Publications Repository - Helmholtz-Zentrum Dresden-Rossendorf

A systematic study of the influence of interstitial hydrogen on the structure, morphology of surface, magnetic and magnetothermal properties in multicomponent (Nd_0.5Pr_0.5)₂Fe₁₄BH_x (x = 0; 2.7; 4.3) are reported. Partial substitution of Pr for Nd allows a decrease of the spin-reorientation transition temperature from 135 K for Nd₂Fe₁₄B to 73 K for (Nd_0.5Pr_0.5)₂Fe₁₄B. Hydrides (Nd_0.5Pr_0.5)₂Fe₁₄BH_x crystallize in a tetragonal crystal structure (space group P42/mnm) of the Nd₂Fe₁₄B-type. Both lattice constants and unit cell volume increase upon hydrogen absorption. It was also found that the surface of the hydrogenated sample was very severely damaged by the introduction of hydrogen. Magnetic studies of both initial compound and the hydrides were performed on bulk and powder samples in static and pulsed magnetic fields up to 14 and 58 T, respectively. Hydrogenation has a significant effect on magnetic properties of a multicomponent alloy (Nd_0.5Pr_0.5)₂Fe₁₄B: Curie temperature and saturation magnetization increase, while temperature of SRT decreases (T_SRT = 63 K for (Nd_0.5Pr_0.5)₂Fe₁₄BH_x with x = 2.7 and 4.3). The magnetocaloric effect (MCE) in the range of spin-reorientation transition also decreases significantly. We analyzed magnetic properties of (Nd_0.5Pr_0.5)₂Fe₁₄BH_x and compare them with that of Nd₂Fe₁₄BH_x. Magnetic phase diagrams are constructed.

We report on low-temperature heat-transport properties of the spin-1/2 triangular-lattice antiferromagnet Cs₂CuCl₄. Broad maxima in the thermal conductivity along the three principal axes, observed at about 5 K, are interpreted in terms of the Debye model, including the phonon umklapp scattering. For thermal transport along the b axis, we found a pronounced field-dependent anomaly, close to the transition into the three-dimensional long-range-ordered state. No such anomalies were found for the transport along the a and c directions.We argue that this anisotropic behavior is related to an additional heat-transport channel through magnetic excitations, that can best propagate along the direction of the largest exchange interaction. In addition, peculiarities of the heat transport of Cs₂CuCl₄ in magnetic fields up to the saturation field and above are discussed.

Liquid metal electrodes are one of the key components of different electrical energy storage technologies. The understanding of transport phenomena in liquid electrodes is mandatory in order to ensure efficient operation. In the present study we focus our attention on the positive electrode of the Li||Bi liquid metal battery. Starting from a real experimental setup, we numerically investigate the charge transfer in a molten salt electrolyte and the mass transport in the positive electrode. The two phenomena are tightly coupled, because the current distribution influences the concentration field in the positive electrode. The cell is studied during charging when compositional convection becomes apparent. First results of compositional convection from a non-uniform current distribution are presented, highlighting its capability to affect the flow in the positive electrode and the cell performance.

The present work initially studies the impact of a laboratory microwave (MW)’s location (before and after a jaw crusher) on grindability of a copper ore. Additionally, the role of MW’s radiation time (15–150 sec) and grinding time (13, 15 and 17 min) on the produced particle size distribution (PSD), mineral liberation degree (LD) and energy consumption are investigated. relative work index (RWI), standard Bond work index (Wi), and grindability index (GI) together with the breakage and selection functions were utilized to assess the grinding efficiency and its kinetics of the untreated and MW-pretreated (at a constant power of 0.9 kW) samples. Bond work indices were obtained 13.70, 13.04 and 10.86 kWh/t for the untreated, MW-treated uncrushed and MW-treated crushed samples, respectively. Besides, the results confirmed that the microwave pretreatment was comparatively effective at the shortest grinding time (13 min). Furthermore, locating the microwave after the crushing stage indicated substantial improvements in the sample’s grindability and its kinetics rate. The product size (P80) of the MW-treated crushed sample (13 min, 0.9 kW, 150 sec) showed enhancements of 27% and 17% in comparison with the un-microwaved and MW-treated uncrushed samples. Finally, the comparative GIs acquired in the entire spectrum of the particle range were reasonably higher if the microwave was located after the jaw crusher, particularly for the coarse fraction sizes.

The present work aims at investigating the effect of microwave local positions (i.e. before crushing (BC), after crushing (AC) and after milling (AM)) on microwave-assisted flotation of chalcopyrite and pyrite in a porphyry copper complex deposit. Individual given samples for each state were pre-treated with a variable power microwave at a power level of 90 to 900W for 15, 30, and 60s. Furthermore, froth floatation experiments were carried out using a laboratory mechanical Denver flotation cell on both microwave-treated and untreated samples. Particle surface properties were characterized by a scanning electron microscopy (SEM) and an energy-dispersive X-ray spectroscopy (EDX) analysis. The results showed that the chalcopyrite and pyrite floatabilities increased monotonically by rising the exposure time and power level for the uncrushed preconditioned samples (BC) due to the enhancement of mineral liberation degrees together with the formation of sulphide species and polysulphides on the mineral surfaces. However, flotation results of treated samples for the crushed one (AC) revealed an optimum range. Formation of intensive oxide layers on the mineral surfaces of milled samples (AM) led to a substantial reduction in their recoveries by increasing the microwave’s power level and the sample’s exposure time. The results obtained from mineral’s floatabilities in recleaner stage showed that the microwave-assisted sample at 900W for 30s at BC state favourably provided 5% higher S.E.’s than that of the untreated sample. Finally, it was concluded that the microwave pretreatment of samples induced the best floatability responses if it located before the crusher.

By means of Rutherford backscattering spectrometry, electron microscopy, and energy-dispersive X-ray spectroscopy, the distribution and interaction of In and As atoms implanted into thermally grown SiO2 films to concentrations of about 1.5 at % are studied in relation to the temperature of subsequent annealing in nitrogen vapors in the range of T = 800–1100°C. It is found that annealing at T = 800–900°C results in the segregation of As atoms at a depth corresponding to the As+-ion range and in the formation of As nanoclusters that serve as sinks for In atoms. An increase in the annealing temperature to 1100°C yields the segregation of In atoms at the surface of SiO2 with the simultaneous enhanced diffusion of As atoms. The corresponding diffusion coefficient is DAs = 3.2 × 10–14 cm2 s–1.

Hyperspectral image (HSI) classification has become a hot topic in the field of remote sensing. In general, the complex characteristics of hyperspectral data make the accurate classification of such data challenging for traditional machine learning methods. In addition, hyperspectral imaging often deals with an inherently nonlinear relation between the captured spectral information and the corresponding materials. In recent years, deep learning has been recognized as a powerful feature-extraction tool to effectively address nonlinear problems and widely used in a number of image processing tasks. Motivated by those successful applications, deep learning has also been introduced to classify HSIs and demonstrated good performance. This survey paper presents a systematic review of deep learning-based HSI classification literature and compares several strategies for this topic. Specifically, we first summarize the main challenges of HSI classification which cannot be effectively overcome by traditional machine learning methods, and also introduce the advantages of deep learning to handle these problems. Then, we build a framework that divides the corresponding works into spectral-feature networks, spatial-feature networks, and spectral-spatial-feature networks to systematically review the recent achievements in deep learning-based HSI classification. In addition, considering the fact that available training samples in the remote sensing field are usually very limited and training deep networks require a large number of samples, we include some strategies to improve classification performance, which can provide some guidelines for future studies on this topic. Finally, several representative deep learning-based classification methods are conducted on real HSIs in our experiments.

By considering the spectral signature as a sequence, recurrent neural networks (RNNs) have been successfully used to learn discriminative features from hyperspectral images (HSIs) recently. However, most of these models only input the whole spectral bands into RNNs directly, which may not fully explore the specific properties of HSIs. In this paper, we propose a cascaded RNN model using gated recurrent units to explore the redundant and complementary information of HSIs. It mainly consists of two RNN layers. The first RNN layer is used to eliminate redundant information between adjacent spectral bands, while the second RNN layer aims to learn the complementary information from nonadjacent spectral bands. To improve the discriminative ability of the learned features, we design two strategies for the proposed model. Besides, considering the rich spatial information contained in HSIs, we further extend the proposed model to its spectral-spatial counterpart by incorporating some convolutional layers. To test the effectiveness of our proposed models, we conduct experiments on two widely used HSIs. The experimental results show that our proposed models can achieve better results than the compared models.

Spectral features cannot effectively reflect the differences among the ground objects and distinguish their boundaries in hyperspectral image (HSI) classification. Multi-scale feature extraction can solve this problem and improve the accuracy of HSI classification. The Gaussian pyramid can effectively decompose HSI into multi-scale structures, and efficiently extract features of different scales by stepwise filtering and downsampling. Therefore, this paper proposed a Gaussian pyramid based multi-scale feature extraction (MSFE) classification method for HSI. First, the HSI is decomposed into several Gaussian pyramids to extract multi-scale features. Second, we construct probability maps in each layer of the Gaussian pyramid and employ edge-preserving filtering (EPF) algorithms to further optimize the details. Finally, the final classification map is acquired by a majority voting method. Compared with other spectral-spatial classification methods, the proposed method can not only extract the characteristics of different scales, but also can better preserve detailed structures and the edge regions of the image. Experiments performed on three real hyperspectral datasets show that the proposed method can achieve competitive classification accuracy.

Colourless crystalline compounds of centrosymmetric [Np(NO3)6]2− were yielded from 3 M HNO3 aq under presence of double-headed 2-pyrrolidone derivatives (L). In the obtained crystal structures, H+ was also involved as a countercation to compensate the negative charge of [Np(NO3)6]2−, where initial hydration around H+ was fully removed during crystallization despite its strongest hydration enthalpy. Instead, such an anhydrous H+ was captured by L to form a [H+···L]n hydrogen bond polymer. In [Np(NO3)6]2−, Np4+ centre is twelve-coordinated with 6 bidentate NO3−, and therefore, present in an icosahedral geometry bearing inversion centre. In such a centrosymmetric system, any f-f transitions stemming from 5f3 electronic configuration of Np4+ are electric-dipole forbidden. This is the reason why the compounds currently obtained were colourless unlike ordinary Np(IV) species with olive-green.

We report the optical and magneto-optical properties of amorphous and crystalline Co60Fe20B20 films with thicknesses in the range of 10 nm to 20 nm characterized using spectroscopy ellipsometry (SE) and magneto-optical Kerr effect (MOKE) spectroscopy. We derived the spectral dependence of the dielectric tensor from experimental data for samples prior and after annealing in vacuum. The features of the dielectric function can be directly related to the transitions between electronic states and the observed changes upon annealing can be ascribed to an increase of the crystalline ordering of CoFeB.

Uranium(VI) and Europium(III) can interact with Brassica napus suspension cell cultures. This can lead to bioassociation (immobilisation of metals due to the cell metabolism), which is discussed in more detail here. Heavy metal stress can also lead to the formation of protective metabolites by the plant cells, whose complex formation behaviour with U(VI) has been investigated.

Resonant X-ray absorption, where an X-ray photon excites a core electron into an unoccupiedvalence state, is an essential process in many standard X-ray spectroscopies. With increasingX-ray intensity, the X-ray absorption strength is expected to become nonlinear. Here, wereport the onset of such a nonlinearity in the resonant X-ray absorption of magnetic Co/Pdmultilayers near the Co L3edge. The nonlinearity is directly observed through the change ofthe absorption spectrum, which is modified in less than 40 fs within 2 eV of its threshold.This is interpreted as a redistribution of valence electrons near the Fermi level. For ourmagnetic sample this also involves mixing of majority and minority spins, due to sampledemagnetization. Ourfindings reveal that nonlinear X-ray responses of materials may alreadyoccur at relatively low intensities, where the macroscopic sample is not destroyed, providinginsight into ultrafast charge and spin dynamics.

In the present work, single-crystalline quasi-van der Waals ferromagnet Fe0.26TaS2 was successfully synthesized with Fe atoms intercalated at ordered positions between TaS2 layers. Its critical behavior was systematically studied by measuring the magnetization around ferromagnetic to paramagnetic phase transition temperature, TC∼100.7K, under different magnetic fields. The critical exponent β for the spontaneous magnetization below TC, γ for the inverse initial susceptibility above TC, and δ for the magnetic isotherm at TC were determined with modified Arrott plots, the Kouvel-Fisher method, the Widom scaling law, and critical isotherm analysis, and found to be the following values: β=0.459(6),γ=1.205(11), and δ=3.69(1). The obtained critical exponents are self-consistent and follow the scaling equation, indicating the reliability and intrinsicality of these parameters. A close analysis within the framework of renormalization group theory reveals that the spin coupling inside Fe0.26TaS2 crystal is of the three-dimensional Heisenberg ({d:n}={3:3}) type with long-range magnetic interaction and that the exchange interaction decays with distance as J(r)∼r-4.71

This work presents new calibration tools in the pyFAI suite for processing scattering experiments acquired with area detectors: a new graphical user interface for calibrating the detector position in a scattering experiment performed with a fixed, large area detector as well as a library to be used in Jupyter notebooks for calibrating the motion of a detector on a goniometer arm (or any other moving table) to perform diffraction experiments.

Rare earth elements (REE) are a group of seventeen elements consisting of scandium, yttrium as well as what are known as lanthanides. These elements are found only in a few regions worldwide in quantities worth mining. REEs are considered key components in the high-tech industry and are utilized, for example, in wind turbines, smartphones and energy-saving lamps.

Noble-metal chalcogenides, dichalcogenides and phosphochalcogenides are an emerging class of two- dimensional materials. Their properties can be broadly tuned via quantum confinement (number of layers) and defect engineering, including metal-to-semiconductor transitions, magnetic ordering, and topological surface states. They possess various polytypes, often of similar formation energy, which can be assessed by selective synthesis approaches. They excel in mechanical, optical and chemical sensing applications, and feature long-term air- and moisture stability. In this review, we summarize the recent progress in the field of noble metal chalcogenides and phosphochalcogenides and highlight the structural complexity and its impact on applications.

The energy-intensive dewatering of algae biomass, the first step of most downstream processes, remains one of the big challenges for economically relevant photoautotrophic bioprocesses. Due to its scalability and easy construction, froth flotation using the interactions between cells and bubbles shows considerable potential for this type of cost-efficient initial dewatering step. Comprehensive knowledge on both the physico-chemical conditions and the cellular surface properties are an important precondition to harvest cells by flotation. This study investigates the impact of changing the medium composition, specifically varying the pH and adding (bio-) collectors, on the zeta potential of Chlorella vulgaris SAG 211-1b. Decreasing the pH value from physiological to acidic conditions (pH 1–1.5) resulted in a strongly reduced cellular zeta potential. As validated by dispersed-air flotation, this yields a significantly enhanced cell recovery R > 95 %. The impact of the synthetic collector cetyltrimethylammonium bromide and the biopolymer chitosan on the cellular zeta potential and flotation performance was studied, resulting in a 3.3-fold decrease in the surfactant dose when chitosan was used . The basic mechanisms of cell-chitosan interaction were analysed in terms of particle size distribution and surface tension measurements, revealing interactions between flocculation and adsorption during the dispersed-air flotation of C.vulgarisSAG 211-1b.

