover gas into the liquid metal in the casting process causes a worsening of the mechanical properties of the casting products. In the field of nuclear engineering, gas entrainment into the coolant is one of the essential safety issues in the design of innovative liquid metal-cooled fast reactors. Model experiments using low-melting metal alloys can be considered as an effective tool to gain a better understanding of the complex character of liquid metal two-phase flows. In this paper, we present exemplary measurements performed at various experimental configurations concerning the behaviour of single bubbles and bubble plumes under the influence of AC and DC magnetic fields and a visualization of gas entrainment at the free surface of a liquid metal.

Entrainment of cover gas into the liquid metal coolant is one of the principal safety issues in the design of innovative liquid metal-cooled fast reactors. We present generic experimental studies of this phenomenon in low-melting metals. Ultrasonic and X-ray diagnostic tools were considered for a visualization of gas entrainment at the free surface of the melt. Laboratory experiments were conducted using the eutectic alloy GaInSn, which is liquid at room temperature. Vortex-activated entrainment of air at the free surface of a rotating flow was revealed by ultrasonic techniques. X-ray radioscopy was used to visualize the behavior of argon bubbles inside a slit geometry. The measurements reveal distinct differences between water and GaInSn, especially with respect to the process of bubble formation and the coalescence and breakup of bubbles. Our results emphasize the importance of liquid metal experiments which are able to provide a suitable data base for numerical code validation.

Herein we report the synthesis of fluorinated inhibitors of phosphodiesterase 10A (PDE10A) which can be used potentially as lead structure for the development of a F-18 labeled PDE10A imaging agent for positron emission tomography. Fluorine is located in the ortho-postion of pyridine to enable the introduction of F-18 into an appropriate labeling precursor by nucleophilic aromatic substitution for a possible radiosynthesis. 2-Fluoropyridines are introduced by a Suzuki coupling at different positions of the molecule. The reference compounds, 1,8-dipyridylimidazo[1,5-a]quinoxalines and 1-pyridylimidazo[1,5-a]quinoxalines, show inhibitory potencies down to the subnanomolar range and selectivity factors greater than 50. 1,8-Dipyridylimidazo[1,5-a]quinoxalines are more potent inhibitors than 1-pyridylimidazo[1,5-a]quinoxalines. Using 2-fluoro-3-pyridyl as residue gave the most potent inhibitors 11A (IC₅₀ = 0.12 nM), 11B (IC₅₀ = 0.048 nM) and 23 (IC₅₀ = 0.037 nM).

Regarding the deposit of radioactive waste in a deep geological formation, salt rock is one possibility in Germany. The archaeon Halobacterium noricense was chosen to study the interactions between a halophilic microorganism and uranium. Biosorption experiments showed that this microorganism is able to bind uranium effectively and that the presence of uranium provokes a reaction from the cells. By the use of spectroscopic methods a coordination of uranium to cellular carboxyl and phosphate groups was proven.

The atomic layer deposition (ALD) of stoichiometric SrTiO3 as well as layers with either Sr or Ti excess from the commercial precursors Bis(tri-isopropylcyclopentadienyl)-strontium Sr((Pr3Cp)-Pr-i)(2),

Tetrakis-(dimethylamido)titanium(IV) TiN(CH3)(2) and H2O on a commercial ALD system is demonstrated. The influence of the stoichiometry on the optical layer properties was investigated.

Spectroscopic ellipsometry shows that all SrxTiyOz layers are transparent up to the optical gap energy, which amounts to 3.87 eV for stoichiometric SrTiO3. A direct correlation between the Sr content, optical properties, layer density and the growth per cycle value was determined. X-ray photoelectron spectroscopy after Ar ion cluster sputtering indicates that the layers are free of carbon. After ex situ annealing under atmospheric conditions we observed a change in microstructure from amorphous to polycrystalline starting at 545 degrees C by atomic force microscopy and grazing incidence X-ray diffraction.
Electrical I-V measurements show very small leakage currents confirming the insulating character of the SrxTiyOz layers.

We have employed quantitative automated mineralogy using a mineral liberation analyser to assess samples of gabbroic dykes of the Lusatian Block. These mafic dykes contain platinum-group elements - locally enriched with Cu and Ni sulphides up to subeconomic concentrations of 0.4 ppm (4PGE+Au). In this study we analysed about 100 polished thin sections and polished blocks with both a mapping method and a search mode for bright phases in BSE images (sparse phase liberation analysis).
The aim of the study was to obtain information regarding the occurrence of platinum-group minerals (PGM) and their relationship to base metal sulphides (BMS). Mineral groups found by sparse phase liberation analysis include several PGE-bearing and non-PGE-bearing tellurides, Pd bismuthides and antimonides, Pt arsenide as well as native gold and native bismuth. Mineral grain sizes of these trace minerals are in general below 10 mu m. The results of the mineral association evaluation show that pyrrhotite is the main host for tellurides, native metals and platinum-group minerals. However, several other minerals show also a high degree of association with the PGM, most notably Ni-Co sulpharsenides, chalcopyrite, hydrothermal feldspar and chlorite. By using quantitative automated mineralogy we can clearly demonstrate that low-alteration, low-BMS gabbroic dyke samples contain no or only small amounts of PGM, whereas intense-alteration, high-BMS gabbroic dyke samples have elevated PGM contents. Furthermore, we show that for PGE concentrations <1 ppm MLA analyses of just one polished thin section per sample show limitations with respect to the representativity of results for calculated element concentration, due to a combination of different limiting factors. Mineral liberation analysis reveals that PGM are much more widespread and abundant in the studied area compared to the results of previous careful light microscopic investigations and single grain electron probe microanalysis that resulted only in very few and isolated PGM grains to be identified.

We use cyclotron resonance THz-spectroscopy in pulsed magnetic fields up to 63 T to measure the electron effective mass in Si-doped GaAsN semiconductor alloys with nitrogen content up to 0.2%. This technique directly probes the transport properties of the N-modified conduction band, particularly the electron effective mass, which has been discussed controversially in the experimental and theoretical literature. We report a slight increase of the electron effective mass and nonparabolicity with Ncontent for different photon energies in agreement with the two-level band anticrossing model calculations. Furthermore, we show a pronounced electron mobility drop with increasing N-content.

Measuring the liquid velocity and turbulence parameters in multiphase flows is a challenging task. In general, measurements based on optical methods are hindered by the presence of the gas phase. In the present work, it is shown that this leads to a sampling bias. Here, particle image velocimetry (PIV) is used to measure the liquid velocity and turbulence in a bubble column for different gas volume flow rates. As a result, passing bubbles lead to a significant sampling bias, which is evaluated by the mean liquid velocity and Reynolds stress tensor components. To overcome the sampling bias a window averaging procedure that waits a time depending on the locally distributed velocity information (hold processor) is derived. The procedure is demonstrated for an analytical test function. The PIV results obtained with the hold processor are reasonable for all values. By using the new procedure, reliable liquid velocity measurements in bubbly flows, which are vitally needed for CFD validation and modeling, are possible. In addition, the findings are general and can be applied to other flow situations and measuring techniques.

Combining semiconducting and ferromagnetic properties, dilute ferromagnetic semiconductors (DFS) have been under intensive investigation for more than two decades. Mn doped III–V compound semiconductors have been regarded as the prototype of DFS from both experimental and theoretic investigations. The magnetic properties of III–V:Mn can be controlled by manipulating free carriers via electrical gating, as for controlling the electrical properties in conventional semiconductors. However, the preparation of DFS presents a big challenge due to the low solubility of Mn in semiconductors. Ion implantation followed by pulsed laser melting (II-PLM) provides an alternative to the widely used low-temperature molecular beam epitaxy (LT-MBE) approach. Both ion implantation and pulsed-laser melting occur far enough from thermodynamic equilibrium conditions. Ion implantation introduces enough dopants and the subsequent laser pulse deposit energy in the near-surface region to drive a rapid liquid-phase epitaxial growth. Here, we review the experimental study on preparation of III–V:Mn using II-PLM. We start with a brief description about the development of DFS and the physics behind II-PLM. Then we show that ferromagnetic GaMnAs and InMnAs films can be prepared by II-PLM and they show the same characteristics of LT-MBE grown samples. Going beyond LT-MBE, II-PLM is successful to bring two new members, GaMnP and InMnP, into the family of III–V:Mn DFS. Both GaMnP and InMnP films show the signature of DFS and an insulating behavior. At the end, we summarize the work done for Ge:Mn and Si:Mn using II-PLM and present suggestions for future investigations. The remarkable advantage of II-PLM approach is its versatility. In general, II-PLM can be utilized to prepare supersaturated alloys with mismatched components.

