Search NASA⌕ Search

SEARCH · Search NASA

Results for “small target”

Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 235 records · Page 13
All sourcesNASA NTRSDOE OSTI
DOE OSTI2024

Chemical screening by time-resolved X-ray scattering to discover allosteric probes

Abstract Drug discovery relies on efficient identification of small-molecule leads and their interactions with macromolecular targets. However, understanding how chemotypes impact mechanistically important conformational states often remains secondary among high-throughput discovery methods. Here, we present a conformational discovery pipeline integrating time-resolved, high-throughput small-angle X-ray scattering (TR-HT-SAXS) and classic fragment screening applied to allosteric states of the mitochondrial import oxidoreductase apoptosis-inducing factor (AIF). By monitoring oxidized and X-ray-reduced AIF states, TR-HT-SAXS leverages structure and kinetics to generate a multidimensional screening dataset that identifies fragment chemotypes allosterically stimulating AIF dimerization. Fragment-induced dimerization rates, quantified with time-resolved SAXS similarity analysis ( k VR ), capture structure–activity relationships (SAR) across the top-ranked 4-aminoquinoline chemotype. Crystallized AIF–aminoquinoline complexes validate TR-SAXS-guided SAR, supporting this conformational chemotype for optimization. AIF–aminoquinoline structures and mutational analysis reveal active site F482 as an underappreciated allosteric stabilizer of AIF dimerization. This conformational discovery pipeline illustrates TR-HT-SAXS as an effective technology for targeting chemical leads to important macromolecular states.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2020

A Foundational Study for Normal F8 -Containing Mouse Models for the miRNA Regulation of Hemophilia A: Identification and Analysis of Mouse miRNAs that Downregulate the Murine F8 Gene

Hemophilia A (HA) is associated with defects in the F8 gene, encoding coagulation factor VIII (FVIII). Our previous studies show that F8-targeting micro RNAs (miRNAs), a group of small RNAs involved in gene regulation, can downregulate F8 expression causing HA in individuals with normal F8-genotypes and increased HA severity in patients with mutations in F8. Understanding the mechanistic underpinnings of human genetic diseases caused or modulated by miRNAs require a small animal model, such as a mouse model. Here, we report a foundational study to develop such a model system. We identified the mouse 3'untranslated region (3'UTR) on murine F8-mRNA (muF8-mRNA) that can bind to murine miRNAs. We then selected three miRNAs for evaluation: miR-208a, miR-351 and miR-125a. We first demonstrate that these three miRNAs directly target the 3'UTR of muF8-mRNA and reduce the expression of a reporter gene (luciferase) mRNA fused to the muF8-3' UTR in mammalian cells. Furthermore, in mouse cells that endogenously express the F8 gene and produce FVIII protein, the ectopic expression of these miRNAs downregulated F8-mRNA and FVIII protein. These results provide proof-of-concept and reagents as a foundation for using a normal F8-containing mouse as a model for the miRNA regulation of normal F8 in causing or aggravating the genetic disease HA.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2024

Gluon double-spin asymmetry in the longitudinally polarized p + p collisions

We derive the first-ever small-x expression for the inclusive gluon production cross section in the central rapidity region of the longitudinally polarized proton-proton collisions. The cross section depends on the polarizations of both protons, therefore comprising the numerator of the longitudinal double-spin asymmetry ALL for the produced gluons. The cross section is calculated in the shock wave formalism and is expressed in terms of the polarized dipole scattering amplitudes on the projectile and target protons. We show that the small-x evolution corrections are included into our cross section expression if one evolves these polarized dipole amplitudes using the double-logarithmic helicity evolution derived in [1–4]. Our calculation is performed for the gluon sector only, with the quark contribution left for future work. When that work is complete, the resulting formula will be applicable to longitudinally polarized proton-proton and proton-nucleus collisions, as well as to polarized semi-inclusive deep inelastic scattering (SIDIS) on a proton or a nucleus. Our results should allow one to extend the small-x helicity phenomenology analysis of [5] to the jet/hadron production data reported for the longitudinally polarized proton-proton collisions at RHIC and to polarized SIDIS measurements at central rapidities to be performed at the EIC.