Gold, Kupfer, Palladium und Seltene Erden sind wichtige Bestandteile von Smartphones und anderen Geräten unseres täglichen Lebens. Jedes dieser Metalle erfüllt ganz gezielt Aufgaben im Gerät und ist daraus nicht wegzudenken. Ihre Gewinnung aus den Bergbauminen dieser Erde ist häufig mit enormen Schäden für Mensch und Natur verbunden. Die Verwendung von recycelten Metallen bietet dazu eine deutlich umweltfreundlichere Alternative. Da die Metalle aber in sehr kleinen Mengen und fein verteilt im Gerät verbaut sind, ist ihr Recycling häufig nicht wirtschaftlich. Hier können neue biologische Recyclingwege Abhilfe leisten. Forscher des Helmholtz Instituts Freiberg für Ressourcentechnologie arbeiten an der Entwicklung von Metallspezifischen Antikörpern, welche gezielt ein Wertmetall nach dem anderen auch in kleinsten Konzentrationen in Form von Bioangeln aus einem Metallgemisch herausfischen können.

Präsentation der Arbeiten der Abteilung Biotechnologie des Helmholtz Institut Freiberg für Ressourcentechnologie sowie der Arbeiten der Nachwuchsforschergruppe BioKollekt

Recycling high-value products is a pivotal part of a circular economy. Current high-tech products contain a highly complex mixture of elements in low concentrations. Elements in these mixtures usually possess similar chemical and physical properties, which poses technical difficulties when considering a potential recycling process. Currently, only 22% terbium, 1% cerium and 1% lanthanum used in electronic devices like fluorescent light bulbs is recycled.1 A large proportion of these precious elements is lost. There is a need for novel techniques to be developed in order to recycle elements that are in low concentrations and in a complex matrix. Junior research group BioKollekt has begun the design and development of highly selective bio-based collector materials for a more sustainable recycling process of these elements. Biological peptide structures were identified in a highly competitive process for their selectivity and affinity for the fluorescent phosphor lanthanum phosphate doped with cerium and terbium (LAP). LAP-selective binding peptides coupled to a carrier material could be used in the future as separation tools for the selective recycling of LAP from lamp phosphors of fluorescent light bulbs. The BioKollekt approach uses LAP as a “proof of principle” to show the efficiency of biocollector materials. Figure 1 demonstrates the BioKollekt concept. The identification of highly selective biomolecules for preferred target materials (step 1) has been already achieved. In the second step, carrier materials (e.g. hydrophobic beads) will be functionalized with material binding-selective peptides. Biocollectors will interact selectively with their target material in a separation process (step 3-4). Finally, the target material and biocollector will be recycled and reused (step 5). The talk will present the BioKollekt concept and its achievements.

(0001) c-plane, (11-20) a-plane, and m-plane (10-10) ZnO bulk crystals were implanted with 400-keV Gd+ ions using fluences of 5 × 10¹⁴, 1 × 10¹⁵, 2.5 × 10¹⁵, and 5 × 10¹⁵ cm^-2. Structural changes during the implantation and subsequent annealing were characterized by Rutherford backscattering spectrometry in channeling mode (RBS-C); the angular dependence of the backscattered ions (angular scans) in c-, a-, and m-plane ZnO was realized to get insight into structural modification and dopant position in various crystallographic orientations. X-ray diffraction (XRD) with mapping in reciprocal space was also used for introduced defect identification. Defect-accumulation depth profiles exhibited differences for c-, a-, and m-plane ZnO, with the a-plane showing significantly lower accumulated disorder in the deeper layer in Zn-sublattice, accompanied by the preservation of ion channeling phenomena in a-plane ZnO. Enlargement of the main lattice parameter was evidenced, after the implantation, in all orientations. The highest was evidenced in a-plane ZnO. The local compressive deformation was seen with XRD analysis in polar (c-plane) ZnO, and the tensile deformation was observed in nonpolar ZnO (a-plane and m-plane orientations) being in agreement with RBS-C results. Raman spectroscopy showed distinct structural modification in various ZnO orientations simultaneously with identification of the disordered structure in O-sublattice. Nonpolar ZnO showed a significant increase in disorder in O-sublattice exhibited by E₂(high) disappearance and enhancement of A₁(LO) and E₁(LO) phonons connected partially to oxygen vibrational modes. The lowering of the E₂(low) phonon mode and shift to the lower wavenumbers was observed in c-plane ZnO connected to Zn-sublattice disordering. Such observations are in agreement with He ion channeling, showing channeling effect preservation with only slight Gd dopant position modification in a-plane ZnO and the more progressive diminishing of channels with subsequent Gd movement to random position with the growing ion fluence and after the annealing in c-plane and m-plane ZnO.

The periventricular region (PVR) has been shown to have an increased susceptibility to dose-dependent brain injury after proton therapy of gliomas (Eulitz 2019, Harrabi 2019). However, the PVR has not been considered in proton treatment planning so far. Here, we present an approach for incorporating the PVR as a novel organ at risk in proton treatment planning.

The PVR was defined as a 4 mm uniformly expanded margin around the ventricular system. The PVR tolerance dose was estimated as the observed near-min dose derived within late post-treatment radiation-associated contrast-enhancements (CE) on T1wCE-follow up images. All grade II/III glioma patients treated between 2014 and 2018 with (adjuvant) proton radio(chemo)therapy to 54/60 Gy(RBE), respectively, were analyzed. Retrospective PVR-sparing treatment planning was performed for 11 (4/7) consecutive glioma patients (Fig.1). Patient-wise comparison to the clinically delivered plans considered the near-max dose D2% and the volume Vx that received more than x% of prescribed dose in PVR tissue outside the target boost volume.

The median distance of the observed CE lesion centers to the cerebral ventricles was 2.5 mm. The median and near-min CE lesion dose was 57.6 Gy(RBE) and 53.0 Gy(RBE), respectively. PVR-sparing treatment planning reduced D2% and V90% by 4.3 (±1.4)% and 53.2 (±22.4)%, respectively, while maintaining clinical goals (Fig.1).

PVR-sparing in treatment planning is a promising approach to reduce late brain injury. In many cases this should be possible without compromising target coverage and field homogeneity. Further experience will improve the arrangement of PVR-sparing in the priority order of planning goals.

Introduction
The impact of adenosine A2A receptors (A2AR) in heart diseases is discussed diversely and only a few preclinical models are available. Therefore, we generated a transgenic mouse (TG) model with heart-specific overexpression of the human A2AR (hA2AR). The overexpressed hA2AR exhibited a cardioprotective, but proarrhythmic function, and A2AR agonists exerted a positive inotropic effect in vitro [1, 2]. Here, we show, that our new radioligand [18F]FLUDA can be used to assess hA2AR overexpression in murine heart by PET and to proof specific A2AR binding in human atrial samples by autoradiography.

Methods
FVB/N mice overexpressing the hA2AR under control of a α-MHC promotor were studied. Receptor autoradiography was used to determine Kd and Bmax of [18F]FLUDA in hearts of WT and TG mice (n=3). A 90 min dynamic µPET acquisition was performed to determine the biodistribution of [18F]FLUDA (7.4±3.4 MBq i.v.; Am=23-154 GBq/µmol) in wildtype (WT) and TG (n=3-5) after preinjection of vehicle or the A2AR antagonist tozadenant (2.5 mg/kg bw). The PET images were attenuation corrected by a T1-weighted MRI and list mode data were reconstructed (dynamic, 3D-OSEM algorithm). For activity quantification in tissues VOIs were determined by MRI images (Fig. 2A). In addition, the impact of 1µM FLUDA on the force of contraction (FOC) in isolated electrically driven atrial preparation was investigated.

Results
In vitro autoradiography of [18F]FLUDA in cryosections of hearts (Fig. 1) revealed a KD of 5.9 ± 1.6 nM and Bmax of 455 ± 78 fmol/mg protein in TG, whereas in WT the receptor density was too low for exact quantification. Using ZM241385 as competitor 36.3 ± 5.3 % specific binding of [18F]FLUDA was demonstrated in normal human atrial samples. PET/MR analyses revealed a 26 % (p<0.05) higher SUV ratio (SUVR) of myocard/blood (Fig.2B) in TG vs. WT mice. In TG mice the SUVR was reduced by tozadenant pre-treatment by 6 % (p<0.05) while no change in WT was observed. In electrically driven atrial preparations of TG (but not WT), FLUDA reduced the increase of FOC after CGS 2180 stimulation by about 20% (p<0.05), indicating a functional antagonism of FLUDA at the human cardiac A2AR.

Conclusion
FVB/N mice overexpressing the hA2AR are a useful model for non-invasive investigation of this receptor function with [18F]FLUDA PET. The demonstration of specific radiotracer binding in the human heart provides evidence that [18F]FLUDA might be a suitable radiotracer for assessment the A2AR status of human heart with PET. Our next steps will focus on the disease-related changes of the A2AR expression in human atrial samples with [18F]FLUDA.

Acknowledgments
The authors thank the European Regional Development Fund and Sächsische Aufbaubank (SAB) for financial support (project no. 100226753).

Keywords: [18F]FLUDA, adenosine, A2AR, heart

References
1. Boknik P, Drzewiecki K, Eskandar J, et al (2018) Phenotyping of mice with heart specific overexpression of A2A-adenosine receptors: Evidence for cardioprotective effects of A2A-adenosine receptors. Front Pharmacol 9:1–12. https://doi.org/10.3389/fphar.2018.00013
2. Boknik P, Drzewiecki K, Eskandar J, et al (2019) Evidence for arrhythmogenic effects of A2A-adenosine receptors. Front Pharmacol 10:1–12. https://doi.org/10.3389/fphar.2019.01051

Fig. 1: Representative autoradiography of 20 µm cryosections of a FVB/N mouse heart overexpressing the human adenosine A2AR (A2AR-TG), showing the total binding of [18F]FLUDA (left) and the non-homologous competition of [18F]FLUDA with the A2AR specific antagonist ZM241385 (right).


Fig. 2: A) Representative MR image (left), PET image (middle) and merged overlay (right) of one slice in the short axis orientation of TG mouse heart used for the determination of VOIs.; B) standardized uptake value ratio (SUVR) of myocard over blood under baseline (veh – vehicle) and blocking conditions (toz- tozadenant) in wildtype (WT) and myocard specific hA2AR overexpressing mice (TG); n=3-5, *p≤0.05 WT vs. TG and #p≤0.05 veh vs. toz.

Question
We have shown that A2A adenosine receptors (A2A-AR) are functionally active in human hearts. Moreover, we generated a transgenic mouse model with heart specific overexpression of the human A2A-AR (TG), which responded to agonists with a positive inotropic effect in vitro. Overexpressed A2A-AR were cardioprotective but also proarrhythmic in TG (Boknik et al. Front Pharmacol 2018, 2019). Here, we focused on the question if a cardiac A2A-AR expression could be assessed in vivo utilizing PET imaging in this model.

Methods
The impact of FLUDA (7-(3-(4-(2-(fluoro)ethoxy-1,1,2,2-d4)phenyl)propyl)-2-(furan-2-yl)-7H-pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidin-5-amine; patent: DE 10 2019 116 986.0) on the force of contraction (FOC) in isolated electrically driven (1 Hz) atrial preparation after stimulation with the A2A–AR-agonist CGS 2180 (10 µM, in the presence of the A1A-AR antagonist DPCPX 1 µM) was measured. On cryosections of mouse hearts the KD and Bmax values of [18F]FLUDA were determined by autoradiography. A small animal PET/MRI scanner (nanoscan, Mediso) was used for in vivo imaging of mice under isoflurane anaesthesia. [18F]FLUDA (7.4±3.4 MBq) was applied via the tail vein 20 s after starting the 90-minute PET measurement. A2A-AR specificity of [18F]FLUDA was determined by application of 2.5 mg/kg body weight Tozadenant 10 minutes prior to tracer administration.

Results
FLUDA was able to reduce (p<0.05) the increase of FOC after CGS 2180 stimulation by about 20 % (p<0.05) in isolated electrically driven atrial preparation in TG (but not WT), indicating a functional antagonism of FLUDA at the human cardiac A2A-AR. By in vitro autoradiography of [18F]FLUDA a KD (5.9±1.6 nM) and Bmax (455±78 fmol/mg protein) could be determined in the A2A-AR-TG hearts, whereas in the control hearts the receptor density was below the detection limit. Using PET/MR, an SUV ratio (SUVR) myocardial/cardiac ventricle of ≥1,0 was determined for the A2A-AR-TG animals at 15-30 min p.i.. Tozadenant reduced SUVR by 6 % (p<0.05).

Conclusion
These data suggest that A2A-AR can be in principle quantified in vivo in the heart.

A2AR-Liganden sind bei ischämischen Reperfusionsschäden kardioprotektiv wirksam (1). Somit ist eine Diagnose der kardialen A2AR-Verfügbarkeit für die Behandlung von Patienten mit koronaren Erkrankungen bedeutsam. Unser Ziel war es, anhand eines transgenen Mausmodells mit einer kardialen Überexpression des humanen A2AR das Potential von [18F]FLUDA als potentielles Radiopharmakon für die Darstellung des A2AR zu evaluieren.
Es wurden 4-6 Monate alte FVB/N Mäuse mit einer Kardiomyozyten-spezifischen Überexpression des humanen A2AR (A2AR TG) bzw. Kontrolltiere untersucht. Die Bestimmung der KD- und Bmax-Werte von [18F]FLUDA erfolgte autoradiographisch an Kryoschnitten von Herzexplantaten. Die In-vivo-Untersuchungen fanden unter Isoflurannarkose in einem Kleintier-PET/MRT-Scanner (nanoscan, Mediso) statt. [18F]FLUDA (7,4±3,4 MBq) wurde i.v. über die Schwanzvene 20 s nach Start der 90-minütigen PET-Messung appliziert. Die A2AR-Spezifität von [18F]FLUDA wurde durch Applikation von 2,5 mg/kg Tozadenant 10 min vor der Tracer Gabe bestimmt. Für die anatomische Korrelation und Schwächungskorrektur der PET-Aufnahmen erfolgte eine T1-gewichtete MRT. Die dynamische Rekonstruktion der Listenmodus-Daten erfolgte durch einen 3D-OSEM-Algorithmus. Die Quantifizierung der aufgenommenen Aktivität erfolgte mit PMOD.
Mittels In-vitro-Autoradiografie von [18F]FLUDA konnten in den A2AR-TG Herzen die Rezeptorparameter KD (5,9 ± 1,6 nM) und Bmax (455 ± 78 fmol/mg Protein) bestimmt werden, während in den Herzen der Kontroll-Tiere die Rezeptordichte unter der Nachweisgrenze lag. Mittels PET/MR wurde 15–30 min p.i. für die A2A-R TG Tiere ein SUV-Verhältnis (SUVR) Myokard/Herzventrikel von ≥1,0 bestimmt. Tozadenant verminderte das SUVR um 6 % (p < 0.05).
[18F]FLUDA ist ein vielversprechender Radiotracer zur Untersuchung der A2AR Verfügbarkeit im Herzen.
(1) Boknik P, et al., Front Pharmacol. 2018; 9:1–12.

Multiconfigurational wavefunction based methods are the state of the art methods to quantitatively compute excited state energies and transition moments for heavy element systems where the inclusion of electron correlation and relativistic effects is crucial. Since the advent of these methods, e.g. the complete active-space self-consistent field (CASSCF) method and the density-matrix renormalization group (DMRG) method, it is possible to accurately interpret and predict the UV-Vis spectra of these heavy element systems.
In this talk the CASSCF and DMRG methods are introduced and used to simulate the UV-Vis spectrum of the Uranium-bissalen complex. The active space is set up and varied to accurately describe the wavefunction. CASPT2 and RASSI are used to obtain quantitative results for excited state energies and transition moments.

