Publications Repository - Helmholtz-Zentrum Dresden-Rossendorf

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39127 Publications

A particle-based approach to predict the success and selectivity of leaching processes

Winardhi, C. W.; Da Assuncao Godinho, J. R.; Rachmawati, C.; Duhamel Achin, I.; Unzurrunzaga Iturbe, A.; Frisch, G.; Gutzmer, J.

Encouraged by the need for ecologically and economically sustainable technologies for the recovery of metals from complex raw materials, ionometallurgical leaching using deep eutectic solvents is emerging as a promising alternative to conventional hydro- and pyrometallurgy for metal recovery. Current approaches of studying leaching processes do not provide a mineral-based understanding of the leaching process – thus limiting the opportunities for process optimization. This study addresses this shortcoming by combining laboratory-based X-ray computed tomography (CT) and scanning electron microscopy-based image analysis. The latter method provides robust information on the mineralogy and texture of the leach feed material, whereas CT is used to observe the progress of the leaching process through time. Leaching of a Au-Ag bearing sulfide flotation concentrate by deep eutectic solvent ethaline with iodine as oxidizing agent is used as a relevant case study. Results show that time lapsed CT provides an accurate estimation of the dissolution rate of pyrite, chalcopyrite, galena, telluride minerals and gold. Dissolution rates were used then to simulate metal recoveries from the mineral concentrate as a function of leaching time. Simulation results are within 5% variation of recoveries obtained by batch leaching experiments. The developed workflow can be easily transferred to other mineral concentrates or ore types; results may be used to optimize industrial leaching process.

Keywords: Computed Tomography (CT); Dissolution rates; Deep Eutectic Solvents; Leaching; Particle-based leaching simulation

Publ.-Id: 33593

Modeling the effect of the national borders in the spread of COVID-19: A case study of the Saxony-Czechia border region

Mertel, A.; Calabrese, J.

COVID-19 serves as an opportunity to apply scientific methodologies from various fields to better understand the nature of the spread. In this paper, we are specifically looking into the effect of the presence/absence of national borders on the spread of the disease. We work with the dataset aggregated from the seven-day incidence in the municipalities in Saxony, and Czechia. We further apply the regression model, where a metric to estimate the potential causality of incidence growth in each of two municipalities is dependent on the distance between them, their population ratio, and the existence of the national border. Our preliminary results showed that the effect of the borders is very strong in most of the study areas.

Keywords: COVID-19; epidemiological modeling; spatial regression model; border effect

  • Lecture (Conference)
    International Symposium on Geospatial Approaches to Combating Covid-19, 13.12.2021, Florence, Italien

Publ.-Id: 33592

Spectral X-Ray Computed Micro Tomography: 3-Dimensional Chemical Imaging by Using a Pixelated Semiconductor Detector

Sittner, J.; Merkulova, M.; Da Assuncao Godinho, J. R.; Renno, A.; Cnudde, V.; Boone, M.; de Schryver, T.; van Loo, D.; Roine, A.; Liipo, J.; Guy, B. M.

We present a new approach to 3-dimensional (3D) chemical imaging based on X-ray computed micro tomography (micro-CT), which enables the analysis of the internal elemental chemistry. The method uses a conventional laboratory-based micro-CT scanner (Tescan CoreTOM) equipped with a cadmium telluride (CdTe) semiconductor line detector (Tescan PolyDet). Based on the X-ray absorption spectra, elements in a sample can be distinguished by their specific K-edge energy. The capabilities and performance of this approach are illustrated with different experiments. We present results from various sample materials (e.g., pure element reference samples, mineral mixtures and rocks). Different pure elements and element oxides were measured to compare positions of the theoretical K-edge energy with the measured one. Furthermore, we show the results of a particle mixture with quartz as a low-absorbing matrix. Finally, samples of the Au-U Witwatersrand Supergroup demonstrate the possibilities this approach for geological samples. All results show that the method can distinguish elements with K-edges in the range of 25–160 keV. This corresponds to elements with Z > 48 (Cd). Moreover, the spectral information allows a distinction between materials, which show little to no X-ray attenuation variation in the reconstructed CT image.

  • Book chapter
    Jan S. Iwanczyk; Krzysztof Iniewski: Radiation Detection Systems - Medical Imaging, Industrial Testing and Security Applications, Boca Raton: CRC Press, 2021, 9781003218364, 1-28
    DOI: 10.1201/9781003218364

Publ.-Id: 33591

Prognostic Value of Pretherapeutic Primary Tumour MTV from [18F]FDG PET in Radically Treated Cervical Cancer Patients

Cegla, P.; Hofheinz, F.; CholewińSki, W.; Czepczynski, R.; Kubiak, A.; van den Hoff, J.; Bos-Liedke, A.; Roszak, A.; Ewa Burchardt, E.

The aim of this study was to assess the usefulness of pretherapeutic primary tumor
metabolic tumor volume (MTV) in the prognosis of radically treated cervical cancer patients. Ret-
rospective, single-centre analysis was performed on a group of 508 cervical cancer patients. All
patients underwent a pretreatment [18 F]FDG PET/CT study for the assessment of the disease stage.
Several PET-derived parameters—namely, maximum standardized uptake value (SUVmax ), mean
standardized uptake value (SUVmean ), total lesion glycolysis (TLG) and MTV, as well as the clinical
parameters, were analysed in terms of the overall survival (OS), event-free survival (EFS), locore-
gional control (LRC) and freedom from distant metastases (FFDM). Hyperthermia and brachytherapy
were prognostic for EFS, OS, and LRC.FIGO stage > II showed a significant effect on EFS, OS, and
FFDM. Moreover, hysterectomy was prognostic for OS and histology was prognostic for FFDM. From
the PET-derived parameters only MTV of the primary tumour had a significant influence on OS
(cutoff point: >12.7 mL, HR: 2.8, 1.75–4.48 95% CI, p < 0.001), LRC (cutoff point: >13.7 mL, HR 2.82,
1.42–5.61 95% CI, p = 0.003), EFS (cutoff point: >10.4 mL, HR: 2.57, 1.67–3.97 95% CI, p < 0.001) and
FFDM (cutoff point: >10.4 mL, HR: 5.04, 1.82–13.99 95% CI, p = 0.002). The pretreatment of MTV
in primary tumour is the only independent prognostic parameter in OS, LRC, EFS, and FFDM in
radically treated cervical cancer patients and should be used in clinical practice in assessing prognosis

Keywords: positron emission tomography/computed tomography; cervical cancer; [18 F]FDG; metabolic parameters

Publ.-Id: 33590

16O(n,α) and nat-Fe transmission experiments at GELINA & nELBE

Beyer, R.; Fan, X.; Junghans, A. R.; Kögler, T.; Stach, D.; Urlass, S.; Göök, A.; Heyse, J.; Kopecky, S.; Paradela, M.; Plompen, A. J. M.; Schillebeeckx, P.; Tassan-Got, L.; Leal, L.; Capote, R.; Deboer, R.; Wiescher, M.; Nyman, M.

Vortrag bei der JEFF Nuclear Data Week November 2021, JEF-DOC 2071

Related publications

  • Invited lecture (Conferences) (Online presentation)
    JEFF Nuclear Data Week, 22.-26.11.2021, Paris, France

Publ.-Id: 33588

GeoStat-Examples/gstools-herten-example: v1.0

Schüler, L.; Müller, S.

We are going to analyse the Herten aquifer, which is situated in Southern Germany. Multiple outcrop faces where surveyed and interpolated to a 3D dataset.

Related publications

  • Software in external data repository
    Publication year 2021
    Programming language: Python
    System requirements: Same as GSTools
    License: MIT
    Hosted on GitHub: Link to location
    DOI: 10.5281/zenodo.5159657

Publ.-Id: 33587

GeoStat-Framework/GSTools: v1.3.2 'Pure Pink'

Müller, S.; Schüler, L.

GeoStatTools provides geostatistical tools for various purposes:

  • random field generation
  • simple, ordinary, universal and external drift kriging
  • conditioned field generation
  • incompressible random vector field generation
  • (automated) variogram estimation and fitting
  • directional variogram estimation and modelling
  • data normalization and transformation
  • many readily provided and even user-defined covariance models
  • metric spatio-temporal modelling
  • plotting and exporting routines

Keywords: python; statistics; geospatial; geostatistics; kriging; variogram; spatio-temporal; srf; covariance

Related publications

  • Software in external data repository
    Publication year 2021
    Programming language: Python
    System requirements: Requirements: NumPy >= 1.14.5 SciPy >= 1.1.0 hankel >= 1.0.2 emcee >= 3.0.0 pyevtk >= 1.1.1 meshio>=4.0.3, <5.0 Optional GSTools-Core >= 0.2.0 matplotlib pyvista
    License: LGPLv3 (Link to license text)
    Hosted on GitHub: Link to location
    DOI: 10.5281/zenodo.1313628

Publ.-Id: 33586

Self-Supervised Learning With Adaptive Distillation for Hyperspectral Image Classification

Yue, J.; Fang, L.; Rahmani, H.; Ghamisi, P.

Hyperspectral image (HSI) classification is an important topic in the community of remote sensing, which has a wide range of applications in geoscience. Recently, deep learning-based methods have been widely used in HSI classification. However, due to the scarcity of labeled samples in HSI, the potential of deep learning-based methods has not been fully exploited. To solve this problem, a self-supervised learning (SSL) method with adaptive distillation is proposed to train the deep neural network with extensive unlabeled samples. The proposed method consists of two modules: adaptive knowledge distillation with spatial–spectral similarity and 3-D transformation on HSI cubes. The SSL with adaptive knowledge distillation uses the self-supervised information to train the network by knowledge distillation, where self-supervised knowledge is the adaptive soft label generated by spatial–spectral similarity measurement. The SSL with adaptive knowledge distillation mainly includes the following three steps. First, the similarity between unlabeled samples and object classes in HSI is generated based on the spatial–spectral joint distance (SSJD) between unlabeled samples and labeled samples. Second, the adaptive soft label of each unlabeled sample is generated to measure the probability that the unlabeled sample belongs to each object class. Third, a progressive convolutional network (PCN) is trained by minimizing the cross-entropy between the adaptive soft labels and the probabilities generated by the forward propagation of the PCN. The SSL with 3-D transformation rotates the HSI cube in both the spectral domain and the spatial domain to fully exploit the labeled samples. Experiments on three public HSI data sets have demonstrated that the proposed method can achieve better performance than existing state-of-the-art methods.


Publ.-Id: 33584

SNG based energy storage systems with subsurface CO₂ storage

Fogel, S.; Yeates, C.; Unger, S.; Rodriguez Garcia, G.; Baetcke, L.; Dornheim, M.; Schmidt-Hattenberger, C.; Bruhn, D.; Hampel, U.

Large-scale energy storage plants based on power-to-gas-to-power technologies incorporating high temperature electrolysis, catalytic methanation of H₂ and CO₂ and novel, highly efficient methane-fired Allam reconversion cycles allow for a confined and circular use of CO₂ and thus an emission-free storage of intermittent renewable energy. The Allam power cycle is considered as a beneficial power plant concept, which employs supercritical CO₂ as working fluid as well as an oxy-combustion process to reach high efficiencies of up to 66%. The combination of said process chain could reach a maximum roundtrip efficiency of 54.2 % assuming the presence of sufficient storage capacities for all relevant technical gases. In a technically feasible scenario, paired with a separate air separation unit instead of stationary O₂ storages, roundtrip efficiencies of 49.0 % were determined..
The implementation of said energy storage systems into existing national energy systems will pose a major challenge, since they will require far-reaching infrastructural changes to the respective systems itself, such as extensive installations of renewable generation and electrolysis capacities as well as sufficient subsurface storage capacities for both CO₂ and CH₂. Furthermore, an exemplary energy system forecast for Germany for the year of 2050 is presented to show the viability of the energy storage concept. In case of a fully circular use of CO₂, when electricity is solely generated by renewable energy sources (RES), 736 GW of RES, 234 GW of electrolysis and 62 GW of gas-to-power capacities are required. The total storage volume on the national scale of Germany for both CO₂ and CH₄ was determined to be 7.8 billion Nm³, respectively, leading to a CH₄ storage capacity of 54.5 TWh. The present investigation illustrates the feasibility of large-scale energy storage systems for renewable electricity based on high temperature electrolysis, catalytic methanation and Allam power cycles paired with large subsurface storages for CO₂ and CH₄.

Keywords: CCUS; CCU; Methanation; SOEC; Subsurface CO₂ storage; sCO₂ power cycles; Carbon loop; Hydrogen storage

Publ.-Id: 33583

Unravelling the secrets of laser plasma particle (ion) acceleration with x-rays from the European XFEL

Schramm, U.

Invited plenary presentation on:

Unravelling the secrets of laser plasma particle (ion) acceleration with x-rays from the European XFEL

Keywords: XFEL; laser plasma

Related publications

  • Invited lecture (Conferences)
    HIBEF Inauguration Festakt, 31.08.2021, Hamburg Schenefeld, Deutschland

Publ.-Id: 33582

Unsupervised Deep Learning for Landslide Detection from Multispectral Sentinel-2 Imagery

Shahabi, H.; Maryam, R.; Sepideh, T. P.; Omid, G.; Saied, H.; Thomas, B.; Samsung, L.; Ghamisi, P.

This paper proposes a new approach based on an unsupervised deep learning (DL) model for landslide detection. Recently, supervised DL models using convolutional neural networks (CNN) have been widely studied for landslide detection. Even though these models provide robust performance and reliable results, they depend highly on a large labeled dataset for their training step. As an alternative, in this paper, we developed an unsupervised learning model by employing a convolutional auto-encoder (CAE) to deal with the problem of limited labeled data for training. The CAE was used to learn and extract the abstract and high-level features without using training data. To assess the performance of the proposed approach, we used Sentinel-2 imagery and a digital elevation model (DEM) to map landslides in three different case studies in India, China, and Taiwan. Using minimum noise fraction (MNF) transformation, we reduced the multispectral dimension to three features containing more than 80% of scene information. Next, these features were stacked with slope data and NDVI as inputs to the CAE model. The Huber reconstruction loss was used to evaluate the inputs. We achieved reconstruction losses ranging from 0.10 to 0.147 for the MNF features, slope, and NDVI stack for all three study areas. The mini-batch K-means clustering method was used to cluster the features into two to five classes. To evaluate the impact of deep features on landslide detection, we first clustered a stack of MNF features, slope, and NDVI, then the same ones plus with the deep features. For all cases, clustering based on deep features provided the highest precision, recall, F1-score, and mean intersection over the union in landslide detection.

Publ.-Id: 33581

High dose-rate in-vivo proton irradiation at DRACO-PW, pilot study results and prerequisites

Schramm, U.

invited talk on "High dose-rate in-vivo proton irradiation at DRACO-PW, pilot study results and prerequisites"

Keywords: laser proton acceleration

Related publications

  • Invited lecture (Conferences) (Online presentation)
    SPIE 2021 ALPA Workshop, 19.-22.04.2021, Prag, Tschechien
  • Invited lecture (Conferences) (Online presentation)
    47th Conference on Plasma Physics - Satellite Meeting Laser-driven particle and radiation sources for application (LASA), 28.-29.06.2021, Barcelona, Spanien
  • Invited lecture (Conferences) (Online presentation)
    ELI Beamlines user conference 2021, 20.-21.10.2021, Prag, Tschechien
  • Invited lecture (Conferences)
    INANOTHERAD International Meeting, 15.-17.11.2021, Orsay, Frankreich
  • Invited lecture (Conferences) (Online presentation)
    42nd Int. Workshop on High-Energy-Density Physics with Intense Ion and Laser Beams, 31.01.-03.02.2022, Hirschegg, Österreich

Publ.-Id: 33580

Remote Sensing Image Scene Classification via Label Augmentation and Intra-Class Constraint

Xie, H.; Chen, Y.; Ghamisi, P.

In recent years, many convolutional neural network (CNN)-based methods have been proposed to address the scene classification tasks of remote sensing images. Since the number of training samples in RS datasets is generally small, data augmentation is often used to expand the training set. It is, however, not appropriate when original data augmentation methods keep the label and change the content of the image at the same time. In this study, label augmentation (LA) is presented to fully utilize the training set by assigning a joint label to each generated image, which considers the label and data augmentation at the same time. Moreover, the output of images obtained by different data augmentation is aggregated in the test process. However, the augmented samples increase the intra-class diversity of the training set, which is a challenge to complete the following classification process. To address the above issue and further improve classification accuracy, Kullback–Leibler divergence (KL) is used to constrain the output distribution of two training samples with the same scene category to generate a consistent output distribution. Extensive experiments were conducted on widely-used UCM, AID and NWPU datasets. The proposed method can surpass the other state-of-the-art methods in terms of classification accuracy. For example, on the challenging NWPU dataset, competitive overall accuracy (i.e., 91.05%) is obtained with a 10% training ratio.

Publ.-Id: 33579

The impact of high hydrostatic pressure maintenance after high-pressure torsion on phenomena during high hydrostatic pressure annealing

Krawczynska, A. T.; Kerber, M.; Suchecki, P.; Romelczyk-Baishya, B.; Liedke, M. O.; Butterling, M.; Hirschmann, E.; Wagner, A.; Lewandowska, M.; Setman, D.

The impact of high hydrostatic pressure release after high-pressure torsion on subsequent high hydrostatic pressure annealing was analyzed by performing experiments on nanostructured Ni. Ni was deformed by high-pressure torsion at a pressure of 6GPa in 5 turns. Directly after deformation, the pressure was reduced to 2GPa, and under 2GPa annealing at 400 °C was conducted for 5 min. For comparison, samples were also annealed under 2GPa after deformation without loading between processes. Microhardness measurements, detailed microscopy observations and positron annihilation spectroscopy investigations were performed to elucidate the changes in the microstructures obtained after different processing routes. It is demonstrated that the pressure applied between deformation and high hydrostatic pressure annealing caused an increase in microhardness by 20% in comparison with pressure realize. Moreover, the pressure applied had an impact on the vacancy concentration, and consequently on the microstructure, leading to a smaller average grain size and a more heterogenous microstructure in terms of grain size, leaving space for optimizing the strength-ductility balance.

Keywords: high hydrostatic pressure; Ni; nickel; deformation; positron annihilation spectroscopy

Related publications


  • Secondary publication expected from 18.04.2023

Publ.-Id: 33578

Experimentelle und numerische Untersuchung der Aufschlusszerkleinerung von Multi-Material-Strukturen zur Abschätzung der Recyclingfähigkeit

Heibeck, M.; Richter, J.; Rudolph, M.; Hornig, A.; Modler, N.; Reuter, M.; Filippatos, A.

Im Rahmen einer ressourceneffizienten Kreislaufwirtschaft (engl. Circular Economy) hat das Recycling von Produkten am Ende ihrer Lebenszyklen das Potenzial, den Ressourcenverbrauch und klimaschädliche Umweltauswirkungen von Produktsystemen zu verringern. Für eine nachhaltige Etablierung von Recycling-Lösungen sind neben der Recyclingindustrie auch Produkthersteller bereits in der Konstruktionsphase mit einzubeziehen. Hierfür fehlt es derzeit jedoch meist an Methoden, um die Auswirkungen von Designentscheidungen auf die Recyclingfähigkeit abzuschätzen und zu optimieren (engl. Design-for-Recycling). Deshalb arbeiten wir an einem digitalen Modell, das die Bewertung der Recyclingfähigkeit schon im Produktentstehungsprozess ermöglichen soll. Ein besonderer Fokus liegt dabei auf dem Prozessschritt der Aufschlusszerkleinerung, da eine zunehmende Anzahl von Produkten, von Fahrzeugen bis Haushaltsgeräten, aus Multi-Material Strukturen bestehen. Hier müssen Verbindungen zwischen unterschiedlichen Materialien im Recycling meist wieder gelöst werden, um hohe Recyclingraten für alle verbauten Materialien zu erzielen. Dies erfolgt typischerweise mechanisch durch Zerkleinerungsprozesse.
Vor diesem Hintergrund wollen wir herausfinden, welche Parameter bereits während der Bauteilentwicklung beeinflussbar sind, um den Materialaufschluss bei der mechanischen Aufbereitung zu optimieren, ohne dabei Funktion und Lebensdauer der Struktur in der Nutzungsphase zu beeinträchtigen. Dazu haben wir zum einen Zerkleinerungsexperimente von Prüfkörpern aus der Automobilbranche in einem Rotorreißer durchgeführt. Im Mittelpunkt der Untersuchungen stand dabei insbesondere der Einfluss verschiedener Verbindungscharakteristika auf das Aufschlussverhalten. Da die experimentelle Datenerhebung aufgrund hoher Parametervariabilität im Produktdesign und des Zerkleinerungsprozesses aufwändig ist, entwickeln wir zum anderen ein physikalisch basiertes, numerisches Modell der Aufschlusszerkleinerung mithilfe der Finiten Elemente Methode. Hierzu nutzen wir die Software LS-DYNA, verwenden darin Materialmodelle, welche die Plastizität und das Versagen der beteiligten Werkstoffe sowie deren Interfaces berücksichtigen. Zudem wird die Simulation für verschiedene Lastfälle parametrisiert, wie beispielsweise unterschiedliche Orientierungen des Prüfkörpers im Rotorreißer. Neben dem experimentellen zeigen wir erste numerische Ergebnisse der Berechnungen am Beispiel einer Metall-Kunststoff-Hybridstruktur. Damit leistet unsere Arbeit einen Beitrag dazu, den Einfluss von Konstruktionsentscheidungen auf das Aufschlussverhalten abzuschätzen, sowie Erfahrungen bei der Erstellung einer durchgängigen digitalen Kette vom Design über Fertigung bis hin zum Recycling zu sammeln.