72 PHYSICS OF ELEMENTARY PARTICLES AND FIELDS↗
DOE OSTI2020

Targeting tRNA-synthetase interactions towards novel therapeutic discovery against eukaryotic pathogens

The development of chemotherapies against eukaryotic pathogens is especially challenging because of both the evolutionary conservation of drug targets between host and parasite, and the evolution of strain-dependent drug resistance. There is a strong need for new nontoxic drugs with broad-spectrum activity against trypanosome parasites such as Leishmania and Trypanosoma. A relatively untested approach is to target macromolecular interactions in parasites rather than small molecular interactions, under the hypothesis that the features specifying macromolecular interactions diverge more rapidly through coevolution. We computed tRNA Class-Informative Features in humans and independently in eight distinct clades of trypanosomes, identifying parasite-specific informative features, including base pairs and base mis-pairs, that are broadly conserved over approximately 250 million years of trypanosome evolution. Validating these observations, we demonstrated biochemically that tRNA:aminoacyl-tRNA synthetase (aaRS) interactions are a promising target for anti-trypanosomal drug discovery. From a marine natural products extract library, we identified several fractions with inhibitory activity toward Leishmania major alanyl-tRNA synthetase (AlaRS) but no activity against the human homolog. These marine natural products extracts showed cross-reactivity towards Trypanosoma cruzi AlaRS indicating the broad-spectrum potential of our network predictions. We also identified Leishmania major threonyl-tRNA synthetase (ThrRS) inhibitors from the same library. We discuss why chemotherapies targeting multiple aaRSs should be less prone to the evolution of resistance than monotherapeutic or synergistic combination chemotherapies targeting only one aaRS.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2024

Stochastic Error Cancellation in Analog Quantum Simulation

Analog quantum simulation is a promising path towards solving classically intractable problems in many-body physics on near-term quantum devices. However, the presence of noise limits the size of the system and the length of time that can be simulated. In our work, we consider an error model in which the actual Hamiltonian of the simulator differs from the target Hamiltonian we want to simulate by small local perturbations, which are assumed to be random and unbiased. We analyze the error accumulated in observables in this setting and show that, due to stochastic error cancellation, with high probability the error scales as the square root of the number of qubits instead of linearly. We explore the concentration phenomenon of this error as well as its implications for local observables in the thermodynamic limit. Moreover, we show that stochastic error cancellation also manifests in the fidelity between the target state at the end of time-evolution and the actual state we obtain in the presence of noise. This indicates that, to reach a certain fidelity, more noise can be tolerated than implied by the worst-case bound if the noise comes from many statistically independent sources.

Analog quantum simulation↗
DOE OSTI2022

Inhibition of FOXP3 by stapled alpha-helical peptides dampens regulatory T cell function

Despite continuing advances in the development of novel cellular-, antibody-, and chemotherapeutic-based strategies to enhance immune reactivity, the presence of regulatory T cells (Treg cells) remains a complicating factor for their clinical efficacy. To overcome dosing limitations and off-target effects from antibody-based Treg cell deletional strategies or small molecule drugging, we investigated the ability of hydrocarbon stapled alpha-helical (SAH) peptides to target FOXP3, the master transcription factor regulator of Treg cell development, maintenance, and suppressive function. Using the crystal structure of the FOXP3 homodimer as a guide, we developed SAHs in the likeness of a portion of the native FOXP3 antiparallel coiled-coil homodimerization domain (SAH-FOXP3) to block this key FOXP3 protein-protein interaction (PPI) through molecular mimicry. We describe the design, synthesis, and biochemical evaluation of single- and double-stapled SAHs covering the entire coiled-coil expanse. We show that lead SAH-FOXP3s bind FOXP3, are cell permeable and nontoxic to T cells, induce dose-dependent transcript and protein level alterations of FOXP3 target genes, impede Treg cell function, and lead to Treg cell gene expression changes in vivo consistent with FOXP3 dysfunction. These results demonstrate a proof of concept for rationally designed FOXP3-directed peptide therapeutics that could be used as approaches to amplify endogenous immune responsiveness.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2022

Recent Drug Development and Medicinal Chemistry Approaches for the Treatment of SARS‐CoV‐2 Infection and COVID‐19