The contribution of the f-orbitals to chemical bonding leads to the rich chemistry of the actinides. This is in contrast to the lanthanides, where it is known that this contribution is less important. Of special interest is the influence of these orbitals on the bonding character of actinides and lanthanides with organic ligands reflecting natural binding motifs.
This study compares the different bonding behavior of tetravalent actinides and lanthanides with the Schiff base salen by means of real-space bonding analysis. Our approach makes use of the quantum theory of atoms in molecules (QTAIM), non-covalent interaction (NCI) analysis and density differences complemented by natural population analysis (NPA). Especially the local properties at the bond critical points, for instance charge, density, ellipticity and others, can be used to characterize a bond’s order, strength, and covalent contribution.
First results reveal a strong interaction of the actinides, i.e. Th to Pu, with the oxygen of salen characterized by a high electron density concentration between the atoms. In contrast, the interaction between the actinides and the nitrogen of salen is much weaker. The delocalization index, density and Laplacian reveal a significant increase of covalency for Pa to Pu compared to Th and Ce being an indicator of the contribution of the f-electrons. Tetravalent Ce as a lanthanide analogue of Th is expected to show a similar bonding behavior, but, surprisingly, this is not the case for all investigated bonding properties.
This detailed analysis of the electronic properties of actinide compounds will help to improve understanding of their behavior in the environment as well as in technical processes and leads to the possibility to predict properties of unknown complexes.

The calculation of the excited states of actinide systems is a challenging task because of the delicate influence of electron correlation and relativistic effects. Density functional theory is not applicable for obtaining quantitative results, hence multiconfigurational wavefunction based methods have to be used. State of the art is a combination of spinfree CASSCF and CASPT2/NEVPT2 and a following inclusion of spin-orbit coupling.
This talk presents quantitative excited state energy calculations of simple Protactinium and Uranium systems in comparison with qualitative group-theoretical considerations.

The contribution of the f-orbitals to chemical bonding leads to the rich chemistry of the actinides. This is in contrast to the lanthanides, where it is known that this contribution is less important. Of special interest is the influence of these orbitals on the bonding character of actinides and lanthanides with organic ligands reflecting natural binding motifs.
This study compares the different bonding behavior of tetravalent actinides and lanthanides with the Schiff base salen by means of real-space bonding analysis. Our approach makes use of the quantum theory of atoms in molecules (QTAIM), non-covalent interaction (NCI) analysis and density differences complemented by natural population analysis (NPA). Especially the local properties at the bond critical points, for instance charge, density, ellipticity and others, can be used to characterize a bond’s order, strength, and covalent contribution.
First results reveal a strong interaction of the actinides, i.e. Th to Pu, with the oxygen of salen characterized by a high electron density concentration between the atoms. In contrast, the interaction between the actinides and the nitrogen of salen is much weaker. The delocalization index, density and Laplacian reveal a significant increase of covalency for Pa to Pu compared to Th and Ce being an indicator of the contribution of the f-electrons. Tetravalent Ce as a lanthanide analogue of Th is expected to show a similar bonding behavior, but, surprisingly, this is not the case for all investigated bonding properties.
This detailed analysis of the electronic properties of actinide compounds will help to improve understanding of their behavior in the environment as well as in technical processes and leads to the possibility to predict properties of unknown complexes.

Traditional exploration techniques usually rely on extensive field work supported by geophysical ground surveying. However, this approach can be limited by several factors such as field accessibility, financial cost, area size, climate, and public disapproval. We recommend the use of multiscale hyperspectral remote sensing to mitigate the disadvantages of traditional exploration techniques. The proposed workflow analyzes a possible target at different levels of spatial detail. This method is particularly beneficial in inaccessible and remote areas with little infrastructure, because it allows for a systematic, dense and generally noninvasive surveying. After a satellite regional reconnaissance, a target is characterized in more detail by plane-based hyperspectral mapping. Subsequently, Remotely Piloted Aircraft System (RPAS)-mounted hyperspectral sensors are deployed on selected regions of interest to provide a higher level of spatial detail. All hyperspectral data are corrected for radiometric and geometric distortions. End-member modeling and classification techniques are used for rapid and accurate lithological mapping. Validation is performed via field spectroscopy and portable XRF as well as laboratory geochemical and spectral analyses. The resulting spectral data products quickly provide relevant information on outcropping lithologies for the field teams. We show that the multiscale approach allows defining the promising areas that are further refined using RPAS-based hyperspectral imaging. We further argue that the addition of RPAS-based hyperspectral data can improve the detail of field mapping in mineral exploration, by bridging the resolution gap between airplane- and ground-based data. RPAS-based measurements can supplement and direct geological observation rapidly in the field and therefore allow better integration with in situ ground investigations. We demonstrate the efficiency of the proposed approach at the Lofdal Carbonatite Complex in Namibia, which has been previously subjected to rare earth elements exploration. The deposit is located in a remote environment and characterized by difficult terrain which limits ground surveys.

Active tumor targeting involves the decoration of nanomaterials (NM) with oncotropic vector biomolecules that selectively recognize certain antigens on malignant cells or in the tumor microenvironment. This strategy can facilitate intracellular uptake of NM through specific interactions such as receptor-mediated endocytosis and can lead to prolonged retention in the malignant tissues by preventing rapid efflux from the tumor. Here, the design of actively targeting, renally excretible bimodal dendritic polyglycerols (dPGs) for diagnostic cancer imaging is described. Single-domain antibodies (sdAb) specifically binding to the epidermal growth factor receptor (EGFR) are employed herein as targeting warheads owing to their small size and high affinity for their corresponding antigen. The dPGs equipped with EGFR-targeting feature are compared head-to-head with their non-targeting counterparts in terms of interaction with EGFR-overexpressing cells in vitro as well as accumulation at receptor-positive tumors in vivo. Experimental results reveal a higher specificity and preferential tumor accumulation for the α-EGFR dPGs, resulting from the introduction of active targeting capabilities on their backbone. These results highlight the potential for improving the tumor uptake properties of dPGs by strategic use of sdAb functionalization, which could ultimately prove useful to the development of ultrasmall NM with highly specific tumor accumulation.

Transmission imaging in the helium ion microscope allows to measure mass-thickness contrast and reveal crystallographic information. We recently customized a microchannel plate followed by a delay line readout structure especially for this application. This system can correlate the scanning transmission ion image to the angular distribution of the transmitted ions. An in-vacuum linear support is used to place the detector at different distances from the sample, adjusting the maximum collection angle. Post-processing allows the reconstruction of images for selected scattering angles. The first results show images with nanometer resolution, material contrast, and identification of sub-surface features in biological tissues. This work has been supported by the H2020 Project npSCOPE under grant number 720964.

We report time-resolved X-ray Absorption Near Edge Spectroscopy (XANES) measurements of warm dense MgO. We used a high power nanosecond pulse to drive a strong uniform shock wave into an MgO sample, and a picosecond pulse to generate a broadband X-ray source near the Mg K-edge. We used this setup to obtain XANES spectra across a large area of the phase diagram, with densities up to 6.8 g/cc and temperatures up to 30 000 K, conditions at which no prior investigations of electronic and ionic structure exist. Our XANES results, together with quantum molecular dynamic simulations, demonstrate that the sample metallizes due to the bandgap closure as it melts, after which it shows typical behavior for a disordered ionic liquid.

The presentation gives an overview of the NORM research at the HZDR

Inside evaporators of air-conditioning systems, uneven mass flow distribution of refrigerant leads to a loss of efficiency and finally a reduction of comfort in passenger compartments. The distribution is influenced by the flow field and two-phase distribution (flow pattern) in various elements, comprising developing and developed two-phase flow in straight and angled ducts, headers, flat tubes and the connection between these.
This talk presents on-going efforts to predict this type of flow with CFD.
In a first step, extensive experimental investigations on generic geometries are done using advanced measurement techniques. This data are then used to develop and validate numerical models capable of reproducing the relevant physics.
Important two-phase phenomena are: multiple regimes (continuous-disperse + separated flow), wall films, stripping/impingement, particle size distribution, two-phase heat transfer, boiling/condensation. In a final step, the developed modeling strategy is applied to real evaporators.
In comparing simulation results to experimental data, we find both good agreement as well as discrepancies which confirm that there is still more work on developing appropriate models to do.

The trans influence is an extensively investigated electronic concept in transition metal chemistry. It can be defined as the extent to which a bond in trans position to a ligand L is weakened.[1,2] In contrast, f-block elements exhibit an opposite effect, meaning a bond shortening and thus strengthening can be observed in the trans position to a strongly donating ligand. This is established as the inverse trans influence (ITI),[3–5] and is commonly assumed to be most prominent for actinides in high oxidation states.
A novel UIVbis(carbene) complex [UIV(L¹)₂(TMSA)Cl₃] 1 (L¹ = iPr₂Im, TMSA = (N(SiMe₃)₂)−) was synthesized by salt metathesis from UCl4 in the presence of iPrImHCl and TMSA. In the complex, the U centre is surrounded by two carbenes, three chloro- and one TMSA-ligand. The U–Cl bond in trans position to the TMSA is slightly shorter (0.01 Å) compared to the other U–Cl bonds, indicating an TMSA-induced ITI. However, this change is very small. For comparison, a structural optimization based on the SC-XRD data of 1 was carried out using tetravalent tungsten as a d-block analogue, because of its similar ionic radius to UIV. Tungsten’s transition metal behaviour should result in a trans influence. In the WIVbis(carbene) complex 2, the W–Cl bond trans to the TMSA ligand is indeed 0.05 Å longer than the other W–Cl bonds. This large change expresses the existence of a strong trans influence in 2 and hence ITI in 1.
References:
[1] A. Pidcock, R. E. Richards, L. M. Venanzi, J. Chem. Soc. Inorg. Phys. Theor. 1966, 0, 1707–1710.
[2] T. G. Appleton, H. C. Clark, L. E. Manzer, Coord. Chem. Rev. 1973, 10, 335–422.
[3] R. G. Denning, J. Phys. Chem. A 2007, 111, 4125–4143.
[4] H. S. La Pierre, K. Meyer, Inorg. Chem. 2013, 52, 529–539.
[5] M. Gregson, E. Lu, D. P. Mills, F. Tuna, E. J. L. McInnes, C. Hennig, A. C. Scheinost, J. McMaster, W. Lewis, A. J. Blake, et al., Nat. Commun. 2017, 8, 14137.

The inverse trans influence (ITI) is an effect well-known to occur in high valent U(V/VI) complexes. It appears as a shortening of the M–L bond in trans position to a strongly donating ligand. The effect can be explained by electron density donation from the strong ligand to the metal center, which fills up the electron hole formed through electron density transfer from semi-core 6p to vacant 5f orbitals.[1,2] This results in the observed contraction and strengthening of the bond trans to the donating ligand.
To compare the ITI in UIV and UV complexes, the U compounds UIV(L¹)₂(TMSA)Cl₃] 1 (L¹ = iPr₂Im, TMSA = (N(SiMe₃)₂)−) and [UV(TMSI)Cl₅, but is in the same range as the other chloro ligands. The absence of a notable ITI can be attributed to intermolecular interactions in the crystal structure of 2. Structure optimization of the molecular UV complex dianion by DFT yield a U–Cl5 bond length of 2.55 Å, shorter than any other U–Cl bond by 0.02 Å. The difference between experiment and theory results from a great number of electrostatic interactions and hydrogen bonding between the complex dianion and the carbene counterions in 2. Similar intermolecular interactions are not present in the crystal structure of 1, which is why the ITI could be observed for this compound.
The results demonstrate that the ITI affects complex structures for both, UIV and UV compounds, but additional effects, such as the intermolecular network observed in the structure of 2 can surpass its relatively small structural contribution.

References
[1] M. Gregson, E. Lu, D. P. Mills, F. Tuna, E. J. L. McInnes, C. Hennig, A. C. Scheinost, J. McMaster, W. Lewis, A. J. Blake, et al., Nat. Commun. 2017, 8, 14137.
[2] B. Kosog, H. S. La Pierre, F. W. Heinemann, S. T. Liddle, K. Meyer, J. Am. Chem. Soc. 2012, 134, 5284–5289.

The inverse trans influence (ITI) is an effect well-known to occur in high valent U(V/VI) complexes. It appears as a shortening of the M–L bond in trans position to a strongly donating ligand. The effect can be explained by electron density donation from the strong ligand to the metal center, which fills up the electron hole formed through electron density transfer from semi-core 6p to vacant 5f orbitals.[1,2] This results in the observed contraction and strengthening of the bond trans to the donating ligand.
To compare the ITI in UIV and UV complexes, the U compounds UIV(L¹)₂(TMSA)Cl₃] 1 (L¹ = iPr₂Im, TMSA = (N(SiMe₃)₂)−) and [UV(TMSI)Cl₅, but is in the same range as the other chloro ligands. The absence of a notable ITI can be attributed to intermolecular interactions in the crystal structure of 2. Structure optimization of the molecular UV complex dianion by DFT yield a U–Cl5 bond length of 2.55 Å, shorter than any other U–Cl bond by 0.02 Å. The difference between experiment and theory results from a great number of electrostatic interactions and hydrogen bonding between the complex dianion and the carbene counterions in 2. Similar intermolecular interactions are not present in the crystal structure of 1, which is why the ITI could be observed for this compound.
The results demonstrate that the ITI affects complex structures for both, UIV and UV compounds, but additional effects, such as the intermolecular network observed in the structure of 2 can surpass its relatively small structural contribution.

References
[1] M. Gregson, E. Lu, D. P. Mills, F. Tuna, E. J. L. McInnes, C. Hennig, A. C. Scheinost, J. McMaster, W. Lewis, A. J. Blake, et al., Nat. Commun. 2017, 8, 14137.
[2] B. Kosog, H. S. La Pierre, F. W. Heinemann, S. T. Liddle, K. Meyer, J. Am. Chem. Soc. 2012, 134, 5284–5289.

Introduction
Due to the beneficial inverse physical depth-dose profile, proton radiotherapy (RT) offers the potential to reduce normal tissue toxicity by depositing the maximum dose within the tumor volume while sparing the surrounding tissue. However, range uncertainties and necessary clinical safety margins in combination with varying relative biological effectiveness (RBE) may result in a critical dose in tumor-surrounding normal tissue. Dedicated preclinical studies have been proposed to assess and better understand potential adverse effects of proton RT using image-guided proton irradiation of mouse brain. Here, we present the entire workflow from pre-treatment imaging, over treatment planning, mouse brain irradiation as established at the University Proton Therapy Center Dresden as well as first results from subsequent DNA damage analysis.