  • Lecture (Conference)
    Tagung Aufbereitung und Recycling, 11.-12.11.2021, Freiberg, Deutschland

Publ.-Id: 33577

Environment-induced decay dynamics of anti-ferromagnetic order in the Mott-Hubbard system

Schaller, G.; Queisser, F.; Szpak, N.; König, J.; Schützhold, R.

We study the dissipative Fermi-Hubbard model in the limit of weak tunneling and strong repulsive interactions, where each lattice site is tunnel-coupled to a Markovian fermionic bath. For cold baths at intermediate chemical potentials, the Mott insulator property remains stable and we find a fast relaxation of the particle number towards half filling. On longer time scales, we find that the anti-ferromagnetic order of the Mott-Néel ground state on bi-partite lattices decays, even at zero temperature. For zero and non-zero temperatures, we quantify the different relaxation time scales by means of waiting time distributions which can be derived from an effective (non-Hermitian) Hamiltonian and obtain fully analytic expressions for the Fermi-Hubbard model on a tetramer ring.

Keywords: Fermi-Hubbard model; local master equation; magnetic order; waiting-time distributions


Publ.-Id: 33576

Contribution to recyclability estimation of multi-material structures with focus on modelling material liberation through shredding

Heibeck, M.; Rudolph, M.; Modler, N.; Reuter, M.; Filippatos, A.

Multi-material structures are usually designed into products with the aim of optimizing the operation phase, e.g. lightweight structures leading to higher energy efficiency of vehicles. However, in the recycling phase, most materials connected in multi-material structures should be liberated and separated again to enable high material recoveries. We want to contribute to estimating recyclability of multi-material structures already at the design stage by investigating material liberation through shredding. Therefore, we conducted an experimental shredding study, where we observed liberation behaviour and characterized in- and output particles. Furthermore, we are currently working on the numerical simulation of shredding processes using the Finite Element Method. In the future, we want to analyse the influence of design parameters on liberation behavior and, thereby, contribute to making more sustainable design decisions.

  • Invited lecture (Conferences) (Online presentation)
    24. Internationales Dresdner Leichtbausymposium, 17.-18.06.2021, Dresden, Deutschland

Publ.-Id: 33575

Investigating material liberation of multi-material structures through shredding

Heibeck, M.; Rudolph, M.; Reuter, M.; Filippatos, A.

Most products in consumables, aerospace and automotive industry are multi-material structures, which consist of materials connected through different joining techniques. Multi-material design aims for optimizing performance during production and service phase but usually does not consider the recycling. During recycling, materials combined in multi-material structures need to be liberated, i.e. disconnected, again to enable high material recoveries in subsequent recycling processes.
The goal of this study is to investigate material liberation of multi-material structures through mechanical processing, namely shredding. An experimental study is conducted where automotive A-frame-based specimens are shredded in a rotary shear. Particle analysis and characterization is supported by computer tomography. Furthermore, a first approach to model material liberation using Finite Element Method is introduced. This study is a contribution to estimating product recyclability in terms of material liberation already at the design stage, thereby supporting the design-engineer in sustainable design and product optimization.

  • Lecture (Conference) (Online presentation)
    Sustainable Minerals ´21, 21.-24.06.2021, Falmouth, United Kingdom

Publ.-Id: 33574

Towards multiscale simulations for matter under extreme conditions: Building surrogate models with machine learning

Fiedler, L.; Cangi, A.

The accurate numerical treatment of matter under extreme conditions is crucial for the understanding of important physical phenomena such as radiation damage in fusion reactor walls, or planetary interiors. Yet, such simulations are unfeasible with state-of-art methods, e.g., density functional theory (DFT) if performed at large length and time scales, due to unfavorable scaling behavior. One possible route to mitigate these scaling issues are machine-learning based surrogate models; DFT data is used to calculate models that allow access to the same quantities of interest a DFT simulation would, at drastically reduced computational cost. CASUS (in cooperation with SNL and ORNL) develops a framework called "Materials Learning Algorithms" (MALA), drawing on which DFT surrogate models can easily be created and applied. Here we present an overview of MALA and recent results, such as size transferability and automated model construction.

Keywords: Density Functional Theory; Machine Learning; Surrogate Model

  • Poster (Online presentation)
    MML-Workshop 2021, 22.-24.11.2021, Darmstadt, Deutschland

Publ.-Id: 33573

Materials Learning Algorithms (MALA): Learning the electronic structure of materials with neural networks

Fiedler, L.; Cangi, A.; Kotik, D.

The accurate modeling of materials is a fundamental task in material science. Advanced methods such as Density Functional Theory (DFT) provide quantum chemical accuracy through explicit calculation of the electronic structure of materials, but they come at high computational costs. These computational demands are especially prohibitive in the context of dynamic investigations. Increasingly efficient implementations of DFT can only alleviate this problem to a certain degree.
Here, we present a different approach to tackle this problem. Feed-forward neural networks are trained on electronic structure data in order to replace DFT calculations at a fraction of the computational cost. Such surrogate models can be used to model matter under extreme conditions as they occur in planetary interiors or fusion reactors across multiple length and time scales.
To facilitate the training, testing, and application of DFT surrogate models, the Center for Advanced Systems Understanding develops the Materials Learning Algorithm (MALA) package as an open-source software project in collaboration with the Sandia National Laboratories and Oak Ridge National Laboratory.

Keywords: Density Functional Theory; Machine Learning; Surrogate Model

  • Lecture (Conference) (Online presentation)
    ML@HZDR Symposium 2021, 06.12.2021, Dresden, Deutschland

Publ.-Id: 33572

A Deep Dive into Machine Learning Density Functional Theory for Materials Science and Chemistry

Fiedler, L.; Shah, K.; Bussmann, M.; Cangi, A.

With the growth of computational resources, the scope of electronic structure simulations has increased greatly. Artificial intelligence and robust data analysis hold the promise to accelerate large-scale simulations and their analysis to hitherto unattainable scales. Machine learning is a rapidly growing field for the processing of such complex datasets. It has recently gained traction in the domain of electronic structure simulations, where density functional theory takes the prominent role of the most widely used electronic structure method. Thus, DFT calculations represent one of the largest loads on academic high-performance computing systems across the world. Accelerating these with machine learning can reduce the resources required and enables simulations of larger systems. Hence, the combination of density functional theory and machine learning has the potential to rapidly advance electronic structure applications such as in-silico materials discovery and the search for new chemical reaction pathways. We provide the theoretical background of both density functional theory and machine learning on a generally accessible level. This serves as the basis of our comprehensive review including research articles up to December 2020 in chemistry and materials science that employ machine-learning techniques. In our analysis, we categorize the body of research into main threads and extract impactful results. We conclude our review with an outlook on exciting research directions in terms of a citation analysis.

Keywords: Density Functional Theory; Machine Learning; Review Article


Publ.-Id: 33571

Structural and high-field magnetic properties of Laves phase RFe2-H hydrides

Tereshina, I. S.; Karpenkov, A. Y.; Gorbunov, D.; Doerr, M.; Tereshina-Chitrova, E. A.; Drulis, H.

The crystal structure and magnetic properties of the multicomponent compounds (Tb1−xYx)0.8Sm0.2Fe2Hz (x = 0, 0.2, 0.4, 0.6, 0.8, 1; z = 0 and 3.7) are investigated. The compounds crystallize in the MgCu2 type of structure. While the parent compounds Tb0.8Sm0.2Fe2 and Y0.8Sm0.2Fe2 are single phase, we detect 5%–8% of a second phase with a crystal structure of the PuNi3 type (space group R3m) in the alloys with 0.2 ≤ x < 0.8. Hydrogen absorption does not change the space group of the (Tb,Y,Sm)Fe2 compounds but boosts significantly the lattice parameter a. A large volume change of ΔV/V ∼ 28% upon hydrogen absorption is observed. By applying high magnetic fields up to 58 T, we observed rotations of the magnetic sublattices and hence we were able to determine the critical transition fields, H, from the ferrimagnetic to the ferromagnetic state and the inter-sublattice exchange parameter λ. The magnetic compensation occurs at x ≈ 0.6 and 0.2 in (Tb1−xYx-)0.8Sm0.2Fe2Hz at z = 0 and 3.7, respectively. While maintaining the collinear magnetic structure, the phenomenon of compensation in hydrides should be observed at x ≈ 0.4.

Publ.-Id: 33570

A generalized population balance model for the simulation of polydisperse multiphase flows within the Euler-Euler framework

Lehnigk, R.

Polydisperse multiphase flows appear in a multitude of industrial processes. Depending on the application, the fluid or solid particles differ not only in size, but also with respect to other variables such as their velocity, shape, temperature, crystal structure or chemical composition. These secondary properties can significantly influence the corresponding process or the performance of the end product. An example are bubbly flows in vertical channels. The velocity vectors of the individual bubbles depend on their size, which ultimately determines the gas phase distribution in the pipe cross-section. Another example is the gas phase synthesis of ceramic powder in high temperature processes. The resulting particle aggregates are usually non-spherical due to the competition of aggregation and sintering of primary particles. The aggregate morphology affects the likelihood of collisions and the primary particle size determines the characteristics of the product powder. The evolution of property distributions within the dispersed phase can be described with the population balance equation. Its coupled solution with the governing equations of fluid flow allows to consider spatial dependencies. In the present thesis, a flexible population balance model has been developed and combined with a multifluid solver within the open source Computational Fluid Dynamics library OpenFOAM. The population balance equation is solved with the method of classes. The applied technique preserves the total mass and number of particles and allows for an arbitrary discretization of the distribution function. A new formulation that allows a direct implementation of binary breakup models with an implicitly given daughter size distribution is proposed which eliminates the need for an additional numerical integration. Further, a general approach for predicting the evolution of secondary size-conditioned properties is presented. The flexibility of the developed population balance model is demonstrated by applying it to two fundamentally different problems. First, the cocurrent flow of air and water in a vertical pipe is simulated. Predicting the development of the lateral void fraction profile is still a largely unsolved problem and requires proper modeling of several physical mechanisms. In dealing with the complexity a stepwise validation strategy is adopted, whereby the limits of each model layer are determined for a large matrix of measured superficial velocities. By employing an established model for the momentum exchange between the phases it is shown that, in the case of a nearly developed flow, especially the transition region between bubbly and slug flow can be simulated reliably. Next, using volume-averaged flow parameters, the performance of several coalescence and breakup model combinations is assessed. Promising results are obtained for some cases, albeit the models still require further development and calibration. Finally, the developing flow is simulated and it is shown that a complete model for predicting transitions between flow regimes must account for the size dependency of the bubble motion, as possible with the developed population balance model. The second application is the synthesis of titania in an aerosol reactor. The specific surface area of the aggregates is considered as a secondary property here. In combination with a constant fractal dimension their collision diameter can be modeled. The mean primary particle diameter can be inferred from it as well. The created model helps in explaining the trends observed in the experiment, which is not possible on the basis of considering merely the aggregate size distribution or using a simplified description of the reactor geometry.

  • Doctoral thesis
    TU Dresden, 2020
    Mentor: Prof. Dr.-Ing. habil. Dr. h. c. Uwe Hampel
    127 Seiten

Publ.-Id: 33569

Colossal angular magnetoresistance in ferrimagnetic nodal-line semiconductors

Seo, J.; De, C.; Ha, H.; Lee, J. E.; Park, S.; Park, J.; Scurschii, I.; Choi, E. S.; Kim, B.; Cho, G. Y.; Yeom, H. W.; Cheong, S.-W.; Kim, J. H.; Yang, B.-J.; Kim, K.; Kim, J. S.

Efcient magnetic control of electronic conduction is at the heart of spintronic functionality for memory and logic applications. Magnets with topological band crossings serve as a good material platform for such control, because their topological band degeneracy can be readily tuned by spin confgurations, dramatically modulating electronic conduction. Here we propose that the topological nodal-line degeneracy of spin-polarized bands in magnetic semiconductors induces an extremely large angular response of magnetotransport. Taking a layered ferrimagnet, Mn3Si2Te6, and its derived compounds as a model system, we show that the topological band degeneracy, driven by chiral molecular orbital states, is lifted depending on spin orientation, which leads to a metal–insulator transition in the same ferrimagnetic phase. The resulting variation of angular magnetoresistance with rotating magnetization exceeds a trillion per cent per radian, which we call colossal angular magnetoresistance. Our fndings demonstrate that magnetic nodal-line semiconductors are a promising platform for realizing extremely sensitive spin- and orbital-dependent functionalities.

Publ.-Id: 33568

Maximum performance of an active magnetic regenerator

Benke, D.; Fries, M.; Gottschall, T.; Ohmer, D.; Taubel, A.; Skokov, K.; Gutfleisch, O.

Magnetocaloric materials change their temperature when a magnetic field is applied or removed, which allows building a magnetic cooling device. We derive an analytical expression for the maximum heat that such a material can transfer in one cooling cycle by investigating the operation of a simplified active magnetic regenerator (AMR). The model largely only depends on the adiabatic temperature change, the specific entropy change, and the temperature span between the hot and cold reservoirs. While this expression overestimates the performance of a real AMR due to its simplification, it can predict an upper limit of any AMRs’ performance independent of the implementation details. Based on this, we calculate the upper limit of the cooling power of magnetic cooling devices at any temperature span, frequency, mass, and material. This upper limit is used to predict how the thermal span is scaling with the applied magnetic field, and it can be utilized for the optimization of the magnetic field source. Additionally, we confirm that the product of isothermal entropy and adiabatic temperature change, already used in the literature, is a suitable figure of merit for magnetocaloric materials.

Publ.-Id: 33567

Nano- and microscaled biosensing and (de-)coding in micro- and millifluidics

Schütt, J.

Aim: Further development and improvement of disease diagnostic devices and protocols
So far: Very precise, but bulky, time-consuming and costly, trained personnel and laboratory conditions required

Keywords: Point-of-care

  • Lecture (Conference) (Online presentation)
    European Biosensor Symposium -Emerging trends in bioelectronics-, 19.10.-21.12.2021, Dresden, Deutschland

Publ.-Id: 33566

Electronic and Transport Properties of Novel Two Dimensional Materials

Ramzan, M. S.

The family of 2D layered materials has gained enormous attention of materials scientists and researchers from other fields of science. This stems from the fact that 2D monolayers (1Ls) can exhibit remarkably different electronic properties than their bulk counterparts. Moreover, stacking different 1Ls, results in yet different electronic properties than these of the 1Ls. Recently, among others, van der Waals heterostructures (vdW HS) of transition-metal dichalcogenides (TMDC) have been extensively studied due to their type-II band alignment.
This thesis summarizes four different theoretical studies on layered 2D materials. The first study investigates the potential existence of a new family of bulk layered materials with chemical formula XY3 (where X = group 14; Y = group 15). The low cleavage energies indicate the potential exfoliation as mono- and bi- layers (2Ls), where most of the exfoliated layers are thermally and dynamically stable. Interestingly, many 1Ls and 2Ls show strong quantum confinement and turn into indirect semiconductors, unlike bulks which are all metals. Such metal to semiconductor transition was previously known for noble-metal dichalcogenides. Next study shows one of the potential applications of XY3, that is, single-material logical junction for gas sensing applications. A device that consists of metallic multilayers (3L) as electrodes and semiconducting 1L as scattering region. To do so, one of the exemplary materials (SnP3) was picked to construct a single-material device. The results combining density functional theory (DFT) and non-equilibrium Green’s function (NEGF) calculations revealed that SnP3 is an ideal material for gas sensing applications, especially for poisonous NO gas molecules. For NO molecules, this device showed a negative differential resistance (NDR) at small bias voltages.
Moreover, electronic properties of vdW TMDC HS were investigated for the HS having up to six layers. In this part, it was essentially studied how the electron and hole states in heterobilayer (HBL), namely MoS2/WSe2, will change as a function of additional electron/hole layers. We found that additional electron layers will result in equal delocalization of electron states among all layers forming conduction bands. However, additional hole layers do not alter the holes states distribution much, i.e., hole states stay localized at HBL+1L (WSe2).
The last study, in this thesis, focused on understanding the interplay between the so- called atomic collapse states and moiré potential in twisted bilayer graphene (tBLG) systems. It was found that individual graphene layers did host collapse states. However, moiré potential in tBLG may destroy the collapse states, although tBLG systems have similar band dispersion as in graphene.
The knowledge acquired from the findings presented in this thesis can provide new potential candidates as well as some helpful insights into electronic properties of existing layered materials, for their applications in the future nano(opto)electronic devices.

  • Doctoral thesis
    Jacobs University Bremen, 2022
    Mentor: PD Dr. A. B. Kuc

Publ.-Id: 33565

[¹⁸F]FLUDA - A novel radiotracer for PET imaging of the adenosine A₂A receptor (A₂AR)

Lai, T. H.; Toussaint, M.; Teodoro, R.; Dukić-Stefanović, S.; Gündel, D.; Ludwig, F.-A.; Wenzel, B.; Schröder, S.; Sattler, B.; Moldovan, R.-P.; Sabri, O.; Deuther-Conrad, W.; Brust, P.

Introduction: Selective A₂AR antagonists have emerged as potential therapeutics for multiple diseases. With regard to Parkinson’s disease, adjunctive treatment of A₂AR antagonists potentially reduces adverse effects of long-term L-DOPA treatment. Therefore, imaging of receptor availability during the A2AR-tailored therapy is of utmost importance. We recently developed [¹⁸F]FLUDA as an novel A₂AR-specific PET radiotracer [1].
Methods: [¹⁸F]FLUDA was synthesized by an automated procedure Biological evaluation was performed in healthy mice and piglets. In vitro autoradiography was performed with brain cryosections. In vivo metabolism was analysed by radio-HPLC of plasma and brain homogenate. Pharamcokinetics and biodistribution was assessed by dynamic PET imaging under control and blocking conditions (2.5 mg/kg tozadenant and/or 1.0 mg/kg istradefylline). SUV ratio (SUVr) of striatum-over-cerebellum was used as a metric for specific uptake. A single dose acute toxicity study was performed in Wistar rats according to the ICH guideline M3(R2). Radiation dosimetry was investigated in piglets.
Results: In vitro autoradiography revealed an A₂AR affinity (KD;) of 4.3 and 0.7 nM and an A₂AR density (Bmax) of 556 and 218 fmol/mg in the striatum of mice and piglets. No radiometabolites were detected in the mouse brain at 15 min p.i., whereas radiometabolites were found in piglet plasma but are assumed to not cross the blood-brain barrier. PET demonstrated high specific binding of [¹⁸F]FLUDA in both species (Fig.1). Toxicity studies revealed no adverse effects up to a dose of 30 µg/kg (~4000-fold of expected human dose). The ED to humans is 16.4 µSv/MBq, which is in the range of other ¹⁸F-labeled radiotracers [2].
Conclusion: We have demonstrated that [¹⁸F]FLUDA is suitable for determination of the A₂AR availability in the striatum. No safety concerns are expected upon administration of [¹⁸F]FLUDA according to toxicity and dosimetry data. These results encourage the clinical translation of [¹⁸F]FLUDA.
Acknowledgement: This work (Project No. 100226753) has been funded by the European Regional Development Fund (ERDF) and Sächsische Aufbaubank (SAB).
References: [1] Lai, T.H., Toussaint, M., Teodoro, R., Dukić-Stefanović, S., Gündel, D., Ludwig, F.-A., Wenzel, B., Schröder, S., Sattler, B., Moldovan, R.-P., Falkenburger, B.H., Sabri, O., Winnie Deuther-Conrad, W., Peter Brust, P. Improved in vivo PET imaging of the adenosine A₂A receptor in the brain using [¹⁸F]FLUDA, a deuterated radiotracer with high metabolic stability. Eur J Nucl Med Mol Imaging 2021, 48, 2727–2736. [2] Sattler, B., Kranz, M., Lai, T.H., Gündel, D., Toussaint, M., Schröder, S., Moldovan, R.-P., Winnie Deuther-Conrad, W., Teodoro, R., Sabri, O., Peter Brust, P. Preclincal incorporation dosimetry of [¹⁸F]FLUDA - a novel ¹⁸F-labeled tracer for PET imaging of the expression of the adenosine A₂A receptor (A₂AR). J Nucl Med 2020, 61:1014.

Keywords: adenosine receptors; A₂A receptor; neurodegeneration; positron emission tomography; fluorine-18

  • Poster (Online presentation)
    NRM2021 - XIII international symposium of functional neuroreceptor mapping of the living brain, 14.-16.12.2021, online, online
  • Poster (Online presentation)
    NRM 2021 Mapping NeuroReceptors at Work, 14.-16.12.2021, virtual presentation, virtual presentation

Publ.-Id: 33564

²¹⁰Pb measurements at the André E. Lalonde AMS Laboratory: Potential for the radioassay of materials used in rare event search detectors

Vivo Vilches, C.; Weiser, B.; Zhao, X.; Francisco, B. B. A.; Gornea, R.; Kieser, W. E.

