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At least 1,153 records · Page 64
All sourcesNASA NTRSDOE OSTI
DOE OSTI2022

Development of radiopharmaceuticals for targeted alpha therapy: Where do we stand?

Targeted alpha therapy is an oncological treatment, where cytotoxic doses of alpha radiation are locally delivered to tumor cells, while the surrounding healthy tissue is minimally affected. This therapeutic strategy relies on radiopharmaceuticals made of medically relevant radionuclides chelated by ligands, and conjugated to targeting vectors, which promote the drug accumulation in tumor sites. This review discusses the state-of-the-art in the development of radiopharmaceuticals for targeted alpha therapy, breaking down their key structural components, such as radioisotope, targeting vector, and delivery formulation, and analyzing their pros and cons. Moreover, we discuss current drawbacks that are holding back targeted alpha therapy in the clinic, and identify ongoing strategies in field to overcome those issues, including radioisotope encapsulation in nanoformulations to prevent the release of the daughters. Lastly, we critically discuss potential opportunities the field holds, which may contribute to targeted alpha therapy becoming a gold standard treatment in oncology in the future.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2023

Laser-driven production with advanced targets of Copper-64 for medical applications

Radionuclides are of paramount importance in nuclear medicine both for clinical uses and radiopharmaceutical production. Among the others, nuclides suitable for theranostics like Copper-64 are particularly attractive since they can play both a diagnostic and therapeutic role. In the last years, the growing demand for these nuclides stimulated the research of new solutions, along with cyclotrons already in use, for their production. In this respect, a promising alternative is laser-driven proton accelerators based on the interaction of superintense laser pulses with target materials. Because of their potential compactness and flexibility, they are under investigation for several applications ranging from materials science to nuclear medicine. Moreover, the use of advanced Double-Layer targets (DLTs) was identified as a viable route to increase the number and energy of the accelerated protons to satisfy the requirements of demanding applications. In this contribution, we numerically investigate the use of DLT-based laser-driven sources for Copper-64 production. We show that activities relevant to pre-clinical studies can be achieved with an existing 150 TW laser and DLTs. Moreover, we extend the discussion by considering a broad range of laser systems by exploiting a theoretical model. Our results can guide the choice of laser and target parameters for future experimental investigations.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2021

Use of X-Ray Fluorescence Microscopy for Studies on Research Models of Hepatocellular Carcinoma

Introduction: TheraSphere ® microspheres containing yttrium 90 Y are among many radioembolization agents used clinically to reduce liver tumor burden, and their effects on cancer volume reduction are well-established. At the same time, concerns about off target tissue injury often limit their use. Deeper investigation into tissue distribution and long-term impact of these microspheres could inform us about additional ways to use them in practice. Methods: Healthy rat liver and rabbit liver tumor samples from animals treated with TheraSpheres were sectioned and their elemental maps were generated by X-ray fluorescence microscopy (XFM) at the Advanced Photon Source (APS) synchrotron at Argonne National Laboratory (ANL). Results: Elemental imaging allowed us to identify the presence and distribution of TheraSpheres in animal tissues without the need for additional sample manipulation or staining. Ionizing radiation produced by 90 Y radioactive contaminants present in these microspheres makes processing TheraSphere treated samples complex. Accumulation of microspheres in macrophages was observed. Conclusions: This is the first study that used XFM to evaluate the location of microspheres and radionuclides in animal liver and tumor samples introduced through radioembolization. XFM has shown promise in expanding our understanding of radioembolization and could be used for investigation of human patient samples in the future.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2022

Oxidation of p-[125I]Iodobenzoic Acid and p-[211At]Astatobenzoic Acid Derivatives and Evaluation In Vivo