Materials & Methods
An experimental setup was designed and characterized to shape proton beams with 7 mm range in water and 3 mm diameter allowing for irradiation of the mouse brain´s right hemisphere. To simulate the dose distributions in vivo, a Monte Carlo model of the proton beam was designed in the simulation toolkit TOPAS, experimentally commissioned and validated. Cone-beam computed tomography (CT) and orthogonal X-ray imaging were used to delineate the hippocampus as target and position the mice at the proton beam. Mouse brains of C3H and C57BL/6 mice were irradiated with 4 Gy or 8 Gy in a single fraction and excised at different timepoints after irradiation. The number of remaining DNA double-strand break repair proteins was visualized by staining brain sections for cell nuclei and H2AX. Imaged sections were analyzed with an automated and validated processing pipeline to provide quantitative data on spatially resolved radiation damage distributions.
Results
Animals were planned and treated for proton irradiation of the right hippocampus with a proton beam stopping in the center of the brain. The analysis of irradiated brain sections revealed well-delimited sub-volumes of pronounced DNA damage in the right brain hemisphere. The registration of the brain sections with the CT anatomy revealed that the measured DNA damage pattern were in good spatial agreement with the planned dose distributions simulated in individual mouse brains. The cellular radiation response could be correlated with dose and LET on a sub-milimeter scale.
Conclusion:
Image-guided proton irradiation of mouse brains was established with a clinically oriented workflow that facilitates (back-) translational studies. The geometric accuracy, detailed Monte Carlo dose simulations and cell-based assessment enable a biologically and spatially resolved analysis of radiation response and RBE.

The incorporation of trivalent lanthanides and actinides into zirconia (ZrO₂) was studied using PXRD and spectroscopic methods (EXAFS, TRLFS). In highly doped cubic zirconia three Eu(III) incorporation species could be found using TRLFS. A surface associated species with an excitation maximum of 578.1 nm and two bulk incorporation species with excitation maxima at 579.0 and 579.7 nm were found.

The incorporation of trivalent lanthanides and actinides into zirconia (ZrO₂) was studied using PXRD and spectroscopic methods (EXAFS, TRLFS). In highly doped cubic zirconia three Eu(III) incorporation species could be found using TRLFS. A surface associated species with an excitation maximum of 578.1 nm and two bulk incorporation species with excitation maxima at 579.0 and 579.7 nm were found.

Introduction
The integration of real-time MRI is expected to improve the targeting precision of proton therapy. We have developed a first prototype setup of an in-beam MRI scanner at a proton pencil beam scanning (PBS) beam line. The aim of this study was to investigate the effects of the dynamic magnetic fringe fields of the PBS beam steering magnets on the MR image quality during simultaneous irradiation and MR image acquisition.
Materials and methods
A 0.22 T open MR scanner was positioned in front of the horizontal PBS research beam line. 2D planar dose spot application was achieved by magnetic beam steering in horizontal and vertical direction through a pair of fast scanning magnets.
A proton pencil beam of 220 MeV was subsequently scanned along a horizontal and vertical central line in the MR imaging field. The irradiation time matched the acquisition time of a single-slice gradient echo sequence, while imaging a homogeneous transversal slice of the ACR Small Phantom. The image quality was evaluated qualitatively and compared to reference images acquired without beam scanning.
Results and conclusions
MR images acquired during vertical beam scanning showed no visual differences to reference images, whereas images acquired during horizontal beam scanning showed coherent ghosting artefacts in phase encoding direction. The artefacts exhibit a systematic behavior in which the number of ghosts is inversely proportional to the number of dose spots scanned. The phase maps of the k-space data prove that the artefacts are caused by phase offsets between adjacent lines, which result from changes in the MR resonance frequency due to the dynamic fringe fields of the beam scanning magnets in the PBS nozzle.
Now the origin of the ghosting artefacts is well understood, appropriate means for magnetic shielding or k-space data post-processing have to be implemented and studied to eliminate these artefacts.

Due to its relevance for technical applications, experimental and theoretical investigation on flashing flows through nozzles and tubes has gained great attention. Most of them have focused on area-averaged quantities such as mass flow rate and pressure drop, while little attention has been paid to the internal flow structure and interfacial exchanging processes. More recently, computational fluid dynamics is frequently utilized to explore the phase distribution in the flashing flows. Various gas-liquid mixture or two-fluid models have been proposed in the literature. However, knowledge on the non-equilibrium effects, interphase transfer as well as bubble dynamics under different flashing conditions is still insufficient, and a general and precise definition of the problem in numerical simulations remains a challenge. A broad consensus on the numerical methods for flashing flows is not available. Guidelines for selecting an appropriate model are desirable, which is, however, not an easy task due to the complex physics and lack of insights. The talk is focused on the elucidation of important interfacial processes such as interfacial area density, interfacial heat transfer, bubble nucleation, coalescence and breakup as well as available modelling approaches. Numerical simulations for various flashing scenarios, i.e. converging-diverging flow, pipe-blowdown, natural circulation loop and pressure release transient, are presented. The influence of chosen numerical methods is discussed, especially the mixture model versus two-fluid ones and mono-disperse versus poly-disperse approaches. Progresses towards developing a general framework for modelling of complex gas-liquid flows are demonstrated.

Introduction: We established a 4D logfile-based dose reconstruction for monitoring and potential intervention during intensity-modulated proton therapy (IMPT) of moving tumors. Before clinical application, we assessed the validity of reconstructed doses and the sensitivity against changes of selected input parameters by phantom experiments.
Material/Methods: A dynamic thorax phantom (CIRS, USA) with a soft-tissue target and radiochromic film insert was imaged by 4DCT and irradiated with either quasi-monoenergetic fields or 4D optimized proton plans. The surrogate signal (ANZAI, Japan) of the regular motion was recorded in synchronization with the machine logfiles. Reconstructions were performed with different dose grid resolutions (1mm/3mm), deformable image registrations (DIR; manually defined or automatically generated vector-fields) and artificial asynchronies between machine and motion logfiles.
Results: Characteristic dose patterns on radiochromic films were well reconstructed (Fig.1A). Gamma pass rates (2mm, 2%) for extracted characteristic profiles of the reconstructed and measured doses were >98% under static conditions, ranged between 99% and 86% for 5mm motion depending on applied reconstruction parameters, especially the DIR, and were about 80% for 30mm motion due to the predominant residual motion in the 4DCT (Fig.1B). Fig.1C demonstrates the robustness against potential minor asynchronies (≈5ms) between machine and motion logfiles. A workflow test during a pancreatic cancer IMPT treatment (Fig.2) revealed a data processing time of approximately 20min/fraction.
Conclusions: Due to satisfying accuracy and robustness for clinically aimed motion amplitudes (≤5mm), IMPT treatment of non-small cell lung cancer accompanied by daily 4D logfile-based dose monitoring will start in our institute within the first months of 2020.

Tri- and tetravalent actinide amidinates have been synthesized and characterized in solid state and in solution.

Recently, based on data from Direct Numerical Simulations (DNS), Ma et al. (Phys. Rev. Fluids 2, 034301, 2017) proposed a model for closing the bubble-induced turbulence (BIT) in a typical Euler-Euler two-equation model, which appears to yield improved performance for predicting $k$ and $\varepsilon$ over the previous models. The present study departures from this BIT model and purpose to use the same DNS data to investigate the behavior of the $C_\mu$ constant and standard eddy viscosity definition. It can be shown that $C_\mu$ constant computed using the DNS database has a very different behavior than that in single-phase flow. Checking closely, the deficiency originates from the description of the standard eddy viscosity that is intrinsic to this general hierarchy of Euler-Euler $k-\varepsilon$ type model, hence, cannot be overcome by a more complex correction function for $C_\mu$. Departing from this point, a modification to the definition of the eddy viscosity in bubbly flows is derived for the Euler-Euler two-equation models. The new expression is based on the bubble length-scale and its corresponding velocity scale. We focus on the intermediate region -- a region extended from the core region, where bubble-induced production and dissipation are nearly in balance, and find that the modified model can lead to significantly improved predictions for the mean liquid, when compared with DNS data.

Industrial applications feature a huge variety of different flow patterns, such as bubbly flow, slug flow or annular flow. Thereby a broad range of flow morphologies and different physical scales is involved. With the objective of reproduction of occurring phenomena with one single multi-fluid solver, we present an Euler-Euler-approach, which combines a number of different methods for treatment of the partial aspects. The implementation into OpenFOAM is always with focus on sustainable research, including a state-of-the-art IT concept. A segregated approach is used for treatment of the phase momentum equations, phase fraction equations and the pressure equation, featuring a consistent momentum interpolation scheme (Cubero et al., 2014). To fulfil the kinematic condition at resolved interfaces between different continuous phases, the latter may be coupled either by an isotropic (Strubelj and Tiselj, 2011) or by an anisotropic drag. In both cases, the immensely strong phase coupling requires an adapted numerical method. State and evolution of bubble size distribution in disperse phase context is solved with either class or moment methods.
The overall objective is to take interactions between the all different aspects, such as disperse phases, resolved interfaces and turbulence with effects on momentum and mass transfer into account.

The reactingEulerFoam framework included in OpenFOAM releases since 3.0.0 provides a highly flexible platform for the modelling of multiphase flows. Extensive selection of interfacial force models is provided along with alternate turbulence models. The thermal phase change capability [1,2] was first introduced in OpenFOAM 3.0.1 [3] and has since been extended and refined in subsequent releases.
The current OpenFOAM 7 release features include support for non-equilibrium wall boiling, n-phase thermal phase change and for bubble diameter modelling algebraic, IATE and inhomogeneous class method models are supported.The present simulations have been carried out with the OpenFOAM Foundation development release [4]. The goal is to aid those that intend to use the publicly available reactingEulerFoam by providing a summary of the models and demonstrations of a few modelling details by expanding upon tutorials recently added to the OpenFOAM Foundation development line.
DEDALE experiments [5] are used as a reference for the non-drag interfacial force modelling.
Subcooled nucleate boiling simulation results with different models combinations are compared to the DEBORA experiments [6,7]. Finally, a more complex direct contact condensation simulation of SEF-POOL test facility [8] is presented and results are compared to the experiment.

References

[1] Peltola, J., & Pättikangas, T.J.H. Development and validation of a boiling model for OpenFOAM multiphase solver. CFD4NRS-4 Conference Proceedings, Daejeon, Korea, paper 59, (2012).
[2] Peltola, J., Pättikangas, T., Bainbridge, W., Lehnigk, R., Schlegel, F., On development and validation of subcooled nucleate boiling models for OpenFOAM Foundation release. NURETH-18 Conference Proceedings, Portland, Oregon, United States (2019).
[3] OpenFOAM Foundation, “OpenFOAM 3.0.1,” http://openfoam.org/version/3.0.1/ (2015).
[4] OpenFOAM Foundation, “OpenFOAM-dev,” https://openfoam.org/version/dev/ (2014-2019).
[5] Grossetete, C., Experimental investigation and numerical simulations of void profile development in a vertical cylindrical pipe (No. EDF--96-NB-00120). Electricite de France (EDF), (1995).
[6] E. Manon, Contribution à l’anayse et à la modélisation locale des écoulements boillants sous-saturésdans les conditions des Réacteurs à Eau sous Pression, PhD thesis, Ecole Centrale Paris (2000).
[7] J. Garnier, E. Manon, G. Cubizolles, “Local measurements on flow boiling of refrigerant 12 in avertical tube”, Multiphase Science and Technology, pp. 1-111 (2001).
[8] M. Puustinen, J. Laine, A. Räsänen, E. Kotro, and K. Tielinen, “Characterizing tests in SEF-POOLfacility,” Technical Report, Lappeenranta University of Technology, Nuclear Engineering, INSTAB3/2017 (2017).

The presentation gives a detailed insight into the OpenFOAM Developments for Euler-Euler simulations at HZDR, i.p. the multi-field two-fluid model approach, LES simulations, stratified flow simulations, entrainment modelling and more. Furthermore, the successfull development strategy and co-working with the OpenFOAM Foundation is explained.

The AER Working Group D on VVER reactor safety analysis held its 28th meeting in Garching, Germany, during the period 26-27 June, 2019. The meeting was hosted by GRS Garching and was held in conjunction with the second workshop on multi-physics MPMV-2 and the first workshop on the ROSTOV-2 benchmark. Altogether 20 participants from eleven AER member organizations and seven guests attended the meeting of the working group D. The co-ordinator of the working group, Mr. S. Kliem, served as the chairperson of the meeting.

The meeting started with a general information exchange about the recent activities in the participating organizations.

The given 12 presentations and the discussions can be attributed to the following topics:

• Safety analyses methods and results
• Code development and benchmarking
• Future activities

A list of the participants and a list of the handouts distributed at the meeting are attached to the report. The corresponding PDF-files of the handouts can be obtained from the chairperson.

An extensive understanding about the microstructural evolution and thermal stability of the metastable AlCr(Si)N coating system is of considerable importance for applications facing high temperatures, but it is also a challenging task since several superimposed processes simultaneously occur at elevated temperatures. In this work, three AlCr(Si)N coatings with 0 at.%, 2.5 at.% and 5 at.% Si were investigated by in-situ high-temperature high-energy grazing incidence transmission X-ray diffraction (HT-HE-GIT-XRD) and complementary differential scanning calorimetry and thermogravimetric analysis measurements combined with conventional ex-situ X-ray diffraction. The results revealed (i) a change in the microstructure from columnar to a fine-grained nano-composite, (ii) a reduced decomposition rate of CrN to Cr₂N, also shifted to higher onset temperatures from ∼ 1000 ℃ to above 1100 ℃ and (iii) an increase of lattice defects and micro strains resulting in a significant increase of compressive residual strain with increasing Si content. While the Si-containing coatings in the as-deposited state show a lower hardness of 28 GPa compared to AlCrN with 32 GPa, vacuum annealing at 1100℃ led to an increase in hardness to 29 GPa for the coatings containing Si and a decrease in hardness to 26 GPa for AlCrN. Furthermore, the in-situ HT-HE-GIT-XRD method allowed for simultaneously accessing temperature-dependent variations of the coating microstructure (defect density, grain size), residual strain state and phase stability up to 1100℃. Finally, the results established a deeper understanding about the relationships between the elemental composition of the materials, the resulting microstructure including crystallographic phases and residual strain state, and the coating properties from room temperature up to 1100℃.

Purpose
Emerging clinical evidence for a varying relative biological effectiveness (RBE) in proton therapy poses the urgent need to consider RBE-driving physical parameters such as the linear energy transfer (LET). However, no harmonized concept exists on how to calculate the LET in clinical practice. Therefore, a multi-centric study was set up with the objective to standardize LET-calculations in Europe.

Materials and Methods
Eight European proton therapy institutions generated non-robust single-field-uniform-dose PBS treatment plans using common strict dose objectives. Multiple treatment field arrangements (single-field SOBP, perpendicular fields, opposing fields) were employed to cover a target cube in a water phantom. The institutions provided their dose and corresponding LET distributions. Here, four different LET-calculation methods (including analytical codes, dedicated LET scripts, Monte Carlo engines) were analyzed.

Results
Single-field SOBP ranges (distal R80) and average dose (range: D99 to D1) in the target volume agreed within 2% (Fig.1). In contrast, the corresponding near minimum LET values (LET99), average LET and near maximum LET (LET1) in the target volume differed up to 30%, 19% and 5%, respectively. In the volume 1 cm distal to the target, absolute (relative) LET1 values differed by up to 1.63 keV/µm (17%) in voxels with average physical dose above 40 Gy. Individual institutions included different ions in their LET-calculations partially explaining the observed differences in LET-values and LET-distributions (Fig.2).

Conclusion
Despite comparable dose distributions, substantial LET-differences occurred among the participating institutions. They hamper the consistent analyses of clinical follow-up data and might lead to discrepancies in predicting variable RBE. Therefore, standardized clinical LET-calculations are recommended.