²¹⁰Pb (𝑇1∕2=22.2 y) is an important source of background in rare event searches, such as neutrinoless double-𝛽 decay and dark matter direct detection experiments. In this paper, the capabilities of the A.E. Lalonde AMS Laboratory at the University of Ottawa for ²¹⁰Pb measurements are discussed.
For fluoride targets, the blank ²¹⁰Pb/²⁰⁶Pb ratio was in the 1e-14 to 1e-13 range, but (PbF₃)- current output was lower and less stable. For oxide targets, (PbO₂)- current output showed better stability, despite a significant difference in current output for commercial PbO and processed samples, and background studies suggested a background not much higher than that of the fluoride targets. Both target materials showed, therefore, good performance for ²¹⁰Pb Accelerator Mass Spectrometry assay.
Measurements of Kapton ultra-thin films were performed. 90% C.L. upper limits for the ²¹⁰Pb specific activity in the range of 0.74–2.8 Bq/kg were established for several Kapton HN films.

Keywords: ²¹⁰Pb contamination; Accelerator mass spectrometry; Rare event searches; Astroparticle physics; Radiopurity


Publ.-Id: 33562

EANM Guideline on Quality Risk Management for radiopharmaceuticals

Gillings, N.; Hjelstuen, O.; Behe, M.; Decristoforo, C.; Elsinga, P.; Ferrari, V.; Kiß, O.; Kolenc, P.; Koziorowski, J.; Laverman, P.; Mindt, T.; Ocak, M.; Patt, M.; Todde, S.; Walte, A.

This document is intended as a supplement to the EANM “Guidelines on current Good Radiopharmacy Practice (cGRPP)” issued by the Radiopharmacy Committee of the EANM [1]. The aim of the EANM Radiopharmacy Committee is to provide a document that describes how to manage risks associated with small-scale “in-house” preparation of radiopharmaceuticals, not intended for commercial purposes or distribution.

Keywords: Risk assessment; radiopharmaceuticals; quality assurance

Publ.-Id: 33561

Cyclotrons operated for Nuclear Medicine and Radiopharmacy in the German speaking D-A-CH countries: An update on current status and trends

Zippel, C.; Ermert, J.; Patt, M.; Gildehaus, F. J.; Ross, T. L.; Reischl, G.; Neumaier, B.; Kiß, O.; Mitterhauser, M.; Wadsak, W.; Schibli, R.; Kopka, K.

Background: Cyclotrons form a central infrastructure and are a resource of medical radionu- clides for the development of new radiotracers as well as the production and supply of clini- cally established radiopharmaceuticals for patient care in nuclear medicine.
Aim: To provide an updated overview of the number and characteristics of cyclotrons that are currently in use within radiopharmaceutical sciences and for the development of radiopharma- ceuticals to be used for patient care in Nuclear Medicine in Germany (D), Austria (A) and Switzerland (CH).
Methods: Publicly available information on the cyclotron infrastructure was (i) consolidated and updated, (ii) supplemented by selective desktop research and, last but not least, (iii) vali- dated by members of the committee of the academic “Working Group Radiochemistry and Radiopharmacy” (AGRR), consisting of radiochemists and radiopharmacists of the D-A-CH countries and belonging to the German Society of Nuclear Medicine (DGN), as well as the Radiopharmaceuticals Committee of the DGN.
Results: In total, 39 cyclotrons were identified that are currently being operated for medical radionuclide production for imaging and therapy in Nuclear Medicine clinics, 29 of them in Germany, 4 in Austria and 6 in Switzerland. The majority of the cyclotrons reported (69%) are operated by universities, university hospitals or research institutions close to a university (clinic), less by/in cooperation with industrial partners (26%) or a (non-university) clinic/PET-center (5%). Most of the cyclotrons (82%) are running with up to 18 MeV proton beams, which is sufficient for the production of the currently most common cyclotron-based radionuclides for PET imaging.
Discussion: The data presented provide an academically-updated overview of the medical cy- clotrons operated for the production of radiopharmaceuticals and their use in Nuclear Medi- cine in the D-A-CH countries. In this context, we discuss current developments and trends with a view to the cyclotron infrastructure in these countries, with a specific focus on organi- sational aspects.

Keywords: (Medical) Cyclotron; radionuclide production; nuclear medicine; infrastructure for radiopharmaceutical production

Publ.-Id: 33560

Automated radiosynthesis of the adenosine A2A receptor-targeting radiotracer [18F]FLUDA

Lai, T. H.; Wenzel, B.; Moldovan, R.-P.; Brust, P.; Kopka, K.; Teodoro, R.

[18F]FLUDA is a selective radiotracer for in vivo imaging of the adenosine A2A receptor (A2AR) by positron emission tomography (PET). Promising preclinical results obtained by neuroimaging of mice and piglets suggest the translation of [18F]FLUDA to human PET studies. Thus, we report herein a remotely controlled automated radiosynthesis of [18F]FLUDA using a GE TRACERlab FX2 N radiosynthesizer. The radiotracer was obtained by a one-pot two-step radiofluorination procedure with a radiochemical yield of 9 ± 1%, a radiochemical purity of ≥ 99% and molar activities in the range of 69 333 GBq/µmol at the end of synthesis within a total synthesis time of approx. 95 min (n = 16). Altogether, we successfully established a reliable and reproducible procedure for the automated production of [18F]FLUDA.

  • Open Access Logo Journal of Labelled Compounds and Radiopharmaceuticals 65(2022), 162-166
    Online First (2022) DOI: 10.1002/jlcr.3970

Publ.-Id: 33558

Data Publication: Nondiffusive Transport and Anisotropic Thermal Conductivity in High-Density Pt/Co Superlattices

Shahzadeh, M.; Andriyevska, O.; Salikhov, R.; Fallarino, L.; Hellwig, O.; Pisana, S.

This dataset is a sample preparation description and magnetic property characteristics for Co/Pt multilayers, where the ballistic-like anisotropic thermal conductivity is detected. 

Keywords: heat transport; metallic multilayers; anisotropic thermal conductivity; nondiffusive transport; frequency domain thermoreflectance

Related publications


Publ.-Id: 33556

Warm dense matter and many body theory

Vorberger, J.

The talk will cover some recent attempts to recreate and describe the states of matter as in brown dwarfs, ice giant planets, or the earth. In particular, state of the art methods will be described to model the x-ray scattering signal of such warm dense matter states. Density functional theory seems to be a very promising tool, although upon close inspection, several problems arise that strongly limit the predictive power of this method. This leads to investigations of the underlying model system, the electron gas, using quantum Monte Carlo methods. Finally, we show a promising new method to study higher order correlations in the system by nonlinear excitations.

  • Lecture (others) (Online presentation)
    CFEL Theory Seminar, 26.01.2021, online, Germany

Publ.-Id: 33555

Intrinsic energy flow in laser-excited 3d ferromagnets

Zahn, D.; Jakobs, F.; Seiler, H.; Butcher, T. A.; Engel, D.; Vorberger, J.; Atxitia, U.; William Windsor, Y.; Ernstorfer, R.

Ultrafast magnetization dynamics are governed by energy flow between electronic, magnetic, and lattice degrees of freedom. A quantitative understanding of these dynamics must be based on a model that agrees with experimental results for all three subsystems. However, ultrafast dynamics
of the lattice remain largely unexplored experimentally. Here, we combine femtosecond electron diffraction experiments of the lattice dynamics with energy-conserving atomistic spin dynamics (ASD) simulations and ab-initio calculations to study the intrinsic energy flow in the 3d ferromagnets cobalt (Co) and iron (Fe). The simulations yield a good description of experimental data, in particular an excellent description of our experimental results for the lattice dynamics. We find that the lattice dynamics are influenced significantly by the magnetization dynamics due to the energy cost of demagnetization. Our results highlight the role of the spin system as the dominant heat sink in the first hundreds of femtoseconds. Together with previous findings for nickel, our work demonstrates that energy-conserving ASD simulations provide a general and consistent description of the laser-induced dynamics in all three elemental 3d ferromagnets.

Keywords: ferromagnet; iron; cobalt; lattice; spin; relaxation

Publ.-Id: 33554

Proton stopping measurements at low velocity in warm dense carbon

Malko, S.; Cayzac, W.; Ospina-Bohorquez, V.; Bhutwala, K.; Bailly-Grandvaux, M.; Fedosejevs, R.; McGuffey, C.; Vaisseau, X.; Tauschwitz, A.; Apinaniz, J. I.; Gatti, G.; de Luis, D.; Perez Hernandez, J. A.; Huault, M.; Hu, S. X.; White, A. J.; Collins, L. A.; Neumayer, P.; Faussurier, G.; Vorberger, J.; Prestopino, G.; Verona, C.; Santos, J. J.; Batani, D.; Beg, F.; Volpe, L.

Ion stopping in warm dense matter is a process of fundamental importance for the understanding of the properties of dense plasmas, the realization and the interpretation of experiments involving ion beam-induced warm dense matter samples, and for inertial confinement fusion research. The theoretical description of the ion stopping power in warm dense matter is difficult notably due to electron coupling and degeneracy, and measurements are still largely missing. In particular, the low-velocity stopping range around the Bragg peak, that features the largest modelling uncertainties, remains virtually unexplored. Here, we report proton energy-loss measurements in warm dense plasma at lower projectile velocities than previous experiments, coming significantly closer to the Bragg peak region. Our energy-loss data, combined with a precise target characterization based on plasma temperature measurements us-
ing two different diagnostics, demonstrate a significant deviation of the stopping power from classical models in this regime. In particular, we show
that our results are consistent with recent first-principles simulations based on time-dependent density functional theory.

Keywords: stopping power; fusion

Publ.-Id: 33553

Quasiparticle electronic structure and optical response (G0W0+BSE) of anatase TiO2 starting from modified HSE06 functionals

Sruthil Lal, S. B.; Sharan, A.; Devaraj, M.; Posselt, M.; Sasikala Devi, A. A.

The quasiparticle electronic structure and optical excitation of anatase TiO2 is determined within the framework of many-body perturbation theory (MBPT) by combining the G0W0 method and the Bethe-Salpeter Equation (BSE). A modified version of the HSE06 screened hybrid functional, that includes 20% exact Fock exchange (HSE06(20)) as opposed to 25% in the standard HSE06 functional, is used to set up the starting Hamiltonian for G0W0+BSE calculations. The HSE06(20) functional accurately predicts the ground state electronic band structure. BSE calculations based on data from G0W0+HSE06(20) yield direct optical excitation energies and oscillator strengths in excellent agreement with existing experiments and theoretical calculations characterizing direct excitation. In particular, an exciton binding energy of 229 +- 10 meV is obtained, in close agreement with experiments. The projections of excitonic states onto the quasiparticle band structure in a fatband representation shows that the lowest optical transition of anatase TiO2 consists of excitons originating from the mixing of direct transitions within band pairs running parallel to the Gamma-Z direction in the tetragonal Brillouin zone. This implies a strong spatial localization of excitons in the xy plane of the lattice. This investigation highlights the importance of a suitable non-interacting Hamiltonian for the MBPT based quasiparticle G0W0 and subsequent BSE calculations and suggests HSE06(20) as an optimal choice in the case of anatase TiO2.

Keywords: Quasiparticle electronic structure; Anatase Ti dioxide; Optical response; Density functional theory; HSE06 hybrid functional; Many body pertubation theory; G0W0 approach; Bethe-Salpeter equation; Excitons

Publ.-Id: 33551

Selenium nanowire formation by reaction of selenate with magnetite

Poulain, A.; Fernandez-Martinez, A.; Greneche, J.-M.; Prieur, D.; Scheinost, A.; Menguy, N.; Bureau, S.; Magnin, V.; Findling, N.; Drnec, J.; Martens, I.; Mirolo, M.; Charlet, L.

The mobility of 79Se, a long half-life radioisotope and fission product of 235U, and contaminant of drainage waters from black shale mountains and from coal mines, is an important parameter in the safety assessment of radioactive nuclear waste disposal systems. Highly mobile and soluble in its high oxidation states (Se(VI)O42-, Se(IV)O32-), selenium oxyanions can interact with magnetite, a mineral present in anoxic natural environments and in steel corrosion products, and be precipitated by reduction, and thus immobilized. Here, the sorption and reduction capacity of synthetic nanomagnetite towards Se(VI) was investigated at neutral and acidic pH, under reducing, oxygen free conditions. The additional presence of Fe(II)aq, released during magnetite dissolution at pH 5, is shown to have an effect on the reduction kinetics. XANES analyses revealed that, at pH 5, trigonal gray Se(0) formed, and that outer-sphere Se(IV) complexes existed at the nanoparticle surface at longer reaction times. The Se(0) nanowires grew during the reaction, which points to a complex transport mechanism of reduced species or to active reduction sites at the tip of the Se(0) nanowires. The concomitant uptake of aqueous Fe(II) and Se(VI) ions is interpreted as a consequence of small pH oscillations that result from the Se(VI) reduction, leading to a re- adsorption of aqueous Fe(II) onto the magnetite, renewing its reducing capacity. This effect is not observed at pH 7, indicating that the presence of aqueous Fe(II) may be an important factor to be considered when examining the environmental reactivity of magnetite.

Keywords: Nuclear wastes; Magnetite to maghemite interconversion; Selenium reduction; Sorption on magnetite; Selenium needles

Related publications


  • Secondary publication expected from 02.10.2023

Publ.-Id: 33550

Using neutrons and x rays to measure plasma conditions in a solid sphere of deuterated polyethylene compressed to densities of 35 g/cc at temperatures of 2 keV and pressures of 40 Gbar

Nilsen, J.; Bachmann, B.; Zimmerman, G. B.; Hatarik, R.; Döppner, T.; Swift, D. C.; Hawreliak, J.; Collins, G. W.; Falcone, R. W.; Glenzer, S. H.; Kraus, D.; Landen, O. L.; Castor, J. I.; Whitley, H. D.; Kritcher, A. L.

This paper describes an experiment that shock compresses the center of a solid deuterated polyethylene sphere, CD2, to densities of 35 g/cc and temperatures of 2 keV with corresponding pressure of 40 Gbar. The design employs a strong spherically converging shock launched through a solid ball of material using a Hohlraum radiation drive. As the shock coalesces at the center it produces a hot spot that we
characterize by measuring the x-ray self-emission and 2.45MeV neutrons emitted. Two-dimensional images and time-resolved measurements of the x rays emitted determine the size and time duration of the hot spot, leading to an estimated 2 keV electron temperature. The neutron time of flight spectrometer measures an average ion temperature of 1.06 +/- 0.15 keV and neutron yield of 7.0 (+/-0.5) x 10^9 DD neutrons. Our new distribution function tool enables us to create a forward model of the experimental data based on 1D radiation-hydrodynamic simulations, leading to a better understanding of the plasma conditions that produce the measured neutrons and x rays. Our simulations indicate that the x rays are produced in a short-lived hot-dense core over tens of picoseconds, whereas the neutron emission continues for about 200 ps, as the hot core starts to expand, thereby leading to a lower mean temperature of the plasma during neutron production. This finding is in agreement with the experimental data, and we therefore conclude that the forward-modeling is a useful tool forinferring the conditions of the hot spot in a laser-driven implosion during burn.

Publ.-Id: 33549

Teaching ML workshop at ECML/PKDD - 2 years in, 3 thoughts out

Steinbach, P.; Kinnaird, K. M.; Guhr, O.

As a co-organizer of the Teaching Machine Learning Workshop at ECMLPKDD, I'd like to share our experience in striving to host a mixture of communities to share and discuss advances in teaching of ML to any level of prior knowledge.

What was thought of a small event on the European level, has now become an event at international scale. I'll distill essential outcomes that have relevance to Helmholtz.

This presentation was delivered at the TEACH conference:

Keywords: machine learning; teaching; training; data science; artificial intelligence; conference; didactics

  • Open Access Logo Lecture (Conference) (Online presentation)
    TEACH - Talk about Education Across Communities in Helmholtz, 07.-10.12.2021, virtuell, Deutschland
    DOI: 10.6084/m9.figshare.17134580.v1

Publ.-Id: 33548

Do We Need Complex Image Features to Personalize Treatment of Patients with Locally Advanced Rectal Cancer?

Shahzadi, I.; Lattermann, A.; Linge, A.; Zwanenburg, A.; Baldus, C.; Peeken, J. C.; Combs, S. E.; Baumann, M.; Krause, M.; Troost, E. G. C.; Löck, S.

Radiomics has shown great potential for outcome prognosis and presents a promising approach for improving personalized
cancer treatment. In radiomic analyses, features of different complexity are extracted from clinical imaging datasets, which
are correlated to the endpoints of interest using machine-learning approaches. However, it is generally unclear if more
complex features have a higher prognostic value and show a robust performance in external validation. Therefore, in this
study, we developed and validated radiomic signatures for outcome prognosis after neoadjuvant radiochemotherapy in
locally advanced rectal cancer (LARC) using computed tomography (CT) and T2-weighted magnetic resonance imaging
(MRI) of two independent institutions (training/validation: 94/28 patients). For the prognosis of tumor response and freedom
from distant metastases (FFDM), we used different imaging features extracted from the gross tumor volume: less complex
morphological and first-order (MFO) features, more complex second-order texture (SOT) features, and both feature classes
combined. Analyses were performed for both imaging modalities separately and combined. Performance was assessed by
the area under the curve (AUC) and the concordance index (CI) for tumor response and FFDM, respectively. Overall,
radiomic features showed prognostic value for both endpoints. Combining MFO and SOT features led to equal or higher
performance in external validation compared to MFO and SOT features alone. The best results were observed after
combining MRI and CT features (AUC = 0.76, CI = 0.65). In conclusion, promising biomarker signatures combining MRI and
CT were developed for outcome prognosis in LARC. Further external validation is pending before potential clinical

Keywords: Biomarkers; Distant metastases; Rectal cancer; Tumor response

  • Book chapter
    in: Medical Image Computing and Computer Assisted Intervention – MICCAI 2021, Cham: Springer Nature Switzerland AG, 2021, 775-785
    DOI: 10.1007/978-3-030-87234-2_73

Publ.-Id: 33547

Lamellipodin-rictor signaling mediates glioblastoma cell invasion and radiosensitivity downstream of egfr

Moritz, S.; Krause, M.; Schlatter, J.; Cordes, N.; Vehlow, A.

Glioblastoma is a tumor type of unmet need despite the development of multimodal treatment strategies. The main factors
contributing to the poor prognosis of glioblastoma patients are diverse genetic and epigenetic changes driving glioblastoma
persistence and recurrence. Com-plemented are these factors by extracellular cues mediated through cell surface receptors,
which further aid in fostering pro-invasion and pro-survival signaling contributing to glioblastoma therapy resistance. The
underlying mechanisms conferring this therapy resistance are poorly understood. Here, we show that the cytoskeleton
regulator Lamellipodin (Lpd) mediates invasiveness, proliferation and radiosensitivity of glioblastoma cells.
Phosphoproteome analysis identified the epidermal growth factor receptor (EGFR) signaling axis commonly hyperactive in
glioblastoma to depend on Lpd. Mechanistically, EGFR signaling together with an interaction between Lpd and the
Rapamycin-insensitive companion of mammalian target of rapamycin (RICTOR) jointly regulate glioblastoma radiosensitivity.
Collectively, our findings demonstrate an essential function of Lpd in the radiation response and invasiveness of
glioblastoma cells. Thus, we uncover a novel Lpd-driven resistance mechanism, which adds an additional critical facet to the
complex glioblastoma resistance network. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

Keywords: EGFR; Glioblastoma; Invasion; Lamellipodin; Radiosensitivity; RICTOR

Publ.-Id: 33546

Towards online adaptive proton therapy: first report of plan-library-based plan-of-the-day approach

Troost, E. G. C.; Menkel, M.; Tschiche, M.; Thiele, J.; Jaster, M.; Haak, D.; Kunath, D.

letter to editor


Publ.-Id: 33545

Reduced diffusion in white matter after radiotherapy with photons and protons

Dünger, L.; Seidlitz, A.; Jentsch, C.; Platzek, I.; Kotzerke, J.; Beuthien-Baumann, B.; Baumann, M.; Krause, M.; Troost, E. G. C.; Raschke, F.

Background and purpose

Radio(chemo)therapy is standard in the adjuvant treatment of glioblastoma. Inevitably, brain tissue surrounding the target volume is also irradiated, potentially causing acute and late side-effects. Diffusion imaging has been shown to be a sensitive method to detect early changes in the cerebral white matter (WM) after radiation. The aim of this work was to assess possible changes in the mean diffusivity (MD) of WM after radio(chemo)therapy using Diffusion-weighted imaging (DWI) and to compare these effects between patients treated with proton and photon irradiation.
Materials and methods

70 patients with glioblastoma underwent adjuvant radio(chemo)therapy with protons (n = 20) or photons (n = 50) at the University Hospital Dresden. MRI follow-ups were performed at three-monthly intervals and in this study were evaluated until 33 months after the end of therapy. Relative white matter MD changes between baseline and all follow-up visits were calculated in different dose regions.

We observed a significant decrease of MD (p < 0.05) in WM regions receiving more than 20 Gy. MD reduction was progressive with dose and time after radio(chemo)therapy (maximum: −7.9 ± 1.2% after 24 months, ≥50 Gy). In patients treated with photons, significant reductions of MD in the entire WM (p < 0.05) were seen at all time points. Conversely, in proton patients, whole brain MD did not change significantly.

