Publications Repository - Helmholtz-Zentrum Dresden-Rossendorf

We investigate sustenance and dependence on magnetic Prandtl number (Pm) for magnetorotational instability (MRI)-driven turbulence in Keplerian disks with zero net magnetic flux using standard shearing box simulations. We focus on the turbulence dynamics in Fourier space, capturing specific/noncanonical anisotropy of nonlinear processes due to disk flow shear. This is a new type of nonlinear redistribution of modes over wavevector orientations in Fourier space—the nonlinear transverse cascade—which is generic to shear flows and fundamentally different from the usual direct/inverse cascade. The zero flux MRI has no exponentially growing modes, so its growth is transient, or nonmodal. Turbulence self-sustenance is governed by constructive cooperation of the transient growth of MRI and the nonlinear transverse cascade. This cooperation takes place at small wavenumbers (on the flow size scales) referred to as the vital area in Fourier space. The direct cascade transfers mode energy from the vital area to larger wavenumbers. At large Pm, the transverse cascade prevails over the direct one, keeping most of modes' energy contained in small wavenumbers. With decreasing Pm, however, the action of the transverse cascade weakens and can no longer oppose the action of the direct cascade, which more efficiently transfers energy to higher wavenumbers, leading to increased resistive dissipation. This undermines the sustenance scheme, resulting in the turbulence decay. Thus, the decay of zero net flux MRI turbulence with decreasing Pm is attributed to the topological rearrangement of the nonlinear processes when the direct cascade begins to prevail over the transverse cascade.

We report the influence of static mechanical deformation on the zero-field splitting of silicon vacancies in silicon carbide at room temperature. We use AlN/6H-SiC heterostructures deformed by growth conditions and monitor the stress distribution as a function of distance from the heterointerface with spatially-resolved confocal Raman spectroscopy. The zero-field splitting of the V1/V3 and V2 centers in 6H-SiC, measured by optically-detected magnetic resonance, reveal significant changes at the heterointerface compared to the bulk value. This approach allows unambiguous determination of the spin-deformation interaction constant, which turns out to be 0.75 GHz for the V1/V3 centers and 0.5 GHz for the V2 centers. Provided piezoelectricity of AlN, our results offer a strategy to realize the on-demand fine tuning of spin transition energies in SiC by deformation.

The European metallurgical industries are the enablers for the realization of the goals of the EU Green Deal and the Agenda 2030 for Sustainable Development. The realization of these goals requires a metallurgical industry that is even more resource-efficient, eco-friendly and responsible than it is today. Accordingly, the metallurgical industry and system must be protected and strengthened, rather than having its socioeconomic importance undermined because of misconceptions about its residue generation, energy consumption, and environmental impacts. To understand and quantify the opportunities and limits associated with creating more circular and sustainable metallurgical infrastructure systems, rigorous digitalization is imperative. The European Training Network SOCRATES has taken this up by developing ground-breaking metallurgical processes for the valorization of industrial intermediate products. Additionally, this project quantified the impact of its developed metallurgical processes on the sustainability of the current material and metal supply chain through the creation of large simulation-based digital twins of the metallurgical system.

As of 2016, gold from electronic scrap was estimated to value almost e 19,000 million of the global e-waste [1]. This thesis aims at quantication of gold in scrap Printed Circuit Boards using Spectrum Radiography. The thesis is divided into two main sections- rst is where calibration of the detector takes place in order to estimate amount of x-rays that are transmitted through dierent thicknesses of gold and the second section is based on the results from scrap PCBs. The nal focus is to use the calibration, to quantify gold in Printed Circuit Board sample. Spectrum Radiography can help obtain the transmission of x-rays by a sample and based on the k-edge absorption theory, one can identify the element present in the sample.
The amount of transmission was estimated to relate to the thickness of the sample and the calibration data showed that with increasing sample thickness, gradual reduction in transmission was observed with the Spectrum Radiography. Hence, the thesis was based on quantifying elements based on k-edge transmission spectra. The resolution limit of the detector comes along, contributing to errors in quantication.
The thesis enlists and elaborates the statistical approaches for the quantication of gold using the radiographs obtained from the new prototype Spectral Detector and concludes the correlation of results obtained for geometrically analogous sample to x-ray beam orientations and also concludes the inapplicability of this method for samples with inhomogeneous thickness across the x-ray beam path.

A photon counting detector gives X-ray transmission radiographs of a slice of a sample in which transmission is resolved into 128 bins of X-ray energies from 20 keV to 160 keV. After plotting the graph of transmission over energy bins, the K-edge can be traced. By using machine learning and computer vision techniques on these ‘energy bins vs derivative of X-ray transmission’ information, slices were not only classified much faster in an automated way but also performed better when compared to the manual classification of minerals by using intensities or gray scale values of particles.
Machine learning was implemented on the slices of manually prepared sample containing gold and lead particles, Printed Circuit Board (PCB) and a rock sample. Slices were also classified by implementing machine learning on intensity properties of gold and galena to further confirm an advantage of using spectrum information. Results helped to understand the challenges in the project and thus paved a way for advanced research.

Processing behaviour of a mineral resource highly depends on the characteristics of particles such as shape, size and composition. Therefore, comprehensive particle characterization is crucial to understand and optimize processing behaviour to enhance recoveries and reduce waste production. Nevertheless, despite the obvious importance of particle characteristics, current analysis techniques are restricted to two-dimensional (2D) particle characterization. In order to have advance three-dimensional (3D) characterization, this study aims to present a new X-CT methodology for single particle characterization with a special sample preparation method to reduce the X-CT artefacts.
A homogenous and dispersed particle sample reduce the X-CT artefacts and ease the segmentation process for individual particle labelling. This labelled data then further used for image processing combined with a new single particle peak analysis method for enhanced mineral classification based on greyscale. Classification of mineral phases for X-CT data was performed with the correlation of Mineral Liberation Analyzer (MLA). All the major mineral phases present in the ore were successfully classified except the gold grains. Characterization using 2D (MLA) and 3D (X-CT) was compared and mineralogy difference of around 2% observed. The effect of particle properties measured by both methods also investigated in processing simulation

The coordination behavior of the calixarene-based N4O4 donor ligand H6L bearing two pendant 8-hydroxyquinoline-2-hydrazone arms towards the lanthanide ions Tb3+, Dy3+, and Yb3+ has been investigated. H6L was found to support tetra- and dinuclear mixed-ligand complexes with the pendant hydrazone units in a deprotonated enolate and/or a neutral amide form. The direct reaction of H6L with Ln(NO3)3(H2O)6 and NEt3 in a 1:1:2 molar ratio leads to tetranuclear [Ln4(H3L)2(µ-OH)2(η2-NO3)4] complexes {Ln = Tb (1), Dy (2), Yb (3)} containing a rectangular arrangement of four eight-coordinate Ln3+ ions bridged by two hydroxido- and four quinolinolato-O atoms as established by X-ray crystallography. Degradation of 2 occurs upon addition of further equiv. of H6L to give dinuclear [Dy2(H4L)(NO3)2(MeCN)2]NO3 (4) with eight- and ten-coordinated Dy3+ ions. ESI-MS studies reveal that such dinuclear species exist also in the solution state. The results of variable temperature direct and alternating current magnetic susceptibility measurements for 1–4 and high frequency EPR study on 4 are also reported.

Highly compliant electronics, naturally conforming to human skin, represent a paradigm shift in the interplay with the surroundings. Solution-processable printing technologies are yet to be developed to comply with extreme requirements to mechanical conformability of on-skin appliances. Here, it is demonstrated that high-performance spintronic elements can be printed on ultrathin 3 μm thick polymeric foils enabling the mechanically imperceptible printed magnetoelectronics. Benefiting from their extreme compliancy, the printed magnetic-field sensors well adapt to the periodic buckling surface to be biaxially stretched over 100% of strain rate. They constitute the first example of printed and stretchable giant magnetoresistive sensors, revealing 2 orders of magnitude improvements in mechanical stability and sensitivity at small magnetic fields, compared to the state-of-the-art printed magnetoelectronics. The key aspect of this performance enhancement is the use of elastomeric triblock copolymers as a binder for the magnetosensitive paste. Even when bent to a radius of 16 μm, the sensors screen printed on ultrathin foils remain fully intact and possess unmatched sensitivity for printed magnetoelectronics of 3 T-1 in a low magnetic field of 0.88 mT. With this performance, the compliant printed sensors can be used as components of on-skin interactive electronics as it is demonstrated with a touchless control of virtual objects including zooming in and out of interactive maps and scrolling through electronic documents.

Ore sorting is a technology that is increasingly used to process primary raw materials. Time-consuming and expensive empirical state-of-the-art test work is carried out to assess whether the use of ore sorting for the enrichment of a particular ore makes technical and economic sense. With the innovative simulation-based approach presented here, it is possible to direct the selection of a suitable sensor based on quantitative mineralogical and textural data, thus avoiding much of the empirical studies. Required data can be collected quickly and cost-effectively using available methods of automated mineralogy. The obtained parameters such as mineral grain size distribution, modal mineralogy, mineral area and mineral density distribution have been utilized in this study to simulate the prospects of success of ore sorting applying different types of sensors. Empirical tests with commercially available sensor systems have been conducted to experimentally validate the predictions of the simulations. The estimation of the target mineral grade can be further optimized by the use of machine learning algorithms for the integration of automated mineralogy data and sensor data. The approach can easily be adapted to other types of raw materials and thus has great potential to become a key technology for the optimization of processing experiments.

Presentation about optimal sensor for ore sorting

The INFACT project (Innovative, Non-Invasive and Fully Acceptable Exploration Technologies) aims to change raw material exploration in a way that it becomes socially accepted, environmentally-friendly and technologically advanced. It strives to establish a view of the best practices for exploration that is shared by civil society, state and industry. A set of permanent reference sites representing a variety of social, physical and technical challenges in the EU are used to conduct stakeholder dialogue and to provide an industry-relevant environment for the development of non-invasive exploration methods.

Liquid metal batteries (LMBs) are introduced as future candidates for grid scale electricity storage. Their completely liquid cell interior entails a prominent role of fluid mechanics to understand and model their behaviour. We describe the equations used to compute electrochemical reactions, heat and mass transfer, electromagnetic fields, and fluid flow and explain the simplifications that can be made in the case of LMBs. The implementation of solution algorithms in OpenFOAM pertaining to domain coupling, multiphase simulations, mesh mapping, and operator discretisation are discussed in detail and accompanied by example code.

Presentation at FLUKA collaboration meeting (virtual), December 4, 2020

The talk gives an overview on status and recent developments of the "HELmholtz ScIentific Project WORk-flow PlaTform" called HELIPORT. The idea is it to accommodate the complete life cycle of a scientific project and to links all corresponding programs and systems. The HELIPORT architecture has a modular structure such that the core application can be used in different Helmholtz centers and only individual components have to be replaced or added. HELIPORT is based on modern web technologies and can be used on different platforms. In addition to the entire project flow, computational workflows are also managed via the system in order to document all work steps as seamlessly as possible according to the FAIR principles and to publish them later.

Background and purpose: Positron emission tomography (PET) is a functional imaging modality which is able to deliver tracer specific biological information, e.g. about glucose uptake, inflammation or hypoxia of tumors. We performed a proof-of-principle study that used different tracers and expanded the analytical scope to non-tumor structures to evaluate tumor-host interactions.
Materials and Methods: Based on a previously reported prospective imaging study on 50 patients treated with curative intent chemoradiation (CRT) for head and neck squamous cell carcinoma, PET-based hypoxia and normal tissue inflammation measured by repeat 18F-fluoromisonidazole (FMISO) PET and 18F-fluorodesoxyglucose (FDG) PET, respectively, were correlated using the Spearman correlation coefficient R. PET parameters determined before and during CRT (week 1, 2 and 5), were associated with local tumor control and overall survival.
Results: Tumor hypoxia at all measured times showed an inverse correlation with mid-treatment FDG-uptake of non-tumor affected oral (sub-)mucosa with R values between -0.35 and -0.6 (all p<0.05). Mucosal FDG-uptake and mucosal hypoxia correlated positively but weaker (R values between 0.2 and 0.45). More tumor hypoxia in FMISO-PET (week 2) and less FDG-uptake of (sub-)mucosa in FDG-PET (week 4) were significantly associated with worse LC (FMISO TBRpeak: HR=1.72, p=0.030; FDG SUVmean: HR=0.23, p=0.025) and OS (FMISO TBRpeak: HR=1.71, p=0.007; FDG SUVmean: HR=0.30, p=0.003). Multivariable models including both parameters showed improved performance, suggesting that these modalities still bear distinct biological information despite their strong inter-correlation.
Conclusion: We report first clinical evidence that tumor hypoxia is inversely correlated with increased FDG-uptake during radiation, potentially expressinginflammation. This observation merits further research and may have important implication for future research on tumor hypoxia and radio-immunology. Our study demonstrates that functional imaging can be utilized to assess complex tumor-host interactions and generate novel biological insights in vivo vero.