The aim of the present report was to obtain an overview of current strategies and methods for the detection of (manufactured) nanomaterials (NMs) in the environmental compartments surface water, soil, sediment, air, biota and sewage sludge. Based on this several recommendations for future needs of action in the short to long term are derived in order to establish a standardized detection of NMs in the environment that is necessary in order to check the pollution in the environment, to check whether or not potential risk management measures take the intended effect and to validate NM release models with real data.
A literature review was performed using predominantly “Web of Science” and screening for literature, such as review articles summarising the state of the art of NM detection techniques for environmental samples. More than 160 scientific publications were evaluated concerning NM detection methods. Results of the literature survey clearly show that a combination of detection techniques is necessary in order to detect and identify NMs, and to differentiate between natural NMs and manufactured NMs. The crucial step is accurate sample preparation for the selected detection method which means in most cases complete removal of the (disturbing) matrix and transfer of the NM in appropriate media for measurement. So far field studies in terms of detection of unknown amounts of unspecific engineered NMs in natural samples are rare and only existing for a few compartments, mainly surface waters.
Hence, it is concluded that the need of action is focused on the development, standardization and validation of existing methods in a combinatory approach.

Despite being a member of the zircon type silicate family, the conditions allowing the hydrothermal synthesis of HfSiO4 were not well constrained. A multiparametric study was performed in order to follow the synthesis of this phase under soft hydro-thermal conditions and thus to determine the most efficient conditions to form single phase samples. Among the experi-mental parameters investigated, concentration of reactants, pH of the reactive media, temperature and duration of the hydrothermal treatment impacted significantly the formation rate of hafnon and its crystallization state. Pure HfSiO4 was obtained in acid reactive media with an acidity ranging from CHCl = 1.5 M to pH = 1.0 and for CSi ≈ CHf ≥ 0.21 mol·L 1. The silicate phase was prepared after a 24-hours treatment at temperatures ranging from 150°C to 250°C. However, rise of tem-perature and extension of the duration of the hydrothermal treatment favored the crystallization state of the final HfSiO4 samples.

Solutal buoyancy has a large impact on the flow of the alloy phase composing the positive electrode in liquid metal batteries. During discharge solutal buoyancy creates a stabilizing stratification, during charge it creates a vigorous solutal convection. In this article we provide new physical understandings of the role of solutal buoyancy during both charge and discharge. In particular we find that during discharge the electrovortex mechanism is in general not strong enough to counter the stabilizing effect of solutal buoyancy, and therefore this mechanism cannot be used to mix the alloy as is sometimes suggested in the literature. We show that the mixing capability of a generic flow in the alloy phase can be estimated by comparing the typical flow magnitude U to two velocity scales: Up and Um. Below Up the flow cannot mix the alloy, and above Um the flow significantly opposes solutal buoyancy. Although we focus on Li||Pb-based batteries, these simple mixing criteria can be used during the discharging phase in other types of liquid batteries. We also present new, fully three-dimensional simulations of solutal convection during the charging cycle. These simulations suggest scaling laws for the magnitude of the convective flow, the time for the onset of solutal convection, and the typical inhomogeneity level in the alloy during charge. We propose physical arguments to explain these scaling laws.

A natural silicon target was investigated in a natSi(gamma,gamma' ) photon-scattering experiment using fully polarised, quasi-monochromatic gamma rays in the entrance channel. The mean photon energies used were = 9.33, 9.77, 10.17, 10.55, 10.93, and 11.37 MeV, while the relative energy spread (Full Width Half Maximum) of the incident beam amounts to dE / E ~ 3.5 - 4 %. The observed angular distribution in the ground-state decay channel allows to propose a firm spin and parity assignment for several levels of the stable even-even silicon isotopes.

The adenosine A2A receptor (A2AR) is regarded as a particularly appropriate target for non-dopaminergic treatment of Parkinson’s disease (PD). An increased A2AR availability has been found in the human striatum at early stages of PD and in patients with PD and dyskinesias. The aim of this small animal positron emission tomography/magnetic resonance (PET/MR) imaging study was to investigate whether rotenone-treated mice reflect the aspect of striatal A2AR upregulation in PD. For that purpose, we selected the known A2AR-specific radiotracer [18F]FESCH and developed a simplified two-step one-pot radiosynthesis. PET images showed a high uptake of [18F]FESCH in the mouse striatum. Concomitantly, metabolism studies with [18F]FESCH revealed the presence of a brain-penetrant radiometabolite. In rotenone-treated mice, a slightly higher striatal A2AR binding of [18F]FESCH was found. Nonetheless, the correlation between the increased A2AR levels within the proposed PD animal model remains to be further investigated.

Alterations in mechano-physiological properties of a tissue instigate cancer burdens in parallel to common genetic and epigenetic alterations. The chronological and mechanistic interrelation between the various extra- and intracellular aspects remains largely elusive. Mechano-physiologically, integrins and other cell adhesion molecules present the main mediators for transferring and distributing forces between extracellular matrix (ECM), via focal adhesomes to cytoskeleton and nucleus and vice versa of the single cell thereby affecting the pathophysiology of multicellular cancer tissues. In combina-tion with simultaneous activation of diverse downstream signaling pathways, the phenotypes of can-cer cells are created and driven characterized by deregulated transcriptional and biochemical cues that elicit the hallmarks of cancer. It, however, remains unclear how elastostatic modifications, i.e. stiffness, in the extracellular, intracellular and nuclear compartment contribute and control the re-sistance of cancer cells to therapy. In this review, we discuss how stiffness of unique tumor compo-nents dictates therapy response and what is known about the underlying molecular mechanisms.

In the geosciences it is still uncommon to include measurement uncertainties into numerical analysis such as discriminant analysis. The implementation of uncertainties is not trivial because data sets in geosciences often present a compositional nature, e.g. they are given as concentrations, proportions, percentages or any other form of information about the relative abundance of a set of components forming a whole. For these data the respective uncertainties are nearly never considering their compositional nature. The uncertainties can be incorporated in discriminant analysis either by each measured variable, by each observation or by using the individual, cell-wise uncertainties (each observation has for each variable an individual uncertainty). Most DA methods incorporating uncertainties use the uncertainties as weights for the variables or observations of the data set. In contrast, the here proposed method uses uncertainties to calculate a better estimation of the group variances and group means, which then influence the decision rules of quadratic respectively linear discriminant algorithm. This methodological framework does not only allow to incorporate cell-wise uncertainties, but also would largely be valid if the information about the co-dependency between uncertainties within each observation is reported.

Tracking in magnetic fields with the FLUKA radiation transport and reaction code

Usage of the FLAIR Geometry-Editor
(Lecture given at the 5th Advanced FLUKA Course at NEA, Paris)

The adjustment of photoluminescence emission spectrum and an enhancement in the thermal stability of red/orange-red emitting phosphors is an important issue for the whole lighting industry. Herein, we present our results on the luminescence spectroscopy of a single crystal sample of SmPO4 exhibiting a prominent orange-red emission at 597 nm, along with a charge-transfer absorption (O2− → Sm3+) around 200 nm. We study the temperature dependence of emission spectra in SmPO4 for excitations at 365 and 455 nm, to mimic experimental conditions for phosphor converted light emitting diodes, to show that the sample has a non-quenching photoluminescence emission up to at least 865 K for an excitation at 365 nm, and ∼865 K for an excitation at wavelength, 455 nm. The thermal stability of SmPO4 was found to be much higher than its structural analogue, EuPO4, which is also an orange-red emission phosphor, but possesses a thermal quenching temperature of 710 K (exc. 365 nm), and 735 K (exc. 455 nm). The extraordinary thermal stability of SmPO4 is a result of the energy transfer from deep defects to the Sm3+ ions at high temperatures. The color purity of SmPO4 (65%) was found to be slightly lower than the EuPO4 sample (70%), at room temperature. The results suggests that the rare earth orthophosphate, SmPO4, has a large potential for near-UV excited phosphor converted solid state lighting devices.

The X2 VVER-1000 benchmark provides a unique set of VVER-1000 plant data: the detailed core definition, operational history of the first four fuel cycles and various measurement results. This paper presents the second revision of the benchmark specification with significant improvements such as detailed reflector definition, corrected material compositions, clear illustrations etc. The reference solution for the hot zero power experiments conducted during the fresh core start-up was obtained with the Serpent-2 Monte Carlo code. The calculated and measured values of a critical boron concentration, temperature reactivity effect, and control rod worth are in a very good agreement while the deviations lay within the measurement uncertainties. Further extension of the benchmark definition is foreseen for a future work.

The electronic structure and dielectric properties of the diamond, body centered cubic diamond (bc8), and hexagonal diamond (lonsdaleite) phases of carbon are computed using density functional theory and many-body perturbation theory with the emphasis on the excitonic picture of the solid phases relevant in the regimes of high-pressure physics and warm dense matter. We also discuss the capabilities of reproducing the inelastic x-ray scattering spectra in comparison with the existing models in light of recent x-ray scattering experiments on carbon and carbon bearing materials in the Megabar range.

In this paper, a mechanistic analysis of the adsorption and reduction of gold(III) chloride complex ions on the activated carbon surface were described. All experiments were performed in the presence of nickel ions. Obtained results confirm that there is no influence of light and heavy cations on the adsorption process. From the Arrhenius equation, activation parameters such as activation energy (17.53±0.98 kJ/mol) and pre-exponential (28.7±8.91 min-1 ) factor were determined. SEM and XRD, as well as XPS analysis, have confirmed the presence of metallic gold on the surface of activated carbon. The concentration distribution of gold inside activated carbon after adsorption process both for continuous stirred tank reactor and continuous flow reactor was determined. New estimator for interfacial area of mass transfer was defined.

Today’s mechanical fluid separators in industry are mostly operated without any control to maintain efficient separation for varying inlet conditions. Controlling inline fluid separators, on the other hand, is challenging for two reasons: the process is very fast and measurements in the multiphase stream are difficult as conventional sensors typically fail here. With recent improvement of process tomography sensors alongside with an increase in processing power of smart computers, such sensors can now be potentially used in inline fluid separation. Within the European Innovative Training Network TOMOCON we develop concepts for tomography-controlled inline fluid separation. It comprises of electrical tomography and wire-mesh sensors, a fast and massive data processing and an appropriate control strategy to control the process via valve action or alternative actuation principles. Solutions and ideas presented in this paper base on process models derived from theoretical investigation, numerical simulations and analysis of experimental data.

An important parameter for the safety assessment of radioactive waste repositories is the prediction and modelling of aqueous complex formation reactions between actinides (An) and common dissolved inorganic or organic ligands.Alteration processes at the contact zone between the backfill material, bentonite, or the clay host rock and the cementitious materials of the geotechnical barrier will lead to high silicate concentrations in the groundwater, which may strongly influence the aqueous speciation of actinides[1]. A detailed knowledge of the An–silicate complex formation is therefore very important. In the present study, we have investigated the U(VI)-complexation in with aqueous silicates using two approaches: 1) Time-resolved laser-induced luminescence spectroscopy(TRLFS) in the acidic pH-range (pH 3.5)was used to determine the in-situU(VI) speciation in dependency of temperature(1-25°C)and silicon concentration, 2) the Schubert method was used to acquire the U(VI)-silicate complexation constant and stoichiometryin the alkaline pH-range where no literature data for U(VI)-silicates currently exists. For the TRLFS studythe uranium concentration was fixed at 5×10-6Mwith an ionic strength of 0.2 M (NaClO4),while the silicon concentration was varied between 3×10-4and1.5×10-3M. In the absence of silicate the 1:1 U-hydroxo complex was found to play a significant role in the U-speciationin the acidic pH-range. With increasing silicon concentration an increase of the luminescence intensity and a bathochromic shift of the emission spectra couldbe observed. Based on the peak deconvolution the free component spectra of U-hydroxo and U-silicate complexeswere extracted. The following slope analysis resulted in aslope close to 1 for all temperatures, confirming the formation of the UO2OSi(OH)3+complex at pH 3.5. The temperature dependent measurements enabledthe determination of the thermodynamicparameters ΔrH0=46.3kJ∙mol-1and ΔrS0=154.1J∙K-1∙mol-1. For the Schubert method, the U(VI) sorption distribution coefficient Rdon ZrO2was determined by LSC-measurements as a function of the ligand concentration and the pH in the alkaline pH range. By plotting the Rd-values as a function of the ligand concentration, information about the number of involved ligands in the U(VI)-silicate complex could be obtained. When further plotting the fitting constant (obtained from the Rd-plot) as a function of log[H+], the number of protons involved in the complexation reaction and the conditional complexation constant could be determined. With the obtained stoichiometry, two possible complexes could be proposed in the alkaline pH-range.DFT-calculations supportedthe formation of the UO2(OH)2OSi(OH)3complex.References:[1]D. Savage, Mineral. Mag., 2011, 75

An important parameter for the safety assessment of radioactive waste repositories is the prediction and modelling of aqueous complex formation reactions between actinides (An) and common dissolved inorganic or organic ligands. Alteration processes at the contact zone between the backfill material, bentonite, or the clay host rock and the cementitious materials of the geotechnical barrier will lead to high silicate concentrations in the groundwater, which may strongly influence the aqueous speciation of actinides such as uranium, which is stable in the hexavalent oxidation state under oxidizing conditions. [1]. A detailed knowledge of the U(VI) –silicate complex formation is therefore very important.
Depending on the used host rock and backfill material, the pH of the groundwater will be in the neutral to alkaline range. However, in this pH-range, reliable thermodynamic data for aqueous An(VI) - silicate complexes are scarce. In the acidic pH-range, only the 1:1 An(VI)-Si complex, i.e. An(VI)O2OSiOH3+, has been determined for U(VI), Np(VI), and Pu(VI), and the complex formation constants differ by almost two orders of magnitude (Table 1) [2].
Table 1: Complex formation constants for An(VI)-Si complexes [2].
An logK0
U(VI) -1,86
Np(VI) -2,61
Pu(VI) -3,65

In the alkaline pH-range (pH ~8), Yusov et al. [3] postulated the formation of either a ternary Pu-OH-Si complex: (PuO2(H2O)3(OH)OSi(OH)3) with the H3SiO4- ligand or a binary Pu-Si complex (PuO2(H2O)3O2Si(OH)2) with H2SiO42-. For other hexavalent actinides, no complexes in the alkaline pH-range have been reported, however, in analogy with Pu(VI), comparable complexes should also exist for U(VI) and Np(VI).
This contribution reports on a study of the U(VI) complexation with silicate in the pH range between 3.4 and 11.5. Two approaches were used: 1) Time-resolved laser-induced luminescence spectroscopy (TRLS) was applied to determine the in situ U(VI) speciation in U(VI) solutions with various silicate concentrations and various pH. 2) U(VI)-silicate complexation constants and complex stoichiometries were determined using Schubert’s method. For the TRLFS measurements, a U(VI) concentration of 5×10-6 M (pH = 3.5) or 1×10-7 M (pH = 9) was used, while the silicon concentration was varied between 3×10-4 and 1.5×10-3 M. To determine the thermodynamic parameters ΔrH0 and ΔrS0, temperature dependent measurements were performed in the range from 1°C to 25°C. The ionic strength was fixed with NaClO4 at 0.2 M. The Schubert method allows determination of complex stoichiometry and complexation constant by measuring the solid/liquid distribution ratio (Rd value) for the U(VI) sorption on a solid phase in absence and in the presence of increasing concentrations of silicate. Here, monoclinic ZrO2 was used as a solid phase. The U(VI) concentration in the experiments was 1×10-7 M and silicate concentrations were varied between 5×10-5 and 5×10-3 M, at pH values ranging from 6.0 to 11.5 at an ionic strength of 0.1 M NaCl. LSC measurements of the 233U activity were used to determine the U(VI) concentration in solution.
In the absence of aqueous silicates, the 1:1 uranium hydrolysis species UO2OH+ plays a significant role in the speciation starting from a pH of 3.5. Therefore, this species has to be taken into account in the speciation. Figure 1 shows the luminescence spectra with increasing Si-concentration at different temperatures. The obtained spectra show a bathochromic shift and an increase in the luminescence intensity with increasing silicate concentration. Based on peak deconvolution, the pure component spectra of the UO2OSi(OH)3+ and UO2OH+ complex were extracted. The species distributions were calculated by a least-square fit method. The following slope analysis resulted in a slope close to 1 for all temperatures, confirming the formation of a UO2OSi(OH)3+ complex at pH 3.5. The obtained complexation constants were corrected to standard conditions using the Davies equation. The obtained stability constant at 25°C is significantly higher than the literature values due to the consideration of the hydroxo complex and the solubility limit of the aqueous silicates [2]. A van’t Hoff plot was used to extract the reaction enthalpy and entropy, which were found to be ΔrH0 = 46.3 kJ∙mol-1 and ΔrS0 = 154.1 J∙K-1∙mol-1.