Thermohydraulische Phänomene im Kühlkreislauf von Kernkraftwerken sind ein wichtiges Teilgebiet der Reaktorsicherheitsforschung. Relevante Fragestellungen umfassen die Strömung und Wärmeübertragung von den Brennstäben im Reaktorkern bis zum Dampferzeuger im Reaktornormalbetrieb, Probleme der Vermischung, Strömung und Wärmeabfuhr bei Auslegungsstörfällen und schweren Störfällen bis hin zur sicheren Funktion passiver Nachzerfallswärmeabfuhrmechanismen. Während heute die zugrundeliegenden Strömungs- und Wärmetransportprozesse oft mit Systemcodes berechnet werden, geht ein Trend hin zur Anwendung geometrieunabhängiger, dreidimensional auflösender CFD-Verfahren. Besondere Schwierigkeiten bereiten hierbei die Maßstabübertragung vom Laborexperiment an Einzelkomponenten hin zur Gesamtanlage sowie die Komplexität von Zweiphasenströmungen, die insbesondere im Störfall vorherrschend sind. Die Entwicklung von Strömungsberechnungsverfahren ebenso wie das grundlegende Verständnis von Strömungsphänomenen erfordern Experimente mit hohem Detaillierungsgrad, die aber gleichzeitig wegen der Übertragbarkeit bei anlagenrelevanten Prozessparametern und Stoffwerten führen sind. Insbesondere Experimente zu Zweiphasenströmungen erfordern darüber hinaus eine Instrumentierung, die Strömungsstrukturen mit möglichst hoher räumlicher und zeitlicher Auflösung wiedergibt. Hierzu eignen sich insbesondere bildgebende Messverfahren. Der Vortrag gibt eine Einführung in wichtige, in diesem Bereich verwendete Mess- und Bildgebungsverfahren und demonstriert deren Anwendung im Kontext der Reaktorsicherheitsforschung.

Liquid metal batteries (LMBs) are high temperature systems consisting of liquid metal electrodes and a molten salt ionic conductor. The densities are chosen in such a way that a stable density stratification of the inmiscible layers results. LMBs were considered mainly as part of energy conversion systems in the 1960s \ and have only recently received renewed interest for economic large-scale storage. Our work concentrates on the fluid dynamic aspects of this cell type with a special focus on the effects and properties of the Tayler instability (TI).
Due to the completely liquid interior of LMBs, fluid flow is an important aspect of their operation. It can be beneficial, when enhancing mass transfer in the cathode, or it might have harmful consequences, if the integrity of the electrolyte layer is disrupted.
The latter case can result form the action of the current-driven TI. We therefore studied the characteristics of the TI depending on the cell's aspect ratio using an integro-differential approach implemented in the open source library OpenFOAM. The TI occurs if a critical value of a dimensionless parameter Ha is exceeded. Ha, the Hartmann number, is in our case solely determined by the total current I and the material properties density, kinematic viscosity, and electrical conductivity. The critical Ha is lowest for an infinitely high cuboid and corresponds to a total current of approx. 1 kA in the case of Na. Decreasing the aspect ratio increases Hacrit since the wavelength selection for the TI becomes more and more restricted.
Current densities in LMBs are typically very high. A current density of 10 kA/m2 is a characteristic value for a Na|NI-NaCl-NaF|Bi-system and results in an approximately 10 mm thick sodium layer transferred per hour from the anodic to the cathodic compartment. Depending on the design capacity and cell area, aspect ratios of the anodic compartment up to one seem imaginable.

Energieeffizienz ist ein wesentlicher Baustein nachhaltigen Wirtschaftens und unabdingbare Voraussetzung zur Erreichung aktueller klimapolitischer Ziele. Die von der Helmholtz-Gemeinschaft Deutscher Forschungszentren geförderte Energie-Allianz „Energieeffiziente chemische Mehrphasenprozesse“ bündelt Kompetenzen und Forschungsaktivitäten im Bereich der chemischen Verfahrenstechnik mit dem Ziel der Weiterentwicklung von Entwurfs- und Auslegungsmethoden, numerischen und experimentellen Techniken sowie neuer Messeverfahren zur Effizienzsteigerung chemischer Mehrphasenprozesse. Der Vortrag führt in wesentliche Zielstellungen, Methoden und Ergebnisse der von sechs deutschen Forschungseinrichtungen getragenen Allianz ein. Insbesondere werden die Themen Systemanalysen für chemische Prozesse, neue Prozessfenster und Katalysatoren, Wärmeintegration, optimale Prozessführungskonzepte, strukturierte Reaktoren, Hydroydynamik mehrphasiger Reaktionen, fortgeschrittene CFD-Modellierung reaktiver Mehrphasenprozesse und innovative Mehrphasen und Prozessanalyse-Messtechniken für behandelt.

The chemical and process industry is one of the major industrial consumers of primary energy resources worldwide. Hence, this industry is especially concerned with rising energy prices and demands for reduction of greenhouse gas emissions [1]. In recent years, many advances in energy efficiency have been made especially in the production of bulk chemicals. Efficient heat recovery, efficient plant and production structures as well as improved synthesis routes and catalysts are examples for that. A further increase of efficiency is hardly achievable by simple improvements and game-changing technologies will most possibly only punctually come up. Gradual improvement of processes and equipment still has the highest potential to achieve a broader impact, particularly if a methodological base for optimal process designs is developed that can be applied to many of the different processes and process classes in chemical production.

The crystal and molecular structure of 2-(diphenylphosphano) phenyl benzoate borane adduct are reported. The title compound crystallizes from a petroleum ether/ethyl acetate mixture in the triclinic space group P (1) over bar with two molecules in the unit cell. The unit cell parameters are: a = 8.67(1) angstrom, b = 9.202(1) angstrom, c = 14.224(2) angstrom; a = 72.600(7)degrees, beta = 73.577(7)degrees, gamma = 84.349(7)degrees and V = 1039.5(2) angstrom(3). Bond lengths and angles are typical for this phosphane borane adduct.

NK cells are emerging as new effectors for immunotherapy of cancer. In particular, the genetic engraftment of chimeric Ag receptors (CARs) in NK cells is a promising strategy to redirect NK cells to otherwise NK cell-resistant tumor cells. On the basis of DNAX-activation protein 12 (DAP12), a signaling adaptor molecule involved in signal transduction of activating NK cell receptors, we generated a new type of CAR targeting the prostate stem cell Ag (PSCA). We demonstrate in this article that this CAR, designated anti-PSCA-DAP12, consisting of DAP12 fused to the anti-PSCA single-chain Ab fragment scFv(AM1) confers improved cytotoxicity to the NK cell line YTS against PSCA-positive tumor cells when compared with a CAR containing the CD3ζ signaling chain. Further analyses revealed phosphorylation of the DAP12-associated ZAP-70 kinase and IFN-γ release of CAR-engineered cells after contact with PSCA-positive target cells. YTS cells modified with DAP12 alone or with a CAR bearing a phosphorylation-defective ITAM were not activated. Notably, infused YTS cells armed with anti-PSCA-DAP12 caused delayed tumor xenograft growth and resulted in complete tumor eradication in a significant fraction of treated mice. The feasibility of the DAP12-based CAR was further tested in human primary NK cells and confers specific cytotoxicity against KIR/HLA-matched PSCA-positive tumor cells, which was further enhanced by KIR-HLA mismatches. We conclude that NK cells engineered with DAP12-based CARs are a promising tool for adoptive tumor immunotherapy.

Changes in the expression of α₇ nicotinic acetylcholine receptors (α₇ nAChRs) in the human brain are widely assumed to be associated with neurological and neurooncologial processes. Investigation of these receptors in vivo depends on the availability of imaging agents such as radioactively labelled ligands applicable in positron emission tomography (PET).
We report on a series of new ligands for α₇ nAChRs designed by combination of dibenzothiophene-dioxide as novel hydrogen bond acceptor functionality with diazabicyclononane as an established cationic center. To assess the structure-activity relationship (SAR) of this new basic structure, we further modified the cationic center systematically by introduction of three different piperazine-based scaffolds. Based on in vitro binding affinity and selectivity, assessed by radioligand displacement studies at different nAChR subtypes, we selected compound 10a (7-(1,4-diazabicyclo[3.2.2]nonan-4-yl)-2-fluorodibenzo[b,d]thiophene 5,5-dioxide) for radiolabeling and further evaluation in vivo. Radiosynthesis of [¹⁸F]10a was optimized manually and then transferred to an automated module. Dynamic PET imaging studies with [¹⁸F]10a in piglets and a monkey demonstrated robust uptake of radioactivity in the brain, followed by washout and target-region specific accumulation by the radioligand under baseline conditions. Kinetic analysis of [¹⁸F]10a in pig was performed using a two-tissue compartment model with arterial-derived input function and non-displaceable binding potential (BPND) values were estimated in various brain regions. Our initial evaluation revealed that the dibenzothiophene-based PET radioligand [¹⁸F]10a has high potential to provide clinically relevant information about the expression and availability of α₇ nAChR in the brain.

The Tudun deposit is a medium-sized Cu–Ni sulfide deposit, located at the westernmost edge of the Huangshan–Jing’erquan Belt in the northern part of Eastern Tianshan, NW China. Sulfide separates including pentlandite, pyrrhotite and chalcopyrite from the Tudun deposit, contain Re, common Os and 187Os ranging from 40.46 to 201.2, 0.8048 to 6.246 and 0.1709 to 0.9977 ppb, respectively. They have very low 187Os/188Os ratios of 1.224–2.352. The sulfides yield a Re–Os isochron age of 270.0 ± 7.5 Ma (MSWD = 1.3), consistent within uncertainty with the SHRIMP zircon U–Pb age for the Tudun mafic intrusion (gabbro) of 280.0 ± 3.0 Ma. The calculated initial 187Os/188Os ratio is 0.533 ± 0.022, and γOs values range from 283 to 307, with a mean of 297, indicating significant crustal contamination of the parent melt prior to sulfide saturation. The Tudun deposit shares the same age and Re–Os isotopic compositions with other orthomagmatic Cu–Ni sulfide deposits in Huangshan–Jing’erquan Belt, suggesting that they have formed in Early Permian.