Conventional external beam radiation therapy with high-energy photons is one of the pillars of treatment for patients with intrathoracic tumors. Due to technical advances, e.g., highly conformal, image-guided irradiation techniques, it has been possible to increase local tumor control while simultaneously reducing treatment-associated side effects. In recent years, proton beam therapy has become an alternative at an increasing number of national and international sites. At present, only four German sites offer protons for treatment of tumors outside of the eye, but the demand is increasing continually. Due to the physical characteristics of protons, i.e., the steep dose fall-off beyond the point of maximum dose deposition that is normally located in the tumor, normal tissue and organs at risk beyond the tumor can be spared. This review highlights the value of proton beam therapy for intrathoracic tumors.

Background: Whole brain radiotherapy (WBRT) is a common treatment option for brain metastases secondary to non-small cell lung cancer (NSCLC). Data from the QUARTZ trial suggest that WBRT can be omitted in selected patients and treated with optimal supportive care alone. Nevertheless, WBRT is still widely used to treat brain metastases secondary to NSCLC. We analysed decision criteria influencing the selection for WBRT among European radiation oncology experts.
Methods: Twenty-two European radiation oncology experts in lung cancer as selected by the European Society for Therapeutic Radiation Oncology (ESTRO) for previous projects and by the Advisory Committee on Radiation Oncology Practice (ACROP) for lung cancer were asked to describe their strategies in the management of brain metastases of NSCLC. Treatment strategies were subsequently converted into decision trees and analysed for agreement and discrepancies.
Results: Eight decision criteria (suitability for SRS, performance status, symptoms, eligibility for targeted therapy, extra-cranial tumour control, age, prognostic scores and ‘‘Zugzwang” (the compulsion to treat)) were identified. WBRT was recommended by a majority of the European experts for symptomatic patients not suitable for radiosurgery or fractionated stereotactic radiotherapy. There was also a tendency to use WBRT in the ALK/EGFR/ROS1 negative NSCLC setting.
Conclusion: Despite the results of the QUARTZ trial WBRT is still widely used among European radiation oncology experts.

It has been known that the power ultrasound is used as a pretreatment and rarely applied as a simultaneous method to improve grade and recovery during froth flotation processes. This work aimed at investigating the impact of simultaneously used ultrasonic waves under variant operating configurations on the flotation of representative porphyry copper ore during rougher and re-cleaner stages. For this purpose, four different operating outlines were examined as (I) conventional flotation, (II) homogenizer, (III) ultrasonic bath, and (IV) combination of a homogenizer and an ultrasonic bath. The ultrasonic vibration was generated by the homogenizer (21 kHz, 1 kW) in the froth zone and ultrasonic bath (35 kHz, 0.3 kW) in the bulk zone. The rougher and re-cleaner flotation experiments were conducted using Denver-type mechanically agitated cells with 4.2 and 1 L capacities, respectively. The results showed that using the homogenizer (at 0.4 kW) slightly affected the selectivity separation index of chalcopyrite and pyrite, although it positively increased the grade of chalcopyrite from 21.5% to 25.7%. The ultrasonic-assisted flotation experiments with the ultrasonic bath and its combination with the homogenizer (0.4 kW) (i.e., configurations III and IV) led to an increase of approximately 16.1% and 26.9% in the chalcopyrite selectivity index compared to the conventional flotation, respectively. At the cleaning stage, a lower grade of aluminum silicate-based minerals was obtained desirably in every ultrasonic-treated configuration, which was supported with the water recoveries. Finally, applying the homogenizer and its combination with the ultrasonic bath were recommended for re-cleaner and rougher stages, respectively. Further fundamental and practical knowledge gaps required to be studied were highlighted.

Helium Ion Microscopy (HIM) has not been thoroughly exploited for biological studies addressing relevant questions that range from the cellular to the subcellular level. One of the benefits of HIM compared to other high-resolution imaging techniques is definitely the large depth of focus, sub-nm resolution, nm surface sensitivity, and especially that no sample coating is needed that can change the nanostructure morphology on the surface. The prerequisite to getting the most from the technique is thus the appropriate sample preparation. Besides, to get the most from understanding the addressed biological question, a successful correlative microscopy approach is necessary. This is best shown in our recently published study (H Kokot, Advanced Materials, 2020), where we have addressed one of the most critical issues in toxicology, that is the poor understanding of chronic inflammation initiation in lung tissue caused by inhaled nanoparticles, with the correlative microscopy approach using advanced multimodal optical microscopy and HIM. HIM nicely revealed the TiO2 nanotube organization and passivation on the cell surface and confirmed lipid and protein binding to the TiO2 surface (Figure below), identified as well by in silico simulations. In brief, HIM is an extremely powerful technique for the surface, and in the case of porous samples also in-depth morphology characterization on an nm scale. In combination with complementary imaging techniques and proper sample preparation, many relevant biological questions can be addressed and solved. Still, there are many limitations and challenges in cell preparation and imaging using helium ions, such as imaging of internal structures, definitely pursuing discussions and new developments in the future.

Stratified flows are one of the most important multiphase flow regimes for safety analyses of the loss-of-coolant accident in pressurized water reactors. The present paper considers simulations of an isothermal counter-current stratified flow case in the channel of the WENKA experiment using a morphology adaptive multi-field two-fluid modelling framework. A consistent momentum interpolation approach is applied together with the partial elimination algorithm, as it is required for strong momentum coupling, which enforces the no-slip condition at the interface and mirrors the behaviour of a homogeneous model. To model the turbulent flow conditions near an interface, the framework is extended with a turbulence damping model based on the damping scale formulation from the literature, which is introduced into the k-w SST (Shear Stress Transport) turbulence model. The presented modelling approach is validated with experimental data for the pressure difference and vertical profiles of volume fraction, velocity and turbulent kinetic energy. Results of a mesh sensitivity study of the model are presented. Simulations were performed on two- and three-dimensional models of the channel geometry. Two turbulence damping strategies are investigated: symmetric, with damping in both phases, and asymmetric with damping only in the gas phase. The comparison shows that the asymmetric approach offers improved prediction of turbulent kinetic energy on the liquid side of the interface, but with a cost of diminished accuracy of the predicted velocity profiles on the gas side.

The development of a switch circuit to gate charge sensitive preamplifiers for use at pulsed radiation sources will be presented.This development was used for the 16O(n,alpha)13C reaction measurement with a Double Frisch Grid Ionization Chamber (DFGIC) at the neutron time-of-flight facility CERN nTOF in Geneva, Switzerland. The so-called gamma-flash, which is produced in the spallation target of the nTOF facility can saturate charge sensitive preamplifiers and prevent signals from being registered in the detection system. The switch circuit made it possible for the first time to perform a measurement with the DFGIC with gamma-flash gated off at nTOF in November 2018. Nano-second gating of charge sensitive preamplifiers has a wide range of applicability at pulsed radiation sources, where short burst of radiation must be gated off to avoid saturation, e.g. with HPGe detectors for gamma-ray detection. Nano-second gating requires the stray-capacitance of the wideband reflective switch to be compensated to avoid a strong signal during the switch operation. Spectral analysis of the switch circuit shows that additional noise is insignificant.

A digital LLRF control has been implemented at the CW linac ELBE at Helmholtz-Zentrum Dresden-Rossendorf. The system is based on the MicroTCA.4 standard and drives four superconducting TESLA cavities and two normal conducting buncher cavities. The system enables a higher flexibility of the field control, improved diagnostics and field stability compared to the analogue system which was used before. The presentation will give an overview on the system performance in terms of noise measurements. In addition a review of the user operation started in August 2020 will be given. Finally, planned future features are presented.

A digital LLRF control has been implemented at the CW linac ELBE at Helmholtz-Zentrum Dresden-Rossendorf. The system is based on the MicroTCA.4 standard and drives four superconducting TESLA cavities and two normal conducting buncher cavities. The system enables a higher flexibility of the field control, improved diagnostics and field stability compared to the analogue system which was used before. The presentation will give an overview on the system, its performance and a review of the user operation started in August 2020.

Agate - a spectacular form of SiO2 and a famous gemstone - is commonly characterized as banded chalcedony. In detail, chalcedony layers in agates can be intergrown or intercalated with macrocrystalline quartz, quartzine, opal-A, opal-CT, cristobalite and/or moganite. In addition, agates often contain considerable amounts of mineral inclusions and water as both interstitial molecular H2O and silanol groups. Most agate occurrences worldwide are related to SiO2-rich (rhyolites, rhyodacites) and SiO2-poor (andesites, basalts) volcanic rocks, but can also be formed as hydrothermal vein varieties or as silica accumulation during diagenesis in sedimentary rocks. It is assumed that the supply of silica for agate formation is often associated with late-or post-volcanic alteration of the volcanic host rocks. Evidence can be found in association with typical secondary minerals such as clay minerals, zeolites or iron oxides/hydroxides, frequent pseudomorphs (e.g., after carbonates or sulfates) as well as the chemical composition of the agates. For instance, elements of the volcanic rock matrix (Al, Ca, Fe, Na, K) are enriched, but extraordinary high contents of Ge (>90 ppm), B (>40 ppm) and U (>20 ppm) have also been detected. Calculations based on fluid inclusion and oxygen isotope studies point to a range between 20 and 230◦C for agate formation temperatures. The accumulation and condensation of silicic acid result in the formation of silica sols and proposed amorphous silica as precursors for the development of the typical agate micro-structure. The process of crystallisation often starts with spherulitic growth of chalcedony continuing into chalcedony fibers. High concentrations of lattice defects (oxygen and silicon vacancies, silanol groups) detected by cathodoluminescence (CL) and electron paramagnetic resonance (EPR) spectroscopy indicate a rapid crystallisation via an amorphous silica precursor under non-equilibrium conditions. It is assumed that the formation of the typical agate microstructure is governed by processes of self-organization. The resulting differences in crystallite size, porosity, kind of silica phase and incorporated color pigments finally cause the characteristic agate banding and colors.

In this letter we report the first multi-differential measurement of correlated pion-proton pairs from 2 billion Au+Au collisions at \sqrt{s_{NN}} = 2.42 GeV collected with HADES. In this energy regime the population of \Delta(1232) resonances plays an important role in the way energy is distributed between intrinsic excitation energy and kinetic energy of the hadrons in the fireball. The triple differential d3N/dM{\pi}pdpTdy distributions of correlated {\pi}p pairs have been determined by subtracting the {\pi}p combinatorial background using an iterative method. The invariant-mass distributions in the \Delta(1232) mass region show strong deviations from a Breit-Wigner function with vacuum width and mass. The yield of correlated pion-proton pairs exhibits a complex isospin, rapidity and transverse-momentum dependence. In the invariant mass range 1.1 < Minv (GeV/c2) < 1.4, the yield is found to be similar for {\pi}+p and {\pi}-p pairs, and to follow a power law ^{\alpha}, where is the mean number of participating nucleons. The exponent {\alpha} depends strongly on the pair transverse momentum (pT) while its pT-integrated and charge-averaged value is {\alpha} = 1.5 \pm 0.08stat \pm 0.2sys.

Most human tumors possess a high heterogeneity resulting from both clonal evolution and cell differentiation program. The process of cell differentiation is initiated from a population of cancer stem cells (CSCs), which are enriched in tumor‐regenerating and tumor‐propagating activities and responsible for tumor maintenance and regrowth after treatment. Intrinsic resistance to conventional therapies, as well as a high degree of phenotypic plasticity, makes CSCs hard-to-target tumor cell population. Reprogramming of CSC metabolic pathways plays an essential role in tumor progression and metastatic spread. Many of these pathways confer cell adaptation to the microenvironmental stresses, including a shortage of nutrients and anti-cancer therapies. A better understanding of CSC metabolic dependences as well as metabolic communication between CSCs and the tumor microenvironment are of utmost importance for efficient cancer treatment. In this mini-review, we discuss the general characteristics of CSC metabolism and potential metabolic targeting of CSC populations as a potent strategy to enhance the efficacy of conventional treatment approaches.

Tumorigenesis is driven by metabolic reprogramming. Oncogenic mutations and epigenetic alterations that cause metabolic reprogramming may also upregulate the reactive oxygen species (ROS). Precise regulation of the intracellular ROS levels is critical for tumor cell growth and survival. High ROS production leads to the damage of vital macromolecules, such as DNA, proteins, and lipids, causing genomic instability and further tumor evolution. One of the hallmarks of cancer metabolism is deregulated amino acid uptake. In fast-growing tumors, amino acids are not only the source of energy and building intermediates but also critical regulators of redox homeostasis. Amino acid uptake regulates the intracellular GSH levels, endoplasmic reticulum stress, unfolded protein response signaling, mTOR-mediated antioxidant defense, and epigenetic adaptations of tumor cells to oxidative stress. This review summarizes the role of amino acid transporters as the defender of tumor antioxidant system and genome integrity and discusses them as promising therapeutic targets and tumor imaging tools.

In the investigation of the mutual interaction of self-assembled monolayers (SAMs) of helical organic molecules with metal surfaces, the goals are both to understand how surface properties, like magnetisation, influence the formation of the SAM and how the ensemble of electron-spin selective molecules influences magnetic properties of the carrier materials, specifically on a buried ferromagnetic layer.