Figure 1: Emission spectra of the U-Si complexation at pH 3.5 with varying [Si] between 3×10-4 and 1.5×10-3 M, [U] = 5×10-6 M, fixed [NaClO4] = 0.2 M, in the temperature range between 1°C to 25°C.
For the Schubert method, the U(VI) sorption distribution coefficient Rd on ZrO2 was determined by LSC-measurements as a function of the ligand concentration and the pH in the alkaline pH range. By plotting the Rd-values as a function of the ligand concentration, information about the number of involved ligands in the U(VI)-silicate complex could be obtained. When further plotting the fitting constant (obtained from the Rd-plot) as a function of corrected pH, the number of protons involved in the complexation reaction and the conditional complexation constant could be determined. With the obtained stoichiometry, two possible complexes could be proposed in the alkaline pH-range, (i) UO2(OH)O2Si(OH)2- or (ii) UO2(OH)2OSi(OH)3-. DFT-calculations support the formation of the second complex with a corrected stability constant of logK0 = -16.30.

[1] D. Savage, Mineral. Mag.,2011, 75, 2401-2418.
[2] R. Guillaumont et al., Update on the Chemical Thermodynamics of Uranium, Neptunium, Plutonium, Americium and Technetium, 2003, NEA-TBD.
[3] A. B. Yusov, A. M. Fedoseev, Russ. J. Coord. Chem., 2003, 29, 625-634.

Background: Changes in the expression of homomeric α7 nicotinic acetylcholine receptors (α7 nAChR) in the human brain are widely assumed to be associated with neuropsychiatric and neurooncologial processes. Indeed, thoroughly performed studies have shown the ability of α7 nAChR modulators to minimise the extent of cell death as well as to promote synaptic plasticity in different diseases including depression, schizophrenia, stroke and Alzheimer´s disease. Nonetheless, up to date, the clinical meaningful findings obtained with these agents were not always supported by a complete understanding of the downstream effects initiated by α7 nAChR modulators.
Methods: To help understanding these processes an extensive work has been done by our and other groups on the development of positron emission tomography (PET) α7 nAChR agents labeled with the radioisotopes fluorine-18 (18F) and carbon-11 (11C). So far two main classes of α7 nAChR PET tracers have advanced to clinical trials: scaffolds composed of a three-side binding mode to the receptor (e.g., hydrogen bond acceptor, hydrophobic element and a rigid basic amine as the cationic centre), and the scaffolds containing fused functionalities belonging to the interferon inducer tilorone class of derivatives.
Results and Discussion: Structure-activity relationship studies on these two classes have been the subject of continuous research aiming at the development of highly affine and selective α7 nAChR PET tracers with suitable pharmacokinetic properties for an accurate receptor occupancy quantification and distribution of α7 nAChR in the brain. As a result, [18F]NS10743, [18F]NS14490, [11C]NS14992, [18F]DBT10 and its ortho isomer [18F]ASEM emerged as the most promising α7 nAChR PET tracers developed so far. Studies in piglets were done for [18F]NS10743 and [11C]NS14992. Ongoing clinical trials have been reported using [18F]ASEM. Efforts to translate [18F]DBT10 into the clinics have been initiated with its transfer onto an automated synthesis in compliance to clinical production. The results of a successful pre-clinical imaging study, including dosimetry in piglets and evaluation in monkeys suggests the suitability of [18F]DBT10 for imaging α7 nAChR. Very recently a pilot study in a large animal model of ischemic stroke in sheep revealed a high inflammation-related specific uptake of [18F]DBT10 in the stroke border 14 days after permanent middle cerebral artery occlusion.
Conclusion: Among the receptor-specific α7 nAChR PET tracers developed so far, the dibenzothiophene isomers [18F]DBT10 and [18F]ASEM are under continuous investigation due to their suitable pharmacokinetics and high target-specific signal. More proof-of-concept studies are required to support the usefulness of these tracers for sensitive and specific α7 nAChR PET imaging.

Introduction: The monoamine oxidase B (MAO B) isoenzyme is known to be involved in the oxidative deamination of biogenic amines. While the use of MAO B inhibitors is already well-established for the treatment of Parkinson’s disease, recent reports suggest its involvement in certain types of brain tumors.1 We herein aim at the synthesis and preclinical evaluation of fluorinated indanone-based derivatives targeting MAO B in the brain via positron emission tomography (PET).
Methods: A small series of fluorinated indanone derivatives was obtained via the O-alkylation or esterification starting with the commercially available 6-hydroxy-2,3-dihydro-1H-inden-1-one in two steps. Binding affinities towards the human MAO isoenzymes were estimated in vitro by radioligand displacement. HL126 was selected for radiofluorination via its corresponding boronic acid pinacol ester. In vitro autoradiography of [18F]HL126 was performed in mice brain slices. In vivo evaluation of [18F]HL126 in CD-1 mice was carried out and metabolism studies were performed in plasma and brain samples via radio-HPLC.
Results: The fluorinated indanone derivatives were synthesized in yields ranging from 65-89%. The fluorophenyl ether derivative, HL126, was further selected for radiofluorination based on its high binding affinity towards MAO B (Ki = 6.9 ± 5.33 nM). [18F]HL126 was obtained by an alcohol-enhanced copper-mediated approach via the corresponding boronic acid pinacol ester precursor with radiochemical yields of about 11 ± 3%, high radiochemical purities (≥99%) and molar activities in the range of 20 GBq/mol. In vitro autoradiography showed a specific blockade with selective MAO-A/B inhibitors. PET/MRI analyses revealed that [18F]HL126 readily enters the brain. Some radiometabolites do cross the blood-brain barrier.
Conclusion: Although metabolism studies with [18F]HL126 revealed the presence of radiometabolites in the brain, the high binding affinity towards MAO B and the pronounced selectivity in in vitro autoradiography studies encourage further derivatization of indanone-based scaffolds for targeting MAO B.
Acknowledgments
The authors thank the Deutscher Akademischer Austausch Dienst (DAAD) for financial support.
References
1. Tripathi, R. K. P. and Ayyannan, S. R. Med. Res. Rev., 39, p.1603, 2019.

This work consists of a Computational Fluid Dynamics (CFD) modeling of a reference experiment on boron dilution in the Rossendorf coolant mixing Model (ROCOM) as part of a coordinated research project of the International Atomic Energy Agency, namely, “Application of numerical codes of fluid dynamics to the design of nuclear power plants”. This coordinated project aims to address the application of CFD codes to the process of optimizing the design of nuclear power plants related to pressurized water reactors and to evaluate the performance and predictive capabilities of these codes and to contribute to their validation. In this context, a three-dimensional numerical simulation study was carried out using CFD code ANSYS CFX v14.5, to study the boron mixing phenomenon at the core inlet and the downcomer of the ROCOM test facility. The phenomenon of experimental mixing occurs by the injection of a tracer (sodium chloride) into one of the loops of the ROCOM installation mainly containing demineralized water in its primary circuit. The concentration field of the tracer is measured and simulated at the entrance of the heart and in the lowering. The SST-kω turbulence model used in this study could reasonably predict the distribution of the injected tracer in measurement locations within the test facility. The results of this numerical simulation were compared to the Benchmark data provided by the ROCOM experimental facility of the Helmholtz-Zentrum Dresden-Rossendorf Institute.

Airway surface dehydration is a pathological feature of cystic fibrosis (CF) lung disease. 20 CF is caused by mutations in the CF transmembrane conductance regulator (CFTR), a cyclic 21 AMP-regulated Cl- channel controlled in part by the adenosine A2B receptor. An alternative, 22 CFTR-independent mechanism of fluid secretion is regulated by ATP, via the P2Y2 receptor 23 (P2Y2R) that activates Ca2+-regulated Cl- channels (CaCC/TMEM16) and inhibits Na+ 24 absorption. However, due to rapid ATP hydrolysis, steady-state ATP levels in CF airway surface 25 liquid (ASL) are inadequate to maintain P2Y2R-mediated fluid secretion. Therefore, inhibiting 26 airway epithelial ecto-ATPases to increase ASL ATP levels constitutes a strategy to restore 27 airway surface hydration in CF. Using [γ32P]ATP as radiotracer, we assessed the effect of a 28 series of ATPase inhibitory compounds on the stability of physiologically occurring ATP 29 concentrations. We identified the polyoxometalate [Co4(H2O)2(PW9O34)2]10- (POM-5) as the 30 most potent and effective ecto-ATPase inhibitor in CF airway epithelial cells. POM-5 caused 31 long-lasting inhibition of ATP hydrolysis in airway epithelia, which was reversible upon removal 32 of the inhibitor. Importantly, POM-5 markedly enhanced steady-state levels of released ATP, 33 promoting increased ASL volume in CF cell surfaces. These results provide proof-of-concept for 34 ecto-ATPase inhibitors as therapeutic agents to restore hydration of CF airway surfaces. As a test 35 of this notion, cell-free sputum supernatants from CF subjects were studied and found to have 36 abnormally elevated ATPase activity, which was markedly inhibited by POM-5.

Gas bubble dispersion determines the efficiency of the aeration process in biological wastewater treatment plants (WWTP). The purpose of aeration is to provide an aerobic environment for microbial degradation of organic matters. This is an expensive procedure, which is responsible for the largest share of energy bill in the whole WWTP in the range from 45% to 75% [1]. The state of the art of aerators, which are currently in use at the activated sludge facilities, is the rubber membrane diffusers. These diffusers offer relatively low standard oxygen transfer efficiency (SOTE) in the range of 40% to 60% [2]. Several factors affect the SOTE, e.g. the gas holdup, bubble size, bubble residence time, and the apparent viscosity [3]. Among these parameters, the bubble size is of a great importance, since it directly influences the gas holdup and the bubble residence time. Moreover, the bubble size determines the surface area to volume ratio, which affects the volumetric oxygen transfer coefficient k_L a and the oxygen transfer rate OTR. To specify the oxygen transfer, one needs to know the mass transfer coefficient from a gas bubble as a function of its diameter and accurate information on the terminal bubble rising velocity. Accordingly, Motarjemi and Jameson have measured the initial bubble size required to achieve 95% transfer of available oxygen from an air bubble as a function of the depth of the basin [3].
To achieve the optimal bubble size, it is important to know the relation between the initial bubble volume and other influential parameters, e.g. the gas flow rate, orifice diameter, gas reservoir volume, and physical properties of both phases. Since 1960, many authors have tried to calculate the initial bubble volume. The majority of these models divide the bubble formation into two stages, namely the growing stage and the elongation stage through a neck. Each stage can be solved either by its corresponding force balance, or by empirical assumptions related to the moment of bubble detachment. Although these models are quite reliable in low flow rates, by increasing the gas flow rate, they diverge. Latter is due to the fact that, the assumptions, which are used to close the equations in each stage, do not take into account the variation in the detachment condition at different bubbling regimes.By increasing the gas flow rate, the bubble surface moves more dynamic and the influence of the gas momentum force is more pronounced. In this case, the final bubble is a product of multiple coalescence of smaller bubbles right above the orifice. Moreover, the three-phase contact of the gas phase, the liquid phase, and the solid phase during the bubble formation is generally a dynamic procedure. However, in most of the models this measure is assumed to be a constant value.

In the current study, we investigate the bubble formation from a submerged orifice at different bubbling regimes. To track the three-contact phase point inside and above the orifice, we use an optical setup with a matched refractive index of the solid and the liquid phase. Consequently, we are able to follow the three-phase contact point even inside of the orifice. To mimic the bubble formation in water, we keep the dimensionless Reynolds number constant. The bubble formation is recorded with a high-speed camera with a maximum spatial resolution of 2 μm and a temporal resolution of up to 25 μs.
The gas flow rate is set via a mass flow controller. We cover the full range of bubbling regimes, from the quasi-static to the chaotic regime. Similar to Badam et al., the change in the map of the bubbling regime is reported according to the dimensionless Froude and Bond number [4]. By increasing the gas flow rate, we track the progressive bubble volume and the trajectory of the bubble’s center of mass using an in-house bubble tracking algorithm. Latter enables us to report the change in the distance of the bubble’s center of mass to the orifice surface, until one instant before the bubble pinch-off, and correlate it to its corresponding bubbling regime. By implementing these detachment conditions, we develop a model to estimate the final bubble volume. Finally, using this model we are able to estimate the appropriate operating parameters, e.g. the gas flow rate, and the orifice diameter, in order to achieve the optimal bubble size for enhanced aeration efficiency.

References
1. Zimmerman, W.B., V. Tesař, and H.H. Bandulasena, Towards energy efficient nanobubble generation with fluidic oscillation. Current Opinion in Colloid & Interface Science, 2011. 16(4): p. 350-356.
2. Wang, L.K., N.K. Shammas, and Y.-T. Hung, Advanced biological treatment processes. Vol. 9. 2010: Springer Science & Business Media.
3. Motarjemi, M. and G. Jameson, Mass transfer from very small bubbles—the optimum bubble size for aeration. Chemical Engineering Science, 1978. 33(11): p. 1415-1423.
4. Badam, V., V. Buwa, and F. Durst, Experimental investigations of regimes of bubble formation on submerged orifices under constant flow condition. The Canadian Journal of Chemical Engineering, 2007. 85(3): p. 257-267.

Improved understanding of complex hemodynamic impairments in asymptomatic internal carotid artery stenosis (ICAS) is crucial to better assess stroke risks. Multimodal MRI is ideal to measure brain hemodynamics and has the potential to improve diagnostics and treatment selection. We applied MRI-based perfusion and oxygenation sensitive imaging in ICAS, hypothesizing that sensitivity to hemodynamic impairments will improve within individual watershed areas (iWSA).We studied cerebral blood flow (CBF), cerebrovascular reactivity (CVR), relative cerebral blood volume (rCBV), relative oxygen extraction fraction (rOEF), oxygen extraction capacity (OEC) and capillary transit time heterogeneity (CTH) in 29 patients with asymptomatic, unilateral ICAS (age 70.3±7.0y) and 30 age-matched healthy controls (HCs). In ICAS, we found significant impairments of CBF, CVR, rCBV, OEC, and CTH (strongest lateralization ∆CVR=-24%) – but not of rOEF. Even though spatial overlap of compromised hemodynamic parameters within each patient varied in a complex manner, most pronounced changes of CBF, CVR and rCBV were detected within iWSAs (strongest effect ∆rCBV=+96%). At the same time, CTH impairments were iWSA independent, indicating widespread dysfunction of capillary-level oxygen diffusivity. In summary, complementary MRI-based perfusion and oxygenation parameters offer deeper perspectives on complex microvascular impairments in individual patients. Furthermore, knowledge about iWSAs improves sensitivity to hemodynamic impairments.