The mean sputter yield produced by the impact of a single ion depends on the radii of curvature of the target surface at the point of impact. Using the Sigmund model of ion sputtering, we develop analytical formulas for this dependence for the case in which the radii of curvature are large compared to the size of the ion-induced collision cascade; both locally perpendicular and oblique ion impact are considered. The sputter yield is increased for impact on convex surfaces. The influence of surface curvature along the incident-ion azimuth and perpendicular to it are discussed separately. Our analytical results are in good agreement with Monte Carlo simulations for the specific case of 20 keV Ar ion impact on a cylindrical nanowire consisting of amorphous silicon. We also extend the results for this case to small radii of curvature using both Monte Carlo and molecular dynamics simulations.

The substitution of tetradentate bispidine ligands with rhodamine and cyanine dye molecules, coupled to an amine donor, forming an amide as potential fifth donor, is described. Bispidines are known to lead to very stable Cu^II complexes, and the coordination to Cu^II was expected toefficiently quench the fluorescence of dyemolecules. However, at physiological pH the amide is not coordinated, as shown by titration experiments and crystallographic structural data of three possible isomers of these complexes. This may be due to the specific cavity shape of bispidines and the Jahn–Teller lability of the Cu^II center. While Cu^II coordination in aqueous solution leads to efficient fluorescence quenching, experiments show that the complex stabilities are not large enough for Cu^II sensing in biological media, and possibilities are discussed, how this may be achieved by optimized bispidine–dye conjugates.

The flow induced by a single-phase alternating magnetic field is studied numerically and in a physical model. It is shown that the flow structure depends drastically on the frequency of the field, owing to a changeover of the rotor of the Lorentz force in the corners from a single local maximum to a pair of local maxima, one in close vicinity of another, with different signs of vorticity.

The aim of this study was to assess the capability of bacterial isolates immobilized on poly(ethylene oxide) (PEO) cryogels to degrade and utilize phenol as a sole source of carbon and energy. Two xenobiotic-degrading bacteria were isolated from industrial areas polluted with heavy metals and aromatics. Sequencing of their 16S rDNA classified them as Pseudomonas rhodesiae (denoted as KCM R-5) and Bacillus subtilis (denoted as KCM RG(5)). The following operation parameters were used: sequencing batch process, 24 h cycle of feeding, increasing phenol concentrations from 300 to 1000 mg center dot L-1, volume of inflow - 250 mL, volume of outflow - from 212 to 7 mL and temperature of 28 degrees C. The PEO-KCM R-5 biofilter was found to remove phenol at a concentration of 1000 mg center dot L-1, while the PEO-KCM RG(5) system was unable to degrade phenol at a concentration of about 600 mg center dot L-1. After four weeks of biodegradation, the PEO biofilms remained compact, porous and elastic, while containing compact microbial biofilm as shown by scanning electron microscopy analysis of the cryogels. Taken together, our results demonstrate that our novel bacterial entrapment system in PEO cryogels is highly effective and sustainable for phenol degradation and can be relevant for application in the detoxification technologies of industrially polluted waters.

Single crystals of Ca4GdO[BO3]3 and Sr3Gd2[BO3]4 were synthesized using the Czochralski method, both in different crystallographic directions. Best result were obtained for View the MathML source010 orientated seeds and growth rates of 1 mmh−1. The morphology of the as-grown crystals reflects the symmetry and for Ca4GdO[BO3]3-crystals a typical rhombohedral and for Sr3Gd2[BO3]4-crystals almost circular cross section are formed. UV–VIS and IR measurements show a wide range of transmission of light. Between 350–1100 and 1600–2500 nm no absorption was observed. Below 350 nm the crystals show distinct absorption peaks caused by electron transitions of Gd. In the IR region most vibration modes can be assigned to [BO3]3−-groups and Gd/Ca-O or Gd/Sr-O-polyhedra.

The formation equilibria of salicylatoborate, lactatoborate and 3-hydroxybutyratoborate were studied by means of 11B NMR spectroscopy. The smaller the pKa of the respective organic acid, the higher is the formation constant of the organoborate. The complexation of Eu(III) with salicylatoborate and lactatoborate was investigated by means of TRLFS (time-resolved laser-induced fluorescence spectroscopy) and 11B NMR spectroscopy, yielding complexation constants lg β0(11) = 2.6–3.2. A Eu(III)–3-hydroxybutyrate complex was characterized by TRLFS and 1H NMR spectroscopy (lg β0(11) = 2.89). DFT calculations of the investigated Eu(III)–organoborates and inorganic Eu(III)–(poly)borates provided information about the Eu(III) coordination (most likely chelate). They support the hypothesis that the complexation of Eu(III) with organic as well as inorganic borate structures containing the binding site “B(OR)4−” (R = H, threefold coordinated boron center(s), organic moiety) is comparable.

One natural retardation process to be considered in risk assessment for contaminants in the environment is sorption on mineral surfaces. A realistic geochemical modeling is of high relevance in many application areas such as groundwater protection, environmental remediation, or disposal of hazardous waste. Most often concepts with constant distribution coefficients (Kd-values) are applied in geochemical modeling with the advantage to be simple and computationally fast, but not reflecting changes in geochemical conditions.
In this paper, we describe an innovative and efficient method, where the smart Kd-concept, a mechanistic approach mainly based on surface complexation modeling, is used (and modified for complex geochemical models) to calculate and apply realistic distribution coefficients. Using the geochemical speciation code PHREEQC, multidimensional smart Kd-matrices are computed as a function of varying (or uncertain) environmental conditions. On the one hand, sensitivity and uncertainty statements for the distribution coefficients can be derived. On the other hand, smart Kd-matrices can be used in reactive transport (or migration) codes (not shown here). This strategy has various benefits: (1) rapid computation of Kd-values for large numbers of environmental parameter combinations; (2) variable geochemistry is taken into account more realistically; (3) efficiency in computing time is ensured, and (4) uncertainty and sensitivity analysis are accessible.
Results are presented exemplarily for the sorption of uranium(VI) onto a natural sandy aquifer material and are compared to results based on the conventional Kd-concept. In general, the sorption behavior of U(VI) in dependence of changing geochemical conditions is described quite well.

The detection of bubbles in liquid metal is important for many technical applications. The opaqueness and the high temperature of liquid metals set high demands on the measurement system. The electrical conductivity of the liquid metal is relatively high, which can be exploited with contactless methods based on electromagnetic induction. We will present a measurement system which consists of one transmitting coil and a planar gradiometer on opposite sides of the pipe. With this sensor we were able to detect bubbles in a sodium flow inside a stainless steel pipe.

The detection of bubbles in liquid metals is important for many technical applications like for continuous casting and for liquid metal cooled reactors. The opaqueness and the high temperature of liquid metals set high demands on the measurement system. Exploiting the high electrical conductivity contactless electromagnetic methods can be used. For instance, Mutual Inductance Tomography is able to visualize the distribution of gas and liquid metal in one cross section of a pipe using a sensor array of 8 induction coils.

Liquid metal batteries are currently discussed as a means to economic large scale energy storage. They consist of three fluid layers in stable density stratification. This fully liquid arrangement relies on the stable stratification to remain intact in order to function properly. Fluid motion has the potential to disrupt the molten salt layer sandwiched in-between the upper and lower metal electrodes. A situation like this would result in an internal short-circuit and thus in a malfunction of the cell. We consider here two electromagnetic flow driving mechanisms: the Tayler instability and rotational Lorentz force distributions leading to electro-vortex flows. In a simplified setting, the stabilization of the electrolyte layer can be described fairly well by the ratio of potential to kinetic energy, i.e., the Richardson number.

Es ist kein Abstract vorhanden.

Nuclear level densities and γ-ray strength functions have been extracted for 89,90Y, using the Oslo Method on data sets from the 89Y(p,p')89Y and 89Y(d,p)90Y reactions. The γ-ray strength functions display a low-energy enhancement consistent with previous observations in this mass region (93-98Mo). Shell-model calculations give support that the observed enhancement is due to strong, low-energy M1 transitions at high excitation energies. The data were further used as input for calculations of the 88 Sr(p,γ)89Y, 88Y(n,γ)89Y, and 89Y(n,γ)90Y cross sections with the TALYS reaction code. Comparison with cross-section data, when available, shows a satisfying agreement, as well as with values from the BRUSLIB library.

Remote sensing data can provide valuable information about ore deposits and their alteration zones at surface level. High spectral and spatial resolution of the data is essential for detailed mapping of mineral abundances and related structures.

Carbonatites are well known for hosting economic enrichments in REE, Ta, Nb and P (Jones et al. 2013). These make them a preferential target for exploration for those critical elements. In this study we show how combining geomorphic, textural and spectral data improves classification result. We selected a site with a well-known occurrence in northern Namibia: the Epembe dyke. For analysis LANDSAT 8, SRTM and airborne hyperspectral (HyMap) data were chosen. The overlapping data allows a multi-scale and multi-resolution approach. Results from data analysis were validated during fieldwork in 2014.

Data was corrected for atmospherical and geometrical effects. Image classification, mineral mapping and tectonic geomorphology allow a refinement of the geological map by lithological mapping in a second step. Detailed mineral abundance maps were computed using spectral unmixing techniques. These techniques are well suited to map abundances of carbonate minerals, but not to discriminate the carbonatite itself from surrounding rocks with similar spectral signatures. Thus, geometric indices were calculated using tectonic geomorphology and textures. For this purpose the TecDEM-toolbox (SHAHZAD & GLOAGUEN 2011) was applied to the SRTM-data for geomorphic analysis. Textural indices (e.g. uniformity, entropy, angular second moment) were derived from HyMap and SRTM by a grey-level co-occurrence matrix (CLAUSI 2002). The carbonatite in the study area is ridge-forming and shows a narrow linear feature in the textural bands.

