Publications Repository - Helmholtz-Zentrum Dresden-Rossendorf

Purpose: to determine how ESTRO can collaborate with Radiation Oncology National Societies (NS) according to its mission and values, and to define the new roadmap to strengthen the NS network role in the forthcoming years.

Materials and methods: the ESTRO NS committee launched a survey addressed to all European National Societies, available online from June 5th to October 30th 2018. Questions were divided into three main sections: 1. general information about NS; 2. relevant activities (to understand the landscape of each NS context of action); 3. relevant needs (to understand how ESTRO can support the NS). Eighty-nine European NS were invited to participate. Respondents were asked to rank ESTRO milestones in order of importance, indicating the level of priority to their society.

Results: a total of 64 out of 89 NS (72%) from 32 European countries completed the questionnaire. The majority of NS ranked “Optimal patient care to cure cancer and to reduce treatment-related toxicity” as the highest level of priority. This aligns well with the ESTRO vision 2030 “Optimal health for all together.” NS also indicated a high need for more consensus guidelines and exchange of best practices, access to high quality accredited education, implementation of the ESTRO School Core Curriculum at the national level, and defining quality indicators and standard in Radiation Oncology, improved communication and increased channelling of information.

Conclusion: The results of this survey will be used to strengthen the relations between ESTRO and European NS to promote and develop initiatives to improve cancer care.

Introduction
Monocarboxylate transporters 1-4 (MCT1-4) are involved in several metabolism-related diseases, especially cancer, providing the chance to be considered as relevant targets for diagnosis and therapy. Recently, we reported on [18F]FACH as a novel MCT-targeting imaging agent (1), whose limited blood-brain barrier permeability, however, excludes application in brain diseases. Accordingly, we aimed to develop a more lipophilic FACH-derived radiotracer possessing higher brain uptake.
Materials and Methods
Two 2-fluoropyridinyl-substituted analogs of FACH (1 and 2) were obtained by Buchwald-Hartwig cross coupling reaction.
The potency of 1 and 2 to inhibit MCT1 was measured by [14C]lactate uptake assay using rat brain endothelial-4 cells. Radiolabeling of [18F]1 was proceeded using 1 mg nitro precursor and [18F]fluoride in the presence of Kryptofix and K2CO3 in dimethyl sulfoxide at 130 °C within 15 min. The logD7.4 value of [18F]1 was experimentally determined in the n-octanol-PBS system. For biological evaluation of [18F]1, in vitro autoradiography on cryosections of mouse kidney and small animal PET-MRI studies in female CD-1 mice were performed. Target specificity was proven by using the sodium salt of the MCT inhibitor α-cyano-4-hydroxycinnamic acid (α-CCA-Na).

Results
The analogs 1 and 2 inhibited MCT1 with IC50 values of 118 and 274 nM, respectively. [18F]1 was obtained by radiofluorination of the nitro precursor via nucleophilic aromatic substitution reaction with radiochemical yields of 73 ± 12% (n = 4, non-isolated, radio-HPLC), a high radiochemical purity of ˃ 98% and molar activities in the range of 180-200 GBq/µmol (n = 3, end of synthesis) using starting activities of 2-3 GBq. The logD7.4 value of 0.82 achieved for [18F]1 indicated 2-fold higher lipophilicity in comparison to [18F]FACH (2). In vivo and in vitro studies revealed high uptake of the new radiotracer in kidney and other peripheral MCT-expressing organs together with significant reduction by using α-CCA-Na (10 µM). The brain uptake of [18F]1 was similar to [18F]FACH without significant washout and an almost unchanged SUV of 0.15 between 15 and 60 min p.i.
Conclusion
Despite a higher lipophilicity of [18F]1 compared to [18F]FACH, the brain uptake of [18F]1 was in a similar low range, revealing the need for further structural modification. However, a high and specific uptake of the new radiotracer in the kidneys suggests suitability of [18F]1 for investigations on the expression of MCT in vivo.
References
(1) Sadeghzadeh M, et al. J Label Compd Radiopharm.2019; 62: 411-424.
(2) Sadeghzadeh M, et al. Sci Rep. 2019; 9: 18890-18897.

Introcution into the OpenFOAM activties at HZDR

A long-standing issue in persistent luminescence is settled by providing direct evidence that Dy³⁺ is the main electron trap in Sr₄Al₁₄O₂₅:Eu,Dy by combining laser excitation with X-ray spectroscopy. A reversible electron transfer is demonstrated, controlled by light and showing the same kinetics as the persistent luminescence. Exposure to violet light induces charging by oxidation of the excited Eu²⁺ while Dy³⁺ is simultaneously reduced. Oppositely, detrapping of Dy²⁺ occurs at ambient temperature or by infrared illumination, yielding afterglow or optically stimulated luminescence, respectively.

The liquid reaction in a submerged top-blow agitation process was studied using planar laser-induced fluorescence (PLIF) technology based on the principle of fluorescence quenching. The liquid reaction effects were analyzed using the reaction degree θ(t) and reaction time t95 under different conditions. The results show that the liquid reaction time decreases obviously for an increase in the air flow rate and submerged depth of the spray gun. The injection position of Fe3+ has a great influence on the reaction process; the reaction process is also different under other blowing conditions when Fe3+ is injected at the bottom. The reaction time of Fe3+ at the bottom injection position is higher than that at the top injection position; increasing the air flow rate and submerged depth of the spray gun can effectively reduce the difference in the reaction times at the two injection points. The effect of the injection position on the reaction time is eliminated when the spray gun submerged depth is close to the reactor bottom. The initial volume of Fe3+ has no obvious effect on the reaction time; however, an increase in the initial molarity of Fe3+ can decrease the reaction time.

We present a combined numerical, theoretical and experimental study on stimulated three-magnon splitting in a magnetic disk in the vortex equilibrium state. Our micromagnetic simulations and Brillouin-light-scattering results confirm that three-magnon splitting can be triggered even below threshold by exciting one of the secondary modes by magnons propagating in a waveguide next to the disk. The experiments show that stimulation is possible over an extended range of excitation powers and a wide range of frequencies around the eigenfrequencies of the secondary modes. Rate-equation calculations predict an instantaneous response to stimulation and the possibility to prematurely trigger three-magnon splitting even above threshold in a sustainable manner. These predictions are confirmed experimentally using time-resolved Brillouin-light-scattering measurements and are in a good qualitative agreement with the theoretical results. We believe that the controllable mechanism of stimulated three-magnon splitting could provide a possibility to utilize magnon-based nonlinear networks as hardware for reservoir or neuromorphic computing.

Phaeochromocytomas and paragangliomas (PPGL) are rare neuroendocrine tumours with a hereditary background in over one third of patients. Mutations in succinate dehydrogenase (SDH) genes increase the risk for PPGLs and several other tumours. Mutations in subunit B (SDHB) in particular are a risk factor for metastatic disease, further highlighting the importance of identifying SDH mutations for patient management. Genetic variants of unknown significance, where implications for the patient and family members are unclear, are a problem for interpretation. For such cases, reliable methods for evaluating protein functionality are required. Immunohistochemistry for SDHB (SDHB-IHC) is the method of choice, but does not assess functionality at the enzymatic level. Liquid chromatography mass spectrometry-based measurements of metabolite precursors and products of enzymatic reactions provides an alternative method. Here, we compare SDHB-IHC with metabolite profiling in 189 tumours from 187 PPGL patients. Besides evaluating succinate:fumarate ratios (SFR), machine learning algorithms were developed to establish predictive models for interpreting metabolite data. Metabolite profiling showed higher diagnostic specificity compared to SDHB-IHC (99.2% vs 92.5%, p=0.021), whereas sensitivity was comparable. Application of machine learning algorithms to metabolite profiles improved predictive ability over that of the SFR, in particular for hard-to-interpret cases of head and neck paragangliomas (AUC 0.9821 vs. 0.9613, p=0.044). Importantly, the combination of metabolite profiling with SDHB-IHC has complementary utility, as SDHB-IHC correctly classified all but one of the false-negatives from metabolite profiling strategies while metabolite profiling correctly classified all but one of the false-negatives/positives from SDHB-IHC. From 186 tumours with confirmed status of SDHx variant pathogenicity, the combination of the two methods resulted in 185 correct predictions, highlighting the benefits of both strategies for patient management.

The inducible isoenzyme cyclooxygenase-2 (COX-2) is closely associated with chemo-/radioresistance and poor prognosis of solid tumors. Therefore, COX-2 represents an attractive target for functional characterization of tumors by positron emission tomography (PET). In this study, the celecoxib derivative 3-([18F]fluoromethyl)-1-[4-(methylsulfonyl)phenyl]-5-(p-tolyl)-1H-pyrazole ([18F]5a) was chosen as a lead compound having a reported high COX-2 inhibitory potency and a potentially low carbonic anhydrase binding tendency. The respective deuterated analog [D2,18F]5a and the fluoroethyl-substituted derivative [18F]5b were selected to study the influence of these modifications with respect to COX inhibition potency in vitro and metabolic stability of the radiolabeled tracers in vivo. COX-2 inhibitory potency was found to be influenced by elongation of the side chain but, as expected, not by deuteration. An automated radiosynthesis comprising 18F-fluorination and purification under comparable conditions provided the radiotracers [18F]5a,b and [D2,18F]5a in good radiochemical yields (RCY) and high radiochemical purity (RCP). Biodistribution and PET studies comparing all three compounds revealed bone accumulation of 18F-activity to be lowest for the ethyl derivative [18F]5b. However, the deuterated analog [D2,18F]5a turned out to be the most stable compound of the three derivatives studied here. Time-dependent degradation of [18F]5a,b and [D2,18F]5a after incubation in murine liver microsomes was in accordance with the data on metabolism in vivo. Furthermore, metabolites were identified based on UPLC-MS/MS.

ImageJ/Fiji is a widely-used tool in the biomedical community for performing everyday image analysis tasks. However, its 3D viewer component (aptly named 3D Viewer) has become dated and is no longer actively maintained. We set out to create an alternative tool that not only brings modern concepts and APIs from computer graphics to ImageJ, but is designed to be robust to long-term, open-source development. To achieve this we divided the visualization logic into two parts: the rendering framework, scenery, and the user-facing application, sciview. In this paper we describe the development process and design decisions made, putting an emphasis on sustainable development, community building, and software engineering best practises. We highlight the motivation for the Java Virtual Machine (JVM) as a target platform for visualisation applications. We conclude by discussing the remaining milestones and strategy for long-term sustainability.

We present high-statistic data on charged pion emission from Au+Au collisions at sqrt(s_NN) = 2.4 GeV (corresponding to E_beam = 1.23 A GeV) in four centrality classes in the range 0 - 40% of the most central collisions. The data are analyzed as a function of transverse momentum, transverse mass, rapidity, and polar angle. Pion multiplicity per participating nucleon decreases moderately with increasing centrality. The polar angular distributions are found to be non-isotropic even for the most central event class. Our results on pion multiplicity fit well into the general trend of the world data, but undershoot by 2.5σ data from the FOPI experiment measured at slightly lower beam energy. We compare our data to state-of-the-art transport model calculations (PHSD, IQMD, PHQMD, GiBUU and SMASH) and find substantial differences between the measurement and the results of these calculations.

We report on the impact of nonlinear four-magnon scattering on magnon transport in microstructured waveguides with low magnetic damping. Using microfocused Brillouin light scattering, we analyze magnon propagation lengths in a broad range of excitation powers and observe a decrease of the attenuation length at high powers, which is consistent with the onset of nonlinear four-magnon scattering. Hence, when measuring magnon propagation lengths and deriving damping parameters from those results, one needs to be careful to stay in the linear regime. Otherwise, the intrinsic nonlinearity of magnetization dynamics may lead to a misinterpretation of magnon propagation lengths and, thus, to wrong values of the magnetic damping of the system.

Purpose: Prompt-gamma imaging (PGI) based range verification has been successfully implemented in clinical proton therapy recently and its sensitivity to detect treatment deviations is currently investigated. The cause of treatment deviations can be multiple - e.g. CT-based range prediction, patient setup, and anatomical changes. Hence, it would be beneficial, if PGI-based verification would not only detect a treatment deviation but would also be able to directly identify its most probable source. Here, we propose a heuristically derived decision tree approach to automatically classify the sources of range deviation in proton pencil-beam scanning (PBS) treatments of head and neck tumors based on range information obtained with a PGI slit camera.
Materials and Methods: The decision tree model was iteratively generated on a training dataset of different anatomical complexities, for an anthropomorphic head phantom and patient CT data (planning and control CTs) from 5 patients. Different range prediction errors, setup changes and relevant and non-relevant anatomical changes were introduced or derived from control CTs, summing up to a total of 98 training scenarios. Independent validation was performed for another 98 scenarios, derived solely from patient CT data of another 7 patients. PBS head and neck treatment plans were generated for the nominal scenario. For all PBS spots in the investigated field, PGI profiles were simulated using a dedicated analytical model of the slit camera for the nominal as well as the different error scenarios. From comparison of PGI profiles for nominal and error scenarios, a spot-wise range shift was determined for each error scenario. The heuristic approach includes a pre-filtering of the most suitable PBS spots for PGI treatment verification. From the validation, the accuracy, sensitivity and specificity of the model were determined.
Results: A five-step consecutive filter was developed to pre-select PBS spots. On average, 31% of spots (1044 spots) remained as input for the classification model. The derived heuristic decision tree model is based on five parameters: The coefficient of determination (R2), the slope and intercept of the linear regression between PGI-derived range shifts and the respectively predicted proton ranges for the investigated PBS spots, as well as the average and standard deviation of the PGI-derived shifts. With this approach, 94 of 98 error scenarios could be classified correctly in validation (accuracy of 96%). A sensitivity and specificity of 100% and 86% was reached.
Conclusions: In this simulation study it was demontrated that the source of a treatment deviation can be identified from simulated PGI information in head and neck tumor treatments with high sensitivity and specificity. The application, refinement and evaluation of the approach on measured PGI data will be the next step to show the clinical feasibility of PGI-based error source classification.