The phenomenology of the effects on both sides can be modelled via kinetic Metropolis Monte Carlo (KMC) simulations in different ways. In both cases, this class of simulations models the kinetics of non-equilibrium systems based on local interaction energies using stochastic cellular automata based on non-equilibrium thermodynamics. This stochastic modeling replaces the physical dynamics simulated in, e.g., molecular dynamics (MD) simulations. Such a simplification is often necessary when simulating large ensembles required to observe phase ordering processes in order make these simulations possible or achieve sufficient throughput to create parameter maps like phase diagrams.

Anisotropic low-temperature properties of the cubic spinel helimagnet ZnCr2Se4 in the single-domain spinspiral state are investigated by a combination of neutron scattering, thermal conductivity, ultrasound velocity, and dilatometry measurements. In an applied magnetic field, neutron spectroscopy shows a complex and nonmonotonic evolution of the spin-wave spectrum across the quantum-critical point that separates the spin-spiral phase from the field-polarized ferromagnetic phase at high fields. A tiny spin gap of the pseudo-Goldstone magnon mode, observed at wave vectors that are structurally equivalent but orthogonal to the propagation vector of the spin helix, vanishes at this quantum critical point, restoring the cubic symmetry in the magnetic subsystem. The anisotropy imposed by the spin helix has only a minor influence on the lattice structure and sound velocity but has a much stronger effect on the heat conductivities measured parallel and perpendicular to the magnetic propagation vector. The thermal transport is anisotropic at T ≲ 2K, highly sensitive to an external magnetic field, and likely results directly from magnonic heat conduction. We also report long-time thermal relaxation phenomena, revealed by capacitive dilatometry, which are due to magnetic domain motion related to the destruction of the single-domain magnetic state, initially stabilized in the sample by the application and removal of magnetic field. Our results can be generalized to a broad class of helimagnetic materials in which a discrete lattice symmetry is spontaneously broken by the magnetic order.

The inverse magnetocaloric effect in Ni-Mn based Heusler compounds occurs during the magnetostructural transition between low-temperature, low-magnetization martensite and high-temperature, high-magnetization austenite. In this study, we analyze the metamagnetic transformation of a Ni_49.8Mn₃₅In_15.2 compound by simultaneous adiabatic temperature change ΔT_ad and strain Δl/l₀ measurements in pulsed magnetic fields up to 10 T. We observe a ΔT_ad of −10 K and a Δl/l₀ of −0.22% when the reverse martensitic transition is fully induced at a starting temperature of 285 K. By a variation of the magnetic field-sweep rates between 316, 865, and 1850 T s⁻¹, the transitional dynamics of the reverse martensitic transformation have been investigated. Our experiments reveal an apparent delay upon the end of the reverse martensitic transformation at field rates exceeding 865 T s⁻¹ which is related to the annihilation of retained martensite. As a consequence, the field hysteresis increases and higher fields are required to saturate the transition. In contrast, no time-dependent effects on the onset of the reverse martensitic transformation were observed in the studied field-sweep range. Our results demonstrate that kinetic effects in Heusler compounds strongly affect the magnetic cooling cycle, especially when utilizing a multicaloric “exploiting-hysteresis cycle” where high magnetic field-sweep rates are employed.

Mineral dissolution plays a key role in many environmental and technical fields, e.g., weathering, reservoir and host rock characterization, as well as building materials. The rate of mineral dissolution in water is determined by two parameters: (1) transport of dissolved species over and from the interface determined by advective fluid flow and diffusion (transport control) and (2) crystal surface reactivity (surface reactivity control). Current reactive transport models (RTM) simulating species transport commonly calculate mineral dissolution by using rate laws (e.g., Agrawal et al., 2020). These rate laws solely depend on species concentration in the fluid and therefore do not include intrinsic surface reactivity. Experimental studies at surface reactivity controlled conditions have shown a heterogeneous distribution of reaction rates (e.g., Bibi et al., 2018). This rate heterogeneity is caused by nanotopographical structures on the crystal surface, such as steps and etch pits that are generated at lattice defects. At these structures, the high density of reactive kink sites is leading to a local increase in dissolution rates.
In this study, we test whether experimentally observed rate heterogeneities can be reproduced by using current RTMs. We apply a standard RTM approach combined with the measured surface topography of a calcite single crystal (Bibi et al., 2018). The calculated surface dissolution rate maps are compared to experimentally derived rate maps. The results show that the measured rate heterogeneities cannot be reproduced with the existing RTM approach. To improve the predictive capabilities of RTMs, the surface reactivity that is intrinsic to the mineral needs to be implemented into dissolution rate calculations. We discuss parameterization of surface reactivity via proxy parameters, such as surface roughness or surface slope.

Agrawal, P., Raoof, A., Iliev, O. and Wolthers, M. (2020): Evolution of pore-shape and its impact on pore conductivity during CO2 injection in calcite: Single pore simulations and microfluidic experiments. Advances in Water Resources, 136, 103480.
Bibi, I., Arvidson, R.S., Fischer, C. and Lüttge, A. (2018): Temporal Evolution of Calcite Surface Dissolution Kinetics. Minerals, 8, 256

A key component of performance assessment (PA) for radioactive waste repositories in deep geological formations is the forecast of potential radionuclide transport through the repository system. Understanding and appropriate modelling of all relevant (hydro-)geochemical processes is essential for predicting the migration of radionuclides. One important retardation process is sorption on mineral surfaces of the host rock or sedimentary overburden. For the quantification of the radionuclide retention the solid/liquid distribution coefficients (Kd-values) calculated for a given groundwater/rock system are traditionally used in reactive transport modelling (RTM) and most often considered as a constant value due to the large temporal and spatial scales considered in PA. Such a conventional concept has the advantage to be simple and computationally fast but cannot reflect changes in geochemical conditions that are expected during the evolution of the repository system caused by climatic or geological changes. Due to the German safety criteria with an assessment period of one million years it is necessary to consider the impact of such hydrogeological and geochemical changes on the radionuclide transport and retardation. The challenge for large-scale RTM is the integration of important geochemical parameters and processes at affordable computational costs into the codes. Most often a full direct coupling of a transport code with a geochemical speciation code, however, leads to unacceptably long computational times for PA relevant systems.
As an effective way to integrate variable geochemistry in RTM, we developed the smart Kd-concept (www.smartkd-concept.de), a mechanistic approach mainly based on surface complexation models and implemented it into a transport code [1], [2]. The philosophy behind this approach is to compute a-priori multidimensional look-up tables with distribution coefficients (referred to as smart Kd-values as they are based on mechanistic sorption models) for a wide range of important environmental input parameters. Such parameters are typically pH, ionic strength, concentration of competing cations and complexing ligands such as calcium (Ca) and dissolved inorganic carbon (DIC). These smart Kd-values can be accessed during each transport simulation step. Equations describing pH and concentrations of ions as a function of mineral phases are implemented into the transport code, and the resulting values are used to obtain the corresponding smart Kd-values from the look-up table. The smart Kd values are calculated using the geochemical code PHREEQC [3] with a bottom-up approach, i.e. the mineral-specific sorption of dissolved species on each single mineral phase contributes to the distribution coefficient for the whole sediment. Parameter variation was performed with the numeric tool UCODE [4].
The capability of this approach is demonstrated for the sorption of repository-relevant radionuclides (isotopes of Am, Cm, Cs, Ni, Np, Pu, Ra, Th and U) and possible migration scenarios through a typical sedimentary rock system covering potential repository host rocks, namely salt and clay formations in Northern Germany as natural geological barrier for a deep geological repository site. This serves as a comprehensive proof-of-concept and demonstrates the capability to describe the sorption behaviour in dependence of changing geochemical conditions quite well. As a side-effect, the large Kd-matrices that were computed can be further analysed by sensitivity and uncertainty analysis (SA/UA) as provided by SimLab2.2/4 [5], [6].
Results of this case study showed that the smart Kd approach goes considerably beyond the conventional concepts. We can illustrate that constant Kd values previously used in transport simulations, here exemplarily shown for uranium U(VI) (Figure 1, right, green line [7]), are a rough approximation, as in reality they rather range over several orders of magnitude. Moreover, with the results from SA, those input parameters influencing strongest the radionuclide retardation variation can be identified (key parameters of the model). The calculated sensitivity indices allowed us to rank all parameters with respect to sensitivity on Kd. From the visualized smart Kd matrix for U(VI) (Figure 1, left) it is obvious that mainly the pH value and the DIC determine the sorption of U(VI) under the given conditions. SA is a useful means for reducing the complexity of a geochemical model by focusing on the most important input parameters.

Si-based photodetectors satisfy the criteria of low-cost and environmental-friendly, and can enable the development of on-chip complementary metal-oxide-semiconductor (CMOS)-compatible photonic systems. However, extending their room-temperature photoresponse into the mid-wavelength infrared (MWIR) regime remains challenging due to the intrinsic bandgap of Si. Here, we report on a comprehensive study of a room-temperature MWIR photodetector based on Si hyperdoped with Te. The demonstrated MWIR p-n photodiode exhibits a spectral photoresponse up to 5 µm and a slightly lower detector performance than the commercial devices in the wavelength range of 1.0-1.9 μm. We also investigate the correlation between the background noise and the sensitivity of the Te-hyperdoped Si photodiode, where the maximum room-temperature specific detectivity is found to be 3.2 × 1012 cmHz1/2W-1 and 9.2 × 108 cmHz1/2W-1 at 1 µm and 1.55 µm, respectively. This work contributes to pave the way towards establishing a Si-based broadband infrared photonic system operating at room temperature.

High-Frequency and -Field EPR (HFEPR) studies of Fe(TPP)X (X = F, Cl, Br; I, TPP²−=meso-tetraphenylporphyrinate dianion) and far-IR magnetic spectroscopic (FIRMS) studies of Fe(TPP)Br and Fe(TPP)I have been conducted to probe magnetic intra- and inter-Kramers doublet transitions in these S = 5/2 metalloporphyrin complexes, yielding zero-field splitting (ZFS) and g parameters for the complexes: Fe(TPP)F, D = +4.67(1) cm⁻¹, E = 0.00(1) cm⁻¹, g_⊥ = 1.97(1), g = 2.000(5) by HFEPR; Fe(TPP)Cl, D = +6.458(2) cm⁻¹, E = +0.015(5) cm⁻¹, E/D = 0.002, g_⊥ = 2.004(3), g_|| = 2.02(1) by HFEPR; Fe(TPP)Br, D = +9.03(5) cm⁻¹, E = +0.047(5) cm⁻¹, E/D = 0.005, g_iso = 1.99(1) by HFEPR and D = +9.05 cm⁻¹, g_iso = 2.0 by FIRMS; Fe(TPP)I, D = +13.84 cm⁻¹, E = +0.07 cm⁻¹, E/D = 0.005, g_iso = 2.0 by HFEPR and D = +13.95 cm⁻¹, g_iso = 2.0 by FIRMS (the sign of E was in each case arbitrarily assigned as that of D). These results demonstrate the complementary nature of field- and frequency-domain magnetic resonance experiments in extracting with high accuracy and precision spin Hamiltonian parameters of metal complexes with S > 1/2. The spin Hamiltonian parameters obtained from these experiments have been compared with those obtained from other physical methods such as magnetic susceptibility, magnetic Mössbauer spectroscopy, inelastic neutron scattering (INS), and variable-temperature and -field magnetic circular dichroism (VT-VH MCD) experiments. INS, Mössbauer and MCD give good agreement with the results of HFEPR/FIRMS; the others not as much. The electronic structure of Fe(TPP)X (X = F, Cl, Br, I) was studied earlier by multi-reference ab initio methods to explore the origin of the large and positive D-values, reproducing the trends of D from the experiments. In the current work, a simpler model based on Ligand Field Theory (LFT) is used to explain qualitatively the trend of increasing ZFS from X = F to Cl to Br and to I as the axial ligand. Tetragonally elongated high-spin d⁵ systems such as Fe(TPP)X exhibit D > 0, but X plays a key role. Spin delocalization onto X means that there is a spin–orbit coupling (SOC) contribution to D from X^•, as opposed to none from closed-shell X⁻. Over the range X = F, Cl, Br, I, X^• character increases as does the intrinsic SOC of X^• so that D increases correspondingly over this range.

In the scope of the European IVMR (In-Vessel Melt Retention) project, calculations of In-Vessel retention (IVR) strategy with state of the art Severe Accident (SA) computer codes were performed, including the integral codes ASTEC, ATHLET-CD, MAAP, MELCOR and RELAP5/SCDAPSIM. Further codes dedicated to the study of lower plenum behaviour were also included. Simulations were performed for several types of reactors (PWR, VVER-440, VVER-1000, BWR) and several severe accident scenarios (Station Blackout (SBO) accidents and Loss-Of-Coolant accidents of several leak sizes combined with SBO). The code improvements for IVR simulation, implemented during the project, are summarized and the results obtained with the improved codes are presented in the paper.

Ferromagnetism has been observed in ion and neutron irradiated SiC single crystals. In this paper, we present a structural and magnetic investigation on 6H–SiC irradiated by swift heavy ions. The co-exist of paramagnetism, superparamagnetism and ferromagnetism is revealed by using different magnetometry methods. The ferromagnetic component persists well above room temperature. This study confirms the general existence of defect-induced magnetism in SiC.