Spectral and geometric information were combined using kohonen Self-Organizing Maps (SOM) for unsupervised clustering. The resulting class spectra were visually compared and interpreted. Classes with similar signatures were merged according to geological context.

The major conclusions are:

1. Carbonate minerals can be mapped using spectral unmixing techniques.
2. Carbonatites are associated with specific geometric pattern
3. The combination of spectral and geometric information improves classification result and reduces misclassification.

References
Clausi, D. A. (2002): An analysis of co-occurrence texture statistics as a function of grey-level quantization. - Canadian Journal of Remote Sensing, 28 (1), 45-62
Jones, A. P., Genge, M. and Carmody, L (2013): Carbonate Melts and Carbonatites. - Reviews in Mineralogy & Geochemistry, 75, 289–322
Shahzad, F. & Gloaguen, R. (2011): TecDEM: A MATLAB based toolbox for tectonic geomorphology, Part 2: Surface dynamics and basin analysis. - Computers & Geosciences, 37 (2), 261-271

An ultra-fast electron beam X-ray tomography measuring system (Fischer et al., 2008) was developed at the Helmholtz-Zentrum Dresden-Rossendorf (HZDR) that is prior applied to fundamental multiphase flow investigations, e.g. in various technical devices, and for validation of enhanced flow simulation models, e.g. developed for computational fluid dynamic codes (CFD). The ultra-fast computed tomography (CT) system delivers contactless cross-sectional material distributions with a spatial resolution of approximately 1 mm and a temporal resolution of max. 8 kHz. Currently, both measuring data transfer as well as data processing has been identified as the most time consuming processes that have to be tackled to ensure an optimal use of that worldwide unique CT technique. As a first step, the data reconstruction algorithm is transferred to many-core graphics processing units (GPUs) using the so called ultra-fast X-ray imaging UFO framework (in this case: the filtered back projection algorithm). Subsequently, most of the data processing algorithms, originally implemented as sequentially executed code on single-core central processing units (CPUs), are adapted for both multi-core CPUs and, eventually, many-core GPUs application. To increase the performance improvements once more, an advanced performance PC (AP-PC) with two parallel operated high performance graphics processing units (Tesla K20c, NVIDIA®), a six-core processor (Xeon E5-1650 v3, Intel®) and a high data bus speed and memory and transfer volume (DDR4, 2133 MHz, 128 GByte) is assembled. Thus, data processing performance could be improved again using the specifically assembled hardware configurations. The timing results show that an optimized multi-core CPU-based code increases the data processing performance by a factor of 40. Moreover, the applied many-core GPU-optimized code, including the AP-PC hardware configuration adaptions, led to a data processing performance improvement factor of 138.

Es ist kein Abstract vorhanden.

The optimisation of methods and facilities for material processing technologies such as melting, refining or casting of metals or alloys has to be considered as an enduring challenge. Key issues are an improvement of the final product quality, an enhancement of the process efficiency and an economical consumption of resources and energy. Further advancement often requires a better knowledge with respect to the details of the flow structure, the heat and mass transfer properties of the flow especially during phase transitions like melting or solidification. Experimental studies on industrial scale with hot metallic melts (T > 600°C) may require formidable effort and expense. Cost-saving model experiments using low melting point metallic melts permit detailed investigations of the flow structure and related problems with a high grade of flexibility. Experiments at room temperature are possible using the ternary alloy GaInSn. The ultrasound Doppler velocimetry (UDV) became an accepted method for flow investigations in various liquid metals. In this presentation various applications of UDV in liquid metal flows will be shown to demonstrate the capabilities and current restrictions of this technique. For instance, we consider single- and multi-transducer arrangements for flow mapping or present velocity measurements obtained during the solidification of a metallic melt. Besides the determination of velocity profiles in the liquid phase the UDV data allow for an assessment of the current position of the solidification front, too. Specific problems arising in the context of UDV measurements in liquid metal experiments will be discussed. The following examples have been selected to demonstrate the benefit of using UDV for flow measurements in cold model experiments, namely the electromagnetic stirring of a metallic melt in a pool, the directional solidification of Pb-Sn alloys under the influence of an electromagnetically driven flow and the
behaviour of the mould flow in continuous casting under the effect of a DC magnetic field.

Investigating the complex interaction of conductive fluids and magnetic fields is relevant for a variety of applications from basic research in magnetohydrodynamics (MHD) to modeling industrial processes involving metal melts, such as the crystal growth process in the photovoltaic industry. This enables targeted optimizations of the melt flow and allows to significantly increase the yield and energy efficiency of an industrial process. However, experimental studies in this field are often limited by the performance of flow instrumentation for opaque liquids. We present an ultrasound array Doppler velocimeter (UADV) for flow mapping in opaque liquids at room temperature. It is modular and flexible regarding its measurement configuration, for instance it allows capturing two velocity components in two planes (2d-2c). It uses up to 9 linear arrays with a total element count of 225, driven in a parallelized time division multiplex (TDM) scheme. A FPGA-based signal pre-processing allows to handle the massive data bandwidth of typ. 1.2 GB/s and enables a continuous and near-realtime operation of the measurement system. Combining the velocity information of multiple arrays necessitates precise knowledge of their relative geometric position. We present a novel method for spatial self-calibration by a mutual time of flight measurement that significantly reduces the alignment errors.
The capabilities of the UADV system are demonstrated in an experiment for basic MHD research. A cubic plexiglas container (67mm3) is filled with a metal melt (GaInSn, melting point 10°C). The flow induced by time-varying rotating magnetic fields is captured with a temporal resolution of 250ms and an uncertainty of approx. 1% for the horizontal and vertical central cross-section of the cube (2d- 2c).

Der Einsatz elektromagnetischer Felder zum Rühren metallischer Schmelzen stellt eine elegante Möglichkeit einer völlig kontaktlosen Strömungskontrolle in erstarrenden Metalllegierungen dar, wobei die Strömungsintensität über die elektrischen Regelgrößen Strom und Frequenz gesteuert werden kann.
Trotz der nachweislichen Verbesserung der Gefügeeigenschaften, wie Kornfeinung und Vergrößerung des equiaxialen Erstarrungsbereiches, sowie der Verbesserung der Oberflächenqualität, ist der Einsatz des elektromagnetischen Rührens auch problembehaftet. Negative Auswirkungen wie strömungsinduzierte Porosität oder Gefügeinhomogenitäten (z. B. weiße Bänder beim Stahlguss) erschweren eine industrielle Anwendung des Verfahrens im Strangguss.
Der Einsatz maßgeschneiderter Magnetfelder bietet die Perspektive, die oben genannten, nachteiligen Effekte zu vermeiden. Mit dem Konzept der maßgeschneiderten Magnetfelder können Strömungsregime erzeugt werden, welche die für die Herausbildung vorteilhafter Gefüge notwendigen Temperatur- und Konzentrationsfelder in der erstarrenden Schmelze liefern. Dies erfordert jedoch ein genaues Verständnis der Wechselwirkung von Magnetfeld, induzierter Strömung und Erstarrungsvorgang.
In diesem Vortrag wird die Wirkung des elektromagnetischen Rührens der Schmelze mittels Magnetfelder in einem Continuous Casting - Rundstrang Modellexperiment untersucht. Des Weiteren wird die Auswirkung einer erzwungenen Konvektion auf das Gefüge am Beispiel einer gerichtet erstarrten, binären Al-Si-Legierung gezeigt. Für eine optimale Gefügebeeinflussung dieses Verfahrens sind geeignete Kombinationen der Magnetfeldparameter zu ermitteln. Zu diesem Zweck wurden Strömungsmessungen in einer isothermen Modellschmelze unter dem Einfluss modulierter Magnetfelder durchgeführt. Die Erstarrungsversuche demonstrieren, dass es möglich ist, mit Hilfe zeitmodulierter magnetischer Felder korngefeinte, equiaxiale Gefüge unter Vermeidung der Herausbildung makroskopischer Gefügeinhomogenitäten herzustellen.
Die Ergebnisse veranschaulichen das große Potenzial des elektromagnetischen Rührens zur Verbesserung der Materialeigenschaften der erstarrten Struktur und einer Optimierung der Prozesskontrolle.

The application of electric currents during solidification can cause grain refinement in metallic alloys. However, the knowledge about the mechanisms underlying the decrease in grain size remains fragmentary. This study considers the solidification of Al-Si alloys under the influence of electric currents for the configuration of two parallel electrodes at the free surface. Solidification experiments were performed under the influence of both direct currents (DC) and rectangular electric current pulses (ECP). The interaction between the applied current and its own induced magnetic field causes a Lorentz force which produces an electro-vortex flow. Numerical simulations were conducted to calculate the Lorentz force, the Joule heating and the induced melt flow. The numerical predictions were confirmed by isothermal flow measurements in eutectic GaInSn. The results demonstrate that the grain refining effect observed in our experiments can be ascribed solely to the forced melt flow driven by the Lorentz force.