Consistent cerebral blood flow (CBF) is fundamental to brain function. Cerebral autoregulation ensures CBF stability. Chronic hypertension can lead to disrupted cerebral autoregulation in older people, potentially leading to blood pressure levels interfering with CBF. We investigated the associations of CBF with blood pressure and antihypertensive treatment, using arterial spin labelling MRI, in a prospective longitudinal cohort of 186 community-dwelling older individuals (77±3 years, 53% female) with hypertension, 125 (67%) of whom with 3-year follow-up. We assessed concurrent and longitudinal associations of diastolic blood pressure, systolic blood pressure, mean arterial pressure, pulse pressure, and antihypertensive drug use, with grey matter and white matter CBF (mL/100g/min), and the CBF spatial coefficient of variation (SCoV): a measure of CBF heterogeneity which may be more sensitive to cerebrovascular damage. We found no associations between blood pressure and concurrent CBF, nor between changes in blood pressure and CBF over 3-year follow-up. Antihypertensive use was associated with lower CBF and higher SCoV. Within antihypertensive types, calcium channel blockers and angiotensin receptor blockers were not associated with lower CBF. This aligns with previous evidence suggesting a protective effect of these antihypertensive classes on dementia, and may provide an important lead for future research.

In the last decade, there have been extensive efforts to open up the Eph/ephrin subfamily of the receptor tyrosine kinase family for diagnostic and therapeutic applications. Besides classical pharmaceutical developments, which focus either on drugs targeting the extracellular ligand binding domains or the intracellular tyrosine kinase domains of these receptors, there also have been first radiopharmaceutical approaches. Here the focus is on the development of specific and selective probes for molecular imaging, particularly, by means of positron emission tomography, and the functional characterization of the Eph/ephrin subfamily in certain target tissues. The aim of this mini-review is to summarize the different approaches towards Eph-targeting radiotracers by using antibodies, peptides, and small molecules, and to discuss their radiopharmacological characterization. With regard to the small molecules, further considerations will focus on the design and synthesis of non-radioactive reference compounds and precursors as well as on radiolabeling strategies.

The Institute of Ion Beam Physics and Materials Research conducts materials research for future applications in, e.g., information technology. To this end, we make use of the various possibilities offered by our Ion Beam Center (IBC) for synthesis, modification, and analysis of thin films and nanostructures, as well as of the free-electron laser FELBE at HZDR for THz spectroscopy. The analyzed materials range from semiconductors and oxides to metals and magnetic materials. They are investigated with the goal to optimize their electronic, magnetic, optical as well as structural functionality. This research is embedded in the Helmholtz Association’s programme “From Matter to Materials and Life”. Seven publications from last year are highlighted in this Annual Report to illustrate the wide scientific spectrum of our institute.
After the scientific evaluation in the framework of the Helmholtz Programme-Oriented Funding (POF) in 2018 we had some time to concentrate on science again before end of the year a few of us again had to prepare for the strategic evaluation which took place in January 2020, which finally was also successful for the Institute.
In 2019, there have been a number of organizational changes. First, and most prominently, we were able to hire Prof. Dr. Anton Wallner as new head of our department Accelerator Mass Spectrometry (AMS) and Isotope Research. This appointment is jointly with the TU Dresden where Toni has recei¬ved a chair in the Institute of Nuclear and Particle Physics. Along with this employment, our scientific advisory board and board of trustees approved the acquisition of a dedicated 1 MV accele¬rator for AMS including a laser detachment system. With this move, we hope to widen the scope of the user facility Ion Beam Center to new user communities in the field of nuclear astrophysics, environmental and geosciences. Second, the department Ion Beam Center is now headed by Dr. Stefan Facsko, who took over the responsibility from Dr. Johannes von Borany who stepped down for partial retirement. Stefan has been working in the Ion Beam Center since 2003 in various functions and is one of our most established researchers. We wish him all the best for this responsible position. Third, after the successful evaluation of Dr. Denys Makarov we created a new department Intelligent Materials and Devices, which is now headed by Denys. For his outstanding work in the field of mag¬netic sensor technology he also received the HZDR Research Award 2019. In the same ceremony, Dr. Jacob König-Otto received the HZDR Doctoral Prize 2019 for his dissertation at our Institute. Fourth, in fall we struck a new path and created a young researcher group on “Immuno-oncology on a chip: nano-assisted screening for cancer therapy” across disciplines and Institutes headed by Dr. Larysa Baraban. Larysa heads a group in the Institute of Radiopharmaceutical Cancer Research and collabo¬rates closely with our colleagues Dr. Artur Erbe on nanodevices and Dr. Denys Makarov on sensorics. We believe that this synergetic approach will pave the way to a fast and cost-efficient screening technology for personalized health care.
Again, in 2019, the level of newly received third-party funding was very good. In particular, we received the funding for two Helmholtz Innovation Laboratories (HIL); one on thermal treatment technology for defect engineering (UltraTherm) headed by Dr. Lars Rebohle and one on flexible sensors (FlexiSens) headed by Dr. Denys Makarov. The main emphasis of both HILs is to provide support of and technology transfer to small and medium enterprises in the respective technological areas. We are sure that in addition to our ion technology service provided via the HZDR Innovation GmbH both Innovation Labs will boost our technology transfer activities.
Several conferences and workshops were organized by scientists from our institute: the “Ion Beam Physics Workshop” as the annual meeting of the German Ion Beam Community was organized by Dr. Stefan Facsko and attracted around 50 participants to discuss the newest national developments and research in the field of ion beam physics. In addition, the “3rd European Focused Ion Beam Network Workshop” was organized by Dr. Hans-Jürgen Engelmann and co-workers; 135 participants from 17 countries found their way to HZDR to discuss current research topics and exchange experience in Focused-Ion-Beam (FIB) and Scanning-Electron-Microscopy (SEM) work.
Finally, we would like to cordially thank all partners, friends, and organizations who supported our progress in 2019. Special thanks are due to the Executive Board of the Helmholtz-Zentrum Dresden-Rossendorf, the Minister of Science and Arts of the Free State of Saxony, and the Ministers of Education and Research, and of Economic Affairs and Energy of the Federal Government of Germany. Numerous partners from universities, industry and research institutes all around the world contributed essentially, and play a crucial role for the further development of the institute. Last but not least, the directors would like to thank again all members of our institute for their efforts and excellent contributions in 2019.

Dear Colleagues,

Theoretical calculations and computer simulations are very important methods to improve our understanding of atomic-level processes in materials and to extend our knowledge on their static, dynamic, kinetic, and thermodynamic properties. Furthermore, the response of the material to external pertubations, in particular mechanical or thermal load and irradiation, can be studied using such computational techniques. This Special Issue of Materials shall include articles dealing with applications of first-principle density functional theory (DFT) and atomistic modelling based on interatomic potentials (AM). Both techniques are widely used to investigate ground state properties, finite-temperature effects, and dynamic processes. Based on the fundamental data delivered by DFT or AM, Monte Carlo simulations are employed to study the thermodynamics and kinetics of the respective materials. The present issue shall also include publications in which such a combination of the different computational methods is presented and be focused on solid inorganic materials with a crystalline or amorphous structure. Short communications on recent results, original research articles, as well as reviews may be submitted. This issue provides the opportunity for a detailed explanation of new computational techniques and for the publication of results obtained by the application of known theoretical methods to nonconventional classes of materials.

Dr. Matthias Posselt
Guest Editor

Contributions were submitted continuously from 2019 to 2021 and published after peer review.
Final Status (March 2021): 10 Articles, 1 Letter, 1 Editorial
https://www.mdpi.com/journal/materials/special_issues/Princ_Model

The combination of different exotic properties in materials paves the way for the emergence of their new potential applications. An example is the recently found coexistence of the mutually antagonistic ferromagnetism and superconductivity in hydrogenated boron-doped diamond, which promises to be an attractive system with which to explore unconventional physics. Here, we show the emergence of Yu-Shiba-Rusinov (YSR) bands with a spatial extent of tens of nanometers in ferromagnetic superconducting diamond using scanning tunneling spectroscopy. We demonstrate theoretically how a two-dimensional (2D) spin lattice at the surface of a three-dimensional (3D) superconductor gives rise to the YSR bands and how their density-of-states profile correlates with the spin lattice structure. The established strategy to realize new forms of the coexistence of ferromagnetism and superconductivity opens a way to engineer the unusual electronic states and also to design better-performing superconducting devices.

The package enables reading and writing binary and ASCII data to RS232/RS422/RS485 or any other virtual serial interface of the computer. The major extensions are made with new functions and an improved robustness.

Background
The targeting accuracy of proton therapy (PT) for moving soft-tissue tumours is expected to greatly improve by real-time magnetic resonance imaging (MRI) guidance. The integration of MRI and PT at the treatment isocenter would offer the opportunity of combining the unparalleled soft-tissue contrast and real-time imaging capabilities of MRI with the most conformal dose distribution and best dose steering capability provided by modern PT. However, hybrid systems for MR-integrated PT (MRiPT) have not been realized so far due to a number of hitherto open technological challenges. In recent years, various research groups have started addressing these challenges and exploring the technical feasibility and clinical potential of MRiPT. The aim of this contribution is to review the different aspects of MRiPT, to report on the status quo and to identify important future research topics.

Methods
Four aspects currently under study and their future directions are discussed: modelling and experimental investigations of electromagnetic interactions between the MRI and PT systems, integration of MRiPT workflows in clinical facilities, proton dose calculation algorithms in magnetic fields, and MRI-only based proton treatment planning approaches.

Conclusions
Although MRiPT is still in its infancy, significant progress on all four aspects has been made, showing promising results that justify further efforts for research and development to be undertaken. First non-clinical research solutions have recently been realized and are being thoroughly characterized. The prospect that first prototype MRiPT systems for clinical use will likely exist within the next 5 to 10 years seems realistic, but requires significant work to be performed by collaborative efforts of research groups and industrial partners.

Purpose.
First-line treatment of patients with recurrent, metastatic prostate cancer involves hormone therapy with or without additional systemic therapies. Prostate-specific membrane antigen (PSMA) positron emission tomography (PET)/computed tomography (CT) allows the detection of oligometastatic disease that may be amenable to image-guided radiotherapy. The current study classifies the type and localization of metastases and the clinical outcome of PSMA-PET/CT-guided radiotherapy to selected metastases.
Materials and methods.
Between 2011 and 2019, 86 patients with recurrent, oligometastatic prostate carcinoma were identified by PSMA-PET/CT and were treated with image-guided radiotherapy of their metastases. Sites of relapse were characterized, and the primary endpoint overall survival (OS), biochemical progression-free survival (bPFS), and androgen deprivation therapy (ADT)-free survival were tabulated.
Results
In total, 37% of the metastases were bone metastases, 48% were pelvic nodalmetastases, and 15% were nodalmetastases outside of the pelvis. After PSMA-guided radiotherapy, a biochemical response was detected in 83% of the cohort. A statistically significant decrease in the standard uptake value (SUV) was seen in irradiated metastases. After a median follow-up of 26 months, the 3-year OS and bPFS were 84% and 55%, respectively. The median time of ADT-free survival was 13.5 months. A better clinical outcome was observed for patients receiving concomitant ADT or more than 24 fractions of radiation.
Conclusion.
PSMA-guided radiotherapy is a promising therapeutic approach with excellent infield control for men with oligorecurrent prostate carcinoma. However, prospective, randomized trials are necessary to determine if this approach confers a survival advantage.

The deformation of the free surface of a paramagnetic liquid subjected to a non-uniform magnetic field has been studied. A transient deformation of the surface caused by the interplay of gravity, magnetic field and surface tension is observed when a permanent magnet is moved vertically downwards to the free surface of the liquid. Different concentrations of rare-earth metal salt (DyCl 3 ) were used and different magnet velocities were studied. The deformation of the interface was followed optically by means of a microscope and recorded with a high-speed camera. The experimental results are compared and discussed with complementary numerical simulations. Detailed results are given for the static shape of the deformed surface and the temporal evolution of the surface deformation below the center of the magnet. The frequency of the surface oscillations is found to depend on the concentration of the salt and is compared with analytical findings. Finally, a potential application of the effects observed is presented.

For the first time, a low-field open magnetic resonance (MR) scanner was combined with a proton pencil beam scanning (PBS) research beamline. The aim of this study was to characterize the magnetic fringe fields produced by the PBS system and measure their effects on MR image quality during simultaneous PBS irradiation and image acquisition. A magnetic field camera measured the change in central resonance frequency (Δfres) and magnetic field homogeneity (ΔMFH) of the B0 field of the MR scanner during operation of the beam transport and scanning magnets. The beam energy was varied between 70−220 MeV and beam scanning was performed along the central horizontal and vertical axis of a 48 × 24 cm2 radiation field. The time structure of the scanning magnets’ fringe fields was simultaneously recorded by a tri-axial Hall probe. MR imaging experiments were conducted using the ACR (American College of Radiology) Small MRI Phantom and a spoiled gradient echo pulse sequence during simultaneous volumetric irradiation. Computer simulations were performed to predict the effects of B0 field perturbations due to PBS irradiation on MR image formation in k-space. Setting the beam transport magnets, horizontal and vertical scanning magnets resulted in a maximum Δfres of 50, 235 and 4 Hz, respectively. The ΔMFH was less than 3 ppm for all measurements. MR images acquired during beam energy variation and vertical beam scanning showed no visual loss in image quality. However, MR images acquired during horizontal beam scanning showed severe coherent ghosting artefacts in phase encoding direction. Both simulated and measured k-space phase maps prove that these artefacts are caused by phase-offsets. This study shows first experimental evidence that simultaneous in-beam MR imaging during proton PBS irradiation is subject to severe loss of image quality in the absence of magnetic decoupling between the PBS and MR system.