1 Introduction
The disposal of nuclear waste including the assessment of long-term safety is still an open question in Germany. In addition to the pending decision about the repository host rock (salt, granite, or clay) and the associated site selection, the basic necessity of a consistent and obligatory thermodynamic reference database persists. Such a database is essential to assess potential radionuclide migration scenarios accu-rately and to make well-founded predictions about the long-term safety up to one million years. Specific challenges are comprehensive datasets covering also elevated temperatures and high salinities. Concern-ing the required elements (actinides, fission products as well as matrix and building materials), no other thermodynamic database is available that is compatible with the expected conditions. Due to these defi-ciencies THEREDA [1,2], a joint project of institutions leading in the field of safety research for nuclear waste disposal in Germany and Switzerland, was started in the year 2006.

2 Database features
THEREDA offers evaluated thermodynamic data for many compounds (solid phases, aqueous species, or constituents of the gaseous phase) of elements relevant according to the present state of research. In particular, all oxidation states expected for disposal site conditions are considered. In the present release, THEREDA includes data for actinides and their chemical analogues (Th, U, Np, Pu, Am, Cm & Nd), fission products (Se, Sr, Tc & Cs) and matrix elements (Na, K, Mg, Ca, Al, Si | Cl, SO₄, CO₃). For the calculation of cementitious phases the current version of CEMDATA (18.1) was integrated [3].
THEREDA is based on a relational databank whose structure intrinsically ensures the internal consisten-cy of thermodynamic data. Data considered respond to the needs of both Gibbs Energy Minimizers (ChemApp, GEMS) and Law-of-Mass-Action codes (Geochemist’s Workbench, PHREEQC, ToughReact). The database is designed generically so that it can store interaction parameters for various models. Namely, the PITZER ion interaction approach to describe activity coefficients of hydrated ions and molecules in saline solutions [4] as well as ideal and non-ideal solid solution approaches are consid-ered in the actual dataset.
After free registration, THEREDA is accessible via internet through www.thereda.de. This is not only a portal to view the data itself, their uncertainties and the primary references of the data; it provides also additional information on issues concerning the database. Ready-to-use parameter files are available for download in a variety of formats (geochemical code specific formats and generic ASCII type). They are also used for internal test calculations – one essential element of the quality assurance scheme. The capa-bilities of THEREDA are demonstrated using approx. 400 application case calculations, whose results were compared with experimental values published in literature.

References
[1] Altmaier, M. et al., “THEREDA - Ein Beitrag zur Langzeitsicherheit von Endlagern nuklearer und nichtnuklearer Abfälle”, atw, 53, 249–253 (2008).
[2] Moog, H.C. et al., “Disposal of nuclear waste in host rock formations featuring high-saline solutions – Implementation of a thermodynamic reference database (THEREDA)”, Appl. Geochem., 55, 72–84 (2015).
[3] Lothenbach, B. et al., “Cemdata18: A chemical thermodynamic database for hydrated Portland cements and alkali-activated materials”, Cem. Concr. Res., 115, 472–506 (2019).
[4] Pitzer, K.S., Activity Coefficients in Electrolyte Solutions, 2nd Ed., pp. 542, CRC Press, Boca Raton (1991).
[5] Ryan, J. L., et al. “The solubility of uranium(IV) hydrous oxide in sodium hydroxide solutions under reducing conditions”, Polyhedron, 2, 947 (1983).
[6] Rai, D. et al. “The Solubility of Th(IV) and U(IV) Hydrous Oxides in Concentrated NaCl and MgCl₂ Solutions” Radiochim. Acta, 79, 239–247 (1997).
[7] Neck, V. et al. “Solubility and hydrolysis of tetravalent actinides”, Radiochim. Acta, 89, 1–16 (2001),

Estimating animal home ranges is a primary purpose of collecting tracking data. Many widely used home range estimators, including conventional kernel density estimators, assume independently sampled data. In stark contrast, modern GPS animal tracking datasets are almost always strongly autocorrelated. The incongruence between estimator assumptions and empirical reality often leads to systematically underestimated home ranges. Autocorrelated kernel density estimation (AKDE) directly models the observed autocorrelation structure of tracking data during home range estimation, and has been shown to perform accurately across a broad range of tracking datasets. However, compared to conventional estimators, AKDE requires additional modeling steps and has heretofore only been accessible via the command-line ctmm R package. Here, we introduce ctmmweb, which provides a point-and-click graphical interface to ctmm and streamlines AKDE, its prerequisite autocorrelation modeling steps, and a number of additional movement analyses. We demonstrate ctmmweb’s capabilities, including AKDE home range estimation and subsequent home range overlap analysis, on a dataset of four jaguars from the Brazilian Pantanal. We intend ctmmweb to open AKDE and related autocorrelation-explicit analyses to a wider audience of wildlife and conservation professionals.

In the present work, modified embedded atom potential and large-scale molecular dynamics’ simulations were used to explore the effect of grain boundary (GB) segregated foreign interstitials on the deformation behavior of nanocrystalline (nc) iron. As a case study, carbon and nitrogen (about 2.5 at.%) were added to (nc) iron. The tensile test results showed that, at the onset of plasticity, grain boundary sliding mediated was dominated, whereas both dislocations and twinning were prevailing deformation mechanisms at high strain. Adding C/N into GBs reduces the free excess volume and consequently increases resistance to GB sliding. In agreement with experiments, the flow stress increased due to the presence of carbon or nitrogen and carbon had the stronger impact. Additionally, the simulation results revealed that GB reduction and suppressing GBs’ dislocation were the primary cause for GB strengthening. Moreover, we also found that the stress required for both intragranular dislocation and twinning nucleation were strongly dependent on the solute type.

Deep trenches, as essential elements of silicon chips used in electronic high-power and high-frequency devices, are known as starting points for dislocation generation under the influence of internal mechanical stresses resulting mainly from the difference in the thermal expansion coefficients between silicon and silicon dioxide. Since the electrical insulation of the devices requires a sequence of mechanical, chemical, and high-temperature processes during the preparation of the deep trenches, including the formation of an amorphous SiO2 edge layer, the emergence of the internal stresses is hardly avoidable. The method of cross correlation backscattered electron diffraction in the scanning electron microscope is used here to quantitatively determine the magnitude and local distribution of internal stresses in silicon around the deep trenches after four different process steps. For this purpose, Kikuchi diffraction images are recorded of the wafer cross section areas along lines perpendicular and parallel to the deep trenches. After Fourier transformation, these images are cross correlated with the Fourier transform of the diffraction image from a stressfree reference sample site. The well-established numerical evaluation of cross correlation functions provides the complete distortion tensor for each measuring point of the line scan, from which the stress tensor can be calculated using Hooke’s law. It is found that the in-plane normal stress component σ11 perpendicular to the long edges of the deep trench is larger than the other stress components. That means it essentially determines the magnitude of the von-Mises stress, which was determined as a general stress indicator for all measuring points, too. A characteristic feature is the local distribution of the stress component σ11 with maximum tensile stresses of some hundred megapascals at transition between Si and amorphous SiO2 on the long edges of the deep trench, and with even higher maximum compressive stresses immediately below the bottom of the deep trench. At a distance of about 2 μm from the edges of a single deep trench, all stress components decrease to negligibly small values so that steep stress gradients occur. The range and distribution of tensile and compressive stresses are in accordance with finite element simulations; however, the measured stresses are higher than expected for all investigated states so that dislocation formation seems to be possible. The influence of the electron acceleration voltage on the determination of the internal stresses is discussed as well.

The focus of this work is the validation of Serpent-SCF-TU, a high-fidelity multiphysics tool combining Monte Carlo neutron transport, subchannel thermalhydraulics and fuel-performance analysis. A full-core pin-by-pin depletion calculation for the first operating cycle of a Pre-Konvoi PWR plant is presented and the results are assessed using experimental data. The critical boron concentration and a set of pin-level neutron flux profiles are compared against measurements, with very good agreement. The impact of using fuel performance analysis is discussed as well, comparing the three-code coupling with the traditional neutronic-thermalhydraulic approach. The studies presented here are part of the final stage of the EU Horizon 2020 McSAFE project, closing the development cycle of the Serpent-SCF-TU system, from implementation to validation.

Herein we report the design and synthesis of a series of highly selective CCR2 antagonists as 18F-labeled PET tracers. The derivatives were evaluated extensively for their off-target profile at 48 different targets. The most potent and selective candidate was applied in vivo in a biodistribution study, demonstrating a promising profile for further preclinical development. This compound represents the first potential nonpeptidic PET tracer for the imaging of CCR2 receptors.

Interacting electrons confined to their lowest Landau level in a high magnetic field can form a variety of correlated states, some of which manifest themselves in a Hall effect. Although such states have been predicted to occur in three-dimensional semimetals, a corresponding Hall response has not yet been experimentally observed. Here, we report the observation of an unconventional Hall response in the quantum limit of the bulk semimetal HfTe₅, adjacent to the three-dimensional quantum Hall effect of a single electron band at low magnetic fields. The additional plateau-like feature in the Hall conductivity of the lowest Landau level is accompanied by a Shubnikov-de Haas minimum in the longitudinal electrical resistivity and its magnitude relates as 3/5 to the height of the last plateau of the three-dimensional quantum Hall effect. Our findings are consistent with strong electron-electron interactions, stabilizing an unconventional variant of the Hall effect in a three-dimensional material in the quantum limit.

Objective: The integration of an MRI scanner into a proton beam line imposes challenges to the dose delivery, since the magnetic field (MF) of the scanner distorts the beams and hence the dose distribution. This study aims to develop a Monte Carlo (MC)-based beam model of the pencil beam scanning nozzle in the OncoRay facility to accurately model the dose delivery in the presence of an open MR scanner.
Materials and Methods: Measurements of proton beam spot size in air at varying distance from the nozzle were used to model beam optics using the Geant4-based MC code TOPAS. The beam energy and energy spread were obtained from the fit of depth-dose profiles measured in water.
A 3D map of the magnetic fringe field of the 0.22 T (vertical field) open MR scanner was generated with COMSOL and used in TOPAS. The simulated beam deflection was compared to measurements 210 cm downstream of the beam isocenter. Horizontal spot scanning positions from 0 to 200 mm and beam energies of 125 and 220 MeV were considered.
Results: The simulated spot sizes without MF agreed with experimental measurements within the experimental uncertainty. With MF, spot deflections of 183.6 (125 MeV) and 135.0 (220 MeV) mm were observed at the central spot position in the horizontal axis compared to their respective experimental values of 226.5 and 164.6 mm. For scan positions from 50 to 200 mm, relative differences between simulations and experimental results were within 6% (125 MeV) and 3.7% (220 MeV).
Conclusions: In the absence of MF, Initial validation of the beam modeling shows good reproducibility of spot sizes. Simulations with MF show large deviations for the beam deflection for central beam spots. The observed disagreement is likely related to deficiencies in the MF map, which has not been experimentally validated. Future work will include the validation of the MF map and a detailed evaluation of beam deflection and changes in spot sizes in the MF.

Introduction:

Radio(chemo)therapy is standard in the (adjuvant) treatment of glioblastoma. Inevitably, brain tissue surrounding the tumor bed or residual tumor is also irradiated, which may lead to acute and late side-effects. Diffusion-weighted imaging (DWI) with magnetic resonance imaging (MRI) has been shown to be a sensitive method to detect early changes in the cerebral white matter after radiation. The aim of this work was to assess possible changes in the mean diffusivity (MD) of the white matter after radio(chemo)therapy using DWI and to compare these effects between patients treated with proton and photon irradiation.
Patients & methods:
70 patients diagnosed with glioblastoma underwent adjuvant radio(chemo)therapy with protons (n=20) or photons (n=50). MRI follow-up examinations were performed at three-monthly intervals and were evaluated until 33 months after the end of therapy. For all time points, MD maps were calculated and normal appearing white matter was segmented in T1-weighted MR images. Relative white matter MD changes between baseline and all follow-up visits were calculated in different dose regions.
Results:
We observed a significant decrease of MD (mean -4,0%, range -0,8 ¬– -7,9%, p<0.05) in white matter in areas, in which a dose of more than 20 Gy had been applied. The MD reduction was progressing with dose and time after radio(chemo)therapy. In patients treated with photons, significant reductions in white matter in the whole brain (mean -2,3%, range -0,9 – -3,1%, p<0.05) were seen at all time points. In proton patients, conversely, MD did not change significantly (mean -0,5%, range 0,5 – -2,4%).
Conclusion:
The results show that irradiation leads to measurable changes in white matter and that treatment with protons reduces this effect due to a lower total dose in the surrounding white matter. Further investigations are needed to assess whether those MD changes correlate with known radiation induced side-effects.