The solidification of Al - 7 wt. % Si alloys under the influence of electric current pulses (ECP) through two parallel electrodes at the melt surface is investigated. An effective grain refinement was found if the ECP is applied during the initial solidification period (nucleation and recalescence). The grain size can be gradually reduced, which is likely due to the remelting process of high-order dendrite arms in the mushy zone driven by solute fluctuation and promoted by thermal fluctuation. This fragmentation process is mainly driven by electromagnetically forced convection. The grain refinement does not require the formation of nuclei from a solidified shell near the electrodes, which would result in a grain rain inside the sample.

Multiphase flows are frequently applied in industrial processes as e.g. in chemical engineering, oil industries or power plants. Reliable predictions of the flow characteristics such as local concentration of species, interfacial area density or heat transfer in gas-liquid flows can contribute to an optimization of the design of corresponding apparatuses and processes. Computational Fluid Dynamics (CFD) in principle allows the simulation of such flows and provides local flow characteristics. While it is frequently used for industrial problems in case of single phase flows it is not yet mature for two-phase flows. The reason is the complex gas-liquid interface. For medium and large scale flow domains it is not feasible to resolve all details of this interface. Averaging procedures have to be applied and in most cases the so-called two- or multi-fluid approach is used. It assumes interpenetrating phases and the information on the interface gets lost by these averaging procedures. This information has to be added to the basic balance equations by so-called closure models. The development and validation of such models is done at Helmholtz-Zentrum Dresden – Rossendorf (HZDR) to obtain tools for reliable predictions of multiphase flow characteristics in medium and large industrial scales.
One difficulty for the model development and validation results from the fact that we still have a lack of knowledge on local phenomena which determine the two-phase flow characteristics and which should be considered in the closure models. Experimental data with high resolution in space and time are required. To get such information on the gas-liquid interface new innovative measuring techniques as wire-mesh sensors and ultrafast X-ray tomography were developed at Helmholtz-Zentrum Dresden – Rossendorf (HZDR) and extensively used to establish comprehensive databases. The corresponding experiments were conducted at the TOPFLOW-facility of HZDR. It can be operated for air-water and steam-water flows with a pressure up to 7 MPa and the corresponding saturation temperature of 286 °C. An electrical steam generator with a power of 4 MW is able provide up to 1.5 kg steam per second.
In this keynote lecture the strategy of the CFD-model development and validation for multiphase flows is presented. This includes the corresponding experimental work and development of innovative measuring techniques.

A clear progress was achieved during the last 20 years in the qualification of CFD-codes for problems of the nuclear safety research. Especially two-phase flows are important, e.g. for LOCA scenarios, but up to now the predictive capabilities of CFD-methods for such flows are limited. Two-phase flows are determined by complex interactions between the phases. Some of them are not yet well understood at the local scale and, therefore, CFD models are limited. This paper discusses such local phenomena and their reflection in presently available CFD-models. It turns out that most of the assumptions in the formulation of closure models for the multi-fluid approach reflect the real phenomena only in a coarse way. Possible uncertainties are listed. Nevertheless, the simulation results obtained by the HZDR baseline model for poly-disperse flows in which all models including model parameter are fixed show in general a rather good agreement with experimental data. One sensitive issue seems to be how to handle the bubble size. In case of poly-disperse flows the sub-division of the gas phase with respect to the bubble size is important and the exact choice of the limits for this division sensitively influences the simulation results.

In this talk an overview on the CFD activities at HZDR is given. The general strategy to qualify CFD for multiphase flows is presented. Examples for specific topics related to nuclear safety research are discussed.

Modifications of magnetic and magnetooptical properties of Pt/Co/Pt tri-layers upon irradiation with ion beam are investigated in this work. They are studied in detail as a function of the Co layer thickness, dCo (up to 5 nm), ion species (Ne+, Ar+, Ga+) the energy of ions, E (up to 30 keV) and ion fluence, F (range from 1013 to 3∙1016 ions/cm2). Modified magnetic properties are correlated with structural features of irradiated samples. Numerical simulations of in-depth atomic concentration profile and surface etching carried out by TRIDYN software complements explanation of the observed effects.
MBE grown Pt/Co/Pt tri-layers display a spin reorientation transition (SRT) at a well-defined Co thickness, dSRT from out-of-plane to in-plane magnetization alignment as dCo increases. Upon ion irradiation various processes undergo: degradation of chemically sharp interfaces, formation of Co-Pt alloys and lattice strain development [1, 2]. Spread interfaces reduce perpendicular anisotropy whereas formation of the ordered alloy may strength this property. Therefore a resulting magnetic state of the sample is a product of interplay of these two opposing trends in anisotropy evolution and the sample surface etching, particularly effective for highest fluences. It is very sensitive to dCo, ion species, their energy and the ion fluence.
Discussion is focused on results obtained with Ar+ ions irradiation, which is commonly used for technological processes especially for nanostructures sputtering. Set of (dCo, log F) diagrams of remanence, mr (Figure. 1), (normalized magnetization perpendicular component) measured by means of magnetooptical Kerr effect magnetometry in polar configuration (PMOKE) upon irradiation with Ar+ ions with different energies. Irradiation of the samples modifies magnetic properties in various manners depending on dCo, F and ion energy. The suppression of the dSRT with F in the range from 1013 to 1014 ions/cm2 and formation of branch(es) corresponding to strong perpendicular anisotropy (higher value of mr) are the most distinguished differences depending on the ion energy. As the ion energy increases a single branch with high mr (for 1.2 keV) begins to split into two parts for 5.0 keV, which are clearly separated for 30.0 keV. Qualitatively this evolution resembles that one already reported for Ga ions [1]. However, the mr modifications strength are weaker due to the lower mass of Ar atoms. Nevertheless, up to 5 transitions between various magnetic states are observed with F increase, e. g. for dCo = 1.6 nm and E = 30 keV. It is worth to notice that even the lowest applied energy of Ar+ ions induces visible modifications of magnetic properties. In the case of the lightest studied Ne ions modification of magnetic anisotropy is weaker than for Ar+ ions and the branches in a similar diagram are non-continuous.
TRIDYN software determined in-depth chemical profile (Figure 2) is helpful in identification of possible alloy composition being responsible for enhanced perpendicular magnetic anisotropy. Also the surface etching extent allows to estimate an amount of sputtered (also magnetic) material that may result in superparamagnetic state observed for the highest ion doses.
Structural properties of the irradiated samples are investigated by Rutherford backscattering (RBS). Evolution of the acquired chemical profiles is correlated with that simulated with TRIDYN software. Moreover, the etching efficiency is estimated from topography step profile between irradiated and non-irradiated areas of the sample investigated by means of profilometer and atomic force microscopy.
Discussed above abundance of magnetic investigated states in combination with controlled structural features developing upon ion irradiation enable a precise tuning of desired magnetic properties. In particular, such approach, exploiting a focused ion beam, might be of great importance in fabrication of magnonic crystals – a new type of metamaterial with reprogrammable band structure.

In this presentation the requirement to consolidate the CFD modelling for two-phase flows in frame of the Euler-Euler approach is discussed. To do that a baseline model strategy is proposed and illustrated by the HZDR baseline model for poly-dispersed bubbly flows.

Ion implantation of metal ions followed by annealing can be used for the formation of buried layers of metal nanoparticles in glasses with optical properties for perspective photonic materials. Results are presented from three samples of silica glasses implanted with Cu+, Ag+ or Au+ ions under the same conditions (energy 330 keV and fluence 1×10^16 ions/cm2) and three silica glass samples implanted with the same metals and conditions but coimplanted subsequently by oxygen into the same depth. All the implanted glasses were annealed at 600°C, which lead to forming of metal nanoparticles. The depth profiles measured by RBS and SIMS indicated that the sequential implantation of oxygen followed by post-annealing caused the shift of Cu, Ag and Au aggregated into nanoparticles deeper into the glass substrate. Both RBS and SIMS are shown to be valuable complementary techniques.

In 1974, Nelson, Kase, and Svenson published an experimental investigation on muon shielding using the SLAC high energy LINAC. They measured muon fluence and absorbed dose induced by a 18 GeV electron beam hitting a copper/water beamdump and attenuated in a thick steel shielding. In their paper, they compared the results with the theoretical models available at the time. In order to compare their experimental results with present model calculations, we use the modern transport Monte Carlo codes to model the experimental setup and run simulations. The results will then be compared between the codes, and with the SLAC data.

A very low background level is a key requirement for underground nuclear astrophysics experiments.
A detailed gamma-background study with two escape-suppressed HPGe detectors has been performed at a medium deep underground site, namely the Reiche Zeche mine (148m) in Freiberg, Germany [1]. The new data complement a data set with the same detector at other underground sites [2,3].
Now, detailed background data are available at the Earth’s surface and at underground sites with depths of 45m, 148m, 1400m from one and the same escape-suppressed HPGe detector. This allows to investigate the effect of the active and passive shielding on the high energy (E_g > 3 MeV) laboratory background.
A detailed interpretation of the behaviour of different background components as a function of the underground depth will be presented.

In addition to this work with gamma-ray detectors, the neutron background has been studied by 3He counters from the BELEN neutron detector, equipped with polyethylene moderators of various thicknesses in the Felsenkeller laboratory (45m). By mean of the varied moderation, spectral information of the neutron flux is derived. The same detectors and same method were used previously deep underground in Canfranc/Spain (850m) to measure the neutron flux and spectrum [4]. This allows a direct comparison of the two sites.