The alpha particle-emitting radionuclide astatine-211 (211At) is of interest for targeted radiotherapy; however, low in vivo stability of many 211At-labeled cancer-targeting molecules has limited its potential. As an alternative labeling method, we evaluated whether a specific type of astatinated aryl compound that has the At atom in a higher oxidation state might be stable to in vivo deastatination. In the research effort, para-iodobenzoic acid methyl ester and dPEG4-amino acid methyl ester derivatives were prepared as HPLC standards. The corresponding para-stannylbenzoic acid derivatives were also prepared and labeled with 125I and 211At. Oxidization of the [125I]iodo- and [211At]astato-benzamidyl-dPEG4-acid methyl ester derivatives provided materials for in vivo evaluation. A biodistribution was conducted in mice with coinjected oxidized 125I- and 211At-labeled compounds. The oxidized radioiodinated derivative was stable to in vivo deiodination, but unfortunately the oxidized [211At]astatinated benzamide derivative was found to be unstable under the conditions of isolation by radio-HPLC (post animal injection). Another biodistribution study in mice evaluated the tissue concentrations of coinjected [211At]NaAtO3 and [125I]NaIO3. Comparison of the tissue concentrations of the isolated material from the oxidized [211At]benzamide derivative with those of [211At]astatate indicated the species obtained after isolation was likely [211At]astatate.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2023

Computational Materials Design for Ceramic Nuclear Waste Forms Using Machine Learning, First-Principles Calculations, and Kinetics Rate Theory

Ceramic waste forms are designed to immobilize radionuclides for permanent disposal in geological repositories. One of the principal criteria for the effective incorporation of waste elements is their compatibility with the host material. In terms of performance under environmental conditions, the resistance of the waste forms to degradation over long periods of time is a critical concern when they are exposed to natural environments. Due to their unique crystallographic features and behavior in nature environment as exemplified by their natural analogues, ceramic waste forms are capable of incorporating problematic nuclear waste elements while showing promising chemical durability in aqueous environments. Recent studies of apatite- and hollandite-structured waste forms demonstrated an approach that can predict the compositions of ceramic waste forms and their long-term dissolution rate by a combination of computational techniques including machine learning, first-principles thermodynamics calculations, and modeling using kinetic rate equations based on critical laboratory experiments. By integrating the predictions of elemental incorporation and degradation kinetics in a holistic framework, the approach could be promising for the design of advanced ceramic waste forms with optimized incorporation capacity and environmental degradation performance. Such an approach could provide a path for accelerated ceramic waste form development and performance prediction for problematic nuclear waste elements.

12 MANAGEMENT OF RADIOACTIVE AND NON-RADIOACTIVE W↗
DOE OSTI2023

Tellurium Corrosion of Type 304/304L Stainless Steel, Iron, Chromium, and Nickel in High-Temperature Liquid Sodium

Investigating tellurium (Te) corrosion on structural materials is crucial for sodium-cooled fast reactors (SFRs) due to radionuclide presence and knowledge gaps. In this study, Type 304/304L stainless steel (SS304), chromium (Cr), iron (Fe), and nickel (Ni) samples were immersed in low-oxygen environments with Te in liquid sodium at 773 K for 30 days. At 10 ppm oxygen, SS304 showed multiple oxide layers, including a compact NaCrO 2 interlayer and porous Na-Fe-Ni-O outer layers. Tellurium penetrated through the porous layers but was hindered by the NaCrO 2 interlayer. At 0.01 ppm oxygen, Cr had no oxide layer, while Fe and Ni had unstable ones. Tellurium-induced pitting was deeper in Fe and Ni compared to Cr. Oxygen levels and Cr composition are critical factors affecting stable oxide compound layer formation and mitigating Te-induced pitting.

36 MATERIALS SCIENCE↗
DOE OSTI2023

Microbial Influence on the Mobility of +3 Actinides from a Salt-Based Nuclear Waste Repository

Biologically enhanced transport of radionuclides is one of several processes that can affect the performance of a nuclear waste repository. In this work, several microbial isolates from the Waste Isolation Pilot Plant (WIPP) were tested for their influence on the concentration of neodymium, as an analog for +3 actinides, in simple sodium chloride solutions and in anoxic WIPP brines. Batch sorption experiments were carried out over a period of 4–5 weeks. In many cases, the effect on neodymium in solution was immediate and extensive and assumed to be due to surface complexation. However, over time, the continued loss of Nd from the solution was more likely due to biologically induced precipitation and/or mineralization and possible entrapment in extracellular polymeric substances. The results showed no correlation between organism type and the extent of its influence on neodymium in solution. However, a correlation was observed between different test matrices (simple NaCl versus high-magnesium brine versus high-NaCl brine). Further experiments were conducted to test these matrix effects, and the results showed a significant effect of magnesium concentration on the ability of microorganisms to remove Nd from solution. Possible mechanisms include cation competition and the alteration of cell surface structures. This suggests that the aqueous chemistry of the WIPP environs could play a larger role in the final disposition of +3 actinides than the microbiology.