Neural precursor cells (NPC) are primary cells intensively used in the context of research on adult neurogenesis and modelling of neuronal development in health and diseased states. Substrates that can facilitate NPC adhesion will be very useful for culturing these cells. Due to the presence of laminin in basal lamina as well as their involvement in differentiation, migration, and adhesion of many types of cells, we focused on surfaces modified with laminin-derived peptides and compared them with the widely used fibronectin-derived RGD peptides. We synthesized an array of 46 peptides on cellulose paper (SPOT) to identify laminin-derived peptides that promote short-term adhesion of murine NPC and human primary endothelial cells. Various previously reported peptide sequences have been re-evaluated in this work. Initial adhesion experiments showed NPC preferred several laminin-derived peptides by up to 5-time higher cell numbers, compared to the well-known promiscuous integrin binding RGD peptide. Importantly, screening of cell adhesion has revealed a synergetic effect of filamentous matrix, peptide sequence, surface property, ligand density, and the dynamic process of NPC adhesion.

Structural investigations of three actinide(IV) 4-phosphoryl 1H-pyrazol-5-olate complexes (An = Th(IV), U(IV), Np(IV)) and their cerium(IV) analogue display the same metal coordination in the solid state. The mononuclear complexes show the metal centre in a square antiprismatic coordination geometry composed by the two O-donor atoms of four deprotonated ligands. Detailed solid state analysis of the U(IV) complex shows that in dependence of the solvent used altered arrangements are observable, resulting in a change in the coordination polyhedron of the U(IV) metal centre to bi-capped trigonal prismatic. Further, single crystal analyses of the La(III) and Ce(III) complexes show that the ligand can also act as a neutral ligand by protonation of the pyrazoyl moiety. All complexes were comprehensively characterized by NMR, IR and Raman spectroscopy. A single resonance in each of the 31P NMR spectra for the La(III), Ce(III), Ce(IV), Th(IV) and Np(IV) complex indicates the formation of highly symmetric complex species in solution. Extended X-ray absorption fine structure (EXAFS) investigations provide evidence for the same local structure of the U(IV) and Np(IV) complex in toluene solution, confirming the observations made in the solid state.

The shape of objects has a strong influence on their dynamics. Here, we present comparative studies of two different motile objects, spherical Ag/AgCl Janus particles and polystyrene Janus nanorods, that move due to an ionic self-diffusiophoretic propulsion mechanism when exposed to blue light. In this paper, we propose a method to fabricate Janus rodlike particles with high aspect ratios and hemispherical tip shapes. The inherent asymmetry due to the ratio between capped and uncapped parts of the particles as well as the shape anistropy of Janus nanorods enables imaging and quantification of rotational dynamics. The dynamics of microswimmers are compared in terms of velocities and diffusion coefficients. We observe that despite a small amount of the Ag/AgCl reagent on the surface of rodlike objects, these new Janus micromotors reveal high motility in pure water. While the velocities of spherical particles reach 4.2 μm/s, the single rodlike swimmers reach 1.1 μm/s, and clusters reach 1.6 μm/s. The effect of suppressed rotational diffusion is discussed as one of the reasons for the increased velocities. These Janus micro- and nanomotors hold the promise for application in light-controlled propulsion transport.

Ion-irradiation and the induced nanostructuring was found, over the last century, to be a very powerful technique for surface modifications on a vast amount of different materials. Especially the formation of nanostructures by strong electronic excitation mediated by slow highly charged ions and swift heavy ions received lots of interest in recent years. The ionic crystal CaF2 was a model system for the underlying processes. In our investigations we reveal the formation of nano-hillocks by slow individual Au-cluster-irradiation on CaF2(111) surface that were found to be very similar to nano-hillocks in former studies with highly charged ions. We show that the high energy density directly transferred to the atomic lattice of the target leads to the same hillock-like structures as in case of indirect energy transfer for slow highly charged ions.

The present paper describes the design and function of the TOPFLOW Pressure Chamber of the Helmholtz Zentrum Dresden-Rossendorf. The facility opened new opportunities for experiments at pressures of up to 50 bar. The actual test equipment can be constructed as a not pressure carrying installation. The TOPFLOW steam generator, located in an adjacent hall, was used to supply steam at saturation conditions. In the paper, three experimental programs that were carried out in the pressure chamber are introduced briefly, mainly with the purpose to highlight the advantages of the pressure chamber technique.

Objectives: For the integration of magnetic resonance imaging (MRI) into proton therapy (PT), a 0.22 T MRI was installed at the pencil beam scanning beam line at OncoRay. As a next step, dosimetry in the magnetic field has to be established. This work aims to study the influence of the static field (B0) of the MRI on ionisation chamber (IC) responses for proton beams through measurements and Monte Carlo (MC) simulations.
Materials & methods: A Semiflex 0.3 and a PinPoint 3D IC were positioned in a water phantom placed in the MR imager isocenter. The absolute dose at five proton energies (70, 110, 150, 190, 226.7 MeV) was measured within the entrance plateau of the depth-dose curve using a 10×10 cm² homogeneous irradiation field. The correction factor kB→,M,Q was obtained by dividing the measured dose with/without B0. For the MC simulations, beam-commissioning data (depth-dose profiles in water, beam spot sizes in air) were used to create a MC beam model in TOPAS (1.5×105 particles). A 3D map of the scanner’s magnetic field (MF) was calculated with COMSOL and used in the simulations to mimic the experimental setup.
Results: The MF correction factor kB→,M,Q showed systematic energy-dependent differences between dose readings with and without B0. For the Semiflex 0.3, kB→,M,Q was 0.9926, 0.9942, 0.9941, 0.9959 and 1.0036 for 70, 110, 150, 190 and 226.7 MeV, respectively. For the same energies, kB→,M,Q for the PinPoint 3D was 0.9920, 0.9931, 0.9938, 0.9952 and 0.9969. For all energies, the standard deviations of kB→,M,Q were smaller than 0.002 for both ICs. MC simulations of the Semiflex 0.3 response to 110 MeV showed no statistically significant B0 effect with kB→,M,Q of 0.997 (95% CI: 0.9893, 1.0049).
Conclusion: Measurements showed a small but significant influence of the MRI scanner’s B0 field on the IC response, which was beam energy-dependent. Further investigations should clarify the necessity of dosimetric correction factors for the MR-integrated PT.

Reaction of the N-heterocylic carbene ligand iPrIm (L1) and lithium bis(trimethylsilyl)amide (TMSA) as a base with UCl4 resulted in U(IV) and U(V) complexes. Uranium’s +V oxidation state in (HL1)2[U(V)(TMSI)Cl5] (TMSI = trimethylsilylimido) (2) was confirmed by HERFD-XANES measurements. Solid state characterization by SC-XRD and geometry optimisation of [U(IV)(L1)2(TMSA)Cl3] (1) indicated a silylamido ligand mediated inverse trans influence (ITI). The ITI was examined regarding different metal oxidation states and was compared to transition metal analogues by theoretical calculations.

Radiochemical conversion is an important term to be included in the “Consensus nomenclature rules for radiopharmaceutical chemistry”. Radiochemical conversion should be used to define reaction efficiency by measuring the transformation of components in a crude reactionmixture at a given time,whereas radiochemical yield is better suited to define the efficiency of an entire reaction process including, for example, separation, isolation, filtration, and formulation.

Pool scrubbing is an effective method for removing radioactive aerosols during severe nuclear accidents and protecting the health of nearby residents and the environment. After the pool scrubbing research is revived by the Fukushima Daiichi accident, experimental studies tend to provide CFD-level data on phase distribution and bubble dynamics owing to improved measuring techniques. In contrast, CFD investigations on bubble dynamics under pool scrubbing conditions are still scarce due to the challenges of reliable models and high computational cost. To achieve best practice guidelines for the use of CFD for such complex multiphase flow situations in nuclear safety analyses, there is still a long way to go and a large amount of simulation practice is desirable. This work aims to investigate the bubble dynamics under pool scrubbing conditions using the interface-tracking method available in the open-source CFD code OpenFOAM. At first, the impact of numerical setups such as domain dimension, mesh resolution, and time step on the simulation results is studied in detail for a basic case, which provides good guidelines for the setup of next benchmark cases. Bubble shape, bubble detachment size, and frequency as well plume structure are compared with the results of other institutions that participate in the benchmark simulations as well as experimental observations. Good qualitative and quantitative agreement was obtained. The work provides a basis for investigation on bubble dynamics in pool scrubbing with aerosol particles using the CFD methodology in the next step.

We understand ¹³¹Ba as a radionuclide, which enables imaging by SPECT in nuclear medicine and provides a diagnostic match for the therapeutic alpha-emitting radionuclides ²²³Ra and ²²⁴Ra. Recently, we reported on a sufficient production route for ¹³¹Ba by irradiating a ¹³³Cs target with 27.5 MeV proton beams, and the straight-forward resin-based radiochemical separation, yielding ¹³¹Ba with high radionuclide purity. An average amount of 190 MBq of ¹³¹Ba was produced per irradiation. Apart from 0.1% isotopic impurity of ¹³³Ba, no more side-products were detectable. For the first time, radiolabeling of the complexing agent macropa (known to be an appropriate ²²⁵Ac chelator) with ¹³¹Ba was reported and mild labeling conditions as well as reaction control using TLC systems were applicable. The radiopharmacological characterization of ¹³¹Ba-labeled macropa was carried out in healthy mice using uncomplexed [¹³¹Ba]Ba²⁺ as a reference, including biodistribution studies and small animal SPECT/CT. The results revealed the rapid bone uptake of free [¹³¹Ba]Ba²⁺ ions, whereas ¹³¹Ba-labeled macropa showed a fast renal clearance and significantly lower (P < 0.001) accumulation in the bones. We therefore conclude, that ¹³¹Ba is a promising “new” radionuclide for SPECT imaging purposes and delivers appropriate quality for preclinical investigations. Moreover, the successful labeling of macropa and the in vivo stability of the ¹³¹Ba-complex are viewed as a promising starting point for the development of new heavy earth alkaline metal chelators, especially for the therapeutically relevant radium isotopes. This enables ¹³¹Ba to achieve its goal as diagnostic match and monitoring tool for ^223/224Ra.

Electron-optical phonon interaction is the dominant energy-loss mechanism in low-dimensional Ge/SiGe heterostructures and represents a key parameter for the design and realization of electronic and optoelectronic devices based on this material system compatible with the mainstream Si complementary metal-oxide semiconductor technology. Here we investigate the intersubband relaxation dynamics of n-type Ge/SiGe multiquantum wells with different symmetry and design by means of single-color pump-probe spectroscopy. By comparing the experimental differential transmittance data as a function of the pump-probe delay with numerical calculations based on an energy-balance rate-equation model, we could quantify an effective value for the optical phonon deformation potential describing the electron-phonon coupling in two-dimensional Ge-based systems. We found nonradiative relaxation times longer than 20 ps even in samples having intersubband energy separations larger than the optical phonon energy, evidencing the presence of a less effective electron-phonon coupling with respect to that estimated in bulk Ge.

Background:

Deriving individual tumor genomic characteristics from patient imaging analysis is desirable. We explore the predictive value of 2-[18F]FDG uptake with regards to the KRAS mutational status of colorectal adenocarcinoma liver metastases (CLM).
Methods:
2-[18F]FDG PET/CT images, surgical pathology and molecular diagnostic reports of
37 patients who underwent PET/CT-guided biopsy of CLM were reviewed under an IRB-approved retrospective research protocol. Sixty CLM in 39 interventional PET scans of the 37 patients were segmented using two different auto-segmentation tools implemented in 37 different commercially available software packages. PET standard uptake values (SUV) were corrected for: 1) partial volume effect (PVE) using cold wall-corrected contrast recovery coefficients derived from phantom spheres with variable diameter; and 2) variability of arterial tracer supply and variability of uptake time after injection until start of PET scan derived from the tumor-to-blood standard uptake ratio (SUR) approach. The correlations between the KRAS mutational status and the mean, peak, and maximum SUV were investigated using Student’s t-test, Wilcoxon rank sum test with continuity correction, logistic regression and receiver operation characteristic (ROC) analysis. These correlation analyses were also performed for the ratios of the mean, peak and maximum tumor uptake to the mean blood activity concentration at the time of scan: SURMEAN, SURPEAK, and SURMAX, respectively.
Results: Fifteen patients harbored KRAS missense mutations (KRAS+) while another 3 harbored KRAS gene amplification. For 31 lesions the mutational status was derived from the PET/CT-guided biopsy. The Student’s-t p-values for separating KRAS mutant cases decreased after applying PVE correction to all uptake metrics of each lesion and when applying correction for uptake time variability to the SUR metrics. The observed correlations were strongest when both corrections were applied to SURMAX and when the patients harboring gene amplification were grouped with the wild type: p ≤ 0.001; ROC area under the curve (AUC) = 0.77 and 0.75 for the two different segmentations respectively with a mean specificity of 0.69 and sensitivity of 0.85.
Conclusions:
The correlations observed after applying the described corrections show potential for assigning probabilities for the KRAS missense mutation status in CLM using 2-[18F]FDG PET images.

Stirred tanks are widely used equipment to process solid-liquid dispersions in the chemical and minerals engineering industries. CFD simulations of such equipment on industrial scales are principally feasible within the Euler-Euler / RANS approach. Practical application, however, requires suitable closure models to account for phenomena on the scale of individual particles, which are not resolved in this approach. The present work applies a set of closure relations that originates from a comprehensive review of existing results from analytical, numerical, and experimental studies. Focus is on the modeling of interfacial forces which includes drag, lift, and turbulent dispersion. To validate the model a comprehensive set of experimental data including particle concentration as well as liquid velocity and turbulence has been assembled from different literature sources. The necessity for model extensions is confirmed via the comparison of simulation results obtained by different sets of closure correlations, i.e. the presently proposed one and others that have been frequently used in previous studies, with the experimental data.