A broadband infrared (IR) light-emitting diode (LED) for versatile spectroscopic use is constructed, based on a novel type of broadband IR luminescence. This peculiar emission is identified in europium and terbium codoped CaS for which the spectrum partially overlaps with the red Eu2+ emission and ranges up to 1200 nm. It can be efficiently excited with visible light. Experimental evidence for metal-to-metal charge transfer (MMCT) luminescence is collected, comprising data from luminescence spectroscopy, microscopy and X-ray spectroscopy. State-of-the-art multiconfigurational ab initio calculations allow to attribute the infrared band to the radiative decay of a metastable MMCT state of a Eu2+-Tb3+ pair. The calculations explain why no MMCT emission is found in the similar compound SrS:Eu,Tb and are used to anticipate how to fine-tune the characteristics of the MMCT luminescence.

The complexation of NpO2+ with lactate in aqueous solution is studied as a function of the total ligand concentration ([Lac-]total), ionic strength (Im = 0.5 – 4.0 mol kg-1 Na+(Cl-/ClO4-)) and temperature (T = 20 – 85 °C) by Vis/NIR absorption spectroscopy. The formation of two NpO2+ lactate species with the stoichiometry NpO2(Lac)n1-n (n = 1, 2) is observed at the studied experimental conditions. The temperature dependent conditional stability constants log beta 'j(T) at different ionic strengths are calculated with the law of mass action. The conditional data are extrapolated to IUPAC reference state conditions (Im = 0) with the specific ion interaction theory (SIT). With increasing temperature up to 85 °C log beta 01(20 °C) = 1.92 ± 0.14 decreases by 0.12 and log beta 02(20 °C) = 2.10 ± 0.13 decreases by 0.17. The thermodynamic stability constants correlate linearly with the reciprocal temperature according to the integrated Van’t Hoff equation. Thus, linear regression analyses yield the standard reaction enthalpy delta rH0 and entropy delta rS0 for the complexation reactions. In addition, the sum of the SIT specific binary ion-ion interaction coefficients delta epsilon j,k(T) of the complexation reactions are determined by variation of the ionic strength.
Structural parameters of the formed complex species and the coordination mode of lactate towards the NpO2+ ion are investigated as a function of pHc by extended x-ray absorption fine structure spectroscopy (EXAFS) and attenuated total reflection Fourier-transform infrared spectroscopy (ATR-FT IR). The results show, that the coordination mode of lactate changes from end-on (coordination via only the COO- group) to side-on (formation of chelate rings involving the OH-group) with increasing pHc. The experiments are supported by quantum chemical calculations.

The role of prophylactic cranial irradiation (PCI) and thoracic radiotherapy (TRT) is unclear in resected small cell lung cancer (SCLC). Methods: Thirteen European radiotherapy experts on SCLC were asked to describe their strategies on PCI and TRT for patients with resected SCLC. The treatment strategies were converted into decision trees and analyzed for consensus and discrepancies. Results: For patients with resected SCLC and positive lymph nodes most experts recommend prophylactic cranial irradiation and thoracic radiotherapy. For elderly patients with resected node negative SCLC, most experts do not recommend thoracic radiotherapy or prophylactic cranial irradiation. Conclusion: PCI and TRT are considered in patients with resected SCLC and these treatments should be discussed with the patient in the context of shared decision-making.

Radiotherapy is a four-dimensional geometrical challenge. For modern radiotherapy planning, gross tumour volume (GTV) is pictured before treatment using CT scanning fused with anatomical and functional imaging. To account for microscopic tumour spread, a safety margin is added to the GTV and corrected for anatomical boundaries to determine the clinical target volume (CTV). Finally, systematic and random errors occurring during the fractionated course of radiotherapy are corrected for by adding another safety margin.

Classical robust optimization considers uncertainties in patient setup and particle range. Usually plan robustness is evaluated from calculation of perturbed dose distributions based on the planning CT, without considering potential anatomical changes that may occur during the treatment course. Our aim was to compare the overall plan robustness of classical robust optimization (cRO) with the recently proposed anatomical robust optimization (aRO) based on an integral multi-scenario evaluation, considering all types of uncertainties including anatomical variations.

Polymer electrolyte fuel cells and electrolysers are low temperature devices whereby both gases and liquids intermingle within the porous transport layers and open channels. The flow of the liquid and gas is of paramount importance to the functioning of the unit. This motion is poorly understood. Cell-level models typically employ volume-averaging techniques to describe the motion of the flowing reactants and products. Until recently, detailed analysis of the two-phase liquid gas mixture, employing front-tracking methods has proved to be computationally prohibitive. Previous work has considered the motion of liquid drops in gas channels, it being assumed the drops are formed at specific nucleation sites on the sides of the channels. The present work considers a detailed numerical analysis of combined liquid-gas co-flow in a gas channel with liquid-gas counter-flow in a porous transport layer, (PTL). The geometry considered is in the form of a ‘T-shape’ with the porous transport layer of a thin rectangular prism of dimensions 0.5×0.5×0.1 mm3 located at the base of the ‘T’, and the gas flowing across the top in channel. The PTL is reproduced by digital reconstruction of nano-computer tomography images of a Freudenberg H2315 PTL as a sterolithography file. From this, the domain is tessellated with an unstructured castellated, or octree, type mesh. Liquid water is introduced at an electrode at the base of the PTL and gaseous oxygen is simultaneously removed by electrochemical reduction; the resulting liquid-gas counter flow in the porous transport layer results in liquid droplets being entrained in co-flow in the gas channels and convected downstream.

The equations of mass and momentum are solved by means of the open source software library OpenFOAM. A volume-of-fluid approach based on the multidimensional universal limiter for explicit solution was employed within a volume-of-fluid method. At T = 0, the channel is presumed to be filled with gas, and the PTL saturated with liquid water. Gas is introduced at the inlet at a given velocity. Water is added and gas removed at the electrode (counter flow) whereas both water and gas are removed at the outlet (coflow). At the channel and PTL walls as well as on the GDL fibres, the static contact angle was fixed. It can be seen that the location and size of the shed drops varies somewhat in space and time, i.e., there is a stochastic component to the motion of the fluid, due to the spatial distribution of the fibres in the PTL, the transient shedding process, and the merging of liquid streams flowing into the gas channel. Nonetheless, a definite periodicity is observed with drops being injected into the channel at a fairly regular rate. Some relatively minor switching with time is observed within the PTL due to the random packing of fibres, but again these transients are relatively quiescent, as might be expected for porous media flow.

In addition to providing new and important information about flow and pressure losses in channels and PTLs of electrochemical cells as a function of gas and liquid flow rates, i.e. current density and stoichiometry, the present model may be also used to enumerate properties such as relative permeability which can subsequently be employed in cell-scale models.

Intricate topographical patterns can form on the surface of crystalline Ge(001) subject to low-energy ion irradiation in the reverse epitaxy regime, i.e., at elevated temperatures which enable dynamic recrystallization. We compare such nanoscale patterns produced by irradiation from varied polar and azimuthal ion incidence angles with corresponding calculated surface topographies. To this end, we propose a continuum equation including both anisotropic erosive and anisotropic diffusive effects. Molecular dynamics simulations provide the coefficients of angle-dependent sputter erosion for the calculations. By merely changing these coefficients accordingly, the experimentally observed surface morphologies can be reproduced, except for extreme ion incidence angles. Angle-dependent sputter erosion is thereby identified as a dominant mechanism in ion-induced pattern formation on crystalline surfaces under irradiation from off-normal incidence angles.

Arrays of interacting 2D nanomagnets display unprecedented electromagnetic properties via collective effects, demonstrated in artificial spin ices and magnonic crystals. Progress toward 3D magnetic metamaterials is hampered by two challenges: fabricating 3D structures near intrinsic magnetic length scales (sub-100 nm) and visualizing their magnetic configurations. Here, we fabricate and measure nanoscale magnetic gyroids, periodic chiral networks comprising nanowire-like struts forming three-connected vertices. Via block copolymer templating, we produce Ni75Fe25 single-gyroid and double-gyroid (an inversion pair of single-gyroids) nanostructures with a 42 nm unit cell and 11 nm diameter struts, comparable to the exchange length in Ni–Fe. We visualize their magnetization distributions via off-axis electron holography with nanometer spatial resolution and interpret the patterns using finite-element micromagnetic simulations. Our results suggest an intricate, frustrated remanent state which is ferromagnetic but without a unique equilibrium configuration, opening new possibilities for collective phenomena in magnetism, including 3D magnonic crystals and unconventional computing.

Controlled doping with an effective carrier concentration higher than 10^20 cm-3 is a key challenge for the full integration of Ge into silicon-based technology. Such a highly doped layer of both p- and n type is needed to provide ohmic contacts with low specific resistance. We have studied the effect of ion implantation parameters i.e., ion energy, fluence, ion type, and protective layer on the effective concentration of electrons. We have shown that the maximum electron concentration increases as the thickness of the doping layer decreases. The degradation of the implanted Ge surface can be minimized by performing ion implantation at temperatures that are below -100 C with ion flux less than 60 nAcm-2 and maximum ion energy less than 120 keV. The implanted layers are flash-lamp annealed for 20 ms in order to inhibit the diffusion of the implanted ions during the recrystallization process.

Good manufacturing practice (GMP) is a crucial part in the production of medicinal products. The quality and safety of medicinal products play an essential role in good manufacturing practice. Radiopharmaceuticals that are used in nuclear medicine for the diagnosis and therapy of diseases are also defined as medicinal products but at the same time underlie radiation safety regulations which is often contradictive to good manufacturing practice regulations. In principle, radiopharmaceuticals can legally wise be divided into three groups, namely radiopharmaceuticals that are holding a marketing authorization, radiopharmaceuticals that are used in clinical trials and radiopharmaceuticals that are prepared extemporaneously. In Europe a large variety of regulations with regards to good manufacturing practice for radiopharmaceuticals is observed and leads sometimes to confusion for large-scale manufacturer of radioactive pharmaceuticals, investigators of clinical trials or a small radiopharmacy in a nuclear medicine hospital department. This chapter gives an overall overview on the existing binding and non-binding regulatory documents issued by important organizations and stakeholders and shows guidelines taking the specific character and requirements of radiopharmaceuticals into account.

Janus nano/micromotors have been developed into various sizes, shapes and functions for a blaze of applications especially in biomedical and environmental fields. Here, we report a fabrication method of Janus micromotors by capping hydrogel microspheres with functional nanoparticles (NPs). Microspheres are prepared in droplet microfluidics relying on hydrogel polymerization to obtain spheres with diameters from 20 μm to 500 μm. By solidifying a hydrogel layer onto microspheres, functional NPs of MnO2 (catalyst of H2O2), TiO2 (photocatalyst) and Fe3O4 (magnetic guidance) are adhered onto microspheres resulting in Janus micromotors revealing different functionalities. We explore dynamics of Janus micromotors (diameter around 250 µm) by analyzing their trajectories in terms of mean squared displacement (MSD) when immersed in H2O2 solutions of different concentrations, illuminated by light and guided in an external magnetic field. TiO2 Janus micromotors perform well for water purification tasks as we exemplarily demonstrate with a degradation of Methylene Blue dye in water. The proposed fabrication method is versatile and enables to achieve adjustable coverage of a microsphere with NPs as well as to realize multi-functional Janus micromotors by adhering different NPs (e.g., MnO2 and Fe3O4) on a sphere. This method provides an attractive way to fabricate multifunctional Janus micromotors in a cost-effective manner for environmental applications.

Dy₂Fe₁₄Si₃ (hexagonal crystal structure of the Th₂Ni₁₇ type) is a highly-anisotropic ferrimagnet with spontaneous magnetic moment M_s=8µB per formula unit (at 2 K), directed along the Fe sublattice, and Curie temperature T_C=500 K. The magnetic anisotropy is of the easy-plane type with the [100] axis as an easy magnetization direction. Large anisotropy is observed also within the basal plane. In fields applied along the [100] and [120] axes, field-induced phase transitions were observed at 33 T (of thefirst order) and at 41 T (of the second order), respectively (at 2 K). Relative changes of sound velocity and changes of sound attenuation at these phase transitions in a Dy₂Fe₁₄Si₃ single crystal were measured in pulsed magneticfields up to 58 T at 2 K and elevated temperatures. The performed theoretical analysis suggests that the interaction of the elastic subsystem with the magnetic one is of the exchange-striction nature.

Background: In limited disease small cell lung cancer, the convert trial has demonstrated similar results with once-daily (QD) radiotherapy (66 Gy) and twice-daily (BID) radiotherapy (45 Gy). The selection among these regimes may be influenced by several factors. Methods: Thirteen European radiotherapy experts in SCLC as defined by the European Society for Therapeutic Radiation Oncology (ESTRO) were asked to describe their strategies in the management of LD-SCLC. The decision criteria were unified, the strategies were converted into decision trees and analysed for consensus and discrepancies. Results: Logistical reasons, performance status of the patient and dose constraints were the three major decision criteria used by most experts in decision making. The use of QD and BID regimes was balanced among European experts, but there was a trend towards the BID regime for fit patients able to travel twice a day to the radiotherapy site. Conclusion: BID and QD radiotherapy are both accepted treatment options among experts and the decision may be influenced by pragmatic factors such as availability of transportation.