Irradiation leads to measurable MD reduction in white matter, progressing with both increasing dose and time. Treatment with protons reduces this effect most likely 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.

Keywords: Diffusion imaging; White matter; Radiotherapy; Proton therapy; Photon therapy

Publ.-Id: 33544

The impact of anatomical changes during photon or proton based radiation treatment on tumor dose in glioblastoma dose escalation trials

Hessen, E. D.; Makocki, S.; van der Heide, U. A.; Jasperse, B.; Lutkenhaus, L. J.; Lamers, E.; Damen, E.; Troost, E. G. C.; Borst, G. R.


Most dose-escalation trials in glioblastoma patients integrate the escalated dose throughout the standard course by targeting a specific subvolume. We hypothesize that anatomical changes during irradiation may affect the dose coverage of this subvolume for both proton- and photon-based radiotherapy.
Material and Methods

For 24 glioblastoma patients a photon- and proton-based dose escalation treatment plan (of 75 Gy/30 fr) was simulated on the dedicated radiotherapy planning MRI obtained before treatment. The escalated dose was planned to cover the resection cavity and/or contrast enhancing lesion on the T1w post-gadolinium MRI sequence. To analyze the effect of anatomical changes during treatment, we evaluated on an additional MRI that was obtained during treatment the changes of the dose distribution on this specific high dose region.

The median time between the planning MRI and additional MRI was 26 days (range 16–37 days). The median time between the planning MRI and start of radiotherapy was relatively short (7 days, range 3–11 days). In 3 patients (12.5%) changes were observed which resulted in a substantial deterioration of both the photon and proton treatment plans. All these patients underwent a subtotal resection, and a decrease in dose coverage of more than 5% and 10% was observed for the photon- and proton-based treatment plans, respectively.

Our study showed that only for a limited number of patients anatomical changes during photon or proton based radiotherapy resulted in a potentially clinically relevant underdosage in the subvolume. Therefore, volume changes during treatment are unlikely to be responsible for the negative outcome of dose-escalation studies.

Keywords: Glioblastoma; Anatomical changes; Radiotherapy; Repeated MRI; Target volume changes; Dose escalation trials

Publ.-Id: 33543

Role of postoperative radiotherapy in the management for resected NSCLC – Decision criteria in clinical routine pre- and post-LungART

Süveg, K.; Le Pechoux, C.; Faivre-Finn, C.; Putora, P. M.; de Ruysscher, D.; Widder, J.; van Houtte, P.; Troost, E. G. C.; Slotman, B.; Ramella, S.; Pöttgen, C.; Peeters, S. T. H.; Nestle, U.; McDonald, F.; Dziadziuszko, R.; Belderbos, J.; Ricardi, U.; Manapov, F.; Lievens, Y.; Geets, X.; Dieckmann, K.; Guckenberger, M.; Andratschke, N.; Glatzer, M.


The role of postoperative radiation therapy (PORT) in stage III N2 NSCLC is controversial. We analyzed decision-making for PORT among European radiation oncology experts in lung cancer.

Twenty-two experts were asked before and after presentation of the results of the LungART trial to describe their decision criteria for PORT in the management of pN+ NSCLC patients. Treatment strategies were subsequently converted into decision trees and analyzed.

Following decision criteria were identified: extracapsular nodal extension, incomplete lymph node resection, multistation lymph nodes, high nodal tumor load, poor response to induction chemotherapy, ineligibility to receive adjuvant chemotherapy, performance status, resection margin, lung function and cardiopulmonary comorbidities. The LungART results had impact on decision-making and reduced the number of recommendations for PORT. The only clear indication for PORT was a R1/2 resection. Six experts out of ten who initially recommended PORT for all R0 resected pN2 patients no longer used PORT routinely for these patients, while four still recommended PORT for all patients with pN2. Fourteen experts used PORT only for patients with risk factors, compared to eleven before the presentation of the LungART trial. Four experts stated that PORT was never recommended in R0 resected pN2 patients regardless of risk factors.

After presentation of the LungART trial results at ESMO 2020, 82% of our experts still used PORT for stage III pN2 NSCLC patients with risk factors. The recommendation for PORT decreased, especially for patients without risk factors. Cardiopulmonary comorbidities became more relevant in the decision-making for PORT.

Keywords: Adjuvant; Decision-making; Decision tree; NSCLC; Radiotherapy

Publ.-Id: 33542

Untersuchung der Wechselwirkung von magnetotaktischen Bakterien mit Uran in wässrigen Systemen

Ramtke, J.

Im Rahmen der Forschungsarbeiten zur Wechselwirkung von magnetotaktischen Bakterien mit Uran am Beispiel des Mikroogranismus Magnetospirillum magneticum AMB-1 konnte gezeigt werden, dass dieser ein interessantes Potential aufweist, Uranyl in wässrigen Systemen zu sorbieren. Es stellte sich heraus, dass unter den gegebenen Bedingungen, zwischen 80 und 95 % der Ausgangskonzentrationen, im Bereich von 0,1 mM, innerhalb von 25 Stunden sorbiert werden konnte. Den Daten ist zu entnehmen, dass die prozentuale Sorptionskapazität durch die Biomassekonzentration beeinflusst werden kann, mit dem Ergebnis, dass mehr Biomasse zu einer höheren Sorption führt und der Sorptionsprozess somit schneller vonstatten geht. Die Variation der Urankonzentration zeigt, dass auch Konzentrationen <0,1 mM Uran zu einem beträchtlichen Teil sorbiert werden können, allerdings im Bereich von 0,01 mM eine eher geringere Sorption stattfindet. Mit Variation des pH-Wertes konnte gezeigt werden, in welchen Bereichen die Bakterien während des Sorptionsprozesses relativ vital bleiben (pH 4,5-6,5) und welche Bereiche zu einem vermehrten Absterben führen (pH 3,5 und 7,5). Hierbei ist zu erwähnen, dass das vermehrte Absterben der Bakterien scheinbar keinen negativen Einfluss auf die Uransorption hat. Die Lokalisierung des Urans mithilfe von Transmissionselektronenmikroskopie und energiedispersiver Röntgenspektroskopie zeigt, dass die Zellwand der gramnegativen Bakterien einen großen Teil des Urans sorbieren kann. Mithilfe der zeitaufgelösten Laser-induzierten Fluoreszenzspektroskopie in Kombination mit paralleler Faktoranalyse konnten insgesamt fünf U(VI)-Spezies an der Biomasse ausfindig gemacht werden, welche mit verschiedenen Liganden wechselwirken. Es war ebenfalls möglich, anhand der Daten zu zeigen, dass diese in Abhängigkeit von dem gewählten pH-Wert in den Stufen 3,5-7,5 variieren. Dies stellt ein interessantes Ergebnis dar, weil es verdeutlicht, dass der pH-Wert einen Einfluss auf die Verteilung des Urans in den Zellen haben kann und womöglich unterschiedliche Mechanismen für die Wechselwirkung mit dem Radionuklid verantwortlich sein können. Durch die Messung von ausgewählten Referenzproben, welche die U(VI)-Spezies genauer identifizieren sollten, war es möglich zu zeigen, dass drei der fünf Spezies eine Übereinstimmung mit Proben des Peptidoglycans aufweisen (Spezies 1, 2, 3). Somit konnte anhand der Ergebnisse gezeigt werden, dass es zu einer Bindung des U(VI) am Peptidoglycan des Bakteriums Magnetospirillum magneticum AMB-1 gekommen ist, was eine neuartige Erkenntnis darstellt. Des Weiteren deuten die Daten von weiteren gemessenen Referenzproben darauf hin, dass es zu keiner Bindung am Lipopolysaccharid oder Kohlenhydraten der o-spezifischen Seitenkette gekommen ist, da die erhaltenen U(VI)-Spektren dieser Referenzen keine Übereinstimmung mit den Biomasse assoziierten U(VI)-Spektren aufweisen.

Keywords: Magnetotactic bacteria; Uranium; Sorption; Spectroscopy; Microscopy

  • Bachelor thesis
    Hochschule Zittau/Görlitz, 2021
    Mentor: Dr. Evelyn Krawczyk-Bärsch, Prof. Dr. Thomas Wiegert
    82 Seiten

Publ.-Id: 33541

Classifying oscillatory brain activity associated with Indian Rasas using network metrics

Pandey, P.; Tripathi, R.; Prasad Miyapuram, K.

Neural oscillations are the rich source to understand cognition, perception, and emotions. Decades of research on brain oscillations have primarily discussed neural signatures for the western classification of emotions. Despite this, the Indian ancient treatise on emotions popularly known as Rasas has remained unexplored. In this study, we collected Electroencephalography (EEG) encodings while participants watched nine emotional movie clips corresponding to nine Rasas. The key objective of this study is to identify the brain waves that could
distinguish between Rasas. Therefore, we decompose the EEG signals into five primary frequency bands comprising delta (1-4 Hz), theta (4-7 Hz), alpha (8-13 Hz), beta (13-30 Hz), and gamma (30-45 Hz). We construct the functional networks from EEG time-series data and subsequently utilize the fourteen graph-theoretical measures to compute the features. Random Forest models are trained on the extracted features, and we present our findings based on classifier predictions. We observe slow (delta) and fast brain waves (beta and gamma)
exhibited the maximum discriminating features between Rasas, whereas alpha and theta bands showed fewer distinguishable pairs. Out of nine Rasas, Sringaram, Bibhatsam, and Bhayanakam displayed the most distinguishing characteristics from other Rasas. Interestingly, our results are consistent with the previous studies, which highlight the significant role of higher frequency oscillations for the classification of emotions. Our finding on the alpha band is consistent with the previous study, which reports the maximum similarity in brain networks across emotions in the alpha band. This research contributes to the pioneering work on Indian Rasas utilizing brain responses.

Keywords: EEG; Emotion; Classification; Natyashastra; Rasa Clips; Random Forest; wPLI; Graph Theory

Publ.-Id: 33539

Treatment verification with prompt-gamma imaging: Detection sensitivity of anatomical changes in HNC

Berthold, J.; Hübinger, L.; Piplack, N.; Pietsch, J.; Khamfongkhruea, C.; Thiele, J.; Appold, S.; Traneus, E.; Janssens, G.; Smeets, J.; Stützer, K.; Richter, C.

In this systematic study, we investigate the sensitivity of prompt-gamma imaging (PGI) towards the field-wise detection of inter-fractional anatomical changes in proton therapy (PT) of head and neck cancer (HNC) patients.

Spot-wise range shifts ∆RPGI were monitored with a PGI-slit-camera during 22 field deliveries of HNC pencil beam scanning (PBS) treatments of 4 patients (field-wise dose per fraction: 0.7-1.0GyE). In-room CTs were acquired for all monitored fractions and range shifts ∆RIDD at the 80% falloff of spot-wise integrated depth-dose (IDD) profiles served as input for an automatic field-wise ground truth classification (Fig.1). To receive results consistent with an additional manual dose-based classification per field, a PBS spot with relative weight to the field >0.1% was rated as relevant if |∆RIDD| was ≥5mm for that and at least 1 neighboring spot. Subsequently, a field was classified as relevantly changed if at least 1.5% of all spots were rated relevant.
For the independent PGI evaluation, spots were clustered based on Bragg-peak position and proton number to mitigate statistical measurement uncertainty. Clusters with |∆RPGI|≥5mm were classified as relevant. For training of the field-wise PGI classification model, the number of relevant clusters, that is necessary to classify the whole field as relevantly changed, was optimized with respect to the IDD ground truth classification using a training set of 11 fields. Finally, the classification model was validated on an independent test set (11 fields).

On the level of PGI spot clusters, there is a significant correlation (rPearson=0.3, p<0.01) between IDD and PGI range shifts over all 22 monitored fields (Fig.2B). The only moderate correlation is mainly due to statistical uncertainty of the clusters, represented by the mean absolute error between IDD and PGI range shifts of 3.4mm. The correlation might also be affected by difficult range shift determination due to spots traversing highly heterogeneous tissue.
Despite the moderate correlation on cluster level, a field-wise classification, the main endpoint in our study, is possible with high detection sensitivity. Resulting from the training, a field was classified as relevantly changed if >12% of PGI clusters are relevant. The final model achieved a sensitivity of 80% (4/5) and a specificity of 67% (4/6) on the test cohort (Fig.2C).

A first systematic investigation on the sensitivity of a PGI system to field-wise detect anatomical changes in clinical HNC PT treatments was performed using quantitative dose-based ground truth information from up-to-date control CTs. The capability of PGI to detect relevant anatomical changes with high sensitivity was demonstrated, which is essential for its clinical application, e.g. as treatment intervention system for online-adaptive PT. The now available evaluation workflow as well as the permanently growing PGI dataset from the ongoing clinical PGI study are a unique basis for follow-up studies.

  • Lecture (Conference)
    ESTRO 2022, 06.-10.05.2022, Kopenhagen, Dänemark

Publ.-Id: 33538

Synthesis of novel selective histone deacetylase inhibitors for the development of a suitable ¹⁸F-labelled radiotracer for the molecular imaging of HDAC1 in brain tumours

Clauß, O.; Toussaint, M.; Schäker-Hübner, L.; Wenzel, B.; Deuther-Conrad, W.; Dukic-Stefanovic, S.; Ludwig, F.-A.; Gündel, D.; Teodoro, R.; Kopka, K.; Brust, P.; Hansen, F. K.; Scheunemann, M.

Objectives: Epigenetic mechanisms like methylation and acetylation of histones regulate the gene expression on the chromatin level. Thus, the degree of acetylation of lysine residues on histones influences the accessibility of DNA and furthermore the gene expression. Histone deacetylases (HDACs) are overexpressed in various tumour diseases, resulting in the interest in HDAC inhibitors (HDACi) for cancer therapy. The aim of this work is the development of a novel ¹⁸F-labelled HDAC1-selective inhibitor with an ortho-aminoanilide zinc-binding group (ZBG) to visualize this enzyme in brain tumours by positron emission tomography (PET).
Methods: Based on the selective HDAC1-3 inhibitors tacedinaline and entinostat, a series of fluorine-containing derivatives was synthesized and the IC₅₀ values were determined by an in-house biochemical enzyme assay. Out of several ligands with high inhibitory potency and selectivity for HDAC1, N-(2-amino-5-(thiophen-3-yl)phenyl)-4-((2-fluoropropanamido)methyl)benzamide (BA3, Figure 1A) was selected for radiofluorination. The two-step one-pot radiosynthesis of [¹⁸F]BA3 was performed by a nucleophilic aliphatic substitution reaction of the protected 2-bromopropionyl precursor 2 and subsequent deprotection. The process was successfully transferred to a TRACERlab FX2 N radiosynthesizer (Figure 1B). For the characterization of BA3, the in vitro stability in mouse and human liver microsomes and the cell toxicity in glioblastoma cell lines (U251-MG, F98) were assessed. In parallel, the in vivo metabolism of [¹⁸F]BA3 was investigated (mouse plasma and brain samples, 30 min p.i.) as well as PET studies in mice were carried out.
Results: BA3, containing a PAMBA linker (para-aminomethylbenzoic acid), shows a high inhibitory activity against HDAC1 and high selectivity towards HDAC3 and HDAC6 (see Table 1). The cell viability of U251-MG and F98 cells after incubation with 50 µM BA3 for 72h was only 64% and 36%, respectively. The automated radiosynthesis of [¹⁸F]BA3 resulted in a radiochemical yield of 1%, a radiochemical purity of > 96% and a molar activity between 21 and 51 GBq/µmol (n = 5, EOS). The PET studies in mice showed a low [¹⁸F]BA3 accumulation in the brain, suggesting a low blood-brain barrier penetration (SUV₅ₘᵢₙ: 0.24). Furthermore, the amount of intact radiotracer in the brain and plasma at 30 min p.i. was only 25% and 7%, respectively.
Conclusion: Due to the low blood-brain barrier penetration and the high amount of brain-penetrable radiometabolites, [¹⁸F]BA3 is classified as unsuitable for further PET-related investigations. The obtained results will be used in the design of metabolically more stable HDAC inhibitors.
Reference: [1] Krieger et al., J. Med. Chem. 2019, 62(24), 11260-11279.

Keywords: histone deacetylase 1; positron emission tomography; radiochemistry

  • Open Access Logo Poster
    ISRS 2022, 29.05.-02.06.2022, Nantes, Frankreich


Publ.-Id: 33536

Light-driven permanent transition from insulator to conductor

Rana, D.; Agarwal, S.; Islam, M.; Banerjee, A.; Uberuaga, B. P.; Saadatkia, P.; Dulal, P.; Adhikari, N.; Butterling, M.; Liedke, M. O.; Wagner, A.; Selim, F. A.

The transition from insulator to conductor can be realized in some materials but requires modification of both the arrangement of atoms and their electronic configurations. This is often achieved by doping. Here we reveal a different mechanism the lattice may adopt to induce such a transition. Experiments showed the surprising finding that limited exposure to sub-bandgap light caused a permanent transition from an insulator state to a conductor state in the insulating oxide Ga2O3, with 9-orders of magnitude increase in electronic conduction. Furthermore, annealing up to 400 C did not suppress or decrease the induced conductivity. Photoexcitation by light-induced modification in the charge state of defects and subsequent lattice distortion around them was suggested to be the underlying mechanism behind this transition. Density functional theory calculations confirmed that modifying the charge state of defects leads to redistribution of the localized electrons and massive structural distortion in the surrounding lattice, causing large shifts in the density of states and introducing new states with shallower energy levels. Both experimental and theoretical results revealed the introduction of new stable shallow energy levels, explaining the mechanism behind the transition from an insulator to a conductor state by light. We suggest that this mechanism may occur in other wide bandgap metal oxides leading to drastic modification in their electronic properties.

Keywords: Ga2O3; insulator; conductor; doping; light illumination; band-gap

Related publications

Publ.-Id: 33535

On the electrodeposition of conically nano-structured Nickel layers assisted by a capping agent

Skibińska, K.; Huang, M.; Mutschke, G.; Eckert, K.; Włoch, G.; Wojnicki, M.; Żabiński, P.

Capping agents are frequently used in electrodeposition to support spatially inhomogeneous mass transfer at small scales. As such, chloride ions are known to support the deposition of conically nanostructured nickel layers. This work presents a systematic experimental study of the impact of a capping agent on the electrochemical growth of conically-shaped nickel deposits. Furthermore, a modeling approach on the scale of cones for numerical simulations of electrodeposition with capping agents is provided for the first time to give deeper insight on how the capping agent influences the local growth of the deposit. The growth rates of the nano-cones obtained numerically are compared with experimental data, and a good agreement is found. The impact of the capping agent concentration, the deposition time, the electrolyte temperature and the current density are investigated systematically, and optimum conditions for conical growth are derived.

Keywords: Electrodeposition; Nanostructured surface; Ni deposition; Capping agent; Ammonium chloride; Numerical modeling

Publ.-Id: 33534

A critical review of the solution chemistry, solubility, and thermodynamics of europium: recent advances on the Eu3+ aqua ion and the Eu(III) aqueous complexes and solid phases with the sulphate, chloride, and phosphate inorganic ligands

Jordan, N.; Thoenen, T.; Starke, S.; Spahiu, K.; Brendler, V.

This review provides a critical assessment of the published thermodynamic data of the Eu(III) aqua ion as well as complexation constants and solubility products of Eu(III) with the SO42−, Cl−, and PO43− inorganic ligands in aqueous solution. The main source for the selection of thermodynamic data are original experimental data published in peer-reviewed papers from around 1900 until the end of 2020. This review strictly follows, with a few minor deviations, the methodology recommended by the Thermochemistry Database group of the Nuclear Energy Agency, which relies on the Specific ion Interaction Theory (SIT) for describing activity coefficients in aqueous electrolyte solutions. For each inorganic ligand, a discussion is provided on the selected as well as the rejected literature data, and the procedures leading to the derivation of recommended thermodynamic data at infinite dilution, such as solubility products and complexation constants, enthalpies and entropies of reaction, molar entropies, heat capacities, as well as ion interaction coefficients ε, are described in detail. These recommended data will contribute to the establishment of a comprehensive, internally consistent, and quality-assured thermodynamic reference database for the chemical, geochemical and chemotechnical modeling of europium and increase the robustness of applications of chemical analogies for trivalent actinides or linear free energy relationships within the lanthanide group.

Keywords: Europium(III); sulphate; chloride; phosphate; complexation; solubility; SIT; thermodynamic database

Publ.-Id: 33533

Cation exchange on colloidal copper selenide nanosheets: a route to two-dimensional metal selenide nanomaterials

Shamraienko, V.; Spittel, D.; Hübner, R.; Khoshkhoo, M. S.; Weiß, N.; Georgi, M.; Borchert, K. B. L.; Schwarz, D.; Lesnyak, V.; Eychmüller, A.