• Supported by the Helmholtz Association (HGF) through the Nuclear Astrophysics Virtual Institute (HGF VH-VI-417), and via the Helmholtz Young Investigators Group LISA (VH-NG 627).

[1] T. Szücs et al., Eur. Phys. J. A 51, (2015) 33
[2] T. Szücs et al., Eur. Phys. J. A 44, (2010) 513
[3] T. Szücs et al., Eur. Phys. J. A 48, (2012) 8
[4] D. Jordan et al., Astropart. Phys. 42, (2013) 1

In 1974, Nelson, Kase, and Svenson published an experimental investigation on muon shielding using the SLAC high energy LINAC. They measured muon fluence and absorbed dose induced by a 18 GeV electron beam hitting a copper/water beamdump and attenuated in a thick steel shielding. In their paper, they compared the results with the theoretical models available at the time. In order to compare their experimental results with present model calculations, we use the modern transport Monte Carlo codes to model the experimental setup and run simulations. The results will then be compared between the codes, and with the SLAC data.

Results on activation calculation for the CHANDA project are presented.

Single layer thin films have been exposed to low energy alpha particles (4keV). Implanted doses are equivalent to those accumulated in 1, 2, 4 and 6 years of ESA Solar Orbiter mission operation. Two ions fluences have been considered. In order to change the total dose accumulated, for each ion flux the time of exposure was varied. Reflectance in the visible spectral range has been measured prior and after implantation. Results show no significant change in performances in gold and palladium, while a small decrease in performances is observed in iridium. The implantation rate does not seem to affect the experiment.

Ultrafast X-ray electron beam computed tomography (CT) is an imaging technique, which has been developed for measuring phase distributions in multiphase flows. For example, two- and multiphase flow experiments in vertical pipes, conventional and slurry bubble columns, fluidized beds, monolithic structures and bundle geometries could be evaluated by this technique. With extending the measurement system towards dual-plane imaging, the option of velocity measurement has been created and applied for instance in two-phase vertical pipe flow.
In this study, we focus on measuring velocities in particulate systems. Some methods for velocity evaluation can be adapted from gas-liquid flows, such as the cross-correlation technique for determining the velocity of gas bubbles. Now, we present a technique, which allows velocity evaluation of the solid particles. This is achieved by adding marker particles with higher X-ray absorption to the particle phase and determining their velocities representatively.
In this paper, two different velocity evaluation techniques are described and selected results achieved by conducting experiments on a spout fluidized bed are presented. This combination of spouting and fluidized bed is a rather new type of particulate system, which combines the advantages of both, but whose dynamics is yet not fully understood. The capability of ultrafast X-ray CT to recover phase distributions as well as velocity information from particulate systems in order to better understand the dynamics of particulate systems is demonstrated with this exemplary experiment.

I. INTRODUCTION
Defect-induced ferromagnetism provides an alternative for organic and semiconductor spintronics. Though it is weak, it can be stable above room temperature. Till now it has been confirmed at least in oxides [1, 2] and carbon based materials [3, 4]. Interestingly, the relation between magnetism and defects in Silicon was demonstrated decades ago [5]. Since then, some progresses were made [6-9] and push forward the research of magnetic Mn doped Si a lot but it is drawn little attention itself. Here, with the latest growth purifying technique and sensitive measurements, we investigated the magnetism in Silicon after neutron irradiation and try to correlate the observed magnetism to particular defects in Si.

II. RESULTS
Commercially available p-type Si wafer (Hefei Ke Jing) is cut into pieces for performing neutron irradiations. The magnetic impurities are ruled out as they can not be detected by secondary ion mass spectroscopy. The concentration of the main impurity Boron is around 4 × 1014 cm-3. Pieces are irradiated for varying durations, corresponding doses in the ranges of 1.91 × 1017 - 2.29 × 1018 n/cm2. Each piece is irradiated only once and pristine pieces are kept for the purpose of comparison.
Raman spectra show the patterns of Si crystals irradiated similar to that of the pristine one. The relative intensity variation confirms the slight damage induced by irradiation. Positron annihilation lifetime spectroscopy is performed to investigate the defect types. All the measured spectra are fit into an exponential function of three components. The lifetime τ2, usually corresponding to defects, takes value of 375 ps, independent of irradiation dose. This positron trapping center is assigned to a kind of stable vacancy clusters of hexagonal rings (V6) [10]. The fraction of the longer lifetime (τ2) component I2 is closely correlated with irradiation dose, which means the concentration of V6 is enhanced by increasing neutron doses.
After irradiation, the samples still show strong diamagnetism. Only weak paramagnetism can be found in zero-field-cooled / field-cooled magnetization. The ferromagnetic signal in Silicon after irradiation enhances and then weakens with increasing irradiation doses as shown in Fig. 1. The saturation magnetization can reach 6 × 10-5 emu/g at 5 K. At room temperature it still remains as much as 5 × 10-5 emu/g. In such a transition metal free system, the ferromagnetism in neutron irradiated Si is closely associated with V6 defects. A Silicon 2 × 2 × 2 supercell with a defect of V6 is built to understand the magnetism in neutron irradiated Silicon. Unfortunately, the V6 shows no spin-polarized state. The change of charge state or Boron doping can not make it spin-polarized, either. At this end, more efforts are needed to comprehend this phenomenon.

REFERENCES
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NeuLAND (new Large-Area Neutron Detector) is the next-generation neutron detector integrated into the R3B experiment, and is a key instrument for a major part of the physics program. NeuLAND features a high detection effciency, a high resolution, and a large multi-neutronhit resolving power, achieved by a highly granular design with a total of 3000 plastic scintillator bars [1]. In January 2013 the Technical Design Report [2] has been approved by FAIR, following the recommendation by the Expert Committee Experiments (ECE) at its first meeting in November 2012.
Here we report about the progress of the NeuLAND project, which was dominated in 2012 by the transition from prototypes to mass production. During the previous year 200 NeuLAND modules and their readout were purchased and brought into operation.

Absorber layers consisting of nanostructured Si are candidates for next generation thin film Si solar cells. For this aim, Si-SiO2 nanocomposites with crystalline sponge-like Si are promising materials since their band gap is increased by quantum confinement and since they provide electrical interconnectivity. Such nanosilicon has recently been fabricated by annealing of non-reactively sputter deposited SiOx films (x< 1). It is formed by solid state phase separation into a percolated network of Si nanowires. The phase separation is usually accompanied by crystallization of Si. Here, SiOx layers have been grown by ion beam sputter (IBS) as well as by reactive magnetron sputter (RMS) deposition. Phase separation into Si-SiO2 nanocomposites has been achieved by scanning a diode laser line source with dwell times in the ms range and compared to a furnace treatment lasting ~106 times longer. Furnace annealing of IBS and RMS deposited layers result in sponge-like and filament-like silicon nanostructures, respectively. Laser processing of IBS layers leads to morphologies self-similar to furnace annealed samples, but scaled up by a factor of ~10. This indicates that the faster phase separation mechanism occurs in the liquid state. It is expected that laser processing of RMS layers will result in sponge-like morphologies too, and not filament like ones due to the liquid state phase separation.

Line-shaped light beams from diode laser arrays permit homogeneous and long-term stable processing of surface layers. Here we report on thermally activated decomposition of SiOx using a commercial diode laser of the LIMO GmbH, with cw-operation at a wavelength of 808nm, a maximum power density of 30 kW/cm², a minimum line focus < 100 µm, and a variable scan speed. Dwell times from < 1ms to 100ms can be realized by adjusting the scan speed and focus width, which allows very Rapid Thermal Processing (vRTP) of surfaces layers. SiOx layers of < 1µm thickness have been grown on quartz by sputter deposition. Two different modes of thermal treatment have been used: Furnace annealing at 950°C for 90 minutes and vRTP with 17ms dwell time. Energy-Filtered Transmission Electron Microscopy (EFTEM) reveals that in both cases the homogeneous SiOx has been transformed into a sponge-like Si-SiO2 nanocomposite. Raman spectroscopy shows that the crystallinity of spongy Si is higher for the laser treated sample. Whereas the characteristic structure size of the spongy Si of the furnace annealed sample amounts to a few nm only, it is a few tens of nm for vRTP. It will be shown that in the furnace the phase separation proceeds in the solid state, whereas the more complete phase separation by laser treatment can only be understood by liquid state processes. The laser-synthesized Si nanosponge can be applied as new material in next generation solar cells.

In the upcoming R3B-FAIR facility, to achieve the design goal for high resolution neutron time-of-flight [1,2], various types of prototypes have been explored at several places [3,4,5,6]. The possible candidates for active material of such a spectrometer can be either Multigap Resistive Plate Chamber (MRPC) or conventional plastic scintillators. At initial stage of NeuLAND development, at Saha Institute of Nuclear Physics, Kolkata, MRPC design feasibility was studied extensively[3,5].

Shielding and activation analysis status of the MYRRHA research reactor is presented.

NeuLAND, the successor of the LAND time-of-flight neutron spectrometer is planned to be constructed of 5 × 5 × 250 cm3 scintillator bars of RP-408 [1] or equivalent. Light readout will be performed by 1" photomultiplier tubes (PMTs). A demonstration prototype of the detector concept was recently tested at GSI [2]. During the operation of the complete detector with 6,000 channels a significant number of photomultiplier tubes may have to be replaced each year. Recent developments in the field of semiconductor based photon readout systems [2, e.g.] raise the possibility of using Silicon Photomultipliers (SiPMs) for this task.