Background and purpose: Tumor hypoxia plays an important role in head and neck squamous cell carcinomas (HNSCC). Various positron emission tomography (PET) tracers promise non-invasive assessment of tumor hypoxia. So far, the applicability of hypoxia PET is hampered by monocentric imaging trials with few patients.
Materials and methods: Multicenter individual patient data based meta-analysis of the original PET data from four prospective imaging trials was performed. All patients had localized disease and were treated with curatively intended radio(-chemo)therapy. Hypoxia PET imaging was performed with 18F-Fluoromisonidazole (FMISO, 102 patients) or 18F-Fluoroazomycin-arabinoside (FAZA, 51 patients). Impact of hypoxia PET parameters on loco-regional control (LRC) and overall survival (OS) was analyzed by uni- and multivariable Cox regression.
Results: Baseline characteristics between participating centers differed significantly, especially regarding T stage (p<0.001), tumor volume (p<0.001) and p16 status (p=0.009). The commonly used hypoxia parameters, maximal tumor-to-muscle ratio (TMRmax) and hypoxic volume with 1.6 threshold (HV1.6), showed a strong association with LRC (p=0.001) and OS (p<0.001).
These findings were irrespective of the radiotracer and the same cut-off values could be applied for FMISO and FAZA (TMRmax>2.0 or HV1.6>1.5 ml). The effect size of TMRmax was similar for subgroups of patients defined by radiotracer, p16 status and FDG-PET parameters for LRC and OS, respectively.
Conclusion: PET measured hypoxia is robust and has a strong impact on LRC and OS in HNSCC. The most commonly investigated tracers FMISO and FAZA can probably be used equivalently in multicenter trials. Optimal strategies to improve the dismal outcome of hypoxic tumors remain elusive.

Bentonites may be used as a buffer and backfill material in future deep geological repositories of high-level radioactive waste. These clay formations have been reported to host different metabolically active microorganisms with the potential to affect the biogeochemical cycles of carbon, phosphorus and sulfur. Therefore, low porosity bentonites with high swelling capacity might prevent several microbial processes, such as corrosion. In addition, microorganisms occurring in bentonite may be able to interact with released radionuclides affecting their fate and behavior and leading to their mobilization or immobilization.
This chapter reviews the latest findings on the structure and composition of microbial communities in bentonites under repository relevant conditions (high temperature, high pressure, presence of electron donors/acceptors, etc.), to underline the importance of the microbial activity for the long-term effectiveness of the repository. Both, laboratory and large-scale experiment results will be summarized and discussed. In addition, the impact of microbial processes on the mobilization of radionuclides at the bentonite/microbe/radionuclide interface will be reviewed. A multidisciplinary approach combining microscopy, spectroscopy, radiochemistry and microbiology-based techniques used to study the speciation of radionuclides will be highlighted.

Geological objects are characterized by a high complexity inherent to a strong compositional variability at all scales and usually unclear class boundaries. Therefore, dedicated processing schemes are required for the analysis of such data for mineral mapping. On the other hand, the variety of optical sensing technology reveals different data attributes and therefore multi-sensor approaches are adapted to solve such complicated mapping problems. In this paper, we devise an adapted multi-optical sensor fusion (MOSFus) workflow which takes the geological characteristics into account. The proposed processing chain exhaustively covers all relevant stages, including data acquisition, preprocessing, feature fusion, and mineral mapping. The concept includes i) a spatial feature extraction based on morphological profiles on RGB data with high spatial resolution, ii) a specific noise reduction applied on the hyperspectral data that assumes mixed sparse and Gaussian contamination and iii) a subsequent dimensionality reduction using a sparse and smooth low rank analysis. The feature extraction approach allows to fuse heterogeneous data at variable resolutions, scales, and spectral ranges as well as improve classification substantially. The last step of the approach, an SVM classifier, is robust to unbalanced and sparse training sets and is particularly efficient with complex imaging data. We evaluate the performance of the procedure with two different multi-optical sensor datasets. The results demonstrate the superiority of this dedicated approach over common strategies.

In a quantum mechanical description of the free-electron laser (FEL), the electrons jump on discrete momentum ladders, while they follow continuous trajectories according to the classical description. In order to observe the transition from quantum to classical dynamics, it is not sufficient that many momentum levels are involved. Only if additionally the initial momentum spread of the electron beam is larger than the quantum mechanical recoil, caused by the emission and absorption of photons, the quantum dynamics in phase space resembles the classical one. Beyond these criteria, quantum signatures of averaged quantities like the FEL gain might be washed out.

Purpose: Quantification of range uncertainty in proton treatment planning using dual-energy computed tomography (DECT) for direct stopping-power prediction (DirectSPR) and its clinical implementation.
Methods and materials: To assess the overall uncertainty in stopping-power ratio (SPR) prediction of a DirectSPR implementation calibrated for different patient geometries, the influencing factors were categorized in imaging, modelling as well as others. The respective SPR uncertainty was quantified for lung, soft tissue and bone and translated into range uncertainty for several tumor entities. The uncertainty assessment was experimentally validated in various phantom geometries and compared to the standard look-up-table (HLUT) approach. Finally, the dosimetric effect of the assessed margins was quantified for a representative brain tumor patient.
Results: For bone, soft tissue and lung, an SPR uncertainty (1𝜎) of 1.6%, 1.3% and 1.3% was determined for DirectSPR, respectively. This allowed for a reduction of the clinically applied range uncertainty from currently (3.5%+2mm) to (1.7%+2mm) for brain tumor patients and (2.0%+2mm) for
prostate-cancer patients. In all phantom validation setups, DirectSPR outperformed the HLUT approach, with an accuracy in SPR prediction as high as 0.3% in an anthropomorphic head phantom (0.7% using HLUT). In the representative patient case, a dose reduction in organs at risk close-by to the target volume was achieved, with a mean dose reduction of up to 16% in the brainstem. Patient-specific DECT-based treatment planning with reduced safety margins was successfully introduced into clinical routine at our institute in April 2019. Within the first year, 90 brain-tumor and 60 prostate-cancer patients were treated using DirectSPR.
Conclusions: A substantial reduction of range uncertainty in clinical proton treatment planning was achieved by patient-specific DECT-based SPR prediction. Thereby, for the first time since the initial introduction of range margins in proton therapy in the 1980s, a relevant reduction of range uncertainty on a 2% level was achieved.

Polycrystalline Ba₄NbIr₃O₁₂ has recently been shown to be a promising spin liquid candidate. We report an easy and reliable method to grow millimeter-sized single crystals of this trimer-based spin liquid candidate material with the actual stoichiometry of Ba₄Nb_0.8Ir_3.2O₁₂. The growth of large crystals is achieved using BaCl as flux. The crystals show a hexagonal platelike habit with edges up to 3 mm in length. The structure is confirmed by single-crystal X-ray diffraction and is found to be the same as that of the previously reported phase Ba₁₂Nb_2.4Ir_9.6O₃₆ [Ba₄Nb_0.8Ir_3.2O₁₂], indeed with a mixed occupancy of Nb/Ir at the 3a site. The magnetic and calorimetric study on the individual single crystals confirms the possibility of a spin liquid state consistent with a recent report on a polycrystalline sample.

Stratified flows of water and steam can appear in the primary system of a pressurized water reactor during a hypothetical loss-of-coolant accident. Among others, important safety concerns during cold water injection of the emergency core cooling system include the pressurized thermal shock and the possible formation of a condensation induced water hammer. Both mechanisms could cause significant thermal and mechanical stresses on the components of the primary system. Thorough knowledge of turbulent heat and mass transfer processes near the interface is required for safety analyses of both phenomena.
Measurements of industrially relevant turbulent two-phase flows tend to be difficult; therefore computational fluid dynamics simulations represent an important additional analytical tool. The main objective of the present research and development is to advance the capabilities of current state-of-the-art modeling tools towards the simulations of two-phase flow phenomena under realistic reactor conditions. In the present paper, the focus is on turbulence modelling near the gas liquid interface in stratified flows.
An isothermal stratified counter-current flow of air and water in a rectangular channel is simulated. Computational domain and boundary conditions are based on the flow conditions in the test section of the WENKA experiment [1]. The validation case considers supercritical stratified flow with Froude number of 2.36 and Reynolds number 12000 for water and 27000 for air.
The two-fluid modeling approach with interface compression is used to resolve the interface between the two phases. A consistent momentum interpolation numerical scheme is applied, featuring the partial elimination algorithm to handle the strong interphase drag coupling at a resolved interface. The Unsteady Reynolds Averaged Navier-Stokes (URANS) approach is used to describe turbulent two-phase flow. Modelling of turbulence dissipation at the interface requires a special treatment that includes introduction of additional turbulence damping terms into the k-ω Shear Stress Transport (SST) turbulence equations. Simulations, model and source code development are performed with the open source C++ library OpenFOAM.
Simulation results are validated with the measured profiles of volume fraction, velocity and turbulent kinetic energy at two streamwise positions in the test section of the WENKA experiment. Results of the mesh sensitivity study are presented. Furthermore, results of a parametric study reveal that an asymmetric damping approach with a lower coefficient on the liquid side of the interface can improve the prediction of turbulent kinetic energy profiles.

[1] Stäbler, T., Meyer, L., Schulenberg, T., & Laurien, E. (2006). Turbulence Structures in Horizontal Two-Phase Flows Under Counter-Current Conditions. Proceedings of FEDSM2006 (pp. 61–66). ASME.

The ab initio thermodynamic simulation of correlated Fermi systems is of central importance for many applications, such as warm dense matter, electrons in quantum dots, and ultracold atoms. Unfortunately, path integral Monte Carlo (PIMC) simulations of fermions are severely restricted by the notorious fermion sign problem (FSP). In this paper, we present a hands-on discussion of the FSP and investigate in detail its manifestation with respect to temperature, system size, interaction-strength and -type, and the dimensionality of the system. Moreover, we analyze the probability distribution of fermionic expectation values, which can be non-Gaussian and fat-tailed when the FSP is severe. As a practical application, we consider electrons and dipolar atoms in a harmonic confinement, and the uniform electron gas in the warm dense matter regime. In addition, we provide extensive PIMC data, which can be used as a reference for the development of new methods and as a benchmark for approximations.

Radiopharmaceuticals used for diagnosis or therapy induce DNA strand breaks, which may be detectable by single-cell gel electrophoresis (called comet assay). Blood was taken from patients before and at different time points after treatment with radiopharmaceuticals; blood cells were investigated by the comet assay using the percentage of DNA in the tail as the critical parameter. Whereas [²²⁵Ac]Ac-prostate-specific membrane antigen (PSMA)-617 alpha therapy showed no difference relative to the blood sample taken before treatment, beta therapy with [¹⁷⁷Lu]Lu-PSMA-617 3 h post-injection revealed a small but significant increase in DNA strand breaks. In blood of patients who underwent positron emission tomography (PET) with either [¹⁸F]2-fluor-2-deoxy-D-glucose (FDG) or [⁶⁸Ga]Ga-PSMA-11, an increase of DNA migration determined by the comet assay was not found when analysed at different time points (2–70 min) after intravenous tracer injection. Human whole blood was incubated with the targeted clinically relevant therapeutic radiopharmaceuticals [²²⁵Ac]Ac-PSMA-617, [¹⁷⁷Lu]Lu-PSMA-617 and [⁹⁰Y]Y-DOTA(0)-Phe(1)-Tyr(3)-octreotide (DOTA-TOC) at different activity concentrations (kBq/ml) for 5 days and then analysed by the comet assay. DNA damage increased with higher concentrations of all radiolabeled compounds tested. [¹⁷⁷Lu]Lu-PSMA-617 caused higher blood cell radiotoxicity than equal activity concentrations of ⁹⁰Y]Y-DOTATOC. Likewise, whole human blood was exposed to the positron emitters [¹⁸F]FDG and [⁶⁸Ga]Ga-PSMA-11 in vitro for 24 h with activity concentrations ranging between 5 and 40 MBq/ml. The same activity concentration dependent elevated DNA migration was observed for both compounds although decay energies are different. This study demonstrated that the amount of DNA damage detected by the comet assay in whole human blood is similar among different positron emitters and divergent by a factor of 200 between alpha particles and beta radiation.

We determine the strength of laser shock-compressed polycrystalline diamond at stresses above the Hugoniot elastic limit using a novel technique combining x-ray diffraction from the Linac Coherent Light Source with velocity interferometry. X-ray diffraction is used to measure lattice strains and velocity interferometry is used to infer shock and particle velocities. These measurements, combined with density-dependent elastic constants calculated using density functional theory, enable determination of material strength above the Hugoniot elastic limit. Our results indicate that diamond retains approximately 20 GPa of strength at longitudinal stresses of 150–300 GPa under shock compression.

In many applications finned tube bundles are commonly used for heating or cooling purpose. Hence, the natural convection heat transfer from finned heat exchanger configurations with novel design in a chimney was experimentally studied. These novel fin designs use integrated pins to enhance the heat conduction from the fin base to the fin tip as well as the convective heat transfer along the fin surface. Oval tubes with conventional circular plain fins (CPF) as well as novel circular integrated pin fins (CIPF) and serrated integrated pin fins (SIPF) were additively generated by a Selective Laser Melting (SLM) process and installed at the bottom of a 6.5 m long chimney. All heat exchanger designs were tested in a 2-row and 3-row configuration with Rayleigh numbers between 25,000 and 120,000. We found the average Nusselt number of SIPF to be higher and the Nusselt number of the CIPF to be lower compared to the CPF. Furthermore, the 2-row configuration achieved greater Nusselt number compared to the 3-row configuration for all heat exchanger designs. The analysis of the individual tube rows showed highest Nusselt numbers at the first tube row and the lowest at the last tube row for both configurations. However, for the SIPF the difference between the first and second tube row is smaller compared to the CPF and CIPF. In order to evaluate the compactness of the heat exchanger, the volumetric heat flux density was applied. Similar to Nusselt number the volumetric heat flux density enhanced for the SIPF and reduced for the CIPF compared to the conventional design. Also the 2-row configuration reaches greater thermal performance compared to the 3-row configuration. Additionally, the surface area and the volume of the heat exchanger material are 30.7 % and 6.9 % lower for the SIPF compared to the CPF. The experimental outcome was used to develop an empirical heat transfer correlation between Nusselt number, Rayleigh number, fin design and tube row number.