We report a synthesis route to two-dimensional PbSe, HgSe, ZnSe, SnSe, and Cu-Zn-Sn-Se (CZTSe) nanomaterials based on cation exchange (CE) reactions. This approach includes two steps: it starts with the synthesis of hexagonal, up to several micrometers large yet approx. 5 nm-thick CuSe nanosheets (NSs), followed by CE of the host copper ions with the desired guest cation (Pb2+, Hg2+, Zn2+, or Sn4+). In the case of CZTSe, both guest cations can be added simultaneously since the variation of the guest cation ratio and reaction time can lead to various compositions. Mild reaction conditions allow for a preservation of the size and the 2D shape of the parent NSs accompanied by corresponding changes in their crystal structure. We furthermore demonstrate that the crystal structure of CuSe NSs can be rearranged even without addition of guest cations in the presence of tri-n-octylphosphine. Thus, the obtained NSs were further subjected to ligand exchange reactions in order to replace insulating bulky organic molecules on their surface with compact iodide and sulfide ions, a step crucial for the application of nanomaterials in (opto)electronic devices. The resulting NS dispersions were processed into thin films by spray-coating onto commercially available interdigitated platinum electrodes. Light response measurements of PbSe and CZTSe NS-films demonstrated their potential for applications as light-sensitive materials in photodetection or photovoltaics.

Related publications

Publ.-Id: 33532

Mineralogical Mapping with Accurately Corrected Shortwave Infrared Hyperspectral Data Acquired Obliquely from UAVs

Thiele, S. T.; Bnoulkacem, Z.; Lorenz, S.; Bordenave, A.; Menegoni, N.; Madriz Diaz, Y. C.; Dujoncquoy, E.; Gloaguen, R.; Kenter, J.

While uncrewed aerial vehicles are routinely used as platforms for hyperspectral sensors, ap-plications are mostly confined to nadir imaging orientations. Oblique hyperspectral imaging has been impeded by the absence of robust registration and correction protocols, which are essential to extract accurate information. These corrections are especially important for detecting the gen-erally small spectral features produced by minerals, and for infrared data acquired using pushbroom sensors. The complex movements of unstable platforms (such as UAVs) require rigor-ous geometric and radiometric corrections, especially in the rugged terrain often encountered for geological applications. In this contribution we propose a novel correction methodology, and as-sociated toolbox, dedicated to the accurate production of hyperspectral data acquired by UAVs, without any restriction concerning view angles or target geometry. We make these codes freely available to the community, and thus hope to trigger an increasing usage of hyperspectral data in Earth sciences, and demonstrate them with the production of, to our knowledge, the first fully corrected oblique SWIR drone-survey. This covers a vertical cliff in the Dolomites (Italy), and al-lowed us to distinguish distinct calcitic and dolomitic carbonate units, map the qualitative abun-dance of clay/mica minerals, and thus characterise seismic scale facies architecture.

Keywords: infrared; hyperspectral; uncrewed aerial vehicle; calcite; dolomite

Publ.-Id: 33531

GSTools v1.3: A toolbox for geostatistical modelling in Python

Müller, S.; Schüler, L.; Zech, A.; Heße, F.

Geostatistics as a subfield of statistics accounts for the spatial correlations encountered in many applications of e.g. Earth Sciences. Valuable information can be extracted from these correlations, also helping to address the often encountered burden of data scarcity. Despite the value of additional data, the use of geostatistics still falls short of its potential. This problem is often connected to the lack of user-friendly software hampering the use and application of geostatistics. We therefore present GSTools, a Python-based software suite for solving a wide range of geostatistical problems. We chose Python due to its unique balance between usability, flexibility, and efficiency and due to its adoption in the scientific community. GSTools provides methods for generating random fields, it can perform kriging and variogram estimation and much more. We demonstrate its abilities by virtue of a series of example application detailing their use.

Publ.-Id: 33530

Measurement of the photon strength function in ¹¹⁵In at the gELBE facility

Makinaga, A.; Schwengner, R.; Beyer, R.; Grieger, M.; Hammer, S.; Hensel, T.; Junghans, A.; Ludwig, F.; Trinh, T. T.; Turkat, S.

The photon strength function (PSF) in 115In is an important parameter for the estimate of the neutron capture cross section on 114In in the field of astrophysics and nuclear engineering. Until now, the so-called PSF method for 115In was applied only above the neutron-separation energy (Sn), and the evaluated 114In (n,g) cross section has uncertainties caused by the lack of the PSF below Sn. We studied the dipole strength distribution of 115In with a photon-scattering experiment using bremsstrahlung produced by an electron beam of an energy of 10.3 MeV at the linear accelerator ELBE at HZDR.

Keywords: ELBE; gELBE; NRF; photon-scattering; bremsstrahlung; 115In

Related publications

  • Open Access Logo Contribution to proceedings
    2019 Symposium on Nuclear Data, 28.-30.11.2019, Fukuoka, Japan
    Proceedings of the 2019 Symposium on Nuclear Data, 101-105
    DOI: 10.11484/jaea-conf-2020-001

Publ.-Id: 33529

Dose Rate Measurements in Pulsed Radiation Fields by Means of an Organic Scintillator

Werner, T.; Beyer, R.; Biedermann, R.; Gerber, M.; Götze, J.; Herzig, P.; Melzer, V.; Metzner, E.; Weinberger, D.; Kormoll, T.

A deficiency in the implementation of current radiation protection is the determination of the ambient dose equivalent H*(10) and the directional dose equivalent H ́(0.07) in pulsed radiation fields. Conventional dosimeter systems are not suitable for measurements in photon fields comprising short radiation pulses, which consequently leads to high detector loads in short time periods. Nevertheless, due to the implementation of advanced medical accelerators for cancer therapy, new medical diagnostic devices as well as various laser machining systems, there is an urgent need for suitable dosimeter systems for real time dosimetry. In this paper, a detector concept based on an organic scintillator and a full digital data analysis with the aim of developing a portable, battery powered measurement system is presented.

Keywords: ELBE; gELBE; radiation protection; dose rate measurements; pulsed radiation fields; organic scintillation detector

Related publications

Publ.-Id: 33528

Active Dosimetry with the Ability to Distinguish Pulsed and Non-Pulsed Dose Rate Contributions

Makarevich, K.; Beyer, R.; Henniger, J.; Ma, Y.; Polter, S.; Sommer, M.; Teichmann, T.; Weinberger, D.; Kormoll, T.

This paper presents the concept of an active dosimetry system and its operational regime for pulsed radiation dose rate measurements. The plastic scintillator is suggested to be used for absorbed dose rate measurements. As long as the detector can be considered tissue equivalent, the energy weighting of pile-up events in terms of the dose is achieved. The real-time distinction of pulsed and non-pulsed dose rate contributions is based on the time structure of a single interaction and requires only basic information about the beam time structure (pulses duration and period). The detector connected to a fully digital signal processing board creates an active dosimetry system with adjustable parameters. Such a system was used for absorbed dose rate measurements in pulsed photon field mimicking radiation field outside the bunker of a medical LINAC, but also in the presence of a constant radiation component. The results show a linear dependence of a pulsed radiation contribution on the accelerator current in the investigated range of the total dose rate up to 8 μGy/h.

Keywords: ELBE; gELBE; Dosimetry; pulsed radiation fields

Related publications

Publ.-Id: 33527

Organotin derivatives as versatile precursors for the radioiodination and radiofluorination of 1,2,3,4-tetrahydro-7-hydroxyisoquinoline-3-carboxylic acid (TIC(OH)) analogues

Maisonial-Besset, A.; Noelia Chao, M.; Debiton, E.; Canitrot, D.; Witkowski, T.; Degoul, F.; Tarrit, S.; Wenzel, B.; Miot-Noirault, E.; Serre, A.; Chezal, J.-M.

Objective: Organotin compounds are well known as efficient precursors for reliable radioiodination of aromatic derivatives, with high molar activities, via electrophilic aromatic substitution reaction. They can be easily prepared from corresponding halogenated derivatives using metalation or palladium-catalyzed reactions. In the last years, organotin derivatives, together with boronic acid or ester precursors, were also successfully applied to the direct radiolabelling of electron-rich aromatic structures from [18F]F- via Cu-mediated radiofluorination. As evidenced with the progresses reported for the radiosynthesis of the [18F]FDOPA for example, these major developments in the fluorine-18 radiochemistry field created new opportunities to produce radiofluorinated arenes that could not be routinely accessed even a few years ago. Surprisingly, the [123I]8-iodo-L-TIC(OH), a promising radiotracer for SPECT imaging of prostatic tumours, did not benefit from these methodological advances and no corresponding radiofluorinated derivatives, which could allow the use of the TIC(OH) scaffold to PET imaging, were reported so far.

Methods: A convergent synthetic route was developed to produce radioiodinated [125I]iodo-L-TIC(OH), and radiofluorinated [18F]fluoro-L-TIC(OH) tracers from common organotin intermediates, synthesized from iodinated analogues via palladium catalyzed I/SnMe3 exchange. The [125I]iodo-L-TIC(OH) radiotracers were obtained by electrophilic radioiododestannylation with [125I]I+, while the radiofluorinated analogues [18F]fluoro-L-TIC(OH) were produced from the organotin precursors by a copper-mediated aromatic radiofluorination using nucleophilic [18F]F-. For control of the purity, molar activity and enantiomeric excess, corresponding non-radiolabelled iodinated and fluorinated derivatives from the L and D series were synthesized.

Results: Organotin compounds were radiolabelled using no-carrier-added [125I]NaI in the presence of Chloramine-T as mild oxidative agent at room temperature for 5 min with excellent labelling efficiencies (> 95%). After a two-step deprotection sequence and semipreparative RP-HPLC purification, [125I]iodo-L-TIC(OH) compounds were isolated with good radiochemical yields (RCY = 51-78%), high radiochemical purities (RCP, > 98%), molar activities (MA > 1.5 GBq/µmol) and enantiomeric excess (e.e. > 99%). [18F]fluoro-L-TIC(OH) derivatives were obtained by radiofluorination of organotin compounds in presence of tetrakis(pyridine)copper(II) triflate and nucleophilic [18F]F- at 110 °C for 10 min with high labelling efficiencies (54-92%). After purification by C18 solid phase extraction, deprotection under acidic conditions and semipreparative RP-HPLC purification, [18F]fluoro-L-TIC(OH) radiotracers were produced with good RCY (23-37% d.c.), high RCP (> 99%), MA (20-107 GBq/µmol) and e.e. (> 99%).

Conclusion: A short and efficient synthetic pathway was developed to easily produce [125I]iodo-L-TIC(OH) and [18F]fluoro-L-TIC(OH) analogues from common organotin intermediates. Such radiofluorination process could be easily implemented on radiopharmacy automatic synthesis modules and could pave the way to the development of novel radiopharmaceuticals containing the TIC(OH) core.

Acknowledgments : This work was partially funded by the Cancéropôle Lyon Auvergne Rhône Alpes (CLARA), the Auvergne Rhône Alpes Region, the ARTP (Association pour la Recherche sur les Tumeurs de la Prostate), and the Fondation de la Maison de la Chimie.

  • Lecture (Conference)
    International Symposium of Radiopharmaceutical Sciences, 2022, 29.05.-02.06.2022, Nantes, Frankreich

Publ.-Id: 33526

From helical to standard magnetorotational instability: predictions for upcoming liquid sodium experiments

Mishra, A.; Mamatsashvili, G.; Stefani, F.

We conduct a linear analysis of axisymmetric magnetorotational instability (MRI) in a magnetized
cylindrical Taylor-Couette (TC) flow for its standard version (SMRI) with a purely axial background
magnetic field and two further types – helically modified SMRI (H-SMRI) and helical MRI (HMRI)
– in the presence of combined axial and azimuthal magnetic fields. This study is intended as
preparatory for upcoming large-scale liquid sodium MRI experiments planned within the DRESDYN
project at Helmholtz-Zentrum Dresden-Rossendorf, so we explore these instability types for typical
values of the main parameters: the magnetic Reynolds number, the Lundquist number and the ratio
of the angular velocities of the cylinders, which are attainable in these experiments. In contrast to
previous attempts of detecting MRI in the lab, our results demonstrate that SMRI and its helically
modified version can in principle be detectable in the DRESDYN-TC device for the range of the
above parameters, including the astrophysically most important Keplerian rotation, despite the
extremely small magnetic Prandtl number of liquid sodium. Since in the experiments we plan to
approach (H-)SMRI from the previously studied HMRI regime, we characterise the continuous and
monotonous transition between the both regimes. We show that H-SMRI, like HMRI, represents
an overstability (travelling wave) with non-zero frequency linearly increasing with azimuthal field.
Because of its relevance to finite size flow systems in experiments, we also analyse the absolute form
of H-SMRI and compare its growth rate and onset criterion with the convective one.


Publ.-Id: 33525

Using a digital phantom for quality control of ExploreASL image processing

Stritt, M.; Padrela, B.; Dijsselhof, M.; Oliver-Taylor, A.; Barkhof, F.; Golay, X.; Gunther, M.; Gregori, J.; Mutsaerts, H. J.; Petr, J.

In recent years, there has been an increasing focus on
open-science and reproducible research, including reliable and robust
software. To this end, methods of requirements engineering and
quality control were integrated in the ExploreASL pipeline and
development workflow. Here, we used the recently developed digital
reference object (DRO) ’’ASL-DRO‘‘ to evaluate the reliability of
ExploreASL with a main focus on motion correction [1, 2].

  • Contribution to proceedings
    European Society for Magnetic Resonance in Medicine and Biology, 07.10.2021, Virtual, Virtual
  • Poster
    European Society for Magnetic Resonance in Medicine and Biology, 07.10.2021, Virtual, Virtual

Publ.-Id: 33524

Quantification of background suppressed arterial spin labeling images without an M0 image

Prysiazhniuk, Y.; Dijsselhof, M.; van de Ven, K. C. C.; Baas, K. P. A.; Oliver-Taylor, A.; Thomas, D. L.; Mutsaerts, H. J.; Petr, J.

Arterial spin labeling (ASL) is a non-invasive perfusion MRI scan technique used in pathologies such as Alzheimer’’s
disease, cerebrovascular disease, and brain tumors [3]. To obtain
absolute quantification of cerebral blood flow (CBF) in mL/100 g/
min, the blood equilibrium magnetization (M0b) is required [1]. For
that, M0-scan acquisition is recommended [1]; however, in practice,
clinical studies often lack an M0-scan. A control image can be used as
an alternative only when background suppression (BSup) is not used.
Here, we investigate the possibility to reconstruct an M0 scan from a
control image with BS and compare it with acquired M0 scans from
the same patients.

  • Contribution to proceedings
    European Society for Magnetic Resonance in Medicine and Biology, 07.10.2021, Virtual, Virtual
  • Poster
    European Society for Magnetic Resonance in Medicine and Biology, 07.10.2021, Virtual, Virtual

Publ.-Id: 33523

An ExploreASL toolbox for DICOM to BIDS conversion

Stritt, M.; Padrela, B.; Dijsselhof, M.; Clement, P.; Oliver-Taylor, A.; Barkhof, F.; Golay, X.; Gunther, M.; Gregori, J.; Petr, J.; Mutsaerts, H. J.

Most data scientists spend about 45% of their time on
tasks like data loading and cleansing [1]. This is especially problematic in ASL-MRI, which is available in a variety of acquisition
flavors, export forms, and differs between vendors and laboratories.
ASL-BIDS [2] has recently addressed this issue by defining a standardized data structure. Current DICOM to BIDS conversion tools are
still working on a complete support of ASL-BIDS [3]. Here, we
introduce a tool within ExploreASL [4], that converts DICOMs to
ASL-BIDS using DCMTK [5] and dcm2niiX [6].

  • Contribution to proceedings
    European Society for Magnetic Resonance in Medicine and Biology, 07.10.2021, Virtual, Virtual
  • Poster
    European Society for Magnetic Resonance in Medicine and Biology, 07.10.2021, Virtual, Virtual

Publ.-Id: 33522

Assessment of cerebral perfusion symmetry in retired Canadian Football League players

Danielli, E.; Padrela, B.; Doughty, M.; Petr, J.; Mutsaerts, H. J.; Noseworthy, M. D.

High contact sports such as American football can
result in athletes sustaining concussions and countless sub-concussive
blows, leading to cumulative neurological damage [1]. This study
aimed to use cerebral blood flow (CBF) measured with ASL and a
Z-scoring approach to quantify focal brain damage and left/right
symmetry in retired Canadian Football League (rCFL) players. It was
hypothesized that subjects would have asymmetric CBF and regional
hypoperfusion due to their history of repetitive head trauma.

  • Contribution to proceedings
    European Society for Magnetic Resonance in Medicine and Biology, 07.10.2021, Virtual, Virtual
  • Poster
    European Society for Magnetic Resonance in Medicine and Biology, 07.10.2021, Virtual, Virtual

Publ.-Id: 33521

ExploreASL GUI: processing large arterial spin labeling datasets without programming skills

Pasternak, M.; Keil, V.; Clement, P.; Pinter, N.; Dijsselhof, M.; Stritt, M.; Petr, J.; Mutsaerts, H. J.

While several arterial spin labelling (ASL) processing
pipelines are freely available, programming skills are usually needed
to efficiently process large datasets (1), deterring clinicians from analyzing ASL data. Leaving data unanalysed reduces the speed of
progress in medical research and this unavailability keeps research
restricted to a select few specialized academic institutions. These
hurdles are addressed by ExploreASL, an ASL processing pipeline
that analyzes ASL data on an individual and population level, and is
free for non-commercial purposes (2). To enable its use for
researchers without any coding knowledge, a graphical user interface
(GUI) was developed in collaboration with clinical radiologists to
specifically address their needs (3).

  • Contribution to proceedings
    European Society for Magnetic Resonance in Medicine and Biology, 07.10.2021, Virtual, Virtual
  • Lecture (Conference)
    European Society for Magnetic Resonance in Medicine and Biology, 07.10.2021, Virtual, Virtual

Publ.-Id: 33520

Using ASL perfusion images for spatial normalization in a pediatric population with craniosynostosis

de Planque, C.; Mutsaerts, H.; Keil, V.; Erler, N.; Dremmen, M.; Mathijssen, I.; Petr, J.

Spatial normalization is an important step for image processing and quantification of regional brain perfusion values using arterial spin labeling (ASL) MRI and is typically performed via high-resolution structural scans. Structural segmentation and/or registration is complicated when gray-white matter T1w contrast is low and changing in early phases of myelination in newborns. Craniosynostosis is a condition where the decision for surgical treatment in the first years of life is supported by brain imaging. In this study, we investigate if ASL CBF image contrast can be directly used for spatial normalization, in both healthy controls and a non-syndromic type of craniosynostosis.

  • Contribution to proceedings
    ISMRM '21: Proceedings of the ISMRM 29th Annual Meeting & Exhibition, 15.05.2021, Virtual, Virtual
  • Poster
    ISMRM '21: Proceedings of the ISMRM 29th Annual Meeting & Exhibition, 15.05.2021, Virtual, Virtual

Publ.-Id: 33519

The Open Source Initiative for Perfusion Imaging (OSIPI): ASL Pipeline inventory

Dolui, S.; Fan, H.; Croal, P.; Buchanan, C.; Hirschler, L.; Anazodo, U.; Thomas, D.; Mutsaerts, H.; Petr, J.

As a part of the Open Source Initiative for Perfusion Imaging (OSIPI), we have created an inventory of software for automated processing of Arterial Spin Labeling (ASL) perfusion MRI data. We contacted the ASL community through different channels, inviting software developers to list their pipelines by completing a questionnaire covering different aspects and features of a desired pipeline. We received inputs from 18 developers and have summarized the main characteristics of their pipelines based on the information they provided. We expect that this inventory will facilitate ASL-related research, reduce duplicate development, and enable translation of ASL to clinical practice.

  • Contribution to proceedings
    ISMRM '21: Proceedings of the ISMRM 29th Annual Meeting & Exhibition, 15.05.2021, Virtual, Virtual
  • Poster
    ISMRM '21: Proceedings of the ISMRM 29th Annual Meeting & Exhibition, 15.05.2021, Virtual, Virtual

Publ.-Id: 33518

The Open Source Initiative for Perfusion Imaging (OSIPI) ASL MRI Challenge

Anazodo, U.; Pinto, J.; Kennedy McConnell, F.; Dounavi, M.-E.; Gould Van Praag, C.; Mutsaerts, H.; Oliver-Taylor, A.; Paschoal, A.; Petr, J.; Pineda-Ordóñez, D.; Woods, J.; Zhao, M.; Croal, P.

The OSIPI ASL MRI Challenge is a community-led initiative aiming to establish the range of approaches used for ASL image analysis and cerebral blood flow (CBF) quantification. Challenge data will consist of population-based and synthetic pseudo-continuous ASL images, with participants analysing the data and submitting resulting CBF maps and mean tissue CBF, along with documentation. Entries will be scored on accuracy, reproducibility and documentation quality. Through documenting the analysis choices made within the community, we will begin to better understand sources of variability, ultimately identifying an optimum pipeline, and moving towards the much-needed consensus of ASL image processing standards.

  • Contribution to proceedings
    ISMRM '21: Proceedings of the ISMRM 29th Annual Meeting & Exhibition, 15.-20.05.2021, Virtual, Virtual
  • Poster
    ISMRM '21: Proceedings of the ISMRM 29th Annual Meeting & Exhibition, 15.-20.05.2021, Virtual, Virtual

Publ.-Id: 33517

The Open Source Initiative for Perfusion Imaging (OSIPI)

Bell, L.; Mutsaerts, H.; Fedorov, A.; Ahmed, Z.; Clement, P.; Levy, S.; Zollner, F.; Petr, J.; Dolui, S.; Schmainda, K.; Prah, M.; Schabel, M.; Madhuranthakam, A.; Zhao, L.; Thrippleton, M.; van Houdt, P.; Holmes, J.; Quarles, C.; Cron, G.; Thomas, D.; Suzuki, Y.; Kompan, I.; Buckley, D.; Croal, P.; Anazodo, U.; Fathi Kazerooni, A.; Saligheh Rad, H.; Debus, C.; Sourbron, S.