Arterial spin labeling (ASL) has undergone significant development since its inception, with a focus on improving standardization and reproducibility of its acquisition and quantification. In a community-wide effort towards robust and reproducible clinical ASL image processing, we developed the software package ExploreASL, allowing standardized analyses across centers and scanners. The procedures used in ExploreASL capitalize on published image processing advancements and address the challenges of multi-center datasets with scanner-specific processing and artifact reduction to limit patient exclusion. ExploreASL is self-contained, written in MATLAB and based on Statistical Parameter Mapping (SPM) and runs on multiple operating systems. The toolbox adheres to previously defined international standards for data structure, provenance, and best analysis practice. ExploreASL was iteratively refined and tested in the analysis of >10,000 ASL scans using different pulse-sequences in a variety of clinical populations, resulting in four processing modules: Import, Structural, ASL, and Population that perform tasks, respectively, for data curation, structural and ASL image processing and quality control, and finally preparing the results for statistical analyses on both single-subject and group level. We illustrate ExploreASL processing results from three cohorts: perinatally HIV-infected children, healthy adults, and elderly at risk for neurodegenerative disease. We show the reproducibility for each cohort when processed at different centers with different operating systems and MATLAB versions, and its effects on the quantification of gray matter cerebral blood flow. ExploreASL facilitates the standardization of image processing and quality control, allowing the pooling of cohorts to increase statistical power and discover between-group perfusion differences. Ultimately, this workflow may advance ASL for wider adoption in clinical studies, trials, and practice.

Purpose/Introduction: The Brain Imaging Data Structure (BIDS) is a recently developed data storage standard, that meets the need for a structured manner to organize imaging data in the age of big datasets and data sharing (https://bids.neuroimaging.io). 1 This abstract presents a BIDS extension for ASL, which only supports ASL approaches as recommended in the ASL acquisition consensus paper, and several M0 calibration approaches. 2

Subjects and Methods: A group of ASL experts initiated this extension by defining several concepts and preparing a first draft. This draft was shared online from May 2017 until March 2019 with the international ASL community, and several teleconference and face-to-face meetings were organised. Per BIDS convention, existing BIDS fields were reused for the ASL-BIDS extension if possible. The BIDS fields names were based on the NEMA ASL DICOM fields, where possible. Additionally, three example datasets were collected 3
and efforts were initiated to adapt existing ASL analysis tools and the BIDS validator for ASL-BIDS compatibility.

Results: Six concepts were defined to allow a uniform yet flexible ASL-BIDS specification. First, it was decided to focus solely on the implementation of the ASL approaches discussed in the ASL consensus paper: single- and multi-delay, pulsed, continuous, and pseudo-continuous ASL. 5 Second, the BIDS-structure consists of two mandatory files and several optional files (Fig. 1). Third, it is obligatory to keep the ASL time series in the original acquisition order in a 4D NIfTI file, including any M0, if it was part of the original ASL
time series. If an M0 image was acquired separately, it should be stored as a separate NIfTI file. The ASL-context BIDS field explains the content of each volume in the ASL time series. Fourth, the derivative images DeltaM and CBF are considered to be raw images if the ASL-sequence or vendor only provided derivative images, lacking raw data. This principle follows the prioritization shown in Fig. 2. Fifth, all ASL data need to be stored in at least 32 bit floating point, without any scale slopes. Some vendor implementations store scaled ASL data to increase the precision of the stored data within the traditional 12 bit DICOM files. It is the responsibility of the DICOM to BIDS conversion to apply any existing scale slopes. Sixth, it is recommended to specify as much information as labeling as possible: the exact location of the labeling plane and the labeling efficiency.

Discussion/Conclusion: The current ASL-BIDS extension is restricted to the ASL approaches recommended by the consensus paper. 1 With the current development of more advanced ASL approaches, such as time-encoded and velocity-selective ASL, the ASL-BIDS may be extended for these technique. Also, a derivatives extension for ASL is anticipated.

Purpose/Introduction: Internal carotid-artery stenosis (ICAS) is a major public health issue and causes complex haemodynamic impairments. 1–3 However, influences of microvascular effects remain poorly understood. Furthermore, increased sensitivity for regional pathophysiological changes is required to detect early disease stages.
The aim of our study was therefore to establish a multi-modal MRI protocol allowing deeper insights into the pathology. Furthermore, we hypothesize to be most sensitive to ICAS-impairments within individual watershed areas (iWSAs), which were proposed to be most vulnerable to haemodynamic compromise. 4

Subjects and Methods: Fifty-nine participants (29 unilateral ICAS-patients, age = 70.1 ± 4.8y and 30 age-matched healthy controls [HC]) underwent MRI on a Philips 3T Ingenia. The imaging protocol yielded oxygenation, perfusion and microvascular biomarkers which are summarized in Fig. 1. Additionally, iWSA’s were defined for each participant. 4 Mean haemodynamic parameter values were compared within each hemisphere of ICAS-patients vs. HC and inside vs. outside iWSAs (Fig. 2A, B) in GM and WM.

Results: Exemplary data of an ICAS-patient is shown in Fig. 2. On group-level, significant lateralisation of CBF, CVR, rCBV, CTH and OEC were found in ICAS, while rOEF was not lateralized (Fig. 3). Lateralisation was significantly enhanced inside iWSAs compared to outside of iWSAs for CBF and CVR, with a strong trend for rCBV—and strongest in WM of iWSAs (t test, p \ 0.05). OEC and CTH were indeed lateralized, but not different inside vs. outside iWSAs (Fig. 3). All HC parameters were symmetrical (data not shown).
Discussion/Conclusion: We successfully applied the proposed multimodal MRI-protocol and demonstrated its sensitivity to haemodynamic impairments in ICAS. Specificity was affirmed by symmetrical HC results. Individual parameter lateralisation in ICAS excellently agrees with the literature. Decreased CVR along with increased rCBV indicates chronic vasodilation. 1 Pronounced effects in WM-iWSA fit with the different blood supply in GM/WM. Ipsi-laterally decreased CBF, symmetrical rOEF 2 and increased CTH also coincide with recent studies 3 . The DCBF vs. DrOEF mismatch could relate to variable oxygen diffusivity 8 —potentially moderated by CTH 3, 9 . Interestingly, CTH and OEC lateralisation were iWSA-location independent, which matches previous findings. 10 These complimentary information of TTP and CTH about macrovascular effects, respectively microvascular flow 3 are highly promising to gain deeper insights into the pathology. And as initially hypothesized, evaluation within iWSA significantly increased the sensitivity to
CBF, CVR and rCBV impairments and allows to detect even subtle changes.

Purpose/Introduction
Glioma vascularization and perfusion are important factors for tumor diagnostics. Dynamic Susceptibility Contrast (DSC) provides a proxy of perfusion by measuring mean transit time and blood volume and is sensitive to blood-brain-barrier breakdown. Arterial spin labeling (ASL) measures true tissue perfusion and can thus provide complementary information to DSC that may aid in tumor grading and in imaging the treatment response to, e.g., antiangiogenic drugs. Agreement of ASL and PET was shown in volunteers 1 .
However, ASL can also partly show intravascular signal making ASL imaging of tumors challenging especially in the presence of vascular shunting. We compared ASL and DSC to the gold-standard for perfusion, [ 15 O]H 2 0 PET, to understand their limits as a surrogate of true regional perfusion.

Subjects and Methods
As part of the FRONTIER study, 8 glioma patients underwent multiple biopsies before scanning using Philips 3T Achieva MR and Gemini PET-CT 2 . PET (10min, 370 MBq of [ 15 O]H 2 0, simultaneous arterial blood sampling), ASL (pCASL 2D EPI, post-labeling delay and labeling duration 1800ms, 3x3x5 mm 3 ), DSC (TR 1.9s, TE 30ms, 1.7x2.4x3.6mm 3 , preloaded contrast) images were acquired. Cerebral blood flow (CBF) was quantified for ASL with ExploreASL, for DSC with Olea Sphere 3.0 with AIF obtained manually from MCA 3 . CBF images were aligned to PET and downsampled 6x6x6mm 3 resolution. Mean and voxel-wise CBF was compared between modalities in tumors and in contralateral-hemisphere gray matter (GM). Absolute and relative CBF (divided by subject’s mean whole-hemisphere contralateral GM CBF) were assessed.

Results
Mean hemispheric and voxelwise GM CBF values in the contralateral hemisphere were compared before and after normalization to global GM mean. For relative CBF, we observed a linear relationship between modalities in the tumor maximum values. Voxelwise analysis shows good agreement of PET and ASL for CBF ratio<1.5. For higher values ASL overestimated CBF, however, the relation was monotonic. DSC and ASL differed due to ASL overestimation in shunting vessels or low DSC signal in non-enhancing
gliomas.

Discussion/Conclusion
CBF normalization to contralateral GM improves the agreement of ASL and PET in tumors, after which a linear relationship in tumor-maximum was observed between all three modalities. The voxel-wise analysis, however, showed that ASL overestimates CBF in the presence of vascular shunting offering a different type of contrast than perfusion. We also observed increased CBF in both PET and ASL in non-enhancing tumors where CBF was underestimated by DSC. ASL presents a viable alternative to DSC with a monotonic relation to PET CBF, can present complementary information to DSC and thus warrants further research in its utility for glioma assessment.

Purpose/Introduction
In Europe, 50,000 new cases of primary glioma occur each year, and this number is expected to rise with the aging population 1 . Established international consortia are putting tremendous research efforts into a better understanding of glioma pathology and improved treatment strategies. Magnetic resonance imaging (MRI) only has a minor role in these research efforts, despite being a widely available medical imaging modality and whilst advanced MRI techniques are emerging with great potential for improved characterisation of
glioma. To exploit advanced MRI to the fullest, two issues need to be solved: (1) The scattered research landscape in which advanced MRI is being developed for glioma imaging. (2) The limited presence of advanced MRI research in established consortia for clinical work and research in glioma. To solve these issues, we have recently formed Glioma MR Imaging 2.0 (GliMR), an international consortium funded by the European Cooperation in Science & Technology (COST) 2 . In the coming 4 years, GliMR will establish an
international network of experts in glioma research, patient organisations, and data and MR imaging scientists that aims to progress development and application of MRI for improved decision making in diagnosis, patient monitoring, and assessment of treatment response in clinical trials and practice.

Subjects and Methods
GliMR starts as a network of 37 proposers spread across 22 countries world-wide (Figure 1). There are 5 working groups (WGs) (Figure 2) that will ensure we will reach the Research Coordination and Capacity Building Objectives of the network (Table 1) via the organisation of meetings, workshops, and training schools. Additionally, individual researchers and clinicians can apply for funds to go on Short Term Scientific Missions (STSMs) and gain experience by working in a different hospital/lab abroad. The network will be open to new members and participation for all those interested is highly encouraged.

Results
GliMR will lead to an international network operating at the forefront of glioma imaging diagnostics. It will result into recommendations and open-access software tools for advanced MRI assessment of glioma, the creation of multi-site, cross-border data sets on glioma imaging, and strengthened connections between all stakeholders in glioma diagnostics. GliMR will facilitate further understanding of glioma pathophysiology, scientific breakthroughs in novel therapies and improve personalised patient management, ultimately
increasing the quality of life of patients diagnosed with glioma.

Discussion/Conclusion
We would like to thank all proposers and our advisors for their input to the proposal. Special thanks go to the EORTC, GLASS, INCF, PanCare Society, Gold Standard Phantoms, Medical Software Solutions, Mediri, and Quantib for endorsing GliMR.

Der Adenosin-A2A-Rezeptor (A2AR) ist ein vielversprechendes Target für die molekulare Bildgebung sowohl von neurodegenerativen Erkrankungen als auch von Tumoren mittels PET. Bis zum jetzigen Zeitpunkt ist [18F]MNI 444 [Ki(hA2AR) = 2,8 nM] der einzige 18F-markierte Radiotracer, welcher in einer klinischen Studie an gesunden Probanden untersucht wurde (1). Ausgehend von dem literaturbekannten [18F]FESCH [Ki(hA2AR) = 0,6 nM] sollte durch chemische Modifikation ein deuteriertes Analogon mit einer erhöhter metabolischer Stabilität entwickelt werden (2,3).

Die Synthese von FLUDA basiert auf der Einführung einer deuterierten Fluoroethoxy-Gruppe. Für die Radiosynthese von [18F]FLUDA wurde eine zweistufige Eintopfmethode ausgehend von einem Phenol- und [2H4]Ethylenditosylat-Präkursor entwickelt. Die In vitro- und In-vivo-Evaluierung erfolgte mittels Autoradiographie-, Metaboliten- und PET-Studien in CD-1 Mäusen.

Es wurde eine Radiosynthese von [18F]FLUDA [Ki(hA2AR) = 0,6 nM] mit einer radiochemischen Ausbeute von 19±3% (n = 9) etabliert. Im Vergleich zu [18F]FESCH zeigt das deuterierte [18F]FLUDA eine deutlich gesteigerte In-vivo-Stabilität (15 min p.i., Gehirn: 91% intaktes [18F]FLUDA). Die In-vitro-Autoradiographie von [18F]FLUDA weist eine spezifische Aktivitätsanreicherung im Striatum nach, die durch die Rezeptorparameter KD = 4,3±0,7 nM und Bmax = 556±143 fmol/mg charakterisiert ist. In den PET-Studien wurde ein SUV-Verhältnis (SUVR) Striatum/Cerebellum von >8 (15-30 min) nachgewiesen. Selektive A2AR-Blockadestudien mit 2,5 mg/kg Tozadenant führten zu einem signifikanten Rückgang dieses SUVR um 35%.

Die Radiosynthese des neuen Radiotracers [18F]FLUDA wurde erfolgreich etabliert. Aufgrund der vielversprechenden präklinischen Ergebnisse wird derzeit die Translation von [18F]FLUDA in die Klinik vorbereitet.

(1) Barret et al., J Nucl Med 2015, 56, 586-91
(2) Bhattacharjee et al., Nucl Med Biol 2011, 38, 897-906
(3) Khanapur et al., J Med Chem 2014, 57, 6765-80

In dem Vortag wird der aktuelle Stand der Forschungen zur Funktionalisierung von Oberflächen am HZDR vorgestellt und daraus entsprechende Anforderungen an Materialien zur definierten Immobilisierung von Molekülen und Zellen abgeleitet.