Warm dense matter (WDM) { an exotic state of highly compressed matter { has attracted high interest in recent years in astrophysics and for dense laboratory systems. At the same time, this state is extremely diffcult to treat theoretically. This is due to the simultaneous appearance of quantum degeneracy, Coulomb correlations and thermal effects, as well as the overlap of plasma and condensed phases. Recent breakthroughs are due to the successful application of density functional theory (DFT) methods which, however, often lack the necessary accuracy and predictive capability for WDM applications. The situation has changed with the availability of the first ab initio data for the exchange-correlation free energy of the warm dense uniform electron gas (UEG) that were obtained by quantum Monte Carlo (QMC) simulations, for recent reviews, see Dornheim et al., Phys. Plasmas 24, 056303 (2017) and Phys. Rep. 744, 1-86 (2018). In the present article we review recent further progress in QMC simulations of the warm dense UEG: namely, ab initio results for the static local field correction G(q) and for the dynamic structure factor S(q; w). These data are of key relevance for the comparison with x-ray scattering experiments at free electron laser facilities and for the improvement of theoretical models.
In the second part of this paper we discuss simulations of WDM out of equilibrium. The theoretical approaches include Born-Oppenheimer molecular dynamics, quantum kinetic theory, timedependent DFT and hydrodynamics. Here we analyze strengths and limitations of these methods and argue that progress in WDM simulations will require a suitable combination of all methods. A particular role might be played by quantum hydrodynamics, and we concentrate on problems, recent progress, and possible improvements of this method.

Tumor-targeting peptides radiolabeled with positron-emitting ⁶⁸Ga are promising candidates as new noninvasive diagnostic agents for positron emission tomography (PET). The targeting peptides are tethered to a chelator that forms a stable coordination complex with Ga³⁺ that is inert to dissociation of Ga³⁺in vivo. Metal complexes of macrobicyclic hexaamine “sarcophagine” (sar = 3,6,10,13,16,19-hexaazabicyclo[6.6.6]icosane) ligands exhibit remarkable stability as a result of the encapsulating nature of the cage amine ligand. A Ga³⁺ sarcophagine complex, [Ga-(1-NH₃-8-NH₂-sar)]⁴⁺, has been characterized using X-ray crystallography, demonstrating that Ga³⁺ is coordinated to six nitrogen atoms in a distorted octahedral complex. A bifunctional derivative of (NH₂)₂sar, possessing two aliphatic linkers with carboxylic acid functional groups has been attached to two cyclic-RGD peptides that target the α_vβ₃ integrin receptor that is overexpressed in some types of tumor tissue. This dimeric species can be radiolabeled with ⁶⁸Ga³⁺ in >98% radiochemical yield and ⁶⁸Ga³⁺ does not dissociate from the ligand in the presence of transferrin, an endogenous protein with high affinity for Ga³⁺. Biodistribution and micro-PET imaging studies in tumor-bearing mice indicate that the tracer accumulates specifically in tumors with high integrin expression. The high tumor uptake is coupled with low nonspecific uptake and clearance predominantly through the kidneys resulting in high-quality PET images in animal models.

Ziel des Aufsatzes ist es, wesentliche gesetzliche und regulatorische Aspekte zu beleuchten, die bei multizentrischen klinischen Prüfungen mit kurzlebigen PSMA-PET-Radiopharmaka im Hinblick auf die Etablierung einer dezentralen Herstellung des klinischen Prüfpräparats zu beachten sind. Solche prospektiven Studien spielen in der nuklearmedizinischen Forschung und Entwicklung eine zunehmend wichtige Rolle. Um PSMA-PET-Tracer mit kurzer Halbwertzeit für die Prostatakrebsdiagnostik weiter im behördlichen Zulassungsverfahren und schließlich im Gesundheitssystem etablieren zu können, schließen sich nuklearmedizinische Zentren zunehmend standortübergreifend zusammen, um in angemessener Zeit hierfür die notwendige Anzahl von Studienpatienten zu erreichen. Im Folgenden gehen wir auf das regulatorische Umfeld zur Herstellung von PSMA-PET-Radiopharmaka als klinisches Prüfpräparat (engl. Investigational Medicinal Product, IMP) ein, und führen am Beispiel der frühen multizentrischen klinischen Prüfung der Phasen-I und -II „[⁶⁸Ga]Ga-PSMA-11 in high-risk Prostate Cancer“ wesentliche Aspekte an, die bei der Initiierung einer prospektiven Studie mit dezentraler PSMA-Tracer-Herstellung aus radiopharmazeutisch-organisatorischer Sicht zu berücksichtigen und im Vorfeld abzustimmen sind.

PET radioligands with low molar activity (MA) may underestimate the quantity of the target of interest because of competitive binding of the target with unlabeled ligand. The aim of this study was to evaluate the change in the whole-body distribution of ¹⁸F-PSMA-1007 targeting prostate-specific membrane antigen (PSMA) when solutions with different peptide concentrations are used. Methods: Mouse xenograft models of LNCaP (PSMA-positive prostate cancer) (n = 18) were prepared and divided into 3 groups according to the peptide concentration injected: a high-MA group (1,013 ± 146 GBq/μmol; n = 6), a medium-MA group (100.7 ± 23.1 GBq/μmol; n 5 6), and a low-MA group (10.80 ± 2.84 GBq/μmol; n = 6). Static PET scans were performed 1 h after injection (scan duration, 10 min). SUV_mean in tumor and normal organs was compared by the multiple-comparison test. Immunohistochemical staining and Western blot analysis were performed to confirm expression of PSMA in tumor, salivary gland, and kidney. Results: The low-MA group (SUV_mean, 1.12 ± 0.30) showed significantly lower uptake of ¹⁸F-PSMA-1007 in tumor than did the high-MA group (1.97 ± 0.77) and the medium-MA group (1.81 ± 0.57). On the other hand, in salivary gland, both the low-MA group (SUV_mean, 0.24 ± 0.04) and the medium-MA group (0.57 ± 0.08) showed significantly lower uptake than the high MA group (1.27 ± 0.28). The tumor-to-salivary gland SUV_mean ratio was 1.73 ± 0.55 in the high-MA group, 3.16 ± 0.86 in the medium-MA group, and 4.78 ± 1.29 in the low-MA group. The immunohistochemical staining and Western blot analysis revealed significant overexpression of PSMA in tumor and low expression in salivary gland and kidney. Conclusion: A decrease in the MA level of the injected ¹⁸F-PSMA-1007 solution resulted in decreased uptake in tumor and, to a greater degree, in normal salivary gland. Thus, there is a possibility of minimizing the adverse effects in salivary gland by setting an appropriate MA level in PSMA targeting therapy.

Radiopharmaceuticals labelled with the positron emitter Gallium-68 have had an enormous impact on the diagnostic imaging of neuroendocrine tumors using somatostatin receptor ligands and in recent years on the diagnosis of prostate cancer using PSMA ligands and subsequently their application for radioendotherapy using Yttrium-90, Lutetium-177 or more recently Actinium-225. The release of the monographs for ‘Gallium-68 chloride solution for radiolabelling’ and ‘Gallium-68 Edotreotide injection’ within the European Pharmacopoeia in 2013 tightened the requirements for specifications of Gallium-68 labelled radiotracers and will be enhanced with the ongoing elaboration of monographs for ‘Gallium-68 DOTA-TATE injection’, ‘Gallium-68 DOTA-NOC injection’ and ‘68Ga-PSMA’. In the same way the work environment of the responsible radiochemists and radiopharmacists in terms of quality control has been improved but also the workload has reached a high level with the increasing number of clinical applications and the limitation of the maximum achievable amount of starting activity from the currently available generators and therefore a limited dose number. The change of conditions for the production and quality control of Gallium-68 labelled radiopharmaceuticals will be reviewed with regards to legislating and practical aspects from ‘on bench’ to ‘full GMP’ preparation linked to the specific requirements for a multi-centre clinical trial using 68Ga-PSMA-11 in high-risk prostate cancer.

[¹¹C]-5-Hydroxytryptophan ([¹¹C]HTP) and 6-[¹⁸F]fluoro-3,4-dihydroxy-L-phenylalanine ([¹⁸F]FDOPA) are used to image neuroendocrine tumors with positron emission tomography. The precise mechanism by which these tracers accumulate in tumor cells is unknown. We aimed to study tracer uptake via large amino acid transporters, peripheral decarboxylation (inhibited by carbidopa), and intracellular breakdown by monoamine oxidase (MAO). [¹¹C]HTP and [¹⁸F]FDOPA tracer accumulation was assessed in a human neuroendocrine tumor cell line, BON. The carbidopa experiments were done in a tumor-bearing mouse model. Intracellular [¹¹C]HTP accumulation was 2-fold higher than that of [¹⁸F]FDOPA. Cellular transport of both tracers was inhibited by amino-2-norbornanecarboxylic acid. The MAO inhibitors clorgyline and pargyline increased tracer accumulation in vitro. Carbidopa did not influence tracer accumulation in vitro but improved tumor imaging in vivo. Despite lower accumulation in vitro, visualization of [¹⁸F]FDOPA is superior to [¹¹C]HTP in the neuroendocrine pancreatic tumor xenograft model. This could be a consequence of the serotonin saturation of BON cells in the in vivo model.

To assess individual treatment options for patients with carcinoid tumours, accurate knowledge of tumour localisation is essential. We aimed to test the diagnostic sensitivity of 6-[fluoride-18]fluoro-levodopa (¹⁸F-DOPA PET), compared with conventional imaging methods, in patients with carcinoid tumours. In a prospective, single-centre, diagnostic accuracy study, ¹⁸F-DOPA PET with carbidopa pretreatment was compared with somatostatin-receptor scintigraphy (SRS), CT, and combined SRS and CT in 53 patients with a metastatic carcinoid tumour. The performance of all imaging methods was analysed for individual patients, for eight body regions, and for the detection of individual lesions. PET and CT images were fused to improve localisation. To produce a composite reference standard, we used cytological and histological findings; all imaging tests, including secondary assessments for newly found lesions; follow-up; and biochemical data. Sensitivities were calculated and compared. In patient-based analysis, we recorded sensitivities of 100% (95% CI 93-100) for ¹⁸F-DOPA-PET, 92% (82-98) for SRS, 87% (75-95) for CT, and 96% (87-100) for combined SRS and CT (p=0.45 for ¹⁸F-DOPA PET vs combined SRS and CT). However, ¹⁸F-DOPA PET detected more lesions, more positive regions, and more lesions per region than combined SRS and CT. In region-based analysis, sensitivity of ¹⁸F-DOPA PET was 95% (90-98) versus 66% (57-74) for SRS, 57% (48-66) for CT, and 79% (70-86) for combined SRS and CT (p=0.0001, PET vs combined SRS and CT). In individual-lesion analysis, corresponding sensitivities were 96% (95-98), 46% (43-50), 54% (51-58), and 65% (62-69; p<0.0001 for PET vs combined SRS and CT). If the improved tumour localisation seen with ¹⁸F-DOPA-PET compared with conventional imaging is confirmed in future studies, this imaging method could replace use of SRS, help improve prediction of prognosis, and be used to assess patients' response to treatment for carcinoid tumours.

Purpose
To evaluate and compare diagnostic sensitivity of positron emission tomography (PET) scanning in carcinoid and islet cell tumor patients with a serotonin and a catecholamine precursor as tracers.
Patients and Methods
Carcinoid (n = 24) or pancreatic islet cell tumor (n = 23) patients with at least one lesion on
conventional imaging including somatostatin receptor scintigraphy (SRS) and computed tomography (CT) scan underwent ¹¹C-5-hydroxytryptophan (11C-5-HTP) PET and 6-[F-18]fluoro-L-dihydroxyphenylalanin (¹⁸F-DOPA) PET. PET findings were compared with a composite reference standard derived from all available imaging along with clinical and cytologic/histologic information.
Results
In carcinoid tumor patients, per-patient analysis showed sensitivities for ¹¹C-5-HTP PET, ¹⁸F-DOPA PET, SRS, and CT of 100%, 96%, 86%, 96%, respectively, and in islet cell tumors of 100%, 89%, 78%, 87%, respectively. In carcinoid patients, per-lesion analysis revealed sensitivities for ¹¹C-5-HTP PET, ¹¹C-5-HTP PET/CT, ¹⁸F-DOPA PET, ¹⁸F-DOPA PET/CT, SRS, SRS/CT, and CT alone of, respectively, 78%, 89%, 87%, 98%, 49%, 73%, and 63% and in islet cell tumors of 67%, 96%, 41%, 80%, 46%, 77%, and 68%, respectively. In all carcinoid patients ¹⁸F-DOPA PET and ¹¹C-5-HTP PET detected more lesions than SRS (P < .001). ¹¹C-5-HTP PET was superior to ¹⁸F-DOPA PET in islet cell tumors (P < .0001). In all cases, CT improved the sensitivity of the nuclear scans.
Conclusion
¹⁸F-DOPA PET/CT is the optimal imaging modality for staging in carcinoid patients and ¹¹C-5-HTP PET/CT in islet cell tumor patients.