Open Source Initiative for Perfusion Imaging (OSIPI) was founded by the ISMRM Perfusion Study Group as a community-driven initiative. Supported by six distinct aims, its mission is “to promote the sharing of perfusion imaging open-source software in order to eliminate the practice of duplicate development, improve the reproducibility of perfusion imaging research, and speed up the translation into tools for discovery science, drug development, and clinical practice”. OSIPI seeks to provide centralized resources to deliver reproducible perfusion research. In addition, it provides a platform for exchange where new and more advanced methods may be validated for perfusion accuracy.

  • Contribution to proceedings
    ISMRM '21: Proceedings of the ISMRM 29th Annual Meeting & Exhibition, 15.-20.05.2021, Virtual, Virtual
  • Poster
    ISMRM '21: Proceedings of the ISMRM 29th Annual Meeting & Exhibition, 15.-20.05.2021, Virtual, Virtual

Publ.-Id: 33516

Neuroimaging Pre-Processing and Quality Control for The European Prevention of Alzheimer's Dementia (EPAD) Cohort Study

Lorenzini, L.; Ingala, S.; Wink, A. M.; Kuijer, J.; Wottschel, V.; Sudre, C.; Haller, S.; Molinuevo, J. L.; Gispert, J. D.; Cash, D.; Thomas, D.; Vos, S.; Prados Carrasco, F.; Petr, J.; Wolz, R.; Palombit, A.; Schwarz, A.; Chételat, G.; Payoux, P.; Di Perri, C.; Pernet, C.; Giovanni, F.; Fox, N.; Ritchie, C.; Wardlaw, J.; Waldman, A.; Barkhof, F.; Mutsaerts, H.

The neuroimaging community strives to obtain large data cohorts, usually through association within consortia spanning different sites and countries. This results in increased variability of acquisition parameters and scan quality, which can affect image processing and statistical analyses. We propose a semi-automatic data management pipeline to process raw data, assess quality and compute image-derived phenotypes from multi-modal MRI scans, as developed for the multi-centre European Prevention of Alzheimer Dementia longitudinal cohort study (EPAD LCS).

  • Contribution to proceedings
    ISMRM '21: Proceedings of the ISMRM 29th Annual Meeting & Exhibition, 15.-20.05.2021, Virtual, Virtual
  • Poster
    ISMRM '21: Proceedings of the ISMRM 29th Annual Meeting & Exhibition, 15.-20.05.2021, Virtual, Virtual

Publ.-Id: 33515

Generating virtual brains for MRI-based 3D cerebral blood flow simulations

Józsa, T.; Petr, J.; Wink, A. M.; Barkhof, F.; Mutsaerts, H.; Payne, S.

Human brain perfusion simulations have been limited to less than five patient-specific cases. We propose a pipeline based on MRI to overcome this limitation. Computational geometry is adjusted using T1-weighted MRI, and the perfusion model parameters are tuned based on arterial spin labeling perfusion MRI. A cohort of 75 patients is used to demonstrate that the pipeline is suitable to generate virtual patients with statistically accurate and precise cerebral blood flow maps. Our findings encourage future studies on in silico clinical trials using similar virtual cohorts to improve ischaemic stroke interventions.

  • Contribution to proceedings
    ISMRM '21: Proceedings of the ISMRM 29th Annual Meeting & Exhibition, 15.-20.05.2021, Virtual, Virtual
  • Poster
    ISMRM '21: Proceedings of the ISMRM 29th Annual Meeting & Exhibition, 15.-20.05.2021, Virtual, Virtual

Publ.-Id: 33514

ASLDRO: Digital reference object software for Arterial Spin Labelling

Oliver-Taylor, A.; Hampshire, T.; Smith, N.; Stritt, M.; Petr, J.; Gregori, J.; Günther, M.; Mutsaerts, H.; Golay, X.

ASLDRO is digital reference object software for Arterial Spin Labelling. Here we present the development and demonstration of the DRO software, and its use in a sensitivity and uncertainty analysis of the single-subtraction equation for ASL perfusion quantification.The DRO software was written in python, and can generate synthetic ASL control, label and M0 data in ASL BIDS format. Pulsed and continuous labelling are supported, and patient motion and instrument noise are accurately simulated. It can be used both for testing and validation of image processing software, and for investigating ASL quantification models.

  • Contribution to proceedings
    ISMRM '21: Proceedings of the ISMRM 29th Annual Meeting & Exhibition, 15.-20.05.2021, Virtual, Virtual
  • Poster
    ISMRM '21: Proceedings of the ISMRM 29th Annual Meeting & Exhibition, 15.-20.05.2021, Virtual, Virtual

Publ.-Id: 33513

Advanced image processing outside the academia: The integration of ExploreASL into the workflow of an outpatient imaging center

Pinter, N.; Ganji, S.; Petr, J.; Ajtai, B.; Friel, H.; Fritz, J.; Mechtler, L.; Fischer, A.; Barkhof, F.; Mutsaerts, H.

While neurological imaging is mostly done in non-academic centers, the lack of academic resources, special image processing skillset and the fast paced
workflow prevent radiologists in these data-rich environments from engaging in high quality clinical research that utilizes quantitative imaging. Clinical
adoption of Arterial Spin Labeling could benefit from providing easy-to-use, PACS connected image processing solutions that do not require
neuroscience background and provide truly quantified Cerebral Blood Flow values in any outpatient center or public hospital. Our goal is to create such
a solution and bridge the gap between academic research and real world practice.

  • Contribution to proceedings
    ISMRM '21: Proceedings of the ISMRM 29th Annual Meeting & Exhibition, 15.-20.05.2021, Virtual, Virtual
  • Poster
    ISMRM '21: Proceedings of the ISMRM 29th Annual Meeting & Exhibition, 15.-20.05.2021, Virtual, Virtual

Publ.-Id: 33512

Die Rolle des TRPC6 Kanals im Rahmen der akuten Nierenschädigung

Zheng, Z.; Tsvetkov, D.; Bartolomaeus, T. U. P.; Erdogan, C.; Krügel, U.; Schleifenbaum, J.; Schaefer, M.; Nürnberg, B.; Chai, X.; Ludwig, F.-A.; N’Diaye, G.; Köhler, M.-B.; Wu, K.; Gollasch, M.; Marko, L.

Aims: Transient receptor potential (TRP) channels are non-selective cation channels that promote influx of Ca2+, Mg2+ and monovalent cations into cells. TRP channel subfamily C, member 6 (TRPC6) is widely expressed - next to several other tissues - in the kidney, and gene variations were linked to fibrosing renal disease. Here we aimed to investigate the putative role of TRPC6 channels in acute kidney injury (AKI). Since ischemia/reperfusion injury is known relate to Ca2+ overload, we hypothesized that inhibition of TRPC6 ameliorates AKI.
Methods: We used Trpc6-/- mice and SH045, a pharmacological inhibitor of TRPC6, to evaluate short-term AKI outcomes. Ischemia was induced after right–sided nephrectomy by clipping the renal pedicle of the left kidney for 20 or 17.5 minutes. SH045 was used for intravenous injection (2 mg/kg) 30 minutes before I/R surgery in the pharmacological studies with WT mice.
Results: Here, we demonstrate that neither Trpc6 deficiency nor pharmacological inhibition of TRPC6 influence the short-term outcomes of AKI. Blood markers (Creatinine in WT [131.4±33.3 µmol/l] vs Trpc6-/- [159.6±41.7 µmol/l] mice after 24 hours of reperfusion and in the pharmacological study: 17.5 min-I/R vehicle [199.5±21.8 µmol/l] versus 17.5 min-I/R SH045 [172.6±31.6 µmol/l], and 20 min-I/R vehicle [212.2±8.4 µmol/l] versus 20 min-I/R SH045 [226.2±28.6 µmol/l], all comparisons are n.s.), renal expression of epithelial damage markers, tubular injury and renal inflammatory response assessed by histological analysis were similar in wild-type mice compared to Trpc6-/- mice as well as in vehicle-treated versus SH045-treated mice. In addition, our results also found no effect of TRPC6 modulation on renal myogenic tone by using SH045 to perfuse isolated kidneys.
Conclusion: Therefore, we conclude that TRPC6 does not play role on the acute phase of AKI. Further studies should focus if TRPC6 inhibition could be protective in terms of long-term outcome of an AKI.

  • Poster
    Kongress für Nephrologie 2021, 23.-26.09.2021, Rostock, Deutschland

Publ.-Id: 33510

Rapid Detection of SARS-CoV-2 Antigens and Antibodies Using OFET Biosensors Based on a Soft and Stretchable Semiconducting Polymer

Ditte, K.; Nguyen Le, T. A.; Ditzer, O.; Isabel Sandoval Bojorquez, D.; Chae, S.; Bachmann, M.; Baraban, L.; Lissel, F.

In the midst of the COVID-19 pandemic, adaptive solutions are needed to allow us to make fast decisions and take effective sanitation measures, e.g., the fast screening of large groups (employees, passengers, pupils, etc.). Although being reliable, most of the existing SARS-CoV-2 detection methods cannot be integrated into garments to be used on demand. Here, we report an organic field-effect transistor (OFET)-based biosensing device detecting of both SARS-CoV-2 antigens and anti-SARS-CoV-2 antibodies in less than 20 min. The biosensor was produced by functionalizing an intrinsically stretchable and semiconducting triblock copolymer (TBC) film either with the anti-S1 protein antibodies (S1 Abs) or receptor-binding domain (RBD) of the S1 protein, targeting CoV-2-specific RBDs and anti-S1 Abs, respectively. The obtained sensing platform is easy to realize due to the straightforward fabrication of the TBC film and the utilization of the reliable physical adsorption technique for the molecular immobilization. The device demonstrates a high sensitivity of about 19%/dec and a limit of detection (LOD) of 0.36 fg/mL for anti-SARS-Cov-2 antibodies and, at the same time, a sensitivity of 32%/dec and a LOD of 76.61 pg/mL for the virus antigen detection. The TBC used as active layer is soft, has a low modulus of 24 MPa, and can be stretched up to 90% with no crack formation of the film. The TBC is compatible with roll-to-roll printing, potentially enabling the fabrication of low-cost wearable or on-skin diagnostic platforms aiming at point-of-care concepts.

Publ.-Id: 33509

Quantitation of the A2A adenosine receptor density in the striatum of mice and pigs with [18F]FLUDA by positron emission tomography

Gündel, D.; Toussaint, M.; Lai, T. H.; Deuther-Conrad, W.; Cumming, P.; Schröder, S.; Teodoro, R.; Moldovan, R.-P.; Pan-Montojo, F.; Sattler, B.

The cerebral expression of the A2A adenosine receptor (A2AAR) is altered in neurodegenerative disorders diseases such as Parkinson's (PD) or Huntington’s (HD) diseases, making these recep-tors an attractive diagnostic and therapeutic target. We aimed to further investigate the pharma-cokinetic properties in the brain of our recently developed A2AAR specific antagonist radioligand [18F]FLUDA. For this purpose, we retrospectively analysed dynamic PET studies of healthy mice and rotenone-treated mice, and undertook dynamic PET studies with healthy pigs. We performed analysis of mouse brain time-activity curves to calculate the mean residence time (MRT) by non-compartmental analysis and the binding potential (BPND) of [18F]FLUDA using the simplified reference tissue model (SRTM). For the pig studies, we performed a Logan graphical analysis to calculate the radiotracer distribution volume (VT) at baseline and under blocking conditions with tozadenant. The MRT of [18F]FLUDA in the striatum of mice was decreased by 30 % after treatment with the A2AAR antagonist, istradefylline. Mouse results showed the highest BPND (3.9 to 5.9) in the striatum. SRTM analysis showed a 20% lower A2AAR availability in the rotenone-treated mice compared to the control-aged group. Tozadenant treatment significantly decreased the VT (14.6 vs. 8.5 mL · g-1) and BPND values (1.3 vs. 0.3) in pig striatum. This study confirms the target specificity and a high BPND of [18F]FLUDA in the striatum. We conclude that [18F]FLUDA is a suitable tool for the non-invasive quantitation by PET of altered A2AAR expression in neurodegenerative diseases such as PD and HD.

Keywords: [18F]FLUDA; A2A adenosine receptor (A2AAR); Parkinson’s disease; Huntington’s disease; kinetic analysis; preclinical positron emission tomography; simplified reference tissue model; 7-(3-(4-(2-[18F]fluoroethoxy-1,1,2,2-d4)phenyl)propyl)-2-(furan-2-yl)-7H-pyrazolo[4,3-e][1,2,4]triaz

Publ.-Id: 33508

First evaluation of [18F]RM273 for sigma2 receptor imaging in a pre-clinical brain tumour model

Gündel, D.; Toussaint, M.; Moldovan, R.-P.; Teodoro, R.; Schepmann, D.; Wünsch, B.; Ludwig, F.-A.; Fischer, S.; Brust, P.; Deuther-Conrad, W.

Introduction: The sigma2 receptor (TMEM97) expression correlates well with the Ki67 expression in tumours [1, 2] and therefore represents an attractive marker for the proliferative status. An assessment of the sigma2 receptors in brain tumours by a non-invasive technique as PET depends on the radioligand’s suitability to cross the blood-brain barrier (BBB), which is actually one of the major challenges. Our aim was to develop an 18F-labelled radioligand for sigma2 receptor imaging in brain tumours, based on the well-described 2-(4-(1H-indol-1-yl)butyl)-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline class of compounds. On the basis of a series of novel fluorinated derivatives for 18F-labelling the promising sigma2 receptor ligand [18F]RM273 was synthesized and investigated in healthy mice and an orthotopic rat glioma model.
Methods: [18F]RM273 (2-[4-(6-[18F]fluoro-1H-pyrrolo[2,3-b]pyridin-1-yl)butyl]-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline) has been obtained by automated synthesis by Cu-mediated oxidative radiofluorination of the aryl boronic acid pinacol ester precursor. Radiometabolite analysis was performed ex vivo in mouse plasma samples 30 min p.i. The target specificity was investigated by in vitro autoradiographic studies with or without the sigma2 receptor antagonist ISO-1 in rat brain cryosections with a stereotactically implanted F98 glioma [3]. The biodistribution of [18F]RM273 in healthy mice (female, CD1; n = 4, 7.2 ± 1.1 MBq) and the tumour uptake into the F98 glioma (male, F344; n = 2; 21 – 25 MBq) were investigated by dynamic PET imaging for 60 min (nanoScan®PET-1T MRI, Mediso Kft., Hungary).
Results: [18F]RM273 has been produced with a molar activity of 69 – 233 GBq/μmol at moderate radiochemical yield (8%) and high purity (≥99%). Polar radiometabolites of [18F]RM273, detected in blood plasma samples of mice, were not crossing the BBB, as 100 % parent fraction were detected in brain extracts at 30 min p.i.). We validated the target-specific binding of [18F]RM273 towards the F98 glioma in vitro and determined a 3-times higher density of binding sites in comparison to the healthy brain [3]. PET studies revealed a peak value of the time activity curve of 1.3 at 2.25 min p.i. with a t1/2 of 13.1 min after peak time and a peak-to-endpoint ratio of 6.4 ± 0.9 in the brain of healthy mice [3], whereas in the F98 glioma an SUVmean of 0.8 – 1.3 at 30 – 60 min p.i. was found, which was two times higher than measured in the contralateral brain region.
Conclusions: The reasonable brain penetration in rodents and the tumour specific accumulation of [18F]RM273 in the F98 glioma indicate the suitability of this radioligand for future imaging studies regarding the role of sigma2 receptors in neuro-oncological diseases. Our preliminary finding of a high density of sigma2 receptors in highly proliferative brain tumour cells deserves further investigation by use of larger sample sizes and complementation with immunohistochemistry.
Acknowledgements: This work was supported by the Deutsche Forschungsgemeinschaft (DFG: BR 1360/13-1).
References: [1] Shoghi et al. Plos One 2013, 8: e74188; [2] Yang et al. Molecules 2020, 25 (22): 5439 [3] Moldovan et al. Int. J. Mol. Sci. 2021, 22: 5447

  • Poster
    EMIM 2022, 15.-18.03.2022, Thessaloniki, Greece

Publ.-Id: 33507

Multidisciplinary Characterization of Uranium Mine Waters: A Bioremediation Perspective.

Newman-Portela, A. M.; Krawczyk-Bärsch, E.; Lopez-Fernandez, M.; Bok, F.; Kassahun, A.; Raff, J.; Merroun, M. L.

An intensive uranium mining took place for decades in East Germany. These intensive mining activities have left many uranium contaminated areas. For a remediation purpose, the mine water has to be pumped to the surface and treated by a conventional chemical wastewater treatment plant. However, such chemical treatments are time- and cost-intensive. The resulting release of the soluble uranium into the mine water represents a major health risk. Remediation approaches using indigenous microbial communities are an efficient strategy [1,2]. In this study, we have characterized the microbial diversity and geochemistry of water samples from a german former uranium mine to design bioremediation approach based on uranium enzymatic reduction.

Inductively Coupled Plasma-Mass Spectrometry and Ion-Chromatography studies showed that the mine water exhibited a high concentration of uranium (1.01 mg/L), sulfate (335 mg/L), iron (0.99 mg/L) and manganese (144 mg/L). Cryo-Time-resolved Laser-induced Fluorescence Spectroscopy studies identified an aqueous uranyl carbonate species [UO2(CO3)3]. The 16S and ITS1 rRNA gene sequencing revealed an extensive microbial diversity. The total bacterial community composition indicated a high relative abundance of sulfate-reducing-bacteria (e.g., Desulfovibrio) and iron-oxidizing-bacteria (e.g., Gallionella, Sideroxydans). These bacterial groups are reported to be involved in uranium (VI) reduction as a key process in the bioremediation of anoxic uranium contaminated sites [2].

To design a bioremediation strategy for this uranium-contaminated mine water, the original mine water was used directly as a reference to set up anoxic microcosms. Concretely, uranium-reducing-bacteria were stimulated by glycerol (10mM) as electron donor. ICP-MS and Ion-Chromatography analysis from the microcosms revealed a decrease of uranium (≈90%), sulfate (≈60%), iron (≈86%) and manganese (≈88%). In addition, a drop of Eh and pH of the system was detected. A theoretical thermodynamic Eh-pH predominance diagram was calculated by Geochemist ́s Workbench, indicating the formation of uranium (IV) precipitates, probably uraninite, after 3 months at the latest. Finally, uranium (IV) was detected by UV-Visible spectroscopy in the precipitate at the end of the experiment.

These results show that the uranium reduction of soluble uranium (VI) to insoluble uranium (IV) is favoured by the addition of an electron donor (glycerol) in low concentrated uranium contaminated mines water by biostimulating their native microbial community.

Keywords: Uranium; Bioremediation; Reduction; Spectroscopy

  • Poster (Online presentation)
    Mineralogical Society. New Topics in Mineralogy 2: The mineral–microbe interface through time and space., 02.-03.12.2021, Manchester, United Kingdom

Publ.-Id: 33506

Non-invasive assessment of locally overexpressed human adenosine 2A receptors in the heart of transgenic mice

Gündel, D.; Lai, T. H.; Dukic-Stefanovic, S.; Teodoro, R.; Deuther-Conrad, W.; Toussaint, M.; Moldovan, R.-P.; Kopka, K.; Boknik, P.; Hofmann, B.; Gergs, U.; Neumann, J.; Brust, P.

Abstract: A2A adenosine receptors (A2A-AR) have a cardio-protective function upon ischemia and reperfusion, but on the other hand, their stimulation could lead to arrhythmias. Our aim was to investigate the potential use of the PET radiotracer [18F]FLUDA to determine the A2A-AR availability non-invasively for diagnosis of the A2AR status. Therefore, we compared mice with a cardiomyocyte-specific overexpressing of the human A2A-AR (A2A-AR TG) with the respective wild type (WT). We determined: (1) the functional impact of FLUDA on the contractile function of atrial mouse samples, (2) the binding parameters (Bmax and KD) of [18F]FLUDA on mouse and additionally on human atrial tissue samples by autoradiographic studies, and investigated (3) the in vivo uptake of the radiotracer by dynamic PET imaging in the two A2A-AR TG and WT. After A2A-AR stimulation by CGS 21680 in isolated atrial preparations antagonistic effects of FLUDA were found in A2A-AR-TG animals but not in WT mice. Radiolabeled [18F]FLUDA exhibited a KD of 5.9 ± 1.6 nM and a Bmax of 455 ± 78 fmol/mg protein in cardiac samples of A2A-AR TG, whereas in WT, as well as in human atrial preparations only low specific binding could was found. Dynamic PET studies revealed a significantly higher initial uptake of [18F]FLUDA into the myocardium of A2A-AR TG compared to WT. The hA2A-AR-specific binding of [18F]FLUDA in vivo was verified by pre-administration of the highly affine A2AAR-specific antagonist istradefylline.
Conclusion: [18F]FLUDA is a promising PET probe for the non-invasive assessment of the A2A-AR as a marker for pathologies linked to an increased A2A-AR density in the heart, as shown in patients with heart failure.