In the present project, closure models for chemical reactions as well as the as-sociated mass transport are included in the Euler-Euler description of bubbly flows. This approach allows to capture inhomogeneous distributions of gas fraction as well as local differences in concentration and flow fields on the scale of the bubble column. In this way, calculations up to the size of industrial equipment or components thereof become feasible. To achieve this goal, suit-able closure models for processes occurring on the scale of individual bubbles have to be devised. The simulation results, are then compared with experi-mental data to validate the employed models.
The challenge in this endeavor based on the state-of-the-art at the beginning of the project is threefold: First, the available understanding of mass transfer from or to single bubbles both without and with the simultaneous occurrence of a chemical reaction is limited. Second, experimental data of a quality, which is suitable for the purpose of model validation, are scarce. Third, for re-active systems the intrinsic reaction kinetics and material parameters depend-ing on the concentrations of all involved species and temperature are often not known.

A direct approach for determining the tray and point efficiencies of an industrial-scale distillation tray is proposed. The stripping of isobutyl acetate from an aqueous solution with air was used, which is a manageable and non-hazardous method applicable for performance tests in large hydraulic column mockups. This work represents the first application of this system in the case of tray columns exemplified for a sieve tray. A column of 800 mm internal diameter was used for conducting the stripping experiments. The distribution of isobutyl acetate in the liquid phase on the tray was obtained via liquid sampling at several deck positions and UV-spectroscopy analysis. A definition for the liquid-side tray efficiency at weeping conditions is proposed together with an experimental approach for determining tray and point efficiencies in such conditions. The derived efficiency data show a good agreement with the model predictions and correlations.

Eulerian-Eulerian computational fluid dynamic (CFD) models allow the prediction of complex and large-scale industrial multiphase gas-liquid bubbly flows with a relatively limited computational load. However, the interfacial transfer processes are entirely modelled, with closure relations that often dictate the accuracy of the entire model. Numerous sets of closures have been developed, often optimized over few experimental data sets and achieving remarkable accuracy that, however, becomes difficult to replicate outside of the range of the selected data. This makes a reliable comparison of available model capabilities difficult and obstructs their further development. In this paper, the CFD models developed at the University of Leeds and the Helmholtz-Zentrum Dresden-Rossendorf are benchmarked against a large database of bubbly flows in vertical pipes. The research groups adopt a similar modelling strategy, aimed at identifying a single universal set of widely applicable closures. The main focus of the paper is interfacial momentum transfer, which essentially governs the void fraction distribution in the flow, and turbulence modelling closures. To focus on these aspects, the validation database is limited to experiments with a monodispersed bubble diameter distribution. Overall, the models prove to be reliable and robust and can be applied with confidence over the range of parameters tested. Areas are identified where further development is needed, such as the modelling of bubble-induced turbulence and the near-wall region. A benchmark is also established and is available for the testing of other models. Similar exercises are encouraged to support the confident application of multiphase CFD models, together with the definition of a set of experiments accepted community-wide for model benchmarking.

The peculiarities of computational actinide chemistry concerning the ground and excited state require state-of-the-art electronic structure methods. Currently, the most popular one is the CASSCF- method for the inclusion of static correlation in combination with CASPT2 for dynamic correlation and CASSI for spin-orbit coupling. This combination is used for the evaluation of excited state energies and transitions for simulating electronic spectra and comparing with experimental findings. Furthermore, for the evaluation of a proper active space the DMRG method is used for a choice based on objective reasonings. It is found, that the CASSCF+CASPT2+CASSI combination is able to recover experimental values quite well even for a small basis set. However, the DMRG method reveals that the active space could potentially be improved by not only considering the two electrons in the seven 5f-orbitals but also including C-N-pi and corresponding C-N-pi* orbitals.

The terahertz (THz) region of the electromagnetic spectrum spans the gap between optics and electronics and has historically suffered from paucity of optoelectronic devices, in large part because of inadequate optical materials that function in this spectral range. 2D materials, including graphene and a growing family of related van der Waals materials, have been shown to exhibit unusual optical and electrical properties that can enable diverse new applications in the THz regime. In this review, some of the unusual properties of 2D materials that make them promising for THz applications are explained, the recent work in the field of 2D THz optoelectronics is summarized, and the challenges and opportunities that await this promising new field are outlined.

Graphene patterned into plasmonic structures like ribbons or discs strongly increases the linear and nonlinear optical interaction at resonance. The nonlinear optical response is governed by hot carriers, leading to a red-shift of the plasmon frequency. In magnetic fields, the plasmon hybridizes with the cyclotron resonance, resulting in a splitting of the plasmonic absorption into two branches. Here we present how this splitting can be exploited to tune the nonlinear optical response of graphene discs. In the absence of a magnetic field, a strong pump-induced increase in on-resonant transmission can be observed, but fields in the range of 3 T can change the characteristics completely, leading to an inverted nonlinearity. A two temperature model is provided that describes the observed behavior well.

Antiferromagnets (AFMs) with zero net magnetization are proposed as active elements in future spintronic devices. Depending on the critical thickness of the AFM thin films and the measurement temperature, bimetallic Mn-based alloys and transition metal oxide-based AFMs can host various coexisting ordered, disordered, and frustrated AFM phases. Such coexisting phases in the exchange coupled ferromagnetic (FM)/AFM-based heterostructures can result in unusual magnetic and magnetotransport phenomena. Here, we integrate chemically disordered AFM γ-IrMn3 thin films with coexisting AFM phases into complex exchange coupled MgO(001)/γ-Ni3Fe/γ-IrMn3/γ-Ni3Fe/CoO heterostructures and study the structural, magnetic, and magnetotransport properties in various magnetic field cooling states. In particular, we unveil the impact of rotating the relative orientation of the disordered and reversible AFM moments with respect to the irreversible AFM moments on the magnetic and magnetoresistance properties of the exchange coupled heterostructures. We further found that the persistence of AFM grains with thermally disordered and reversible AFM order is crucial for achieving highly tunable magnetic properties and multi-level magnetoresistance states. We anticipate that the introduced approach and the heterostructure architecture can be utilized in future spintronic devices to manipulate the thermally disordered and reversible AFM order at the nanoscale.

Radionuclides (RN) generated by nuclear and civil industries are released in natural ecosystems and may have a hazardous impact on human health and the environment. RN polluted environments harbor different microbial species that become highly tolerant of these elements through mechanisms including biosorption, biotransformation, biomineralization and intracellular accumulation. Such microbial-RN interaction processes hold biotechnological potential for the design of bioremediation strategies to deal with several contamination problems. This paper, with its multidisciplinary approach, provides a state-of-the-art review of most research endeavors aimed to elucidate how microbes deal with radionuclides and how they tolerate ionizing radiations. In addition, the most recent findings related to new biotechnological applications of microbes in the bioremediation of radionuclides and in the long-term disposal of nuclear wastes are described and discussed.

The potential use of microorganisms in the bioremediation of U pollution has been extensively described.
However, a lack of knowledge on molecular resistance mechanisms has become a challenge for the use of these technologies. We reported on the transcriptomic and microscopic response of Stenotrophomonas bentonitica BII-R7 exposed to 100 and 250 μM of U. Results showed that exposure to 100 μM displayed up-regulation of 185 and 148 genes during the lag and exponential phases, respectively, whereas 143 and 194 were down-regulated, out of 3786 genes (>1.5-fold change). Exposure to 250 μM of U showed up-regulation of 68 genes and down-regulation of 290 during the lag phase. Genes involved in cell wall and membrane protein synthesis, efflux systems and phosphatases were up-regulated under all conditions tested. Microscopic observations evidenced the formation of U-phosphate minerals at membrane and extracellular levels. Thus, a biphasic process is likely to occur: the increased cell wall would promote the biosorption of U to the cell surface and its precipitation as U-phosphate minerals enhanced by phosphatases. Transport systems would prevent U accumulation in the cytoplasm. These findings contribute to an understanding of how microbes cope with U toxicity, thus allowing for the development of efficient bioremediation strategies.

Zinc oxide thin films are fabricated by controlled oxidation of sputtered zinc metal films on a hotplate in air at temperatures between 250 and 450°C. The nanocrystalline films possess high relative densities and show preferential growth in (100) orientation. Integration in thin film transistors reveal moderate charge carrier mobilities as high as 0.2 cm2/(Vs). The semiconducting properties depend on the calcination temperature, whereby the best performance is achieved at 450 °C. The defect structure of the thin ZnO film can be tracked by Doppler-broadening positron-annihilation-spectroscopy as well as positron-lifetime studies. Comparably long positron lifetimes suggest interaction of zinc vacancies (VZn) with one or more oxygen vacancies (Vo) in larger structural entities. Such VO-VZn defect clusters act as shallow acceptors and thus reduce the overall electron conductivity of the film. The concentration of these defect clusters decreases at higher calcination temperatures as indicated by changes of the S and W parameters. Such zinc oxide films obtained by conversion of metallic zinc can be also used as seed-layers for solution-deposition of zinc oxide nanowires employing a mild microwave-assisted process. The functionality of the obtained nanowire arrays was tested in a UV sensor device. Best results with respect to sensor sensitivity are achieved with thinner seed layers for device construction.

High entropy alloys represent a new type of materials with a unique combination of physical properties originating from the occurrence of single-phase solid solutions of numerous elements. The preparation of nanostructured or amorphous structure in a form of thin films promises increased effective surface and high intergranular diffusion of elements as well as a high affinity to oxidation. In this work, we studied HfNbTaTiZr thin films were deposited at room temperature by DC magnetron sputtering from a single bcc phase target. Films exhibit cellular structure (~100 nm) with fine substructure (~10 nm) made of round-shape amorphous clusters. Films composition is close to equimolar with slight Ti enrichment and without any mutual segregation of elements. Oxidation at the ambient atmosphere leads to the formation of Ti, Zr, Nb, Hf, and Ta oxide clusters in the film up to the depth of 200 – 350 nm out of the total film thickness of 1650 nm. Oxygen absorption takes place preferentially in the large vacancy clusters located in between the amorphous cluster aggregates. The dominant type of defect is small open volumes with a size comparable with vacancy. The distribution of these defects is uniform with depth and is not influenced by the presence of oxygen in the film.

This work aims to develop a two-phase DNS data-driven bubble drag model and to implement it into a multiphase flow CFD simulation. To accomplish the goal, a Tensorflow (TF)-OpenFOAM(OF) integration interface has been established. Such an interface is capable of calling and making machine learning model to predict a quantity of interest on the fly. A benchmark case for the bubble drag coefficient is proposed to validate the interface. A Feed forward neural network (FNN) approach was utilized to approximate the drag correlation (Tomiyama et al., 1998) using artificially generated data. Results of the integration showed good consistency in radial void fraction and velocity profiles. As the next step actual DNS bubble tracking datasets are used as a data source (Fang et al., 2017, Cambareri et al., 2019). The data segments where bubble have quasi-stable main-stream velocity were filtered out for drag coefficient calculation. The DNS-informed model predicts bubble drag coefficient by taking bubble Reynolds number (Re) and Eötvös number (Eo) as input to consider the effects from local fluid and bubble shape. The model is applied in a Euler-Euler two-phase flow simulation of a bubbly pipe flow in OF. The required closure terms, except the drag model, utilize the baseline model of Liao et al. (2020) The results of radial void fraction and velocity profiles are discussed and compared to a reference solution with the baseline model.

We aimed to investigate whether short dynamic PET imaging started at injection, complemented with routine clinical acquisition at 60-min post-injection (static), can achieve reliable kinetic analysis.
Methods
Dynamic and static 18F-2-fluoro-2-deoxy-D-glucose (FDG) PET data were generated using realistic simulations to assess uncertainties due to statistical noise as well as bias. Following image reconstructions, kinetic parameters obtained from a 2-tissue-compartmental model (2TCM) were estimated, making use of the static image, and the time duration of dynamic PET data were incrementally shortened. We also investigated, in the first 2-min, different frame sampling rates, towards optimized dynamic PET imaging. Kinetic parameters from shortened dynamic datasets were additionally estimated for 9 patients (15 scans) with liver metastases of colorectal cancer, and were compared with those derived from full dynamic imaging using correlation and Passing–Bablok regression analyses.
Results
The results showed that by reduction of dynamic scan times from 60-min to as short as 5-min, while using static data at 60-min post-injection, bias and variability stayed comparable in estimated kinetic parameters. Early frame samplings of 5, 24 and 30 s yielded highest biases compared to other schemes. An early frame sampling of 10 s generally kept both bias and variability to a minimum. In clinical studies, strong correlation (r ≥ 0.97, P < 0.0001) existed between all kinetic parameters in full vs. shortened scan protocols.
Conclusions
Shortened 5-min dynamic scan, sampled as 12 × 10 + 6 × 30 s, followed by 3-min static image at 60-min post-injection, enables accurate and robust estimation of 2TCM parameters, while enabling generation of SUV estimates.