Neuroendocrine tumors can originate almost everywhere in the body and consist of a great variety of subtypes. This paper focuses on molecular imaging methods using nuclear medicine techniques in neuroendocrine tumors, coupling molecular uptake mechanisms ofradiotracers with clinical results. A non-systematic review is presented on receptor based and metabolic imaging methods. Receptor-based imaging covers the molecular backgrounds of somatostatin, vaso-intestinal peptide (VIP), bombesin and cholecystokinin (CCK) receptors and their link with nuclear imaging. Imaging methods based on specific metabolic properties include meta-iodo-benzylguanide (MIBG) and dimercapto-sulphuric acid (DMSA-V) scintigraphy as well as more modern positron emission tomography (PET)-based methods using radio-labeled analogues of amino acids, glucose, dihydroxyphenylalanine (DOPA), dopamine and tryptophan. Diagnostic sensitivities are presented for each imaging method and for each neuroendocrine tumor subtype. Finally, a Forest plot analysis of diagnostic performance is presented for each tumor type in order to provide a comprehensive overview for clinical use.

Aim/Introduction:

Prospective clinical trials are initiated within the field of nuclear medicine to translate the most promising radioligands into clinical routine [1]. A close cooperation and communication between experts from different fields is necessary for the efficiency and efficacy of the clinical trial which can then have a positive impact on the timely start of recruitment and subsequent patient inclusions [2].
Materials and Methods:
Given the exemplary phase 1/2 multi-center clinical trial ,,Ga-68-PSMA-11 in high-risk Prostate Cancer“ (NCT03362359) [3], we demonstrate how professions from clinical research, drug manufacturing and administration can be involved in the planning, preparation and realisation of prospective clinical trials in nuclear medicine. Organisational measures are derived to support the interprofessional cooperation within diagnostic prospective multicenter clinical trials.
Results:
Besides nuclear medicine physicians, urologists and pathologists, other professions like technicians and technologists (nuclear medicine, biology, chemistry), study nurses, radiochemists/-pharmacists and nursing staff are involved in the clinical setting. In addition, radiation safety officers, quality manager, clinical monitors, lawyers, data protection officers, project managers and study coordinators are embedded in the setting of in total eleven study sites in Germany, Austria and Switzerland.
Conclusion:
Interprofessional cooperation is of great importance for high-quality work in health care and re-search in general, as well as the accomplishment of prospective clinical trials in nuclear medicine in particular. Readiness to put oneself in the position of other professions, cooperation under no professional constraints, adequate time for mutual exchange, the ability and skills for interprofessional project management and an integral view on the required expertise by strengthening overall communication skills are required in particular on senior management level.
References:
1. Zippel C, Ronski SC, Bohnet-Joschko S, Giesel FL, Kopka K. Current Status of PSMA-Radiotracers for Prostate Cancer: Data Analysis of Prospective Trials Listed on ClinicalTrials.gov. Pharmaceuticals (Basel, Switzerland). 2020;13.doi:10.3390/ph13010012.
2. Reeves S, Pelone F, Harrison R, Goldman J, Zwarenstein M. Interprofessional collaboration to improve professional practice and healthcare outcomes. The Cochrane database of systematic reviews. 2017;6:Cd000072. doi:10.1002/14651858.CD000072.pub3.
3. Neels O, Zippel C, Giesel F, Kopka K. Initiation Of A Prospective Clinical Multicentre Trial With Local Production Of A Short-Lived PSMA-PET-Radiopharmaceutical In The D-A-CH-Region: Chances And Experiences. Annual Congress of the European Association of Nuclear Medicine October 12 - 16, 2019. 2019;46:S732. doi:10.1007/s00259-019-04486-2.

The response of the uniform electron gas (UEG) to an external perturbation is of paramount importance for many applications. Recently, highly accurate results for the static density response function and the corresponding local field correction have been provided both for warm dense matter [J. Chem. Phys. 151, 194 104 (2019)] and strongly coupled electron liquid [Phys. Rev. B 101, 045 129 (2020)] conditions based on exact ab initio path integral Monte Carlo (PIMC) simulations. In the present work, we further complete our current description of the UEG by exploring the high energy density regime, which is relevant for, e.g. astrophysical applications and inertial confinement fusion experiments. To this end, we present extensive new PIMC results for the static density response in the range of 0.05 ≤ r s ≤ 0.5 and 0.85 ≤ θ ≤ 8.
These data are subsequently used to benchmark the accuracy of the widely used random phase approximation and the dielectric theory by Singwi, Tosi, Land, and Sjölander (STLS). Moreover, we compare our results to configuration PIMC data where they are available and find perfect agreement with a relative accuracy of 0.001 − 0.01%. All PIMC data are available online.

The 16O(n, alpha)13 C reaction, as the inverse reaction of the astrophysically important 13C(alpha, n)16O reaction, is proposed to be measured at the neutron time-of-flight (nTOF) facility of CERN. To this purpose, a Double Frisch Grid Ionization Chamber (DFGIC) containing the oxygen atoms as a component in the counting gas has been developed and a prototype was constructed at Helmholtz-Zentrum Dresden-Rossendorf(HZDR), in Germany. The first in-beam tests of the detector have been performed in November 2017 in the first (EAR1) and in April 2018 in the second (EAR2) experimental areas of the nTOF facility.

The 16O(n,alpha)13C reaction was proposed to be measured at the neutron time-of-flight (n_TOF) facility of CERN. To this purpose, a Double Frisch Grid Ionization Chamber (DFGIC) containing the oxygen atoms as a component in the counting gas coupled with a switch device in order to prevent the charge collection from the so-called gamma-flash has been developed at Helmholtz-Zentrum Dresden-Rossendorf (HZDR), in Germany.
The first 16O(n, alpha)13C measurement without seeing the charge of the γ-flash at n_TOF has been performed in November 2018. After the electronics did not suffer from the gamma-flash any more, another huge charge collection was discovered. Due to the high instantaneous flux at the n_TOF facility the amount of that induced charge from neutron induced background reactions was piling up so much that the recognition of 16O(n, alpha)13C reactions from that background was very difficult. For that reason another 16O(n, alpha)13C measurement at the time-of-flight facility nELBE at HZDR which has a low instantaneous flux, has been performed in April 2019. Both measurements from n_TOF and nELBE will be presented here.

Background
Pancreatic cancer is a devastating disease with a five-year survival rate of 20-25%. As approximately only 20% of the patients diagnosed with pancreatic cancer are initially staged as resectable, it is necessary to evaluate new therapeutic approaches. Hence neoadjuvant (radio)chemotherapy is a promising therapeutic option, especially in patients with a borderline resectable tumor. The aim of this non-randomized, monocentric, prospective, phase II clinical study was to assess the prognostic value of functional imaging techniques, i.e., [18F]2-fluoro-2-deoxy-D-glucose positron emission tomography / computed tomography (FDG-PET/CT) and diffusion weighted magnetic resonance imaging (DW-MRI), prior to and during neoadjuvant radiochemotherapy.
Methods
Patients with histologically proven resectable, borderline resectable or irresectable non-metastatic pancreatic adenocarcinoma received induction chemotherapy followed by a neoadjuvant radiochemotherapy. Patients underwent FDG-PET/CT and DW-MRI including T1- and T2-weighted sequences prior to and after neoadjuvant chemotherapy as well as following induction radiochemotherapy. The primary endpoint was the evaluation of the response as quantified by the Standardized Uptake Value (SUV) measured with (FDG-PET). Response to treatment was evaluated by FDG-PET and DW-MRI during and after the neoadjuvant course. Morphologic staging was done using contrast-enhanced CT and contrast enhanced MRI to decide inclusion of patients and resectability after neoadjuvant therapy. In those patients undergoing subsequent surgery, imaging findings were correlated with those of the pathologic resection specimen.
Results
A total of 25 patients were enrolled in the study. The response rate measured by FDG-PET was 85% with a statistically significant decrease of the maximal Standardized Uptake Value (SUVmax) during therapy (p <0.001). Using the mean ADC, response was not detectable with DW-MRI. After neoadjuvant treatment 16 patients underwent surgery. In 12 (48%) patients a tumor resection could be performed. The median overall survival of all patients was 25 months (range: 7 – 38 months).
Conclusion
Based on these limited patient numbers, we could show that this trial design is feasible and that the neoadjuvant therapy regime was well tolerated. To evaluate the response to the combined therapy, FDG-PET/CT may be a reliable method. In contrast, the evaluation of the response using mean the mean ADC, DW-MRI did not show conclusive results.

Background and purpose:

Radiotherapy is a standard treatment option for high-grade gliomas. Cognitive impairment is a side effect associated with radiotherapy particularly in long-term survivors. Recent findings suggest involvement of the cerebellum in cognitive function. The goal of this study was therefore to investigate dose dependent cerebellar atrophy using prospective, longitudinal MR data from adult glioma patients who received radiotherapy.
Materials and methods:
Cerebellar volumes were measured using T1-weighted MR images from 91 glioma patients before radiotherapy and every three months thereafter. We calculated the average cerebellar volume change per year per Gy, based on the mean cerebellar dose, using linear regression analysis. Subsequently, patient age was investigated as a confounding factor using multiple linear regression analysis. The impact of chemotherapy was assessed separately in a subgroup of patients receiving a cerebellar dose ≤ 1 Gy. Cerebellar mean dose and cerebellar volume changes were compared between patients treated with proton (N = 38) and photon therapy (N = 52).
Results:
Cerebellar volume decreased 2.4 % per 10 Gy per year (p < 0.001). The cerebellar volume loss was progressive over time without signs of recovery within the observational period of two years. Neither patient age (p = 0.27) nor chemotherapy (p = 0.43) had a significant impact on cerebellar atrophy. Compared to patients treated with photons, the cerebellar dose was significantly lower in patients treated with proton therapy (p < 0.001, r = 0.62) which also translated to a significantly lower cerebellar volume reduction per year (p = 0.016, r = 0.25).
Conclusion:
Cerebellar volume decreased significantly and irreversibly after radiotherapy as function of time and dose. Further work is now needed to correlate these results with cognitive function and motor performance.

The response of the uniform electron gas (UEG) to an external perturbation is of paramount importance for many applications. Recently, highly accurate results for the static density response function and the corresponding local field correction have been provided both for warm dense matter [J. Chem. Phys.151,194104 (2019)] and strongly coupled electron liquid [Phys. Rev. B101, 045129 (2020)] conditions based on exact ab initio path integral Monte Carlo (PIMC) simulations. In the present work, we further complete our current description of the UEG by exploring the high energy density regime, which is relevant for, e.g., astrophysical applications and inertial confinement fusion experiments. To this end, we present extensive new PIMC results for the static density response in the range of 0.05≤rs≤0.5 and 0.85≤θ≤8. These data are subsequently used to benchmark the accuracy of the widely used random phase approximation and the dielectric theory by Singwi, Tosi, Land, and Sjölander (STLS). Moreover, we compare our results to configuration PIMC data where they are available and find perfect agreement with a relative accuracy of 0.001−0.01%. All PIMC data are available online.

Light elements were produced in the first few minutes of the Universe through a sequence of nuclear reactions known as Big Bang nucleosynthesis (BBN). Among the light elements produced during BBN, deuterium is an excellent indicator of cosmological parameters because its abundance is highly sensitive to the primordial baryon density and also depends on the number of neutrino species permeating the early Universe. Although astronomical observations of primordial deuterium abundance have reached percent accuracy3, theoretical predictions based on BBN are hampered by large uncertainties on the cross-section of the deuterium burning D(p,γ)3He reaction. Here we show that our improved cross-sections of this reaction lead to BBN estimates of the baryon density at the 1.6 percent level, in excellent agreement with a recent analysis of the cosmic microwave background7. Improved cross-section data were obtained by exploiting the negligible cosmic-ray background deep underground at the Laboratory for Underground Nuclear Astrophysics (LUNA) of the Laboratori Nazionali del Gran Sasso (Italy)8,9. We bombarded a high-purity deuterium gas target with an intense proton beam from the LUNA 400-kilovolt accelerator11 and detected the γ-rays from the nuclear reaction under study with a high-purity germanium detector. Our experimental results settle the most uncertain nuclear physics input to BBN calculations and substantially improve the reliability of using primordial abundances to probe the physics of the early Universe.

Among the reactions involved in the production and destruction of deuterium during Big Bang Nucleosynthesis, the deuterium-burning D(p,γ)3He reaction has the largest uncertainty and limits the pre- cision of theoretical estimates of primordial deuterium abundance. Here we report the results of a careful commissioning of the experimental setup used to measure the cross-section of the D(p,γ)3He reaction at the Laboratory for Underground Nuclear Astrophysics of the Gran Sasso Laboratory (Italy). The commis- sioning was aimed at minimising all sources of systematic uncertainty in the measured cross sections. The overall systematic error achieved (< 3%) will enable improved predictions of BBN deuterium abundance.

Radioactive tracer methods are very competitive and sometimes unique for online measurement of flow rate in single phase flows flowing inside closed conduits. Radioactive tracer methods are already well accepted from industrial end users and established in routine service worldwide.

ISO standards are basic elements of quality control and accreditation for recognition and cooperation in national and international market. There have been proposed several ISO standards dealing with radioactive tracer methods for measurement of water and gas flows in closed conduits during last five decades:

ISO 2975/VII Measurement of water flow in closed conduits -Tracer methods: Transit time method using radioactive tracers
ISO 4053 Measurement of gas flow in conduits -Tracer methods

The ISO standards ISO2975 and ISO4053 issued in 1975-1977 addressed radioactive tracer methods respectively for water and gas flows. The ISO2975 is limited to water phase only, while ISO4053 dealt with gas phase, was withdrawn in 2001 leaving a void on this subject. The proposed ISO standard will replace both of them.