Keywords: [18F]FLUDA; A2A adenosine receptor; PET; myocardium

Publ.-Id: 33505

Turbulent fluid flow in a precessing cylinder

Pizzi, F.; Giesecke, A.; Stefani, F.

In the framework of DRESDYN (DREsden Sodium facility for DYNnamo and thermohydraulic studies) we study the hy-
drodynamics of a fluid contained in a precessing cylinder. Here we focus on turbulence properties of the flow in dependence of the
precession angle as well as Reynolds number and Poincaré number (ratio of the frequency of the precessional system and the cylinder
itself). The main result is a characteristic peak in the dissipation around Po = 0.1 which goes along with a local maximum of turbulent
kinetic energy.

Keywords: precession; turbulence

  • Poster (Online presentation)
    25th International Congress of Theoretical and Applied Mechanics, 22.-27.08.2021, Milano, Italia

Publ.-Id: 33504

Nondiffusive Transport and Anisotropic Thermal Conductivity in High-Density Pt/Co Superlattices

Shahzadeh, M.; Andriyevska, O.; Salikhov, R.; Fallarino, L.; Hellwig, O.; Pisana, S.

Despite the numerous reports over the last two decades dedicated to the study of interfacial thermal transport,
physics of thermal transport across nanoscale metallic multilayers is less explored. This is in part due to the relatively
high conductance characteristic of these interfaces, which renders them difficult to characterize.
Interfacial transport in these systems has so far appeared to be diffusive, a surprising behavior when the interface density
increases and the layer thicknesses become comparable with the mean free path of electrons.
To address the limit of diffusive theories describing heat transport across high-density metallic interfaces,
we systematically investigate heat transport in and across Pt/Co multilayers via frequency domain thermoreflectance.
Sensitivity gained from offsetting the laser beam and reducing the laser spot size allows for the
measurement of anisotropic thermal conductivity of the multilayers. By changing the number of interfaces while keeping the overall
thickness of Pt and Co in the multilayer structure constant, the effect of interface density on the multilayers’ effective thermal
conductivity is studied. The extracted Pt/Co interface thermal boundary conductance is then compared to the calculations from the
electronic diffuse mismatch model and experimental data available in the literature. We show that as the multilayer period thickness
becomes much smaller than the electron mean free path, measurements markedly deviate from the diffusive transport theory. We
attribute this deviation to the nondiffusive nature of heat transport in subnanometric scales at interface densities above 1/nm.

Keywords: heat transport; metallic multilayers; anisotropic thermal conductivity; nondiffusive transport; frequency domain thermoreflectance


  • Secondary publication expected

Publ.-Id: 33503

Single Atom Counting of Stellar and r-Process Nuclei in Time-Resolved Deep-Sea Archives

Koll, D.; Wallner, A.; Hotchkis, M.; Child, D.; Fifield, K.; Froehlich, M.; Hartnett, M.; Lachner, J.; Merchel, S.; Pavetich, S.; Rugel, G.; Slavkovská, Z.; Tims, S.

Stars are the major element factories in the universe. In 1999, live supernova Fe-60 (t1/2 =2.6 Myr)
was detected in a deep-sea ferromanganese crust (1 ) indicating the accumulation of supernova
dust on Earth about 2 million years ago. This was followed by several projects reinforcing the
initial evidence for a global influx of supernova Fe-60. Recently, a much younger continuous
influx was found in Antarctic snow and in deep-sea sediments (2 –4 ) and an older peak around
6 - 8 Myr in deep-sea crusts (5 , 6 ).
In contrast to the well-known production mechanism and synthesis site of Fe-60, the long-lived
plutonium isotope Pu-244 (t1/2 =80 Myr) is a pure r-process nucleus. The nucleosynthesis site for
the astrophysical r-process is still debated in the astrophysics community. Potential candidates
involve rare supernovae and neutron star mergers. To date no evidence was presented that would
point to an exclusive r-process site and combinations of different sites are considered.
Experimentally, we can search for Pu-244 signatures in samples with known Fe-60 signatures to
test for either common influx patterns or independent Pu-244 influxes disentangled from stellar
Fe-60. Accordingly, this information provides a unique and direct experimental approach for
identifying the production site of the heavy elements.
Based on the recent publication of the first detection of interstellar Pu-244 in a ferromanganese
crust with a time resolution of 4.5 Myr (integrating over much shorter Fe-60 influxes) (6 ), we are
now working on a highly time-resolved profile of Fe-60 and Pu-244 in the large ferromanganese
crust VA13/237KD. This direct experimental input will further constrain models for r-process
nucleosynthesis in the galaxy. The recently determined profile of Fe-60 clearly shows two influxes,
one at 2 Myr, the other at 7 Myr, confirming and refining previous results. Preliminary data on
Pu-244 and an outlook for future measurement campaigns will be given.

1. K. Knie et al., Phys. Rev. Lett. 83, 18–21 (1999).
2. D. Koll et al., Phys. Rev. Lett. 123, 072701 (2019).
3. A. Wallner et al., Proceedings of the National Academy of Sciences 117, 21873–21879 (2020).
4. D. Koll et al., EPJ Web Conf. 232, 02001 (2020).
5. A. Wallner et al., Nature 532, 69–72 (2016).
6. A. Wallner et al., Science 372, 742–745 (2021).

Keywords: 60Fe; 244Pu; AMS; Stars; Supernovae; r-process

Related publications

  • Lecture (Conference) (Online presentation)
    Schools on Nuclear Astrophysics Questions, 13.10.2021, Dresden, Deutschland

Publ.-Id: 33501

Neutronenfluss in Untertagelaboren

Grieger, M.

Das Felsenkellerlabor ist ein neues Untertagelabor im Bereich der nuklearen Astrophysik. Es befindet sich unter 47 m Hornblende-Monzonit Felsgestein im Stollensystem der ehemaligen Dresdner Felsenkellerbrauerei.

Im Rahmen dieser Arbeit wird der Neutronenuntergrund in Stollen IV und VIII untersucht. Gewonnene Erkenntnisse aus Stollen IV hatten direkten Einfluss auf die geplanten Abschirmbedingungen fur Stollen VIII. Die Messung wurde mit dem Hensa-Neutronenspektrometer durchgeführt, welches aus polyethylenmoderierten 3He-Zählrohren besteht.

Mit Hilfe des Monte-Carlo Programmes Fluka zur Simulation von Teilchentransport werden für das Spektrometer die Neutronen-Ansprechvermögen bestimmt. Fur jeden Messort wird außerdem eine Vorhersage des Neutronenflusses erstellt und die Labore hinsichtlich der beiden Hauptkomponenten aus myoneninduzierten Neutronen und Gesteinsneutronen aus (α,n)-Reaktionen und Spaltprozessen kartografiert.

Die verwendeten Mess- und Analysemethoden finden in einer neuen Messung am tiefen Untertagelabor Lsc Canfranc Anwendung. Erstmalig werden im Rahmen dieser Arbeit
vorläufige Ergebnisse vorgestellt.

Des Weiteren werden Strahlenschutzsimulationen fur das Felsenkellerlabor präsentiert, welche den strahlenschutztechnischen Rahmen für die wissenschaftliche Nutzung definieren. Dabei werden die für den Sicherheitsbericht des Felsenkellers verwendeten Werte auf die Strahlenschutzverordnung 2018 aktualisiert.

Letztlich werden Experimente an der Radiofrequenz-Ionenquelle am Felsenkeller vorgestellt, die im Rahmen dieser Arbeit technisch betreut wurde. Dabei werden Langzeitmessungen am übertägigen Teststand am Helmholtz-Zentrum Dresden-Rossendorf präsentiert.

Keywords: Neutronen; Untertagelabor; Spektrometer; Entfaltung; FLUKA; Monte-Carlo; HENSA

  • Open Access Logo Wissenschaftlich-Technische Berichte / Helmholtz-Zentrum Dresden-Rossendorf; HZDR-117 2022
    ISSN: 2191-8708, eISSN: 2191-8716


Publ.-Id: 33500

Fe-60 and Mn-53: The Radionuclide System to Study Meteorites, the Solar Neighborhood and Past Supernova Activity

Koll, D.; Faestermann, T.; Korschinek, G.; Ingo, L.; Merchel, S.; Wallner, A.

Astrophysical studies on extraterrestrial samples often involve long-lived radionuclides to study the evolution
of the solar system and the galaxy on long timescales. Dyadic radionuclide/stable nuclide systems such as
U-Pb, Sm-Nd or Rb-Sr are well-established and widely used for dating and characterization of meteorites and
lunar rocks. Such systems rely on the decay of a long-lived radionuclide and the resulting isotopic anomalies
of the daughter isotope compared to natural abundances.
In contrast, in this talk, the two live radionuclides Fe-60 and Mn-53 are shown to be versatile tools to study
meteorites and past supernova activity. Both radionuclides with half-lives around 3 Myr are produced in massive
stars as well as by spallation in extraterrestrial materials, planetary surfaces and cosmic dust. Measured
and modelled production rates [1,2] and the first use as a dyadic system to disentangle the origin of supernovaproduced
Fe-60 on the surface of the moon [3] and in Antarctic snow [4] will be presented amongst recent
discoveries of the individual radionucides in geological archives.

[1] Leya et al., Meteoritics & Planetary Science 55, 818–831 (2020)
[2] Merchel et al., Nucl. Instr. Meth. Phys. Res. B 172, 806-811 (2000)
[3] Fimiani et al., Phys. Rev. Lett. 116, 151104 (2016)
[4] Koll et al., Phys. Rev. Lett. 123, 072701 (2019)

Keywords: Meteorites; 60Fe; 53Mn; Supernova; Interstellar; Interplanetary

  • Poster (Online presentation)
    The 16th International Symposium on Nuclei in the Cosmos, 21.09.2021, Chengdu, China

Publ.-Id: 33499

Time-Resolved Interstellar Pu-244 and Fe-60 Profiles in a Be-10 Dated Ferromanganese Crust

Koll, D.; Wallner, A.; Hotchkis, M.; Child, D.; Fifield, K.; Froehlich, M.; Hartnett, M.; Lachner, J.; Merchel, S.; Pavetich, S.; Rugel, G.; Slavkovská, Z.; Tims, S.

More than 20 years have passed since the first attempts to find live supernova Fe-60
(t1/2 = 2.6 Myr) in a deep-sea ferromanganese crust [1]. Within these 20 years, strong evidence was presented for a global influx of supernova dust into several geological samples around 2 Myr ago. Recently, a much younger continuous influx was found in Antarctic snow and in deep-sea sediments [2-4] and an older peak around 7 Myr in deep-sea crusts [5,6].

The long-lived isotope Pu-244 (t1/2 = 80 Myr) is produced in the astrophysical r-process similarly to most of the heaviest elements. Although the production mechanism is believed to be understood, the astrophysical site is heavily disputed. Most likely scenarios involve a combination of rare supernovae and neutron star mergers. The search for Pu-244 signatures in samples with known Fe-60 signatures allows to test for either common influx patterns or a independent Pu-244 influxes disentangled from stellar Fe-60. Accordingly, this information provides a unique and direct experimental approach for identifying the production site of the heavy elements.

Very recently and first reported in the AMS-14 conference, the first detection of interstellar Pu-244 was published [6]. This was only feasible by achieving the highest detection efficiencies for plutonium in AMS ever reported [7]. The achieved time resolution of 4.5 Myr integrates over the supernova influxes and is therefore not high enough to unequivocally show a correlated influx pattern of Fe-60 and Pu-244.
Based on this progress, we are now aiming to measure highly time-resolved profiles of Fe-60 and Pu-244 in the largest ferromanganese crust used so far. Results on the characterisation of the crust including cosmogenic Be-10 (t1/2 = 1.4 Myr) dating and a 10 Myr profile of interstellar Fe-60 including the confirmation of the 7 Myr influx will be presented along with first data on interstellar Pu-244.

[1] Knie et. al., Phys. Rev. Lett. 83 (1999).
[2] Koll et al., Phys. Rev. Lett. 123 (2019).
[3] Koll et al., EPJ 232 (2020).
[4] Wallner et al., PNAS 117 (2020).
[5] Wallner et al., Nature 532 (2016)
[6] Wallner et al., Science 372 (2021)
[7] Hotchkis et al., NIMB 438 (2019)

Keywords: Supernova; 60Fe; 244Pu; 10Be; r-process; ferromanganese crust; pacific; AMS

Related publications

  • Lecture (Conference) (Online presentation)
    The 15th International Conference on Accelerator Mass Spectrometry, 19.11.2021, Sydney, Australia

Publ.-Id: 33498

Manipulating magnetic and magnetoresistive properties by oxygen vacancy complexes in GCMO thin films

Beiranvand, A.; Liedke, M. O.; Haalisto, C.; Lähteenlahti, V.; Schulman, A.; Granroth, S.; Palonen, H.; Butterling, M.; Wagner, A.; Huhtinen, H.; Paturi, P.

The effect of in situ annealing is investigated in Gd0.1Ca0.9MnO3 (GCMO) thin films in oxygen and vacuum atmospheres. We show that the reduction of oxygen content in GCMO lattice by vacuum annealing induced more oxygen complex vacancies in both subsurface and interface regions and larger grain domains when compared with the pristine one. Consequently, the double exchange interaction is suppressed and the metallic-ferromagnetic state below Curie temperature turned into spin-glass insulating state. In contrast, the magnetic and resistivity measurements show that the oxygen treatment increases ferromagnetic phase volume, resulting in greater magnetization (MS) and improved magnetoresistivity properties below Curie temperature by improving the double exchange interaction. The threshold field to observe the training effect is decreased in oxygen treated film. In addition, the positron annihilation spectroscopy analysis exhibits fewer open volume defects in the subsurface region for oxygen treated film when compared with the pristine sample. These results unambiguously demonstrate that the oxygen treated film with significant spin memory and greater magnetoresistance can be a potential candidate for the future memristor applications.

Keywords: positron annihilation spectroscopy; positron annihilation lifetime spectroscopy; GaCaMnO3; oxygen vacancy; spin-glass

Related publications


  • Secondary publication expected from 10.02.2023

Publ.-Id: 33497

Band-selective third-harmonic generation in superconducting MgB2: Possible evidence for the Higgs amplitude mode in the dirty limit

Kovalev, S.; Dong, T.; Shi, L.-Y.; Reinhoffer, C.; Xu, T.-Q.; Wang, H.-Z.; Wang, Y.; Gan, Z.-Z.; Germanskiy, S.; Deinert, J.-C.; Ilyakov, I.; van Loosdrecht, P. H. M.; Wu, D.; Wang, N.-L.; Demsar, J.; Wang, Z.

We report on time-resolved linear and nonlinear terahertz spectroscopy of the two-band superconductor MgB2
with a superconducting transition temperature Tc ≈ 36 K. Third-harmonic generation (THG) is observed below
Tc by driving the system with intense narrow-band THz pulses. For the pump-pulse frequencies f = 0.3, 0.4,
and 0.5 THz, the temperature-dependent evolution of the THG signals exhibits a resonance maximum at the
temperatures with the resonance conditions 2 f = 2Delta π (T ) fulfilled, for the dirty-limit superconducting gap
2Delta π . In contrast, for f = 0.6 and 0.7 THz with 2 f > 2Delta π (T → 0) = 1.03 THz, the THG intensity increases
monotonically with decreasing temperature. Moreover, for 2 f < 2Delta π (T → 0) the THG is found nearly isotropic
with respect to the pump-pulse polarization. These results suggest a predominant contribution of the driven
Higgs amplitude mode of the dirty-limit π -band superconducting gap, pointing to the importance of scattering
for observation of the Higgs mode in superconductors.


Publ.-Id: 33496

Radiosynthesis and first preclinical evaluation of an 18F-radiolabelled ligand for cancer stem cells by non-invasive PET imaging

Toussaint, M.; Moldovan, R.-P.; Teodoro, R.; Gündel, D.; Deuther-Conrad, W.; Brust, P.

Objectives: Cancer stem cells (CSCs) are a multipotent cells subpopulation playing a critical role in tumor initiation, therapy resistance and recurrence1. Therefore, their therapeutic targeting is of relevance for highly aggressive entities with poor prognosis such as glioblastoma (NCT02654964). To support the development of such targeted therapy we intended to develop a radiotracer enabling the non-invasive imaging of the CSCs population. Based on the work of Lucki et al.2 who discovered a promising prodrug termed RIPGBM selective of cancer stem cells (CSC), we aimed at developing an 18F-radiolabelled RIPGBM, and to preliminary assess its potential as non-invasive imaging agent of a low-density population such as the CSC in a mouse model of human glioblastoma. We report in this first exploratory study on the synthesis, radiosynthesis, in vivo metabolism and pharmacokinetics of [18F]RIPGBM.
Methods: The reference compound N-(3-(benzylamino)-1,4-dioxo-1,4-dihydronaphthalen-2-yl)-N-(4-fluorobenzyl)acetamide (RIPGBM) and the corresponding boronic acid pinacol ester precursor for radiofluorination (RM361) were obtained by following the synthetic procedure reported by Lucki and co-workers2. The radiosynthesis of [18F]RIPGBM was performed on an automated module in presence of CU(OTf)2(Py)4, [18F]TBAF and DMA/tBuOH. The fraction of radiometabolites was quantified in mice plasma and brain at 30 min post injection (p.i.). Dynamic PET studies (60 min, nanoScan® PET/MRI, MEDISO, Budapest, Hungary) were performed using an orthotopic xenogenic U87 glioblastoma model in nude mice (n=2) presenting a stem cell-like population3,4.
Results: [18F]RIPGBM was obtained with a radiochemical yield of 6.0 ± 1.3% (EOB), a radiochemical purity >99% and a molar activity of 60-200 GBq/µMol (EOS). It shows a similar stability in both mice at 30 p.i. with 26-30% of intact radiotracer in plasma and 73-74% in the brain. About 70% of intact radiotracer was found in the tumor hemisphere. The PET-derived time-activity curves (TACs) of the whole brain, tumor and contralateral regions displayed a sufficient brain uptake (TAC peak value of 1.0-1.4 SUV). Furthermore, [18F]RIPGBM displays a fast washout from all the above mentioned region.
Conclusion: A fully automated copper-mediated radiosynthetic procedure was developed for the promising prodrug RIPGBM targeting CSCs. A first exploration in vivo demonstrates the presence of 30 % of radiometabolites in the brain/tumor region, no high unspecific retention as shown by the fast washout, but also no observable specific retention in the target area presumably due to the lack of affinity of this radioligand given the low density of the targeted cell population in this model.
References: 1. Lathia, J. D., Mack, S. C., Mulkearns-Hubert, E. E., Valentim, C. L. L. & Rich, J. N. Cancer stem cells in glioblastoma. Genes Dev. 29, 1203–1217 (2015).
2. Lucki, N. C. et al. A cell type-selective apoptosis-inducing small molecule for the treatment of brain cancer. PNAS 116, 6435–6440 (2019).
3. Yu, S. et al. Isolation and characterization of cancer stem cells from a human glioblastoma cell line U87. Cancer Letters 265, 124–134 (2008).
4. Toda, Y. et al. DJ-1 Contributes to Self-renewal of Stem Cells in the U87-MG Glioblastoma Cell Line. Anticancer Res 39, 5983–5990 (2019).

Keywords: RIPGBM; 18F-radiolabelled ligand; Positron emission tomography; cancer stem cells

  • Open Access Logo Poster
    International symposium on radiopharmaceutical sciences, 29.05.-02.06.2022, Nantes, France


Publ.-Id: 33495

Data publication: Temperature-induced surface faceting of M-plane Al₂O₃: An in-situ GISAXS study

Erb, D.; Perlich, J.; Roth, S.; Röhlsberger, R.; Schlage, K.

-- raw data of GISAXS experiment

-- AFM data

-- GISAXS simulation files

Keywords: crystal surface reconstruction; nanofaceted Al₂O₃; pattern formation; in-situ GISAXS; AFM

Related publications


Publ.-Id: 33492

Mode conversion and period doubling in a liquid rubidium Alfvén-wave experiment with coinciding sound and Alfvén speeds

Stefani, F.; Forbriger, J.; Gundrum, T.; Herrmannsdörfer, T.; Wosnitza, J.

We report Alfvén-wave experiments with liquid rubidium at the Dresden High Magnetic Field Laboratory (HLD). Reaching up to 63 T, the pulsed magnetic field exceeds the critical value of 54 T at which the Alfvén speed coincides with the sound speed. At this threshold we observe a period doubling of an applied 8 kHz CW excitation, which is consistent with the theoretical expectation of a parametric resonance between magnetosonic waves and Alfvén waves. Similar mode conversions are discussed as a possible mechanism for heating the solar corona.

Keywords: Alfvén waves; Solar physics; Corona heating


Publ.-Id: 33491

Molecular Response to Combined Molecular- and External Radiotherapy in Head and Neck Squamous Cell Carcinoma (HNSCC).

Rassamegevanon, T.; Feindt, L.; Koi, L.; Müller, J.; Freudenberg, R.; Löck, S.; Sihver, W.; Çevik, E.; Christel Kühn, A.; von Neubeck, C.; Linge, A.; Pietzsch, H.-J.; Kotzerke, J.; Baumann, M.; Krause, M.; Dietrich, A.