Absorber layers consisting of nanostructured Si are candidates for next generation thin film Si solar cells. For this aim, Si-SiO2 nanocomposites with crystalline sponge-like Si are promising materials since their band gap is increased by quantum confinement and since they provide electrical interconnectivity. Such nanosilicon has recently been fabricated by annealing of non-reactively sputter deposited SiOx films (x< 1). It is formed by solid state phase separation into a percolated network of Si nanowires. The phase separation is usually accompanied by crystallization of Si. Here, SiOx layers have been grown by ion beam sputter (IBS) as well as by reactive magnetron sputter (RMS) deposition. Formation of sponge-like Si-SiO2 nanocomposites has been achieved for the IBS deposited layers by scanning with a diode laser line source (LIMO GmbH) and furnace treatment. Laser processing leads to morphologies self-similar to furnace annealed samples, but scaled up by a factor of ~10. Moreover, the laser process proceeds approximately 106 times faster. The larger mean structure size for the shorter process is explained by a phase separation in the liquid state in contrast to a solid state process which has been observed for furnace annealing. Furthermore, filament-like morphologies produced by RMS deposition and furnace annealing are compared to those of the IBS deposited layers.

It is investigated whether NeuLAND may be reinstrumented with semiconductor based photosensors. Tests with an 11cm long slab of RP-408 plastic scintillator and a PiLas 45 ps laser diode system show time resolutions of σ = 100 ps.
The NeuLAND time-of flight detector for 1GeV neutrons will consist in its final configuration of 30 double planes of 100 scintillator bars (RP-408) each. Each bar of 270×5×5cm3 must be read out at each end. Thus altogether 6000 timing photomultipliers of 1” diameter are needed [1]. In order to limit their cost impact, it is being investigated whether parts of NeuLAND may be (re-)instrumented with semiconductor-based photosensors, socalled Silicon Photomultipliers (SiPMs). Previous experiments using the one-electron-per-bunch mode of the superconducting electron accelerator ELBE have shown that nearly full efficiency can be reached even when instrumenting one NeuLAND bar with just one 3×3mm2 SiPM [2]. However, in those first tests the charge resolution did not allow to separate single photons, and the time resolution did not fulfill the required σ ≤ 150 ps.

Topographical features on the nanometer scale are known to influence cellular behavior. The response of specific cell types to various types of surface structures is currently still being investigated. Alumina ceramics play an important role as biomaterials, e.g., in medical and dental applications. In this study, we investigated the influence of nanoscale surface features with low aspect ratio (< 0.1) on the response of osteoblast-like MG-63 cells. To this end, low-energy ion irradiation was employed to produce shallow nanoscale ripple patterns on Al2O3(0001) surfaces with lateral periodicities of 24 nm and 179 nm and heights of only 0.7 and 11.5 nm, respectively. The nanopatterning was found to increase the proliferation of MG-63 cells and may lead to pseudopodia alignment along the ripples. Furthermore, focal adhesion behavior and cell morphology were analyzed. We found that MG-63 cells are able to recognize surface nanopatterns with extremely low vertical variations of less than 1 nm. In conclusion, it is shown that surface topography in the sub-nm range significantly influences the response of osteoblast-like cells.

Chalcogen-hyperdoped silicon shows potential applications in silicon-based infrared photodetectors and intermediate band solar cells. Due to the low solid solubility limits of chalcogen elements in silicon, these materials were previously realized by femtosecond or nanosecond laser annealing of implanted silicon or bare silicon in certain background gases. The high energy density deposited on the silicon surface leads to a liquid phase and the fast recrystallization velocity allows trapping of chalcogen into the silicon matrix. However, this method encounters the problem of surface segregation. In this paper, we propose a solid phase processing by flash-lamp annealing in the millisecond range, which is in between the conventional rapid thermal annealing and pulsed laser annealing. Flash lamp annealed selenium-implanted silicon shows a substitutional fraction of ≈ 70% with an implanted concentration up to 2.3%. The resistivity is lower and the carrier mobility is higher than those of nanosecond pulsed laser annealed samples. Our results show that flash-lamp annealing is superior to laser annealing in preventing surface segregation and in allowing scalability.

During 2013 the NeuLAND (new Large-Area Neutron Detector) project passed the important step from prototype tests to series production. Being one of the key instruments of the R3B experiment [1] the NeuLAND demonstrator will be utilized in the 2014 beam times together with demonstrators of other major R3B components. NeuLAND is a highly granular detector composed of 3000 scintillator bars with a total volume of 250x250x300 cm3. It enables the detection of fast neutrons with high efficiency, high time and spatial resolution and a high resolving power for multi-neutron events [2]. Despite the compact cubical arrangement of the NeuLAND components, the detector is built up from individual subgroups with an independent functionality, the so-called NeuLAND double-planes. This modular design facilitates maintenance and it allows upon experimental needs to split the detector in subdetectors being located at different positions with respect to the target area.

Objectives: Ligands based on 3,7-diazabicyclo[3.3.1]nonane (bispidine) form very stable coordination compounds, particularly with Cu^II. Due to the formation of thermodynamically and kinetically very stable ⁶⁴Cu^II complexes, pentadentate I, hexadentate II and macrocyclic bispidines III are well suited for in vivo application. The bispidine scaffold has a number of options for derivatization that permit the introduction of additional functions such as biological vectors and fluorescent molecules. This allows the adjustment of defined features of solubility and of selective binding properties for in vivo applications with controllable targeting.

Methods: Bispidine ligands I and II were synthesized by two consecutive Mannich reactions. The bispidine dioxotetraaza macrocycle III was synthesized by cyclization of 5,7-dimethyl-1,3-diazabicyclononane with the bis(α-chloroacetamide) of o-phenylendiamine. ⁶⁴Cu was produced following an established protocol with high specific activities of 150-250 GBq/µmol. ⁶⁴Cu-labeling of bispidine ligands and peptide conjugates were performed using [64Cu]CuCl2 dissolved in 0.05 M 2-[N-morpholino]ethansulfonic acid (MES)-NaOH buffer (pH 5.5, 6.0, and 6.5). The stability of the ⁶⁴Cu^II-labeled bispidine ligands I – III was studied in the presence of an excess of human superoxide dismutase (SOD) and human serum using standard gel electrophoresis techniques. Biodistribution and PET studies were conducted in male Wistar rats. Small animal PET studies were performed in tumor (PC3, MPC^#) bearing mice.

Results: Bispidine ligands I and II form highly stable metal complexes with ⁶⁴Cu^II under mild conditions (ambient temperature, aqueous solution). ⁶⁴Cu-labeling of bispidine dioxotetraaza macrocycles III shows relatively rapid complex formation at 50°C. Challenge experiments with SOD and human serum indicate a high in vitro stability of ⁶⁴Cu^II complexes with bispidine ligands I – III. Biodistribution studies, showing rapid blood and tissue clearance, support the high complex stability in vivo. ⁶⁴Cu-labeled bispidine bioconjugates, incorporating specific vector molecules, such as bombesin and TATE peptides, permit clear tumor visualization with high target-to-background ratio.
Conclusions: Bifunctional bispidine ligands I - III represent a versatile platform for the development of new copper radiopharmaceuticals. The bispidine scaffold holds promising potential to tune the charge and lipophilicity of the radiocopper complexes and consequently to influence the biodistribution and pharmacokinetic properties. Moreover, bispidine ligands can be readily modified with appropriate vector molecules and fluorescence tags.
Acknowledgements: Financial support by the Helmholtz Virtual Institute NanoTracking (Agreement Number VH-VI-421) is gratefully acknowledged.
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[6] Zarschler K., et al. (2013), RSC Adv. 4, 10157-10164.
[7] Thieme S., et al. (2012) Appl. Radiat. Isot. 70, 602-608.

Objectives: Pyridine containing bifunctional chelating agents (BFCA) based on 1, 4, 7 – triazacyclononane backbones (DMPTACN) are suitable platforms for copper (II) complexes. These ligands rapidly form highly stable, inert square pyramidal complexes that are resistant to metal leaching.¹ The ligand structure enables convenient introduction of additional conjugatable functional groups like -COOH end groups to allow a regioselective coupling to various biomolecules for e.g. bombesin.² Since Cu-64 is a highly useful PET (positron emission tomography) radioisotope because of its intermediate half-life (⁶⁴Cu, t_1/2 -12.7 h) and a high resolution image, these conjugatable DMPTACN chelators can be coupled with various vectors for e.g., proteins, dendritic polymers in order to understand their detailed in vivo pharmacokinetic properties with respect to their ADME behavior. The current objective of the work was to synthesize new maleimide and -SCN derivatives of DMPTACN ligands which could be employed to be conjugated to anti-inflammatory dendritic polyglcerol sulfate (dPGS) & neutral dPG derivatives under mild conditions in order to study the metabolic fate of these potentially therapeutic polymers using positron emission tomography.
Methods: DMPTACN was synthesized by a 10-step process using an established protocol.¹ Two coupling groups such as maleimide (1) or isothiocyanate (2) have been attached for further conjugation. These ligands were then conjugated to the thiolated dPGS via Michael addition of 1 and also via direct labeling of 2 to dPGS amine to yield highly stable conjugates. ⁶⁴Cu was produced following an already established protocol with high specific activities of 150-250 GBq/µmol.^{3 64}Cu-labeling of the conjugates were performed using [⁶⁴Cu]CuCl₂ at ambient temperature in aqueous buffer solution (0.1 M MES/NaOH) and resulted in a radiochemical purity of ≥99% within a few minutes. Challenge experiments were conducted in presence of EDTA or copper seeking superoxide dismutase (SOD) for evaluation of in vitro stability.⁴ Biodistribution and PET studies were conducted in male Wistar rats.
Results: DMPTACN-dPG/S conjugates form highly stable metal complexes with ⁶⁴Cu under mild conditions (ambient temperature, aqueous solution) showing resistance to demetalation in vitro and high in vivo stability. Biodistribution data and PET experiments show a charge dependant excretion of the dPGS and dPG macromolecules.
Conclusions: DMPTACN ligands are a versatile platform which can be applied for labeling small molecules, proteins as well as polymers for detailed insight on their biodistribution profiles using ⁶⁴Cu that allows studying relatively long biochemical processes and thus, prove to be an attractive candidate for PET imaging.
Acknowledgements: This study is part of a research initiative “Technologie und Medizin – Multimodale Bildgebung zur Aufklärung des in-vivo Verhaltens von polymeren Biomaterialien” of the Helmholtz-Portfoliothema.
References:
[1] Gasser G., et al. (2008) Bioconjugate Chem. 19, 719-730.
[2] Bergmann R., et al. (2013) Eur. J. Med. Chem. 70, 434-446.
[3] Thieme S., et al. (2012) Appl. Radiat. Isot. 70, 602-608.
[4] Zarschler K., et al. (2013) RSC Adv. 4, 10157-10164.