This ISO proposal defines the use of radioactive tracer methods in the measurement of single-phase fluid (gas or liquid) flows in closed conduits. This method of measurement is applicable only to single-phase homogeneous fluid mixtures. This ISO proposal is developed to fill the need for a generalized reference based on fundamental principles to measure fluid flow using radioactive tracer methods. It defines the terms and principles needed for intelligent consideration of radioactive tracer methods for any single-phase fluid flow flowing in closed circuits.

Experts from different countries – so called P member states of ISO TC30 SC5 – will discuss the ISO proposal, and finalize it as new international standard in this field in coming years.

Precise staging of neuroendocrine tumors (NET) using positron emission tomography (PET) tracers visualizing their specific metabolic activity is of interest. Besides [¹⁸F]FDOPA, staging NET with carbon-11 labeled 5-hydroxytryptophan (5-HTP) is reported in recent literature. We implemented the multi-enzymatic synthesis of enantiomerically pure [¹¹C]-L-5-HTP on a Zymark robotic system to compare both tracers in patient studies. [¹¹C]-5-HTP can be synthesized in up to 24% radiochemical yields (EOB). Average specific activity is 44 000GBq/mmol in ca. 50 min from [¹¹C]methyl iodide in radiochemical purities >99 %. The synthesis of 5-HTP is difficult due to its multi-enzymatic reaction steps but typical yields can be achieved of ca. 400 MBq. [¹¹C]-5-HTP is now reliably used in ongoing studies for staging NET.

The detection of prostate cancer lesions by PET imaging of the prostate-specific membrane antigen (PSMA) has gained highest clinical impact during the last years. ⁶⁸Ga-labelled Glu-urea-Lys(Ahx)-HBED-CC ([⁶⁸Ga]Ga-PSMA-HBED-CC) represents a
successful novel PSMA inhibitor radiotracer which has recently demonstrated its suitability in individual first-in-man studies. The radiometal chelator HBED-CC used in this molecule represents a rather rarely used acyclic complexing agent with chemical characteristics favourably influencing the biological functionality of the PSMA inhibitor. The simple replacement of HBED-CC by the prominent radiometal chelator DOTA was shown to dramatically reduce the in vivo imaging quality of the respective ⁶⁸Ga-labelled PSMA-targeted tracer proving that HBED-CC contributes intrinsically to the PSMA binding of the Glu-urea-Lys(Ahx) pharmacophore. Owing to the obvious growing clinical impact, this work aims to reflect the properties of HBED-CC as acyclic radiometal chelator and presents novel preclinical data and relevant aspects of the radiopharmaceutical production process of [⁶⁸Ga]Ga-PSMA-HBED-CC.

The EU directive 2001/83 describes the community code for medicinal products for human use including radiopharmaceuticals. In its current definition, also radionuclide precursors, such as fluorine-18, need to hold a marketing authorization before being placed on the market. The potential of novel radiopharmaceuticals for nuclear medicine is, although encouraged by European legislation and its respective guidance documents, therefore hampered by the regulatory framework. An update of EU directive 2001/83 would be beneficial for the development of novel radiopharmaceuticals and a safe advance in nuclear medicine.

Recently, the strongly inhomogeneous current density occuring near a microelectrode was identified as driving a thermocapillary electrolyte flow near gas bubbles growing during electrolysis [Massing et.al. Electrochim. Acta 297, 929 (2019) ]. The present paper is investigating this effect in more detail under various operating conditions. Furthermore, by simplified modeling, the question is answered of whether this effect is also of importance at large planar electrodes. The direction of the thermocapillary force on the bubble is found to change from retarding to advancing the bubble release when the size of the electrode is increased. Conclusions are drawn on how the thermocapillary effect at planar electrodes depends on the electrode coverage and the bubble departure size, also considering industrially relevant values of the current density.

Background: [¹⁸F]PSMA-1007, a positron emission tomography (PET) tracer, specifically targets prostate-specific membrane antigen (PSMA), which is highly expressed in prostate cancer. PSMA-PET is effective especially for regional detection of biochemical recurrence, which significantly affects patient management. Herein, we established and optimized a one-step radiolabeling protocol to separate and purify [¹⁸F]PSMA-1007 with a CFN-MPS200 synthesizer for clinical application.
Results: A dedicated single use cassette and synthesis program for [¹⁸F]PSMA-1007 was generated using a single-step method for direct precursor radiolabeling. In the cassette, three tube types (fluoro-elastomer, PharMed® BPT, silicone) and two different precursor salts (trifluoroacetic acid or acetic acid) were compared for optimization. Furthermore, three-lot tests were performed under optimized conditions for quality confirmation. Activity yields and mean radiochemical purity of [¹⁸F]PSMA-1007 were > 5000 MBq and 95%, respectively, at the end of synthesis, and the decay-corrected mean radiochemical yield from all three cassettes was approximately 40% using a trifluoroacetic acid salt precursor. Fluoro-elastomer tubings significantly increased the amount of non-radioactive PSMA-1007 (8.5 ± 3.1 μg/mL) compared to those with other tubings (0.3 μg/mL). This reduced the molar activity of [¹⁸F]PSMA-1007 synthesized in the cassette assembled by fluoro-elastomer tubings (46 GBq/μmol) compared to that with PharMed® BPT and silicone tubings (1184 and 1411 GBq/μmol, respectively). Residual tetrabutylammonium, acetonitrile, and dimethyl sulfoxide levels were <  2.6 μg/mL, < 8 ppm, and <  11 ppm, respectively, and ethanol content was 8.0–8.1% in all three cassettes and two different salts. Higher activity yields, radiochemical purities, and decay-corrected radiochemical yields were obtained using an acetic acid salt precursor rather than a trifluoroacetic acid salt precursor (7906 ± 1216 MBq, 97% ± 0%, and 56% ± 4%). In the three-lot tests under conditions optimized with silicone cassettes and acetic acid salt precursor, all quality items passed the specifications required for human use.
Conclusions: We successfully automated the production of [¹⁸F]PSMA-1007 for clinical use and optimized synthesis procedures with a CFN-MPS200 synthesizer using a silicone cassette and acetic acid salt precursor. Cassette availability will facilitate a wide spread use of [¹⁸F]PSMA-1007-PET, leading to an effective prostate cancer management.

In the present study, the martensitic transformation (MT) and magnetic properties exhibited by the Ni-Mn-Sn Heusle-type magnetic shape memory alloys (MSMAs) doped with Zn have been investigated experimentally and theoretically. The inverse magnetocaloric effect (MCE) in Ni₄₇Mn₄₀Sn_13−xZn_x (x = 0, 1) was studied by direct measurements of the adiabatic temperature change, ΔT_ad, in pulsed magnetic fields of 5, 10, and 20 T. The Zn doping of the Ni-Mn-Sn alloy led to a striking enhancement of the value of ΔT_ad, e.g., from –2.5 for undoped to –11 K for Zn-doped alloys under a magnetic field amplitude of 20 T. The first-principles calculations were used to understand the origin of Zn-doping influence on MT, magnetic, and magnetocaloric properties. Particularly, the crystal structure and magnetic ordering influenced by the site occupancy in the undoped and Zn-doped alloys were analyzed. The results show that, whereas the usual transition metal elements with more valence electrons tend to enter the Ni sites, Zn atom prefers to occupy the Sn sublattice. The underlying physics of the drastic enhancement of MCE by Zn doping is discussed in terms of a partial disorder in the occupation sites of Zn atoms.

Spin-pumping in a ferromagnet/non-ferromagnet heterostructure is directly imaged with spatial resolution as well as element selectivity. The time-resolved detection in scanning transmission x-ray microscopy allows to directly probe the spatial extent of the ac spin polarization in Co-doped ZnO which is generated by spin-pumping from an adjacent permalloy microstrip. Comparing the relative phases of the dynamic magnetization component of the two constituents is possible and found to be out of phase. The correlation between the distribution of the magnetic excitation in the permalloy and the Co-doped ZnO reveals that literally there is no one-to-one correlation. The observed distribution is rather complex, but integrating over larger areas clearly demonstrates that the spin polarization in the non-ferromagnet extends laterally beyond the region of the ferromagnetic microstrip. Therefore the observations are better explained by a local spin pumping efficieny and a lateral propagation of the ac spin-polarization in the non-ferromagnet over the range of a few micrometers.

Contrary to a wide-spread belief that alkali metal (AM) atoms intercalated into layered materials form single-layer structures only, recent experiments [Nature 564 (2018) 234] showed that multi-layer configurations of lithium are possible in bi-layer graphene. Using state-of-the-art first-principles calculations, we systematically study the intercalation energetics for various AMs (Li, Na, K, Rb, Cs) in bi-layer graphene and MoS2. We demonstrate that for bilayer graphene as host the formation energy of multilayer structures is negative for K, Rb and Cs and only slightly positive for both Li and Na. In view of the previous experimental data on lithium, a multilayer of Na might, therefore, form, while it is well-known that single-layers of Na in graphitic hosts are energetically very unfavorable. In MoS2, multi-layer structures are considerably higher in energy than the single-layer ones, but the formation of the former can still occur, especially for the AMs with the lowest electronegativity. To rationalize the results, we assess the charge transfer from the intercalants to the host material and analyze the interplay between the ionic and covalent bonding of AM and host atoms. While our theoretical effort primarily focuses on the fundamental aspects of AM intercalation, our findings may stimulate experimental work addressing multilayer intercalation to maximize the capacity of anode materials in AM ion batteries.

In this 2-day webinar we will see the problems arising with the conventional statistical analysis of compositional data, and present a general solution. We will learn how to generate and interpret compositional descriptive statistics; how to explore the inner structure of a data set with tools such as logratio principal component analysis; and we will fit predictive models to explain the variability in compositional data sets. These topics will be covered with a bit of theory, some examples from geochemistry and a few exercises in R, the open source environment for data analysis.

Thorite, ThSiO4 with Zircon structure type, is one of the most abundant natural source of thorium on earth. While actinides are known to form nanoparticles in silicate medium, no direct link between those colloids and crystalline form of thorite was evidenced until now. Here we show that thorite can be produced in experimental conditions close to environmental pH and temperature. Thanks to in-situ Small and Wide Angle X-rays Scattering (SWAXS) measurements, colloids of a few nanometers are first evidenced for low reaction time. These colloids exhibit elongated shapes and finally tend to aggregate after the size has reached 10 nm. Once aggregated, the system goes through a maturation step finishing with the emergence of nanocrystallites presenting thorite zircon structure. This maturation step is longer when the reaction temperature is decreased highlighting kinetic considerations. The conclusions of this article have potential implications in the paragenesis of Th minerals deposits, but also in the behaviour of Th and, by analogy, tetravalent actinides in the environment. The Th-silicate colloids evidenced in this work have, at low temperature and at near neutral pH, a long-term stability and a morphology in favor of a high mobility in groundwaters. If these species are formed in more diluted media, this could be problematic regarding to the spreading of Th and, by analogy of others tetravalent actinides in the environment.

The synthesis of a tetravalent neptunium amidinate [NpCl((S)-PEBA)₃] (1) ((S)-PEBA = (S,S)-N,N’-bis-(1-phenylethyl)-benzamidinate) is reported. This complex represents the first structurally characterized enantiopure transuranic compound. Reactivity studies with halide/pseudohalides yielding [NpX((S)-PEBA)₃] (X = F (2), Br (3), N3 (4)) have shown that the chirality-atmetal is preserved for all compounds in the solid state. Furthermore, they represent an unprecedented example of a structurally characterized metal-organic Np complex featuring a Np–Br (3) bond. In addition, 4 is the only reported tetravalent transuranic azide. All compounds were additionally characterized in solution using paramagnetic NMR spectroscopy showing an expected C₃ symmetry at low temperatures.

As of April 28, 2020, a pandemic called coronavirus disease 2019 (COVID-19) has spread to every continent of the world, infecting around three million people, and taken nearly 200,000 lives [1]. Although such deadly events are not new throughout human history, they often cause fear and uncertainty, mostly because of lacking information about the new strain of the virus. Insight about the virus and its working mechanism is perhaps important yet understanding the human immune response is the key to reducing mortality. Our immune system reacts differently depends on ages, genders, races, and health background. That explains dissimilar disease progression in patients where some develop critical conditions while others only have mild symptoms [2]. Accumulating evidences suggest patient with severe COVID-19 symptoms is due to cytokine - a common name for a broad spectrum of small proteins important in cell signalling, especially in the immune system - dysregulation [3-5]. Therefore, many studies have suggested a screening of cytokine profiles together with other immune cells responses for the determination of correct treatment [3,5]. Meanwhile, nanosensors such as silicon nanowire (SiNW) own advantages of being sensitive to small molecules, rapid and label-free [6]. In this poster, we demonstrate the use of a SiNW sensor in immunotherapy research, more specifically, in a system of switchable T-cell expressing chimeric antigen receptors (CARs). The sensor showed better sensitivity and a lower limit of detection compare to standard ELISA test. Moreover, thanks to its compatibility with CMOS technology which enables mass production, reproducibility is ensured [7]. Since the cytokine release syndrome (CRS) found in COVID-19 patients is also observed in patients receiving CAR-T therapy [4], the knowledge and tools generated by the SiNW sensor developed in this field of study may benefit the community. In the end, a full understanding and control of our immune system might be the key to fight any other pandemic in the future.