12 MANAGEMENT OF RADIOACTIVE AND NON-RADIOACTIVE W↗
DOE OSTI2023

Accelerator-Based Production of Scandium Radioisotopes for Applications in Prostate Cancer: Toward Building a Pipeline for Rapid Development of Novel Theranostics

In the field of nuclear medicine, the β + -emitting 43 Sc and β - -emitting 47 Sc are promising candidates in cancer diagnosis and targeted radionuclide therapy (TRT) due to their favorable decay schema and shared pharmacokinetics as a true theranostic pair. Additionally, scandium is a group-3 transition metal (like 177 Lu) and exhibits affinity for DOTA-based chelators, which have been studied in depth, making the barrier to implementation lower for 43/47 Sc than for other proposed true theranostics. Before 43/47 Sc can see widespread pre-clinical evaluation, however, an accessible production methodology must be established and each isotope’s radiolabeling and animal imaging capabilities studied with a widely utilized tracer. As such, a simple means of converting an 18 MeV biomedical cyclotron to support solid targets and produce 43 Sc via the 42 Ca(d,n) 43 Sc reaction has been devised, exhibiting reasonable yields. The Nat Ti(γ,p) 47 Sc reaction is also investigated along with the successful implementation of chemical separation and purification methods for 43/47 Sc. The conjugation of 43/47 Sc with PSMA-617 at specific activities of up to 8.94 MBq/nmol and the subsequent imaging of LNCaP-ENZaR tumor xenografts in mouse models with both 43/47 Sc-PSMA-617 are also presented.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2022

Production of GMP-Compliant Clinical Amounts of Copper-61 Radiopharmaceuticals from Liquid Targets

PET imaging has gained significant momentum in the last few years, especially in the area of oncology, with an increasing focus on metal radioisotopes owing to their versatile chemistry and favourable physical properties. Copper-61 (t1/2 = 3.33 h, 61% β+, Emax = 1.216 MeV) provides unique advantages versus the current clinical standard (i.e., gallium-68) even though, until now, no clinical amounts of 61Cu-based radiopharmaceuticals, other than thiosemicarbazone-based molecules, have been produced. This study aimed to establish a routine production, using a standard medical cyclotron, for a series of widely used somatostatin analogues, currently labelled with gallium-68, that could benefit from the improved characteristics of copper-61. We describe two possible routes to produce the radiopharmaceutical precursor, either from natural zinc or enriched zinc-64 liquid targets and further synthesis of [61Cu]Cu-DOTA-NOC, [61Cu]Cu-DOTA-TOC and [61Cu]Cu-DOTA-TATE with a fully automated GMP-compliant process. The production from enriched targets leads to twice the amount of activity (3.28 ± 0.41 GBq vs. 1.84 ± 0.24 GBq at EOB) and higher radionuclidic purity (99.97% vs. 98.49% at EOB). Our results demonstrate, for the first time, that clinical doses of 61Cu-based radiopharmaceuticals can easily be obtained in centres with a typical biomedical cyclotron optimised to produce 18F-based radiopharmaceuticals.

Fonseca, Alexandra I. (ORCID:000000031924178X)↗
DOE OSTI2023

Laser-Induced Fluorescence for Monitoring Environmental Contamination and Stress in the Moss Thuidium plicatile

The ability to detect, measure, and locate the source of contaminants, especially heavy metals and radionuclides, is of ongoing interest. A common tool for contaminant identification and bioremediation is vegetation that can accumulate and indicate recent and historic pollution. However, large-scale sampling can be costly and labor-intensive. Hence, non-invasive in-situ techniques such as laser-induced fluorescence (LIF) are becoming useful and effective ways to observe the health of plants through the excitation of organic molecules, e.g., chlorophyll. The technique presented utilizes images collected of LIF in moss to identify different metals and environmental stressors. Analysis through image processing of LIF response was key to identifying Cu, Zn, Pb, and a mixture of the metals at nmol/cm 2 levels. Specifically, the RGB values from each image were used to create density histograms of each color channel’s relative pixel abundance at each decimal code value. These histograms were then used to compare color shifts linked to the successful identification of contaminated moss samples. Photoperiod and extraneous environmental stressors had minimal impact on the histogram color shift compared to metals and presented with a response that differentiated them from metal contamination.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2022