The search for a suitable site for a nuclear waste repository in Germany requires linking molecular scale information with the large scale of the repository. Here, we present a novel approach to bridge the gap from the molecular to the millimeter scale.
We complement well-known surface investigation techniques such as Raman microscopy, interferometry and autoradiography with μTRLFS. This newly developed technique allows the investigation of luminescent radionuclides, such as Cm(III) and its chemical homologue Eu(III), on the surface of crystalline rocks with complex mineral composition. The combination of multiple surface investigation techniques allows to draw a correlation between surface mineralogy, topography, radionuclide speciation and the resulting retention behavior.
In an initial μTRLFS study using natural granite from Eibenstock, Germany, it was found that uptake strength, capacity, and homogeneity vary from mineral to mineral. For example, Eu(III) on feldspars adsorbed relatively weakly but in large amounts, whereas only minor sorption was observed on quartz, but with a high sorption strength. In addition, distinct sorption behavior was found on some mineral grain boundaries.[1]
To obtain a more comprehensive picture, granitic drill core samples were obtained from across Europe, from which thin section samples were prepared for μTRLFS experiments. The sorption of Eu(III) and Cm(III) onto these samples was conducted using solutions with defined ionic strength, metal concentration and pH.
We will discuss the speciation differences between varying mineral phases one each rock, as well as differences between the characteristic crystalline rocks from diverse locations and the potential impact of the radionuclide speciation on their migration properties in the geosphere. Additionally the results will be compared to single phase studies from literature to evaluate the validity of an additive component mixing approach.

Background: Watershed areas are most susceptible for ischemia in patients with high-grade internal carotid artery stenosis (ICAS) [1]. Thorough investigation of the currently not well understood hemodynamic impairments is important to improve treatment guidelines. [2] Here, we propose a multimodal-MRI protocol to better characterise hemodynamic impairments in asymptomatic ICAS with increased sensitivity within individual watershed areas (iWSA).
Methods: Twenty-nine asymptomatic, unilateral ICAS patients (age = 70.1 ± 4.8y), and 30 age-matched healthy controls (age = 70.3 ± 7.3y) underwent 3T-MRI. Imaging yielded maps of cerebrovascular reactivity (CVR) [3], cerebral blood flow (CBF) [4], relative oxygen extraction fraction (rOEF), [5] relative cerebral blood volume (rCBV), capillary transit-time heterogeneity (CTH), and oxygen extraction capacity (OEC) [6] (Fig. 1). Based on DSC-derived time-to-peak (TTP) maps, iWSAs were defined for each participant (Fig. 2a) [7]. Mean hemodynamic parameter values within each hemisphere were compared between ICAS-patients vs. HC and inside vs. outside iWSAs (Fig. 2a, b) within GM and WM.
Result: We found significant lateralisation of CBF, CVR, rCBV, CTH, and OEC for ICAS-patients (all p < 0.05), whereas no significant rOEF lateralisation was found (Fig. 2). Inside iWSAs, lateralisation was enhanced for CBF and CVR (p < 0.05), with a strong trend for rCBV.
Overall, lateralisation was stronger within WM than GM (Fig. 2I).
Contrary, OEC and CTH were indeed lateralised, but comparable inside vs. outside iWSAs (Fig. 2I). For HC, all parameters were symmetrical between hemispheres (data not shown).
Discussion: Observed impairments of CBF, CVR, and CBV are in line with recent studies [8]. As proposed, CBF and CVR impairments are specifically pronounced within iWSAs (Fig. 2I). Interestingly, CTH and OEC were lateralized, however not specifically changed within iWSAs, indicating an independently impaired hemodynamic mechanism.
Conclusion: CBF and CVR reductions may be indicative of the severity of hemodynamic changes within iWSAs, and thus future stroke risk. CTH and OEC impairments are independent of iWSA locations.

Background: Treatment of asymptomatic internal carotid artery stenosis (ICAS) patients remains still controversial [1]. Hemodynamic biomarkers such as the cerebrovascular reactivity (CVR) are promising to identify patients who benefit from revascularization precedures [2–4]. However, commonly employed methods are invasive acetazolamide or complicated gas applications [2–6]. The aim of our study was therefore to measure CVR recovery in ICAS-patients after treatment by easily-applicable breath-hold fMRI (BH-fMRI) with increased sensitivity by evaluation within global watershed areas (gWSAs) [7].
Methods: Thirty-three participants (16 asymptomatic, unilateral ICAS-patients, age = 71.4 ± 5.8y, and 17 healthy controls [HC], age = 70.8 ± 5.3y, see Fig. 1) underwent MRI on a 3T Philips Ingenia.
All participants were scanned twice, patients before and at least three months after treatment, HC at similar follow-up delays. BH-fMRI comprised five breath-holds à 15s each; CVR-maps were calculated by data-driven analysis [8] (Fig. 2a, b). Lateralization of CVR was calculated in GM of gWSAs between hemispheres for each participant (Fig. 2c).
Result: Exemplary ICAS-patient’s data shows impaired CVR before treatment, which recovered after treatment (Fig. 1A,B). On group level, CVR was significantly impaired ipsilateral to the stenosis before treatment (Fig. 3a, t-test, p = 0.0038). After treatment, CVR significantly recovered (2-sample t-test, p = 0.0495) resulting in symmetrical CVR between hemispheres (t-test, p = 0.25). HC data was symmetrical between hemispheres (Fig. 3b, p > 0.60).
Discussion: BH-fMRI based evaluation within gWSAs was sensitive to CVR impairments in asymptomatic ICAS, indicating chronic vasodilation [5]. Specificity was affirmed by symmetrical HC results. Consistent with current literature, CVR recovered after ICAS-treatment [4–7], demonstrating improved hemodynamic status.
Conclusion: We successfully analyzed CVR recovery after ICAS treatment by easily applicable, tolerable and non-invasive BH-fMRI within clinically feasible scan times. This technique could potentially improve future treatment decisions.

Understanding of the metal-insulator transition (MIT) in correlated transition-metal oxides is a fascinating topic in condensed matter physics and a precise control of such transitions plays a key role in developing novel electronic devices. Here we report an effective tuning of the MIT in epitaxial SrVO3 (SVO) films by expanding the out-of-plane lattice constant without changing in-plane lattice parameters, through helium ion irradiation. Upon increase of the ion fluence, we observe a MIT with a crossover from metallic to insulating state in SVO films. A combination of transport and magnetoresistance measurements in SVO at low temperatures reveals that the observed MIT is mainly ascribed to electron-electron interactions rather than disorder-induced localization. Moreover, these results are well supported by the combination of density functional theory and dynamical mean field theory (DFT+DMFT) calculations, further confirming the decrease of the bandwidth and the enhanced electron-electron interactions resulting from the expansion of out-of-plane lattice constant. These findings provide insights into the understanding of MIT in correlated oxides and perspectives for the design of unexpected functional devices based on strongly correlated electrons.

Purpose

The prognosis for patients with inoperable esophageal carcinoma is still poor and the reliability of individual therapy outcome prediction based on clinical parameters is not convincing. In a recent publication, we were able to show that PET can provide independent prognostic information in such a patient group and that the tumor-to-blood standard uptake ratio (SUR) can improve the prognostic value of tracer uptake values. The present investigation addresses the question of whether the distinctly improved prognostic value of SUR can be confirmed in a similar patient group that was examined and treated at a different site.
Methods

18F-FDG PET/CT was performed in 147 consecutive patients (115 male, 32 female, mean age: 62 years) with newly diagnosed esophageal squamous cell carcinoma prior to definitive radiochemotherapy. In the PET images, the metabolic active volume (MTV) of the primary tumor was delineated with an adaptive threshold method. For the resulting ROIs, SUVmax and total lesion glycolysis (TLG = MTV × SUVmean) were computed. The blood SUV was determined by manually delineating the aorta in the low-dose CT. SUR values were computed as ratio of tumor SUV and blood SUV. Univariate Cox regression and Kaplan–Meier analysis with respect to overall survival (OS), distant-metastases-free survival (DM), and locoregional control (LRC) was performed. Additionally, a multivariate Cox regression including clinically relevant parameters was performed.
Results

Univariate Cox regression revealed MTV, TLG, and SURmax as significant prognostic factors for OS. MTV as well as TLG were significant prognostic factors for LRC while SURmax showed only a trend for significance. None of the PET parameters was prognostic for DM. In univariate analysis, SUVmax was not prognostic for any of the investigated clinical endpoints. In multivariate analysis (T-stage, N-stage, MTV, and SURmax), MTV was an independent prognostic factor for OS and showed a trend for significance for LRC. SURmax was not an independent predictor for OS or LRC. When including the PET parameters separately in multivariate analysis, MTV as well as SURmax were prognostic factors for OS indicating that SURmax is independent from the clinical parameters but not from MTV. In addition, MTV was an independent prognostic factor for LRC in this separate analysis.
Conclusions

Our study revealed a clearly improved prognostic value of tumor SUR compared to tumor SUV and confirms our previously published findings regarding OS. Furthermore, SUR delivers prognostic information beyond that provided by the clinical parameters alone, but does not add prognostic information beyond that provided by MTV in this patient group. Therefore, our results suggest that pretherapeutic MTV is the parameter of choice for PET-based risk stratification in the considered setting but further investigations are necessary to demonstrate that this suggestion is correct.

Top-Level Architecture of the proposed HZDR Data Management Strategy with an example experiment

Background

In patients with non-small cell lung cancer (NSCLC), asphericity (ASP) of the primary tumor’s metabolic tumor volume (MTV) has shown prognostic significance. This study aimed at validation in an independent, sufficiently large cohort.
Patients and Methods

Retrospective study in 311 NSCLC patients undergoing FDG-PET/CT before curatively intended treatment (always including surgery). 140 patients had UICC stage I, 78 stage II, and 93 stage III (adenocarcinoma [ADC]:153; squamous cell carcinoma [SCC]:141). Primary tumor MTV was delineated with semiautomated background-adapted threshold relative to SUVmax. Cox regression (PFS/OS) for PET (MTV, ASP, SUVmax), clinical (T/N descriptor, UICC stages), histological and treatment variables (Rx/1 vs. R0 resection, chemotherapy/radiotherapy yes/no).
Results

Events (progression/relapse) occurred in 167/311 patients, 137 died (median survivor follow-up, 37 months). In multivariable Cox regression for OS, ASP>33.3% (HR, 1.58 [1.04-2.39]), male sex (1.84), age (1.04 per year), EGOG≥2 vs. 0/1 (2.68), stage II vs. I (1.96), and Rx/1 vs. R0 resection (2.1) were significant. Among separate UICC stages, ASP only predicted OS in stage II (optimal, >19.5%; median OS, 33 vs. 59 months). Regarding PFS, ASP>21.2%, male sex, EGOG≥2, stage II vs. I, and Rx/1 resection were prognostic. ASP remained prognostic in stage II (optimal, >19.5%; PFS, 12 vs. 47 months). Log-rank test for ASP was significant at any cut-off ≥18% (OS) or from 9-59% (PFS).
Conclusion

ASP was validated as prognostic factor for PFS and OS in patients with NSCLC and curative treatment intent, especially stage II. High ASP in stage II could imply intensified treatment or intensified follow-up.

A new Center for Radiopharmaceutical Cancer Research was established at the Helmholtz-Zentrum Dresden-Rossendorf in order to centralize radionuclide production, radiopharmaceutical production and the chemical and biochemical research facilities. The newly installed cyclotron is equipped with two beamlines, two target selectors and several liquid, gas and solid target systems. The cyclotron including the target systems and first results of beam characterization measurements as well as results of the radionuclide production are presented. The produced radionuclides are automatically distributed from the targets to the destination hot cells. This process is supervised and controlled by an in-house developed system.

Ferritic-martensitic ODS steels are one of the candidate materials for Gen-IV nuclear fission and fusion reactors. Residual ferrite was often found in the microstructure of 9Cr ODS steels. This constituent was reported to be responsible for the superior creep and high-temperature strength. Using optical microscopy of an air-cooled batch of ODS EUROFER, inhomogeneous regions in the microstructure have been found with similar appearance to previously reported residual ferrite. Detailed microstructural investigations have been carried out on the inhomogeneous regions using site-specific nanoindentation, scanning electron microscopy including electron backscatter diffraction, and transmission electron microscopy. It is demonstrated that the inhomogeneous regions are formed due to imperfect mechanical alloying leading to the absence of oxide nanoparticles and consequently lower hardness. It is concluded that optical microscopy is insufficient to distinguish beneficial residual ferrite from undesired particle-free regions. The weakness of the inhomogeneous regions is attributed to the absence of nanoparticles and a lower dislocation density. Our findings are underpinned by the consistency between the calculated theoretical yield strength, the yield strength converted from the indentation hardness and the yield strength obtained from tensile testing.

Microbial communities occurring in reference materials for artificial barriers (e.g. bentonites) in future deep geological repositories of radioactive waste can influence the migration behavior of radionuclides such as curium (CmIII). This study investigates the molecular interactions between CmIII and its inactive analogue europium (EuIII) with the indigenous bentonite bacterium Stenotrophomonas bentonitica at environmentally relevant concentrations. Potentiometric studies showed a remarkable high concentration of phosphates at the bacterial cell wall compared to other bacteria, revealing a great potential of S. bentonitica for metal binding. Infrared spectroscopy (ATR-FTIR) and X-ray photoelectron spectroscopy (XPS) confirmed the role of phosphates and carboxylate groups from the cell envelope in the bioassociation of EuIII. The ATR-FTIR spectra also suggested a bidentate bridging EuIII complex with carboxylate groups. Additionally, time-resolved laser-induced fluorescence spectroscopy (TRLFS) identified phosphoryl and carboxyl groups from bacterial envelopes, among other released complexing agents, to be involved in the EuIII and CmIII coordination. Microscopic and kinetic Eu-binding studies indicated biosorption as the main interaction process, in addition to other mechanisms. The ability of this bacterium to form a biofilm at the surface of bentonites allow them to immobilize trivalent lanthanide and actinides in the environment.

A quantum Loschmidt echo (also referred to as quantum time mirror) corresponds to an effective time inversion after which the quantum wave function reverses its previous time evolution and eventually reaches its initial distribution again. We propose a comparably simple protocol for such an effective time reversal for ultra-cold atoms in optical lattices which should be easier to realize experimentally than previous proposals.

This reply contains a brief response to the comment by R. Howl, D. Rätzel, and I. Fuentes [arXiv:1811.10306]

One of the fundamental predictions of Quantum Electrodynamics (QED) is the spontaneous creation of particle--antiparticle pairs from vacuum in presence of a very strong electric field. Under these extreme conditions a strongly bound state can fetch an otherwise unobservable electron from the Dirac sea, leaving behind a hole representing a positron. Although generally known for many decades, the effect has not yet been demonstrated experimentally. We propose an analogue model of the quantum Dirac field, realized by ultra--cold fermionic atoms in an optical lattice, aiming at an experimental simulation of this intriguing non--perturbative phenomenon. Numerical simulations demonstrate the effect of spontaneous pair creation in the optical analogue system, in qualitative agreement with QED: in the adiabatic regime the vacuum can be destabilized only by supercritical fields exceeding a critical threshold.

Quantum theory predicts intriguing dynamics during drastic changes of external conditions. We switch the trapping field of two ions sufficiently fast to tear apart quantum fluctuations, i.e., create pairs of phonons and, thereby, squeeze the ions’ motional state. This process can be interpreted as an experimental analog to cosmological particle creation and is accompanied by the formation of spatial entanglement. Hence, our platform allows one to study the causal connections of squeezing, pair creation, and entanglement and might permit one to cross-fertilize between concepts in cosmology and applications of quantum information processing.

We study relaxation dynamics in a strongly-interacting two-site Fermi-Hubbard model that is induced by fermionic baths. To derive the proper form of the Lindblad operators that enter an effective description of the system-bath coupling in different temperature regimes, we employ a diagrammatic real-time technique for the reduced density matrix. An improvement on the commonly-used secular approximation, referred to as coherent approximation, is presented. We analyze the spectrum of relaxation rates and identify different time scales that are involved in the equilibration of the Hubbard dimer after a quantum quench.