kein Abstract vorhanden

Introduction: The 15.9 kg main mass of the Twannberg meteorite has been found in 1984 in the Canton of Bern, Switzerland. Five additional masses were found until 2007 [1]. Since then, nearly 100 new finds brought the known mass to ~37 kg. The Twannberg meteorite belongs to the small IIG group (6 members), which is characterized by a low concentration of nickel and large inclusions of schreibersite.
Here we study the cosmic ray exposure (CRE) history of 17 individuals of Twannberg using cosmogenic radionuclides and noble gases. We are especially interested in the terrestrial age of Twannberg to better understand its relation with the associated glacial sediments.
Experimental Methods: Noble gas isotopes (He, Ne, and Ar) are analyzed by noble gas mass spectrometry at the University of Bern following procedure described earlier [2,3]. Analyses of the cosmogenic radionuclides (¹⁰Be, ²⁶Al, ³⁶Cl, and ⁴¹Ca) are performed at the DREsden Accelerator Mass Spectrometry facility (DREAMS, [4]) adapted from procedures described in [5].
Results: So far, 17 samples have been analyzed for the noble gas; 6 of them have also been investigated for their cosmogenic radionuclide contents. We observed a wide range of noble gas and radionuclide concentrations (more than one order of magnitude). The noble gas and radionuclide concentration correlate, indicating the reliability of the analysis despite low concentrations. Combining the data with model calculations indicate a preatmospheric radius in range of 1 to 10 meters. Considering an average density of about 8 g/cm³ and assuming a spherical object, the Twannberg preatmospheric mass was greater than at least 33 tons.
The CRE age has been determined using the ³⁶Cl-³⁶Ar method [6]. The average CRE age is 243±64 Ma, which is in the range of typical CRE ages for iron meteorites [7] and which is in good agreement with the adopted age of 230±50 Ma found previously [1]. The average terrestrial age based on the ³⁶Cl/¹⁰Be-¹⁰Be systematics is 88±38 ka, indicating that the meteorite fell during the last glaciation, the Würm event (~110-15 ka), but before the maximum glaciation at 24 ka. We expect ⁴¹Ca measurements soon, which will help to further pin down the terrestrial age of the Twannberg meteorite and bring the fall into context of glacial events, as suggested by geological indicators [1].
References: [1] Hofmann B. et al. 2009. Meteoritics and Planetary Science 44:187-199. [2] Ammon K. et al. 2008. Meteoritics and Planetary Science 43:685-699. [3] Ammon K. et al. 2011. Meteoritics and Planetary Science 46:785-792. [4] Akhmadaliev S. et al. 2013. Nuclear Instruments and Methods in Physic B 294:5-10. [5] Merchel S. and Herpers U. 1999. Radiochimica Acta 84:215-219. [6] Lavielle B. et al. 1999. Earth and Planetary Science Letters 170:93-104. [7] Eugster O. 2003. Chemie der Erde-Geochemistry 63:3-30.
Acknowledgments: This work is supported by the Swiss National Science Foundation. We thank all the ion beam center members in Dresden for their precious help. This study is heavily based on a close cooperation with enthusiastic meteorite hunters.

Objectives: The α₇nAChR is involved in cognition and a potential drug target for treatment of Alzheimer’s disease and schizophrenia. ¹⁸F-DBT-10 is a candidate radioligand for α₇nAChR imaging (Kranz et al. J Nucl Med 2014; 55 (Suppl. 1):1143). We performed PET experiments in rhesus monkeys to assess its kinetic and imaging characteristics.

Methods: ¹⁸F-DBT-10 was prepared from its nitrophenyl precursor by nucleophilic substitution. The affinity of DBT-10 on human nAChRs was determined by radioligand binding studies. Dynamic PET imaging of two monkeys (each control and blockade) was performed using a Focus-220 scanner. Brain and plasma metabolites were analysed by HPLC. Regional volumes of distribution (V_T) were estimated from brain and plasma time-activity data.

Results: DBT-10 has high binding affinity to α₇nAChR (K_i = 0.60 nM) and excellent selectivity over other nicotinic receptor subtypes. ¹⁸F-DBT-10 was prepared in 14.5±4.6% radiochemical yield and >99% radiochemical purity (n=5). Free plasma fraction of ¹⁸F-DBT-10 was 18±2 % (n=4). Plasma metabolism varied considerable between the two animals. Brain uptake was high and tissue kinetics fairly fast, with peak uptake at 10-50 min (Figure 1). No radioactive metabolites were found in brain tissue (thalamus, frontal cortex, hippocampus, and cerebellum) taken from one monkey at 120 min p.i. Time-activity curves were fitted well with the 2-tissue kinetic model. Mean V_T values were 58.0, 57.5, 54.9, 54.5, 52.0, 48.4, 39.9, and 34.8 cm³/mL, respectively, for the thalamus, insular, frontal and cingulate cortices, striatum, temporal cortex, hippocampus, occipital cortex, and cerebellum (n=2). Pre-treatment with the selective α₇ ligand ASEM (0.69 & 1.24 mg/kg) dose-dependently reduced binding of ¹⁸F-DBT-10 in all regions by 30% and 64%, respectively.

Conclusions: ¹⁸F-DBT-10 is a novel PET radiotracer with high affinity and selectivity for the α₇nAChR. In rhesus monkeys it displays high uptake, appropriate kinetics and high specific binding in brain and thus is a promising agent for PET imaging of α₇nAChR in humans.

Figure 1. MR and PET VT images (left) and tissue TACs (right) from a baseline scan with 18F-DBT-10.

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High-energy short-pulse lasers are pushing the limits of plasma-based particle acceleration, x-ray generation, and high-harmonic generation by creating strong electromagnetic fields at the laser focus where electrons are being accelerated to relativistic velocities. Understanding the relativistic electron dynamics is key for an accurate interpretation of measurements. We present a unified and self-consistent modeling approach in quantitative agreement with measurements and differing trends across multiple target types acquired from two separate laser systems, which differ only in their nano-second to picosecond-scale rising edge. Insights from high-fidelity modeling of laser-plasma interaction demonstrate that the ps-scale, orders of magnitude weaker rising edge of the main pulse measurably alters target evolution and relativistic electron generation compared to idealized pulse shapes. This can lead for instance to the experimentally observed difference between 45MeV and 75MeV maximum energy protons for two nominally identical laser shots, due to ps-scale prepulse variations. Our results show that the realistic inclusion of temporal laser pulse profiles in modeling efforts is required if predictive capability and extrapolation are sought for future target and laser designs or for other relativistic laser ion acceleration schemes.

After the Fukushima accident the spent fuel pool has got a stronger focus in nuclear safety research. The objective of the German national joint project SINABEL (Safety of wet storage facilities for spent fuel) is the experimental investigation and modelling of the thermal hydraulics of fuel elements (10 fuel rods in square, D = 10 mm, P/D = 1.24) in the pool dry-out phase. Key parameters for validation of the models are the steam temperatures and velocities in the subchannels. Due to the complex geometry and the thermal insulation of the test facility there is a strong limitation in the optical and mechanical accessibility for measurements. As a result there is a need of novel measurement techniques to provide spatially resolved gas phase temperatures and velocities.
Our approach is a modified wire-mesh sensor that is usually used for phase discrimination in two-phase flows via the measurement of conductivity or capacity in the crossing points of the wires. In the new sensor concept we integrate special miniaturized converters, which are resistance thermometers for the temperature and velocity measurement. The advantage of this technique is the possibility to overheat the sensor by increasing the current through the sensor. By controlling the sensor temperature the use of the thermal anemometry principle becomes possible.
The challenges in the development of this combining measurement system are the boundary conditions. The range of the steam velocity is down to 0.01 m/s. The temperature range is from the water boiling temperature of 100 °C up to 500 °C overheated steam. As a result of this there are high requirements in temperature compensation and the mechanical resistivity of the measurement setup.
In the contribution we will describe both the new sensor technology as well as its application in thermal hydraulic experiments for advanced analysis of safety issues for the spent fuel pool.