Selected contributions of the 17th Multiphase Flow Conference at HZDR were published in a special issue of the Open Access Journal Experimental and Computational Multiphase Flow. In this contribution an overview on the conference and a short introduction to the single papers is given.

Purpose: The current status of German residency training in the field of radiation oncology is provided and compared to programmes in other countries. In particular, we present the DEGRO-Academy within the international context.
Methods: Certified courses from 2018 and 2019 were systematically assigned to the DEGRO-Curriculum, retrospectively for 2018 and prospectively for 2019. In addition, questionnaires of course evaluations were provided, answered by course participants and collected centrally.
Results: Our data reveal a clear increase in curriculum coverage by certified courses from 57.6% in 2018 to 77.5% in 2019. The analyses enable potential improvements in German curriculum-based education. Specific topics of the DEGRO-Curriculum are still underrepresented, while others decreased in representation between 2018 and 2019. It was found that several topics in the DEGRO-Curriculum require more attention because of a low DEGRO-curriculum coverage. Evaluation results of certified courses improved significantly with a median grade of 1.62 in 2018 to 1.47 in 2019 (p=0.0319).
Conclusion: The increase of curriculum coverage and the simultaneous improvement of course evaluations are promising with respect to educational standards in Germany. Additionally, the early integration of radiation oncology into medical education is a prerequisite for resident training because of rising demands on quality control and increasing patient numbers. This intensified focus is a requirement for continued high standards and quality of curriculum-based education in radiation oncology both in Germany and other countries.

Introduction
First measurements with a research prototype system for in-beam MR imaging during proton pencil beam scanning (PBS) have shown that the dynamic magnetic fringe fields of the nearby PBS magnets interfere with the static MRI (B0 =0.22 T) field, causing image ghosting artefacts [1]. Passive magnetic shielding is a possible means of eliminating the artefacts by decoupling the MR and PBS magnetic fields. The aim of this study was to determine the shielding factor required for artefact-free MR imaging during PBS dose delivery.
Materials and Methods
The change in B0 magnitude (ΔB0) due to the PBS fringe field was measured with a magnetic field camera positioned in the MR isocenter both as function of (1) the radiation field size [range 4−40 cm] and (2) the distance between the MR isocenter and the PBS isocenter [range 0.3−2.3 m]. Furthermore, images of the ACR Small Phantom were acquired during dose delivery for (1) and (2), and the percent signal ghosting ratio (PSGR) was assessed to determine the maximum ΔB0 for which the ACR action criterion of ≤0.025 was met.
Results
The magnetic field camera measurements showed that the maximum ΔB0 was 5.66 μT in the worst-case scenario of the minimum distance between MRI and PBS isocenter (0.3 m) and maximum scanning field size (40 cm). For this scenario, the PSGR test passed at a field size of 1.2 cm. Here, the maximum ΔB0 was 0.27 μT. The PSGR test was only passed for field sizes of 4 and 12 cm at distances of 1.3 m and 2.3 m between PBS and MR isocenter, respectively. In both cases, the maximum ΔB0 was 0.28 μT. Hence, a minimum shielding factor of 5.66 μT/0.28 μT = 20.22 would be required for artefact-free MR imaging during PBS dose delivery.
Conclusion
The magnetic shielding factor required for artefact-free MR imaging during PBS dose delivery was experimentally determined for the in-beam MR imaging research prototype system.
References
[1] S. Gantz et al. 2020 Phys. Med. Biol, 65(21), 215014

Treatment verification is expected to improve targeting precision in particle therapy. A promising technique to achieve this goal is the detection of prompt gamma rays emitted along the particle tracks inside the patient. The range of the particle beam can be inferred by determining the time distribution of these gamma-rays relative to the radio frequency of the accelerator, a method commonly referred to as Prompt Gamma-Ray Timing.

However, the translation of this method into a clinical setting is currently hindered by instabilities of the phase relation between the arrival of the proton bunches and the radio frequency of the accelerator. These instabilities include two effects, which have been studied at the clinical treatment facility of the University Proton Therapy Dresden. Firstly, a long-term drift of the proton bunch phase relative to the radio frequency in the order of several hundred picoseconds per hour was observed, which may be caused by small temperature changes in the cyclotron’s magnet resulting in magnetization variations in its iron parts. Secondly, strongly damped oscillations in the mean of measured prompt gamma-ray timing spectra with an amplitude in the order of few hundred picoseconds occur for about two seconds after each change of the particle energy during pencil beam scanning. This oscillation is caused by ramping the acceleration voltage back to its nominal value, which is reduced between energy layers to minimize the dark current of the accelerator and the resulting excess dose to the patient.

While the former effect is only of secondary importance for the treatment due to its comparably long time scale, the phase oscillation has a considerable negative impact on the accuracy of the Prompt Gamma-Ray Timing method, which has to detect time shifts in the order of a few picoseconds for the detection of millimeter range changes. Therefore, the development of a method to monitor the arrival time of the proton bunches independently from the accelerator radio frequency, a so-called proton bunch monitor, is crucial.

To this end, a bunch monitor prototype was developed consisting of scintillating fibers placed in the halo of the proton beam. The fibers were read out on both ends by silicon photomultipliers. A thick acrylic glass target with cylindrical air cavities of varying thickness and different tissue-equivalent inserts was irradiated with protons of clinically relevant energies and typical beam currents. The mean proton arrival time, determined from the time spectra of the proton bunch monitor, was used to correct the prompt gamma-ray timing spectra acquired by Ø2”x2”CeBr3 high-resolution scintillation detectors. This correction allowed to resolve differences in the prompt-gamma ray timing spectra acquired with the different cavities and inserts.

In conclusion, the developed proton bunch monitor was successfully integrated to the Prompt Gamma-Ray Timing method and is expected to enable the clinical application of this method for clinical treatment verification in particle therapy.

Flashing is frequently encountered in nuclear power systems for example as leakage occurring on the steam generator (SG) heat transfer tubes. Pressurized primary coolant flows rapidly through the crack and flashes into vapor. The pressure relief rate and loss rate of coolant, which affects largely the safety of fission reactors, are determined by the flashing phase change process. Information about the flashing phenomenon is of significance for the leakage online monitoring system, which ensures the normal operation of steam generator (SG) and safety of the reactor when tube rupture accidents occur. In this research, steady-state and transient 3D flashing flow inside a short micro-crack channel in the heat transfer tube wall of SG have been studied using FLUENT. The cavitation model and evaporation-condensation model, in combination with both the mixture two-phase flow and the Eulerian two-fluid model, are adopted to simulate the flashing phenomenon. The real geometry and operating conditions of AP1000 nuclear system are adopted to reflect the reality leakage phenomenon in SG. Two types of micro-crack shape including axial crack and circumferential crack, which both can happen in the reality, are considered. The CFD results gained from five different models have been compared with experimental data, and good agreement is demonstrated.
The model comparison shows that the evaporation-condensation model behaves superior to the cavitation model in simulating the flashing phenomenon. Finally, the leakage rates are gained under different crack shapes, sub-cooling degrees and backpressures with the most accuracy scheme. In addition, two-phase choking flow phenomenon is simulated by changing backpressure of cracked tubes. The simulation results in this research could be good reference for leakage prediction of micro-crack in SG to improve the operation performance of SG and safety of the whole nuclear power system.

Normal-incidence 1-keV Ar+ ion bombardment leads to amorphization and ultrasmoothing of Ge at room temperature, but at elevated temperatures the Ge surface remains crystalline and is unstable to the formation of self-organized nanoscale patterns of ordered pyramid-shaped pits. The physical phenomenon distinguishing the high-temperature patterning from room-temperature ultrasmoothing is believed to be a surface instability due to the Ehrlich-Schwoebel barrier for diffusing vacancies and adatoms, which is not present on the amorphous material. This real-time grazing-incidence small-angle x-ray scattering study compares smoothing of a prepatterned Ge sample at room temperature with patterning of an initially flat Ge sample at an elevated temperature. In both experiments, when the nanoscale structures are relatively small in height, the average kinetics can be explained by a linear theory. The linear theory coefficients, indicating surface stability or instability, were extracted for both experiments. A comparison between the two measurements allows estimation of the contribution of the Ehrlich-Schwoebel barrier to the self-organized formation of ordered nanoscale patterns on crystalline Ge surfaces.

Treatment planning in radiotherapy distinguishes three target volume concepts: the gross tumor volume (GTV), the clinical target volume (CTV), and the planning target volume (PTV). Over time, GTV definition and PTV margins have improved through the development of novel imaging techniques and better image guidance, respectively. CTV definition is sometimes considered the weakest element in the planning process. CTV definition is particularly complex since the extension of microscopic disease cannot be seen using currently available in-vivo imaging techniques. Instead, CTV definition has to incorporate knowledge of the patterns of tumor progression. While CTV delineation has largely been considered the domain of radiation oncologists, this paper, arising from a 2019 ESTRO Physics research workshop, discusses the contributions that medical physics and computer science can make by developing computational methods to support CTV definition. First, we overview the role of image segmentation algorithms, which may in part automate CTV delineation through segmentation of lymph node stations or normal tissues representing anatomical boundaries of microscopic tumor progression. The recent success of deep convolutional neural networks has also enabled learning entire CTV delineations from examples. Second, we discuss the use of mathematical models of tumor progression for CTV definition, using as example the application of glioma growth models to facilitate GTV-to-CTV expansion for glioblastoma that is consistent with neuroanatomy. We further consider statistical machine learning models to quantify lymphatic metastatic progression of tumors, which may eventually improve elective CTV definition. Lastly, we discuss approaches to incorporate uncertainty in CTV definition into treatment plan optimization as well as general limitations of the CTV concept in the case of infiltrating tumors without natural boundaries.

Subsurface water-rock interactions involve the coupled phenomena of chemical reactions and fluid transport, in which the chemical reactions between minerals and water can cause mineral dissolution/precipitation and aqueous species adsorption/desorption. The subsurface reactive transport processes play an important role in the enhanced prediction of oil and gas migration in the petroleum reservoirs as well as radionuclides migration in the host rocks. Consequently, an efficient numerical model that can rigorously capture such coupled phenomena is thus essential to the optimized design of implementations for those addressed problems.
In this talk, we first present a 3D mathematical model that couples the Stokes-Brinkman equation and reactive transport model for modeling the coupled processes of reactive flow and transport in fractured porous media. The numerical experiments show that the proposed model can efficiently simulate the coupled processes of fluid flow, reactive transport, and alterations of rock properties in fractured porous media under both linear and radial flow. Secondly, we focus on radionuclides transport and retention in claystone formations using GeoPET analysis and reactive transport modeling. We propose an integrated upscaling workflow to predict effective diffusivity of radionuclides diffusion in the shaly facies of Opalinus clay based on the reconstructed multi-scale digital rocks. The GeoPET measurements provide analytical insights into spatial and temporal tracer distribution, which can be utilized to validate the numerical model. The combination of pore-scale reactivity and core scale transport modeling provides critical insight into the radionuclide migration heterogeneity. We discuss these results with a focus on upscaling strategies to the field scale of host rocks.

We discuss the limitations to material flows from recycling in the circular economy, using as a case the simulation-based analysis of the CdTe Photovoltaic cells. It is important to use a simulation basis for the analysis, since this permits the quantification of all material losses both in terms of exergy and energy simultaneously i.e. 1st and 2nd law of thermodynamics. Harmonizing this with the power supply flowing into the system and minimizing energy usage as well as exergy losses will maximize the resource efficiency.

Low-permeability Opalinus clay formations are considered as a potential host rock for the storage of high-level nuclear waste (Nagra 2002). The diffusion of dissolved species is the dominating transport process in this rock type (Van Loon et al. 2003). Stratification and spatial variability of composition cause anisotropic and heterogeneous diffusion patterns, which could significantly speed up diffusive transport compared to commonly assumed homogeneous conditions. Anisotropy of diffusive transport has been studied on oriented samples in diffusion cells and with positron emission tomography (Kulenkampff et al. 2016). The heterogeneity of the diffusive spreading is increased still further due to sandy layers and diagenetic carbonates, affecting the radionuclide migration behavior at the core scale.
Here, we parameterize a reactive transport model by using experimental and analytical data on Eu(III) sorption efficiency at the pore scale. The effective retention coefficients calculated at the pore scale serve as input values for the reactive transport simulation at the core scale. Diffusive transport model parametrization utilizes GeoPET/μCT results on the migration behavior of 22Na+ at the core scale. Numerical simulation is performed using an existing code (Yuan et al. 2019), which contains the reactive transport model for simulating reactive diffusion process at the core scale. The combination of pore-scale reactivity and core scale transport modeling provides critical insight into the radionuclide migration heterogeneity. We discuss these results with a focus on upscaling strategies to the field scale of host rocks.