Origin of Plutonium-244 in the Early Solar System

We investigate the origin in the early Solar System of the short-lived radionuclide 244 Pu (with a half life of 80 Myr) produced by the rapid (r) neutron-capture process. We consider two large sets of r-process nucleosynthesis models and analyse if the origin of 244 Pu in the ESS is consistent with that of the other r and slow (s) neutron-capture process radioactive nuclei. Uncertainties on the r-process models come from both the nuclear physics input and the astrophysical site. The former strongly affects the ratios of isotopes of close mass ( 129 I/ 127 I, 244 Pu/ 238 U, and 247 Pu/ 235 U). The 129 I/ 247 Cm ratio, instead, which involves isotopes of a very different mass, is much more variable than those listed above and is more affected by the physics of the astrophysical site. We consider possible scenarios for the evolution of the abundances of these radioactive nuclei in the galactic interstellar medium and verify under which scenarios and conditions solutions can be found for the origin of 244 Pu that are consistent with the origin of the other isotopes. Solutions are generally found for all the possible different regimes controlled by the interval (δ) between additions from the source to the parcel of interstellar medium gas that ended up in the Solar System, relative to decay timescales. If r-process ejecta in interstellar medium are mixed within a relatively small area (leading to a long δ), we derive that the last event that explains the 129 I and 247 Cm abundances in the early Solar System can also account for the abundance of 244 Pu. Due to its longer half life, however, 244 Pu may have originated from a few events instead of one only. If r-process ejecta in interstellar medium are mixed within a relatively large area (leading to a short δ), we derive that the time elapsed from the formation of the molecular cloud to the formation of the Sun was 9-16 Myr.

79 ASTRONOMY AND ASTROPHYSICS↗
DOE OSTI2025

Galactic Chemical Evolution of Short-lived Radioactive Isotopes Produced by Explosive Nucleosynthesis: 60 Fe and 53 Mn

Several short-lived radionuclides (SLRs) are know to have existed in the early solar system (ESS). These species, which typically decay with half-lives of the order of a few million years, can be used to probe the timescales of events preceding the birth of the Sun. We investigate the ESS origin of 53 Mn, produced by core-collapse supernovae (CCSNe) and Type Ia supernovae (SNe Ia), and 60 Fe, produced exclusively by CCSNe. We model the evolution of the radioactive-to-stable abundance ratios of these SLRs with a Galactic chemical evolution (GCE) framework accounting for different SN yields, SN Ia delay times, and other Galactic features (K). A further set of models is calculated assuming that SNe Ia did not contribute any 53 Mn to the ESS. The predicted ratios are compared to meteoritic ratios to derive a distribution of solar isolation times that includes uncertainties due to stochastic chemical enrichment and measurements of the ESS values. The isolation times are then compared to those of 107 Pd and 182 Hf calculated in previous work. A self-consistent solution can be found within the current uncertainties, especially when using the GCE setups with K = 1.6 and 2.3, although the maximum likelihood for the 60 Fe distribution is typically ∼4–5 Myr shorter than for 53 Mn. The predicted 60 Fe/ 53 Mn ratio, instead, is completely inconsistent with the ESS value; this could be resolved using a larger fraction of faint CCSNe than usually considered in GCE models.

79 ASTRONOMY AND ASTROPHYSICS↗
DOE OSTI2020

The Nucleosynthetic Yields of Core-collapse Supernovae: Prospects for the Next Generation of Gamma-Ray Astronomy