Two photoactivatable dicarbonyl ruthenium(II) complexes based on an amide-functionalised bipyridine scaffold (4-position) equipped with an alkyne functionality or a green-fluorescent BODIPY (boron-dipyrromethene) dye have been prepared and used to investigate their light-induced decarbonylation. UV/Vis, FT-IR and 13C NMR spectroscopies as well as gas chromatography and multivariate curve resolution alternating least-squares analysis (MCR-ALS) were used to elucidate the mechanism of the decarbonylation process. Release of the first CO molecule occurs very quickly, while release of the second CO molecule proceeds more slowly. In vitro studies using two cell lines A431 (human squamous carcinoma) and HEK293 (human embryonic kidney cells) have been carried out in order characterise the anti-proliferative and anti-apoptotic activities. The BODIPY-labelled compound allows for monitoring the cellular uptake, showing fast internalisation kinetics and accumulation at the endoplasmic reticulum and mitochondria.

We present Bionic Tracking, a novel method for solving biological cell tracking problems with eye tracking in virtual reality using commodity hardware. Using gaze data, and especially smooth pursuit eye movements, we are able to track cells in time series of 3D volumetric datasets. The problem of tracking cells is ubiquitous in developmental biology, where large volumetric microscopy datasets are acquired on a daily basis, often comprising hundreds or thousands of time points that span hours or days. The image data, however, is only a means to an end, and scientists are often interested in the reconstruction of cell trajectories and cell lineage trees. Reliably tracking cells in crowded three-dimensional space over many timepoints remains an open problem, and many current approaches rely on tedious manual annotation and curation. In our Bionic Tracking approach, we substitute the usual 2D point-and-click annotation to track cells with eye tracking in a virtual reality headset, where users simply have to follow a cell with their eyes in 3D space in order to track it. We detail the interaction design of our approach and explain the graph-based algorithm used to connect different time points, also taking occlusion and user distraction into account. We demonstrate our cell tracking method using the example of two different biological datasets. Finally, we report on a user study with seven cell tracking experts, demonstrating the benefits of our approach over manual point-and-click tracking, with an estimated 2- to 10-fold speedup.

The success of conventional chimeric antigen receptor (CAR) therapy in the treatment of refractory hematologic malignancies has triggered the development of novel exciting experimental CAR technologies. Among them, adaptor CAR platforms have received much attention. They combine the flexibility and controllability of recombinant antibodies with the power of CARs. Due to their modular design, adaptor CAR systems propose answers to central problems of conventional CAR therapy such as safety and antigen escape. This review provides an overview on the different adaptor CAR platforms available, discusses the possibilities and challenges of adaptor CAR therapy and summarizes first clinical experiences.

Metallurgical simulation and evaluation of the resource efficiency of whole production processes are of key importance for a sound environmental impact assessment. An exergy dissipation analysis is suitable for quantifying the theoretical limits for a process and pinpoint hotspots for improvement along the value chain. The production of NdFeB permanent magnets is evaluated through a simulation-based life cycle assessment and exergetic analysis, comprising 107 unit operations, 361 flows and 209 compounds. This methodology highlights areas with the greatest potential for improvements in terms of technology and environmental impact, shedding light on the true resource efficiency and minimum exergy dissipation for the production of permanent magnets, present in several low-carbon technologies. A maximum exergy efficiency of 60.7% shows that there is a limit for sustainability, which can be improved by technological improvements and recovery of waste streams, showing the inconvenient truth that the resource efficiency will never reach 100%.

In this work, we investigate magneto-acoustic attenuation in thin film multiferroic Lamb wave delay lines. By leveraging magneto-acoustic interactions, multiferroics have potential to realize passive chip-scale alternatives to bulky ferrite devices. For the first time, magnetic field dependence of magnetoacoustic interactions in multiferroic Lamb wave devices is characterized. Multiferroic heterostructures of aluminum nitride and cobalt iron boron are fabricated into Lamb wave delay lines operating at 7.492 GHz to study the effect of strain nonuniformity on the multiferroic coupling. The attenuation of the Lamb waves is characterized as a function of the magnitude and angle of an applied in-plane bias magnetic field. It is found that the bias magnitude for peak attenuation is a strong function of angle, indicating that it is due to coupling between the Lamb waves and spin wave modes. This is in contrast with current models of attenuation in multiferroic SAW delay lines, where the uniform surface strains couple to ferromagnetic resonance, which has no angular dependence on the in-plane bias field magnitude. These results are the first steps towards passiv chip-scale alternatives to ferrite devices utilizing Lamb wave devices, which have better coupling and scalability than their SAW counterparts.

Topological spin textures such as skyrmions, merons, and vortices in antiferromagnetic (AFM)/ ferromagnetic (FM) materials are actively explored for utilization in future data storage and signal processing devices. An emergent half-integer spin texture such as a magnetic vortex can be stabilized in a soft magnetic NiFe disk structure. Due to the topological nature, the unwinding of the magnetic vortex phase is mediated by the dynamic creation and subsequent annihilation of magnetic singularities, such as Bloch points. This process enables the formation of intermediate topological phases such as vortex-antivortex (V-AV) pairs and edge states. Interfacial interactions between an AFM and a topologically non-trivial spin structure of a FM can stabilize and extend the lifetime of V-AV phases, which are typically considered intrinsic and dynamic are imaged using high-resolution in-field magnetic force microscopy. Additionally, these interactions are used to protect the emerged chirality in an otherwise degenerate chiral spin system, rather than to introduce a preferred chirality.

Spin orbit torque driven switching is a favourable way to manipulate nanoscale magnetic objects for both memory and wireless communication devices. The critical current required to switch from one stored magnetic state to another depends on the multilayer structure of the device and the intrinsic properties of the materials used, which are difficult to control on a local scale. Here we demonstrate how focused helium ion beam irradiation can be used to modulate the local magnetic anisotropy of a Co thin film at the microscopic scale. In-situ characterisation using the anomalous Hall effect showed up to an order of magnitude reduction of the magnetic anisotropy under irradiation in real-time, and using this, a multi-level storage element is demonstrated. The result is that current-driven spin-switching, with as little as 800 kA cm-2 can be achieved on predetermined areas of the film without the need for physical material patterning.

In order to optimize the catalytic functionality of cerium oxide it is important to understand the structural modifications associated with reduction of the material and the role of the proximity of metals, which are often coupled with the oxide in the applications. For this purpose, the evolution of the short- and long-range structure of cerium oxide ultrathin epitaxial films and nanostructures supported on Pt(111) is investigated using x-ray absorption spectroscopy at the Ce L3 edge and surface x-ray diffraction, during reduction by thermal treatments in vacuum. In epitaxial nanoislands, the reduction is associated with a contraction of the Ce-O distance and with the appearance of Ce-Pt bonds. The formation of a phase with a (2×2) periodicity after a thermal treatment at 1023 K is ascribed to the formation of a Pt5Ce alloy. Films of 3 nm thickness do not show, on average, significant structural modifications with the same thermal treatment, consistent with the hypothesis that the reduction involves only the topmost surface layers and it does not influence significantly the bulk structure of the material. This study demonstrates a strong interaction between cerium oxide and platinum, which has implications for the reactivity and stability of catalysts based on metals combined with reducible oxides.

Ultrasonic investigations of the single-site quadrupolar Kondo effect in diluted Pr system Y_0.966Pr_0.034Ir₂Zn₂₀ are reported. The elastic constant (C₁₁C₁₂)/2 is measured down to ~40 mK using ultrasound for the dilute system Y_0.966Pr_0.034Ir₂Zn₂₀ and the pure compound Yir₂Zn₂₀. We found that the elastic constant (C₁₁C₁₂)/2 of the Pr-dilute system exhibits a logarithmic temperature dependence below T₀ ∼ 0.3 K, where non-Fermi-liquid (NFL) behavior in the specific heat and electrical resistivity is observed. This logarithmic temperature variation manifested in the Γ3-symmetry quadrupolar susceptibility is consistent with the theoretical prediction of the quadrupolar Kondo effect by D. L. Cox [1]. On the other hand, the pure compound Yir₂Zn₂₀ without 4f-electron contributions shows nearly no change in its elastic constants evidencing negligible phonon contributions. In addition, clear acoustic de Haas-van Alphen (dHvA) oscillations in the elastic constant were detected for both compounds on applying magnetic field. This is mainly interpreted as contribution from the Fermi surface of Yir₂Zn₂₀.

Non-symmorphic chiral topological crystals host exotic multifold fermions, and their associated Fermi arcs helically wrap around and expand throughout the Brillouin zone between the high-symmetry center and surface-corner momenta. However, Fermi-arc splitting and realization of the theoretically proposed maximal Chern number rely heavily on the spin-orbit coupling (SOC) strength. In the present work, we investigate the topological states of a new chiral crystal, PtGa, which has the strongest SOC among all chiral crystals reported to date. With a comprehensive investigation using high-resolution angle-resolved photoemission spectroscopy, quantum-oscillation measurements, and state-of-the-art ab initio calculations, we report a giant SOC-induced splitting of both Fermi arcs and bulk states. Consequently, this study experimentally confirms the realization of a maximal Chern number equal to ±4 in multifold fermionic systems, thereby providing a platform to observe large-quantized photogalvanic currents in optical experiments.

In this study, ultrasonic measurements were performed on a single crystal of cubic PrNi₂Cd₂₀, down to a temperature of 0.02 K, to investigate the crystalline electric field ground state and search for possible phase transitions at low temperatures. The elastic constant (C₁₁−C₁₂)/2, which is related to the Γ₃-symmetry quadrupolar response, exhibits the Curie-type softening at temperatures below ∼30 K, which indicates that the present system has a Γ₃ non-Kramers doublet ground state. A leveling-off of the elastic response appears below ∼0.1 K toward the lowest temperatures, which implies the presence of level splitting owing to a long-range order in a finite-volume fraction associated with Γ₃-symmetry multipoles. A magnetic field–temperature phase diagram of the present compound is constructed up to 28 T for H || [110]. A clear acoustic de Haas–van Alphen signal and a possible magnetic-field-induced phase transition at H ∼26 T are also detected by high-magnetic-field measurements.

A novel type of sub-lattice of the Jahn-Teller (JT) centers was arranged in Ti-doped barium hexaferrite BaFe₁₂O₁₉. In the un-doped crystal all iron ions, sitting in five different crystallographic positions, are Fe³⁺ in the high-spin configuration (S = 5/2) and have a non-degenerate ground state. We show that the electron-donor Ti substitution converts the ions to Fe²⁺ predominantly in tetrahedral coordination, resulting in doubly-degenerate states subject to the E ⊗ e problem of the JT effect. The arranged JT complexes, Fe²⁺O₄, their adiabatic potential energy, non-linear and quantum dynamics, have been studied by means of ultrasound and terahertz-infrared spectroscopies. The JT complexes are sensitive to external stress and applied magnetic field. For that reason, the properties of the doped crystal can be controlled by the amount and state of the JT complexes.

Transition metal(II) fluoridometallates(IV) AIIMIVF6∙3H2O (AII = Mn, Zn; MIV = Np, Pu) were synthesized from NpO2 or PuO2 and the respective transition metal chlorides from hydrofluoric acid under mild conditions. The olive-green (Np) or orange (Pu) compounds were obtained as single-crystals and the respective structures were determined by single-crystal X-ray diffraction. In the isotypic compounds, chains of edgesharing tricapped trigonal prismatic polyhedra, [MIVF8/2(H2O)1/1] ∞1, are present and an overall threedimensional network structure is observed in which the AII and MIV atoms are arranged according to the simple NaCl structure type. Within the respective U-Pu series of the Zn and Mn salts the cell volumes and the MIV−F distances decrease due to the actinoid contraction.

Die Kenntnis des Strömungsfeldes einer Zweiphasenströmung (fest/flüssig) in Rührkesseln, insbesondere hinsichtlich der Turbulenz, stellt einen Schwerpunkt für das Verständnis des industriell relevanten Flotationsprozesses sowie dessen numerischen Simulation dar. In dieser Arbeit werden die Strömungsfelder der Fluidphase (deionisiertes Wasser) und Feststoffphase (Polyethylen- bzw. Glaspartikel mit d_P = 63...70 μm; d_P = 150...180 μm; d_P = 425...500 μm) mithilfe von Particle Image Velocimetry und Particle Shadow Velocimetry ermittelt sowie mit Ergebnissen aus der Literatur und numerischen Simulationen verglichen. Es wird der Einfluss der Feststoffpartikel auf das Geschwindigkeitsfeld, die turbulenten Schwankungsgeschwindigkeiten sowie die Verteilung der Partikel im Rührkessel (D_K = 90 mm) betrachtet. Hierfür wird die Volumenkonzentration der Partikel in drei Schritten von 0,025 vol-% auf 0,1 vol-% erhöht und die Partikel werden mittels Scheibenrührer (Re_R = 9,7; 14,9 oder 22,4*10⁴) suspendiert. Entscheidend für den Einfluss der Partikel auf die Flüssigphase sind der Partikeldurchmesser und die Partikeldichte. Bei den betrachteten Volumenkonzentrationen scheint diese vernachlässigbar zu sein. Innerhalb des Rührerstrahls wird in Lauflänge eine zunehmende Dämpfung der radialen Geschwindigkeit sowie teilweise eine leichte Ablenkung des Rührerstrahls Richtung Rührkesselboden festgestellt. Bei den axialen Geschwindigkeiten dominieren Partikel großer Stokes-Zahlen die abwärtsgerichtete Zweiphasenströmung und können dem Fluid nicht folgen. Die turbulenten Schwankungsgeschwindigkeiten werden generell durch die Partikel (Re_P < 170) gedämpft. Es wird bestätigt, dass die konkrete Rührerstellung keinen Einfluss auf das Strömungsfeld im äußeren Bereich des Rührkessels besitzt.