Introduction
To date, proton therapy is hampered by the lack of reliable in-vivo real-time feedback on the beam range, profile and energy deposition. So far, no technique enables the determination of beam effects on images also showing anatomical information in 2D/3D with high temporal and spatial resolution. The aim of this study is to demonstrate the possibility of visualizing a stopping proton beam in water using MR imaging.
Materials & methods
An open 0.22 T MR scanner was combined with a static proton research beamline to acquire MR images during simultaneous proton beam irradiation. Proton beams with an energy of 190−225 MeV and current of 3−64 nA impinged centrally on a 20 cm PMMA range modulator and were stopped in a water-filled phantom placed inside a dedicated knee MR receiver coil. A variety of different MR pulse sequences including T1- and T2-weighted Spin Echo (SE), Turbo Spin Echo, spoiled and unspoiled T1-weighted Gradient Echo (GE), inversion recovery gradient echo (IRGE), FLASH, Scout and time-of-flight (TOF) Angio were used. For each sequence, coronal images were acquired both with and without irradiation.
Results
The unspoiled GE sequence exhibited a hyper-intense central line artefact that showed a beam energy and current dependent twist under irradiation. The spoiled GE, IRGE, FLASH, Scout and TOF Angio sequences showed hyper- or hypo-intense signatures in the images that varied with the expected range and mimicked the shape of a 2D dose profile. The intensity of the effects depends on the beam current. The beam range determined from the MR images agrees to the expected range within a few millimeters. No beam induced signal changes were observed in the SE sequences.
Conclusion
A stopping proton beam in liquid water can be visualized with MRI. The observed signatures are beam energy and range as well as beam current and dose dependent. The underlying physical principles and the transferability to non-liquid materials needs further investigation.

The quest for renewable energy sources entails an increasingly intermittent electricity supply.
Transmission grid updates can only partially account for balancing the resulting variations and large-scale stationary storage will gain importance in future energy landscapes dominated by volatile sources.
Today’s battery technologies were, with the notable exception of redox-flow batteries, mainly designed for and driven by mobile applications. Those prioritize properties (energy density, power rating) that are less important for stationary storage. Thus, battery technologies developed from the ground up to meet the needs of stationary storage have the potential to much better address the specifics of huge capacity installations.
Liquid metal batteries (LMBs) are a new technology for grid-scale energy storage. They consist of all liquid cells that operate with liquid metals as electrodes and molten salts as electrolytes. The liquids separate into three stably stratified layers by virtue of density and mutual immiscibility. This conceptually very simple and self-assembling structure has the unique advantage to allow for an easy scale-up at the cell level: single-cell cross sections can potentially reach several square-meters. Such cell sizes enable highly favourable and otherwise unattainable ratios of active to construction material because of the cubic scaling (volume) of the former and the quadratic scaling (surface) of the latter. The total costs should therefore largely be determined by those of the active materials.
The talk will start with a general introduction to LMBs and then focus on the fluid mechanics in these devices. Electric currents, magnetic fields, and heat and mass transfer are tightly coupled with the cells’ electrochemistry. First a number of fluid dynamic instabilities will be discussed in relation to operational safety. The remainder of the talk will deal with transport phenomena in the positive electrode. While transport in most modern battery systems is typically dominated by diffusion and migration in micrometer-scale liquid layers and solids, convection - with exception of the aforementioned redox-flow batteries - rarely plays a role. This is in stark contrast to LMBs were mediated by the fully liquid interior fluid flow can be driven by various mechanisms. The influence of solutal convection on the cycling behavior of a cell will be demonstrated. Electromagnetically induced convection can be used to improve mixing thereby mitigating diffusion overpotentials.

The electronic structure and quasi-particle absorption spectra of anatase titanium dioxide has been calculated by employing state of the art density functional theory(DFT) and Many-Body Perturbation Theory methods(MBPT) within the framework of Hybrid Density Functional(HSE). GW methods are used in combination with Bethe-Salpeter Equation (BSE) to determine the Quasi Particle energy levels and the role of excitons in optical absorption spectra. Accurate optical and electronic band gap are determined from these methods. In addition to it an analysis of charge redistribution within the anatase unit cell is also presented within the PBE - DFT to analyze the orbital hybridization patterns and the character of chemical bonds.

Nonaqueous Pickering emulsions (PEs) are a powerful platform for catalysis design, offering both a large interface contact and a preferable environment for water-sensitive synthesis. However, up to now, little progress has been made to incorporate insoluble enzymes into the nonaqueous system for biotransformation. Herein, we present biocatalytically active nonaqueous PEs, stabilized by particle-enzyme nanoconjugates, for the fast transesterification and esterification, and eventually for biodiesel synthesis. Our nanoconjugates are the hybrid biocatalysts tailor-made by loading hydrophilic Candida antarctica lipase B onto hydrophobic silica nanoparticles, resulting in not only catalytically active but highly amphiphilic particles for stabilization of a methanol-decane emulsion. The enzyme activity in these PEs is significantly enhanced, ca. 375-time higher than in the nonaqueous biphasic control. Moreover, the PEs can be multiply reused without significant loss of enzyme performance. With this proof‐of‐concept, we reasonably expect that our system can be expanded for many advanced syntheses using different enzymes in the future.

The application of polymers to replace oleylamine (OLA) and oleic acid (OA) as ligands for perovskite nanocrystals is an effective strategy to improve their stability and durability especially for the solution-based processing. Herein, we report a mechanosynthesis of lead bromide perovskite nanoparticles (NPs) stabilized by partially hydrolyzed poly(methyl methacrylate) (h-PMMA) and high-molecular-weight highly-branched poly(ethylenimine) (PEI-25K). The as-synthesized NP solutions exhibited green emission centered at 516 nm, possessing a narrow full-width at half-maximum of 17 nm and as high photoluminescence quantum yield (PL QY) as 85%, while showing excellent durability and resistance to polar solvents, e.g., methanol. The colloids of polymer-stabilized NPs were directly processable to form stable and strongly-emitting thin films and solids, making them attractive as gain media. Furthermore, the roles of h-PMMA and PEI-25K in the grinding process were studied in depth. The h-PMMA can form micelles in the grinding solvent of dichloromethane to act as size-regulating templates for the growth of NPs. The PEI-25K with large amounts of amino groups induced significant enrichment of PbBr₂ in the reaction mixture, which in turn caused the formation of CsPb₂Br₅-mPbBr₂3-Cs₄PbBr₆-nCsBr NPs. The presence of CsPbBr₃-Cs₄PbBr₆-nCsBr NPs was responsible for the high PL QY, as the Cs₄PbBr₆ phase with a wide energy bandgap can passivate the surface defects of the CsPbBr₃ phase. This work describes a direct and facile mechanosynthesis of polymer-coordinated perovskite NPs and promotes in-depth understanding of the formation and phase conversion for perovskite NPs in the grinding process.

We report nonlinear charge-carrier response in GaAs/InGaAs core/shell nanowires that are driven by intense THz pulses. In the first experiment, half-cycle THz pulses emitted from an organic DSTMS crystal lead to a red-shift of the plasmon Peak indicating intervalley transfer of the electrons. In the second experiment, a single, highly electron doped nanowire is investigated by scattering near-field infrared microscopy using intense free-electron laser (FEL) pulses. Here the observed red shift of the mid-infrared plasma resonance depends on the pulse energy and can be explained by heating the electron system in the nonparabolic conduction band.

Dysfunctional or incomplete endothelium on cardiovascular devices has been identified as key factor of thrombus formation. Therefore, the establishment of confluent endothelial cell (EC) monolayers is a challenge in cardiovascular device engineering. Previous studies revealed that arterial EC were able to endothelialize gelatin-based hydrogels. However, as EC differ markedly in their function dependent from their origin, this study investigated whether venous EC (HUVEC) also form a monolayer on gelatin-based hydrogels obtained by reacting gelatin with different molar ratios of lysine diisocyanate ethyl ester (using a 3-, 5- or 8-fold excess) exhibiting variations in their elastic properties. The density of adherent HUVEC on the soft hydrogel at 37 °C (G’ = 1.02 kPa, E = 1.1±0.3 kPa) was significantly lower than on the stiffer hydrogels (G’ = 2.515 and 5.02 kPa, E = 4.8±0.8 and 10.3±1.2 kPa). This was accompanied by increased matrix metalloproteases and stress fiber formation, while cell-to-cell contacts were comparable. The pattern of eicosanoids and cytokines corresponded to those results. The expression of pro-inflammatory markers COX-2, COX-1, and RAGE were slightly elevated, indicating a weak inflammation. The study revealed that hydrogels with higher moduli approached the status of a functionally-confluent HUVEC monolayer. The results indicate the promising potential especially of the hydrogels with higher G’ as biomaterials for implants foreseen for the venous system.

Immunocompatibility and non-thrombogenicity are important requirements for biomedical applications such as vascular grafts. Here, gelatin-based hydrogels formed by reaction of porcine gelatin with increasing amounts of lysine diisocyanate ethyl ester were investigated in vitro in this regard. In addition, potential adverse effects of the hydrogels were determined using the “Hen's egg test on chorioallantoic membrane” (HET-CAM) test and a mouse model. The study revealed that the hydrogels were immunocompatible, since complement activation was absent and a substantial induction of reactive oxygen species generating monocytes and neutrophils could not be observed in whole human blood. The density as well as the activation state of adherent thrombocytes was comparable to medical grade polydimethylsiloxane, which was used as reference material. The HET-CAM test confirmed the compatibility of the
hydrogels with vessel functionality since no bleedings, thrombotic events, or vessel destructions were observed. Only for the samples synthesized with the highest LDI amount the number of growing blood vessels in the CAM was comparable to controls and significantly higher than for the softer materials. Implantation into mice showed the absence of adverse or toxic effects
in spleen, liver, or kidney, and only a mild lymphocytic activation in the form of a follicular hyperplasia in draining lymph nodes (slightly increased after the implantation of the material prepared with the lowest LDI content. These results imply that candidate materials prepared with mid to high amounts of LDI are suitable for the coating of the blood contacting surface of cardiovascular implants.

Ziel:

Epigenetische Mechanismen wie die Methylierung und Acetylierung von Histonen regulieren die Genexpression auf Chromatin-Ebene. So beeinflusst der Grad der Acetylierung von Lysinresten der Histone die Zugänglichkeit der DNA und damit die Genexpression. HDACs sind in verschiedenen Tumorerkrankungen überexprimiert, woraus das Interesse an HDAC-Inhibitoren für die Therapie von Krebs resultiert. Das Ziel dieser Arbeit ist die Entwicklung neuer hochaffiner und selektiver fluortragender HDAC-Liganden, um HDAC1 und 2 in onkologischen Erkrankungen mittels PET darzustellen.
Methodik:
Basierend auf Tacedinalin wurden 10 fluorhaltige Derivate in bis zu 8 Synthesestufen hergestellt und ihre IC₅₀-Werte mittels eines biochemischen Enzymassays bestimmt. Von zwei Liganden mit hoher inhibitorischer Potenz und Selektivität für HDAC1 und 2 wurde HD70 ausgewählt und in einem Syntheseautomaten radiofluoriert. Zur biologischen Charakterisierung von [¹⁸F]HD70 wurden Untersuchungen in vitro und in vivo in der Maus durchgeführt.
Ergebnisse:
HD70 mit einem PAMBA-Linker (p-Aminomethylbenzoesäure) zeigt eine hohe inhibitorische Aktivität gegenüber HDAC1 (IC₅₀: 4,8 nM) und HDAC2 (IC₅₀: 39,9 nM). Die Radiosynthese von [¹⁸F]HD70 aus einem 2-Brompropionylpräkursor erfolgte automatisiert in zwei Stufen mit einer radiochemischen Ausbeute von 1 %. Die PET- und Metabolitenuntersuchungen in CD-1-Mäusen zeigten, dass der Radiotracer [¹⁸F]HD70 die Blut-Hirn-Schranke passiert (SUV5 min: 0,24). Allerdings betrug der Anteil an intaktem Tracer im Hirn nach 30 min nur 25 %.
Schlussfolgerungen:
Durch den hohen Anteil an hirngängigen Radiometaboliten wird [¹⁸F]HD70 für weitergehende Untersuchungen als ungeeignet eingestuft. Die erhaltenen Ergebnisse werden in das Design metabolisch stabilerer HDAC-Inhibitoren einfließen.

We report the synthesis of three complex series of the form [AnCl₂(salen)(pyx)₂] (H₂salen = N,N’-bis(salicyl¬idene)ethylene-diamine; Pyx = pyridine, 4-methylpyridine, 3,5-dimethylpyridine) with tetravalent early actinides (An = Th, U, Np, Pu) with the goal to elucidate the affinity of these heavy elements for small neutral N-donor molecules. Structure determination via single-crystal XRD and characterization of bulk powders with infrared spectroscopy reveal isostructurality within each respective series and the same complex conformation in all reported structures. While the trend of interatomic distances for An–Cl and An–N (imine nitrogen of salen or pyridyl nitrogen of Pyx) were found to reflect an ionic behaviour, the trend of the An–O distances can only be described with additional covalent interactions for all elements heavier than thorium. All experimental results are supported by quantum chemical calculations, which confirm the mostly ionic character in the An–N and An–Cl bonds, as well as the highest degree of covalency of the An–O bonds. Structurally, the calculations indicate just minor electronic or steric effects of the additional Pyx substituents on the complex properties.