Though the neutrino-driven convection model for the core-collapse explosion mechanism has received strong support in recent years, there are still many uncertainties in the explosion parameters—such as explosion energy, remnant mass, and end-of-life stellar abundances as initial conditions. Using a broad set of spherically symmetric core-collapse simulations we examine the effects of these key parameters on explosive nucleosynthesis and final explosion yields. The post-bounce temperature and density evolution of zero-age main-sequence 15, 20, and 25 solar mass progenitors are post-processed through the Nucleosynthesis Grid nuclear network to obtain detailed explosive yields. In particular, this study focuses on radio isotopes that are of particular interest to the next generation of gamma-ray astronomical observations: 43 K, 47 Ca, 44 Sc, 47 Sc, 48 V, 48 Cr, 51 Cr, 52 Mn, 59 Fe, 56 Co, 57 Co, and 57 Ni. Furthermore, these nuclides may be key in advancing our understanding of the inner workings of core-collapse supernovae by probing the parameters of the explosion engine. We find that the isotopes that are strong indicators of explosion energy are 43 K, 47 Ca, 44 Sc, 47 Sc, and 59 Fe, those that are dependent on the progenitor structure are 48 V, 51 Cr, and 57 Co, and those that probe neither are 48 Cr, 52 Mn, 57 Ni, and 56 Co. We discuss the prospects of observing these radionuclides in supernova remnants.

79 ASTRONOMY AND ASTROPHYSICS↗
DOE OSTI2026

The Extent of Solar Energetic Particle Irradiation in the Sun’s Protoplanetary Disk

Solar flares emit X-rays and high-energy (MeV to GeV) ions called solar energetic particles (SEPs). Astronomical observations show solar-mass protostellar fluxes are a factor Φ ≈ 3 × 10 2 –3 × 10 3 times higher than the present-day Sun. Constraining Φ in the early solar system is important for modeling ionization in the Sun’s protoplanetary disk, the extent of magnetorotational instability or magnetocentrifugal outflows, or even production of short-lived radionuclides. Recent interpretations of meteoritic data—including cosmogenic Ne in hibonite grains, initial ( 10 Be/ 9 Be) 0 ratios in Ca-rich, Al-rich inclusions (CAIs), or even inferences of live 7 Be in CAIs—suggest values Φ > 10 5 , reaching as high as Φ ≈ 6 × 10 6 , which would make the young Sun extraordinarily active, even for a protostar. We constrain Φ by reexamining these data. We conclude that cosmogenic Ne was produced in hibonite grains as they resided in the disk; 36 Cl was created in Cl-poor grains after the disk dissipated; 10 Be was inherited from the molecular cloud, with almost no (<1%) 10 Be created in the disk; and there is no evidence whatsoever for any live 7 Be in CAIs. We show these data are consistent with a value Φ ≈ 3 × 10 3 for the first >5 Myr of the solar nebula. The early Sun evidently emitted a flux of X-rays and SEPs not atypical for a protostar.

79 ASTRONOMY AND ASTROPHYSICS↗
DOE OSTI2022

The Timing of Potential Last Nucleosynthetic Injections into the Protosolar Molecular Cloud Inferred from 41 Ca– 26 Al Systematics of Bulk CAIs

Short-lived radionuclides (SLRs) provide important information about the chronology of the early solar system. Among them, 41 Ca, due to its decay to 41 K with a half-life of only 0.1 Ma, is particularly valuable in constraining the timescales and origins of both SLRs and the formation of the oldest solar system materials, the Ca–Al-rich inclusions (CAIs). The initial abundance of 41Ca in the solar system, expressed as the ( 41 Ca/ 40 Ca)I ratio, is the key to unveiling the origin of this nuclide. Here, we report a new solar system ( 41 Ca/ 40 Ca)I ratio of 2.0 × 10 −8 derived from the K isotope compositions of two CAIs. This new ratio is about four times higher than the previous value inferred from a mineral isochron. Such a high ( 41 Ca/ 40 Ca)I ratio in the CAIs exceeds that expected for the protosolar molecular cloud by ∼1000×, implying very late injection of the 41 Ca (and possibly other SLRs) into the protosolar molecular cloud. The correlated enrichments of 41 Ca and 26 Al in the bulk CAI samples hint at a common stellar origin of both SLRs. The injection time estimated from our new data depends on the stellar source—it ranges from 0.6 Ma for a Wolf–Rayet wind to 1.0 Ma for a TP-AGB star ejecta.