Combination treatment of molecular targeted and external radiotherapy is a promising strategy and was shown to improve local tumor control in a HNSCC xenograft model. To enhance the therapeutic value of this approach, this study investigated the underlying molecular response. Subcutaneous HNSCC FaDuDD xenografts were treated with single or combination therapy (X-ray: 0, 2, 4 Gy; anti-EGFR antibody (Cetuximab) (un-)labeled with Yttrium-90 (90Y)). Tumors were excised 24 h post respective treatment. Residual DNA double strand breaks (DSB), mRNA expression of DNA damage response related genes, immunoblotting, tumor histology, and immunohistological staining were analyzed. An increase in number and complexity of residual DNA DSB was observed in FaDuDD tumors exposed to the combination treatment of external irradiation and 90Y-Cetuximab relative to controls. The increase was observed in a low oxygenated area, suggesting the expansion of DNA DSB damages. Upregulation of genes encoding p21cip1/waf1 (CDKN1A) and GADD45α (GADD45A) was determined in the combination treatment group, and immunoblotting as well as immunohistochemistry confirmed the upregulation of p21cip1/waf1. The increase in residual γH2AX foci leads to the blockage of cell cycle transition and subsequently to cell death, which could be observed in the upregulation of p21cip1/waf1 expression and an elevated number of cleaved caspase-3 positive cells. Overall, a complex interplay between DNA damage repair and programmed cell death accounts for the potential benefit of the combination therapy using 90Y-Cetuximab and external radiotherapy.

Keywords: Cetuximab; DNA damage response; cell death induction; external beam radiotherapy; molecular targeted radiotherapy

Publ.-Id: 33490

Spin-wave focusing induced by dipole-dipole interaction in synthetic antiferromagnets

Gallardo, R. A.; Alvarado-Seguel, P.; Kákay, A.; Lindner, J.; Landeros, P.

Under certain conditions, spin waves can be channeled into a broad angular spectrum of wave vectors, where the direction
of the group velocity becomes independent of those wave vectors. Such highly focused waves are called caustic waves,
whose properties can be manipulated by anisotropies or chiral interactions, like the Dzyaloshinskii-Moriya interaction. In this
paper, we theoretically study the focusing features of the spin waves induced by the dipole-dipole interaction in synthetic
antiferromagnets. For stacked systems, the dipolar interaction causes a noticeable frequency nonreciprocity when the
magnetizations in both films are antiparallelly aligned, and then the focusing properties of the spin waves are enhanced. The
role of thicknesses and magnetic graduation along the film's normal are systematically analyzed. We found that the degree
of focalization of the spin waves can be manipulated by increasing the layers' thickness. Also, we show that the low- and
high-frequency modes exhibit different focalization properties; the low-frequency mode manifests a similar behavior to the
heavy-metal/ferromagnet systems with interfacial Dzyaloshinskii-Moriya interaction, while the high-frequency one tends the
generate almost reciprocal interference patterns along one axis. In the case of magnetization-graded synthetic
antiferromagnets, we demonstrate that the graduation slightly influences the low-frequency mode, while the focusing and
nonreciprocal dynamic properties of the high-frequency ones are notoriously altered. The theoretical calculations are
compared with micromagnetic simulations, where a good agreement is found between both methods. Our results
demonstrate that a synthetic antiferromagnetic system allows for controlling the propagation of spin waves, assisting in the
transfer of angular momentum and energy.

Keywords: Spin waves; Wave focusing; synthetic antiferromagnets; Dzyaloshinskii-Moriya interaction; Spectrum analysis; dipole-dipole interaction; multilayers


  • Secondary publication expected

Publ.-Id: 33489

Evaluation of [18F]RM273 for sigma2-receptor imaging in an experimental orthotopic glioblastoma model

Gündel, D.; Toussaint, M.; Moldovan, R.-P.; Teodoro, R.; Schepmann, D.; Wünsch, B.; Ludwig, F.-A.; Fischer, S.; Brust, P.; Deuther-Conrad, W.

The proven suitability of the sigma2 receptor as marker for the proliferative status of solid tumors of the body [1] has promoted efforts to develop brain-targeted radioligands for sigma2 receptor imaging in neuro-oncological diseases as well. Accordingly, based on the well described 2-(4-(1H-indol-1-yl)butyl)-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline class of compounds we designed a series of novel fluorinated derivatives for 18F-labelling and investigated the most promising sigma2 receptor ligand in a rat model for glioma.
[18F]RM273 (2-[4-(6-[18F]fluoro-1H-pyrrolo[2,3-b]pyridin-1-yl)butyl]-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline) has been obtained by automated synthesis by Cu-mediated oxidative radiofluorination of the aryl boronic acid pinacol ester precursor. Wildtype mice (female, CD1; n = 4) and rats with intracranial implanted orthotopic F98 glioma (male, F344; n = 2) were injected with the radiotracer (mice: 7.2±1.1 MBq; rats: 21–25 MBq) and investigated by dynamic PET (nanoScan®PET-1T MRI). Complementary ex vivo metabolite as well as in vitro autoradiographic studies were performed in mice after intravenous injection and in rat with cryosections of the brain of one F98 bearing animal, respectively [2].
[18F]RM273 has been produced with a molar activity of 69–233 GBq/μmol at moderate radiochemical yield (8%) and high purity (≥99%). A mean standardized uptake value (SUV) of 1.3 at 2.25 min p.i. in the brain of wildtype CD1 mice indicates fast and adequate penetration of the blood-brain barrier. The polar radiometabolites of [18F]RM273 discovered in blood plasma of mice were not detectable in the brain extracts (100 % parent fraction at 30 min p.i.). The binding pattern of [18F]RM273 in vitro in cryosections of the glioma brain indicates target-specific binding towards the F98 glioma (complete displacement by co-incubation with 1 µM ISO-I) with an about 3-fold higher density of binding sites in comparison to the healthy brain [2]. Also by PET the F98 glioma could be delineated clearly with mean SUVs at 30–60 min p.i. of 0.8–1.3 in the tumor and 0.5 in the contralateral region.
The reasonable brain penetration in rodents as well as the tumor specific accumulation of [18F]RM273 in the F98 glioma indicates the suitability of this radioligand for future imaging studies regarding the role of sigma2 receptors in neuro-oncological diseases. Our preliminary finding of a high density of sigma2 receptors in highly proliferative brain tumor cells deserves further investigation by larger sample sizes and complementation with immunohistochemistry.
This work was supported by the Deutsche Forschungsgemeinschaft (DFG: BR 1360/13-1).
[1] Shoghi et al. Plos One 2013, 8: e74188
[2] Moldovan et al. Int. J. Mol. Sci. 2021, 22: 5447

  • Abstract in refereed journal
    Nuclear Medicine and Biology 108-109(2022)Suppl., S184
    DOI: 10.1016/S0969-8051(22)00384-5
  • Poster
    International Symposium on Radiopharmaceutical Sciences iSRS, 29.05.-02.06.2022, Nantes, Frankreich

Publ.-Id: 33488

Data to 18F-AW09

Wodtke, R.; Löser, R.

radio-TLC, radio-HPLC, radio-SDS, in vitro autoradiography

Related publications


Publ.-Id: 33487

NMR data FBz/FBn polyamines

Wodtke, R.; Löser, R.

Files of NMR data for the different fluorobenz(o)ylated polyamines and radiosynthesis data

Related publications


Publ.-Id: 33486

Americium preferred: LanM, a natural lanthanide-binding protein favors an actinide over lanthanides

Singer, H.; Drobot, B.; Zeymer, C.; Steudtner, R.; Daumann, L.

The separation and recycling of lanthanides is an active area of research with a growing demand that calls for more environmentally friendly lanthanide sources. Likewise, the efficient and industrial separation of lanthanides from the minor actinides (Np, Am - Fm) is one of the key questions for closing the nuclear fuel cycle; reducing costs and increasing safety. With the advent of the field of lanthanide dependent bacterial metabolism, bio-inspired applications are in reach. Here, we utilize the natural lanthanide chelator Lanmodulin and the luminescent probes Eu3+ and Cm3+ to investigate the inter-metal competition behavior of all lanthanides (except Pm) and the major actinide plutonium as well as three minor actinides neptunium, americium and curium to Lanmodulin. Using time resolved laser induced fluorescence spectroscopy we show that Lanmodulin has the highest relative binding affinity to Nd3+ and Eu3+ among the lanthanide series. When equimolar mixtures of Cm3+ and Am3+ are added to Lanmodulin, Lanmodulin preferentially binds to Am3+ over Cm3+ whilst Nd3+ and Cm3+ bind with similar relative affinity. The results presented show that a natural lanthanide binding protein can bind a major and various minor actinides with high relative affinity, paving the way to bio inspired separation applications. In addition, an easy and versatile method was developed, using the fluorescence properties of only two elements, Eu and Cm, for inter-metal competition studies regarding lanthanides and selected actinides and their binding to biological molecules.


Publ.-Id: 33485

Development of “clickable” albumin binders and application to theranostic radioligands for somatostatin receptor subtype 2

Brandt, F.; Ullrich, M.; Löser, R.; Pietzsch, H.-J.; Kopka, K.; Pietzsch, J.; Wodtke, R.

Despite given high affinity and selectivity towards their distinct biological targets, theranostic radioligands can suffer strongly from fast blood clearance and metabolism, which limits the enrichment of the compounds in the tumour tissue. A viable strategy to increase the bioavailability of substances is the conjugation to human serum albumin (HSA). In this context, Nε-4-(4-iodophenyl)butanoyllysine (Nε-IPB-lysine) was recently discovered as potent albumin binder.[1] However, conjugation of Nε-IPB-lysine via its α-amino group to proteins, peptides or small molecules is challenging, as a free α-carboxyl group is required to maintain good binding to HSA.
To allow the broad applicability and late-stage introduction of Nε-IPB-lysine we present a novel approach of Cu-catalyzed azide-alkyne cycloaddition (CuAAC) using Nε-IPB-lysine derivatives with azide/alkyne bearing moieties at the α-amino group. For small scales, a solid phase synthesis strategy starting from Fmoc-Lys(Alloc)-OH was developed. For upscaling, a 3-step synthesis starting from Boc-Lys-OH has been established. The HSA binding affinities were determined using microscale thermophoresis and a fluorescence-based competition assay. A library of azide/alkyne containing compounds with a binding affinity to HSA ranging from 0.4 µM to 100 µM could be obtained.
To demonstrate the suitability of the novel albumin binders, Nα-5-azidopentanoyl-Nε-IPB-D-lysine (Kd = 8 µM) was coupled to the somatostatin receptor subtype 2 ligand NODAGA-Pra-O2Oc-TATE 1 by on-resin CuAAC. For radiolabelling, copper-64 was used. The resulting conjugate [64Cu]Cu-2 showed significantly improved binding to HSA compared to [⁶⁴Cu]Cu-1, [⁶⁴Cu]Cu-NODAGA-TATE, and [⁶⁴Cu]Cu-DOTA-TATE. All TATE derivatives were studied by PET imaging using a mouse phaechromocytoma (MPC)-allograft model highlighting an increased blood circulation time of [⁶⁴Cu]Cu-2 and higher tumor uptake at late time points (24 h) compared to the other radiotracers. Current studies aim to further optimise the biodistribution by selecting HSA binders of higher or lower binding affinity.


[1] Dumelin et al. Angew. Chem. Int. Ed. Engl. 2008, 47(17), 3196-3201.

  • Poster (Online presentation)
    Frontiers in Medicinal Chemistry, 08.-10.03.2021, Darmstadt, Deutschland

Publ.-Id: 33484

Synthesis and characterisation of irreversible transglutaminase 2-inhibitors with albumin binding moiety

Wodtke, R.; Schlitterlau, P.; Brandt, F.; Laube, M.; Kopka, K.; Pietzsch, H.-J.; Pietzsch, J.; Löser, R.

The development of radiotracers for transglutaminase 2 (TGase 2) based on irreversible inhibitors appears highly attractive to further uncover the role of that enzyme for the emergence and progression of various tumours. [1] In this context, the ¹⁸F-labelled analogue of Nε-acryloyl-L-lysine 1, developed in our lab, showed great potential as radiometric tool for in vitro investigations. However, application for in vivo imaging is strongly limited by its unfavourable pharmacokinetic properties such as fast blood clearance and metabolism. A common approach to improve biodistribution and blood circulation time of drugs is the reversible conjugation to human serum albumin (HSA). Recently, compound 2 was identified as HSA binder with good affinity (Kd = 3.2 µM). [2] Successful application of 2 was demonstrated for pharmacokinetic tuning of various radiolabelled compounds, but rather for hydrophilic than for hydrophobic molecules. [3] Moreover, compound 2 offers the possibility for radiolabelling with iodine-123. [4]
For the purpose to develop radiotracers for TGase 2 with HSA binding capability, we designed compound 3 as lead structure containing the HSA binding moiety of 2 linked via a triazole ring as an amide bioisostere to the part of the TGase 2-inhibitor. Conjugation of alkyne-functionalised Nε-acryloyl-L-lysines and Boc-protected (R)-6-amino-2-azidohexanoic acid by copper-catalysed azide/alkyne cycloaddition followed by Boc deprotection and introduction of 4-(4-iodophenyl)butanoic acid via the respective N-hydroxysuccinimide ester gave access to 3 and two further derivatives with 3,5 and 2,5 substitution pattern at the pyridine ring. Evaluation of these compounds (and their alkyne precursors) by in-house assay methods revealed excellent inhibitory potencies towards TGase 2 (kinact/KI = 10,800 and 3,880 M-1s-1 for 3 and 1, respectively) and good binding affinities to HSA (Kd = 2.3 µM for 3). Overall, this indicates a promising basis for the application of this dual-targeting approach. Current studies focus on the radiolabelling of compound 3 with iodine-123 using the respective arylboronic acid as precursor which can be obtained via the same synthetic route.


[1] Pietsch et al. Bioorg. Med. Chem. Lett. 2013, 23, 6528. [2] Dumelin et al. Angew. Chem. Int. Ed. 2008, 47, 3196. [3] Brandt et al. Nucl. Med. Biol. 2019, 70, 46. [4] Wen et al. Mol. Pharmaceutics 2019, 16, 816.

  • Lecture (Conference) (Online presentation)
    Frontiers in Medicinal Chemistry, 08.-10.03.2021, Darmstadt, Deutschland

Publ.-Id: 33483

18F-Chemistry in HPLC vials - a microliter scale radiofluorination approach

Laube, M.; Wodtke, R.; Kopka, K.; Knieß, T.; Pietzsch, J.


Objectives: Finding optimal 18F-fluorination conditions represents a critical and often time-consuming step in radiotracer development. Microfluidic or lab-on-a-chip devices are modern tools for that purpose but not accessible everywhere. Inspired by 18F-chemistry in low volumes based on a MAX/MCX-trapping technique for one complete 18F-batch,[1] we herein present an 18F-labeling approach using low volume aliquots (<100 µL) of defined QMA-eluates in HPLC vials as reaction vessels for optimizations as well as the preparation of radiotracers for preclinical studies.

Methods: For optimization experiments, 1-80 MBq [18F]fluoride was eluted from QMA cartridges with defined mixtures of phase transfer catalyst (Kryptofix®222), base (such as K2CO3, KHCO3, KH2PO4), and 2-3% water in acetonitrile[2]. 25 or 50 µL aliquots of the eluates were pipetted into 1.5 mL HPLC vials and the sealed vials were consecutively dried once at 90°C for 3 min with a helium stream. After processing up to 15 vials in one batch, 25 or 50 µL precursor stock solution (1-20 mg/mL in MeCN, DMF, or DMSO) was added and the sealed vials were heated at defined temperatures (60-140°C) and times (5-15 min) by using three heaters equipped with aluminum blocks. Samples were 4-fold diluted with acetonitrile/water 50/50 for analysis by radio-TLC/radio-HPLC. 18F-trapping/elution at higher activity levels (~20 GBq [18F]fluoride) was performed by using a radiosynthesizer (Tracerlab FXFN) followed by transfer into a lead container having three small bores as inlet, vent needle and withdrawal port. A self-made pipet tip-to-cannula adapter allowed withdrawal of defined 25-100 µL aliquots at an activity level of ~13 MBq/µL for further processing under optimized conditions as described above.

Results: The use of small reaction volumes and HPLC vials enabled an efficient 18F-optimization workflow to examine rapidly a variety of reaction parameters (>50 reactions/day) using minimal amounts of precursor. Utilizing mixtures of 2-3% water in acetonitrile for 18F-elution allowed for radiolabeling even without azeotropic drying in certain cases, which can further accelerate the entire labeling process. For more demanding radiolabeling reactions, drying of only 3 min with helium furnished highly reactive [18F]fluoride with comparable reactivity even several hours after the elution step. This optimization workflow was used successfully to identify high yielding reaction conditions for a variety of precursor molecules like aliphatic tosylates or mesylates as well as aromatic sydnones, boronic acids or trimethylammonium salts. As examples, optimization results for 18F-labeling of the FDG mannose triflate precursor and the tosylate precursor of celecoxib-derivative [18F]A[3] are shown in Figure 1. Transfer into isolated RCY at activity levels suitable for preclinical evaluations was achieved (e.g. for [18F]A: 25-30% after 18F-labeling in acetonitrile at 90°C and purification) and turned out to be comparable to results from conventional automated radiosyntheses.

Conclusion: This microliter scale optimization and labeling procedure can easily be adapted and transferred to the synthesis of known and new radiotracers. The straightforward approach represents a valuable radiochemistry tool to enter rapidly into subsequent preclinical studies.

References: [1] Iwata (2018), J.Labelled.Comp.Radiopharm., 61, 540; [2] Kniess (2017), Appl.Radiat.Isot 127, 260; [3] Laube (2020), RSC Advances, 10, 38601.

Figure 1. Setup of HPLC vial experiments and representative results of optimization.

  • Poster (Online presentation)
    eSRS 2021, 17.-19.05.2021, Online, -

Publ.-Id: 33482

Pages: [1.] [2.] [3.] [4.] [5.] [6.] [7.] [8.] [9.] [10.] [11.] [12.] [13.] [14.] [15.] [16.] [17.] [18.] [19.] [20.] [21.] [22.] [23.] [24.] [25.] [26.] [27.] [28.] [29.] [30.] [31.] [32.] [33.] [34.] [35.] [36.] [37.] [38.] [39.] [40.] [41.] [42.] [43.] [44.] [45.] [46.] [47.] [48.] [49.] [50.] [51.] [52.] [53.] [54.] [55.] [56.] [57.] [58.] [59.] [60.] [61.] [62.] [63.] [64.] [65.] [66.] [67.] [68.] [69.] [70.] [71.] [72.] [73.] [74.] [75.] [76.] [77.] [78.] [79.] [80.] [81.] [82.] [83.] [84.] [85.] [86.] [87.] [88.] [89.] [90.] [91.] [92.] [93.] [94.] [95.] [96.] [97.] [98.] [99.] [100.] [101.] [102.] [103.] [104.] [105.] [106.] [107.] [108.] [109.] [110.] [111.] [112.] [113.] [114.] [115.] [116.] [117.] [118.] [119.] [120.] [121.] [122.] [123.] [124.] [125.] [126.] [127.] [128.] [129.] [130.] [131.] [132.] [133.] [134.] [135.] [136.] [137.] [138.] [139.] [140.] [141.] [142.] [143.] [144.] [145.] [146.] [147.] [148.] [149.] [150.] [151.] [152.] [153.] [154.] [155.] [156.] [157.] [158.] [159.] [160.] [161.] [162.] [163.] [164.] [165.] [166.] [167.] [168.] [169.] [170.] [171.] [172.] [173.] [174.] [175.] [176.] [177.] [178.] [179.] [180.] [181.] [182.] [183.] [184.] [185.] [186.] [187.] [188.] [189.] [190.] [191.] [192.] [193.] [194.] [195.] [196.] [197.] [198.] [199.] [200.] [201.] [202.] [203.] [204.] [205.] [206.] [207.] [208.] [209.] [210.] [211.] [212.] [213.] [214.] [215.] [216.] [217.] [218.] [219.] [220.] [221.] [222.] [223.] [224.] [225.] [226.] [227.] [228.] [229.] [230.] [231.] [232.] [233.] [234.] [235.] [236.] [237.] [238.] [239.] [240.] [241.] [242.] [243.] [244.] [245.] [246.] [247.] [248.] [249.] [250.] [251.] [252.] [253.] [254.] [255.] [256.] [257.] [258.] [259.] [260.] [261.] [262.] [263.] [264.] [265.] [266.] [267.] [268.] [269.] [270.] [271.] [272.] [273.] [274.] [275.] [276.] [277.] [278.] [279.] [280.] [281.] [282.] [283.] [284.] [285.] [286.] [287.] [288.] [289.] [290.] [291.] [292.] [293.] [294.] [295.] [296.] [297.] [298.] [299.] [300.] [301.] [302.] [303.] [304.] [305.] [306.] [307.] [308.] [309.] [310.] [311.] [312.] [313.] [314.] [315.] [316.] [317.] [318.] [319.] [320.] [321.] [322.] [323.] [324.] [325.] [326.] [327.] [328.] [329.]