79 ASTRONOMY AND ASTROPHYSICS↗
DOE OSTI2024

Krypton-85 chronometry of spent nuclear fuel

We describe the use of the radionuclide 85 Kr, which is produced by nuclear fission and has a half-life of 10.76 years, to determine the age of spent nuclear fuel. The method is based on mass-spectrometric measurement of the relative abundance of fissiogenic Kr isotopes extracted from a fuel sample, and we show that it can be applied to micron-scale particles of spent fuel that are analogous to particles that have been released into the environment from various nuclear facilities in the past. 85 Kr chronometry is potentially valuable for identifying and attributing nuclear materials, grouping samples into collections of common origin that can be used to reconstruct the origin and irradiation history of the material, and verifying declared nuclear activities in the context of international monitoring programs.

11 NUCLEAR FUEL CYCLE AND FUEL MATERIALS↗
DOE OSTI2022

Reactive transport modeling for supporting climate resilience at groundwater contamination sites

Abstract. Climate resilience is an emerging issue at contaminated sites and hazardous waste sites, since projected climate shifts (e.g., increased/decreased precipitation) and extreme events (e.g., flooding, drought) could affect ongoing remediation or closure strategies. In this study, we develop a reactive transport model (Amanzi) for radionuclides (uranium, tritium, and others) and evaluate how different scenarios under climate change will influence the contaminant plume conditions and groundwater well concentrations. We demonstrate our approach using a two-dimensional (2D) reactive transport model for the Savannah River Site F-Area, including mineral reaction and sorption processes. Different recharge scenarios are considered by perturbing the infiltration rate from the base case as well as considering cap-failure and climate projection scenarios. We also evaluate the uranium and nitrate concentration ratios between scenarios and the base case to isolate the sorption effects with changing recharge rates. The modeling results indicate that the competing effects of dilution and remobilization significantly influence pH, thus changing the sorption of uranium. At the maximum concentration on the breakthrough curve, higher aqueous uranium concentration implies that sorption is reduced with lower pH due to remobilization. To better evaluate the climate change impacts in the future, we develop the workflow to include the downscaled CMIP5 (Coupled Model Intercomparison Project) climate projection data in the reactive transport model and evaluate how residual contamination evolves through 2100 under four climate Representative Concentration Pathway (RCP) scenarios. The integration of climate modeling data and hydrogeochemistry models enables us to quantify the climate change impacts, assess which impacts need to be planned for, and therefore assist climate resiliency efforts and help guide site management.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2021

Can we safely go to 200 °C? An integrated approach to assessing impacts to the engineered barrier system in a high-temperature repository

Abstract. This presentation gives on overview of the complex thermo-hydro-mechanical-chemical (THMC) processes occurring during the disposal of heat-producing high-level radioactive waste in geologic repositories. A specific focus is on the role of compacted bentonite, which is commonly used as an engineered backfill material for emplacement tunnels because of its low permeability, high swelling pressure, and radionuclide retention capacity. Laboratory and field tests integrated with THMC modeling have provided an effective way to deepen our understanding of temperature-related perturbations in the engineered barrier system; however, most of this work has been conducted for maximum temperatures around 100 ∘C. In contrast, some international disposal programs have recently started investigations to understand whether local temperatures in the bentonite of up to 200 ∘C could be tolerated with no significant changes to safety relevant properties. Raising the maximum temperature is attractive for economical and safety reasons but faces the challenge of exposing the bentonite to significant temperature increases. Strong thermal gradients may induce complex moisture transport processes while geochemical processes, such as cementation and perhaps also illitization effects may occur, all of which could strongly affect the bentonite and near-field rock properties. Here, we present initial investigations of repository behavior exposed to strongly elevated temperatures. We will start discussing our current knowledge base for temperature effects in repositories exposed to a maximum temperature of 100 ∘C, based on data and related modeling analysis from a large heater experiment conducted for over 18 years in the Grimsel Test Site in Switzerland. We then show results from coupled THMC simulations of a nuclear waste repository in a clay formation exposed to a maximum temperature of 200 ∘C. We also explore preliminary data from a bench-scale laboratory mock-up experiment, which was designed to represent the strong THMC gradients occurring in a “hot” repository, and we finally touch on a full-scale field heater test to be conducted soon in the Grimsel Test Site underground research laboratory in Switzerland (referred to as HotBENT).

Birkholzer, Jens T. (ORCID:0000000279891912)↗