Abstract COVID‐19, caused by SARS‐CoV‐2 infection, continues to be a major public health crisis around the globe. Development of vaccines and the first cluster of antiviral drugs has brought promise and hope for prevention and treatment of severe coronavirus disease. However, continued development of newer, safer, and more effective antiviral drugs are critically important to combat COVID‐19 and counter the looming pathogenic variants. Studies of the coronavirus life cycle revealed several important biochemical targets for drug development. In the present review, we focus on recent drug design and medicinal chemistry efforts in small molecule drug discovery, including the development of nirmatrelvir that targets viral protein synthesis and remdesivir and molnupiravir that target viral RdRp. These are recent FDA approved drugs for the treatment of COVID‐19.

Pharmacology & Pharmacy↗
DOE OSTI2022

Structural basis for the inability of chloramphenicol to inhibit peptide bond formation in the presence of A-site glycine

Ribosome serves as a universal molecular machine capable of synthesis of all the proteins in a cell. Small-molecule inhibitors, such as ribosome-targeting antibiotics, can compromise the catalytic versatility of the ribosome in a context-dependent fashion, preventing transpeptidation only between particular combinations of substrates. Classic peptidyl transferase center inhibitor chloramphenicol (CHL) fails to inhibit transpeptidation reaction when the incoming A site acceptor substrate is glycine, and the molecular basis for this phenomenon is unknown. Here, we present a set of high-resolution X-ray crystal structures that explain why CHL is unable to inhibit peptide bond formation between the incoming glycyl-tRNA and a nascent peptide that otherwise is conducive to the drug action. Our structures reveal that fully accommodated glycine residue can co-exist in the A site with the ribosome-bound CHL. Moreover, binding of CHL to a ribosome complex carrying glycyl-tRNA does not affect the positions of the reacting substrates, leaving the peptide bond formation reaction unperturbed. These data exemplify how small-molecule inhibitors can reshape the A-site amino acid binding pocket rendering it permissive only for specific amino acid residues and rejective for the other substrates extending our detailed understanding of the modes of action of ribosomal antibiotics.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2023

Coded aperture and Compton imaging for the development of 225 Ac‐based radiopharmaceuticals

Abstract Background Targeted alpha‐particle therapy (TAT) has great promise as a cancer treatment. Arguably the most promising TAT radionuclide that has been proposed is 225 Ac. The development of 225 Ac‐based radiopharmaceuticals has been hampered due to the lack of effective means to study the daughter redistribution of these agents in small animals at the preclinical stage. Purpose The ability to directly image the daughters, namely 221 Fr and 213 Bi, via their gamma‐ray emissions would be a boon for preclinical studies. That said, conventional medical imaging modalities, including single photon emission computed tomography (SPECT) based on nonmultiplexed collimation, cannot be employed due to sensitivity limitations. Methods As an alternative, we propose the use of both coded aperture and Compton imaging with the former modality suited to the 218‐keV gamma‐ray emission of 221 Fr and the latter suited to the 440‐keV gamma‐ray emission of 213 Bi. Results This work includes coded aperture images of 221 Fr and Compton images of 213 Bi in tumor‐bearing mice injected with 225 Ac‐based radiopharmaceuticals. Conclusions These results are the first demonstration of visualizing and quantifying the 225 Ac daughters in small animals through the application of coded aperture and Compton imaging.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2024

“Off‐Label Use” of the Siderophore Enterobactin Enables Targeted Imaging of Cancer with Radioactive Ti (IV)

Abstract The development of inert, biocompatible chelation methods is required to harness the emerging positron emitting radionuclide 45 Ti for radiopharmaceutical applications. Herein, we evaluate the Ti (IV) ‐coordination chemistry of four catechol‐based, hexacoordinate chelators using synthetic, structural, computational, and radiochemical approaches. The siderophore enterobactin (Ent) and its synthetic mimic TREN‐CAM readily form mononuclear Ti (IV) species in aqueous solution at neutral pH. Radiolabeling studies reveal that Ent and TREN‐CAM form mononuclear complexes with the short‐lived, positron‐emitting radionuclide 45 Ti (IV) , and do not transchelate to plasma proteins in vitro and exhibit rapid renal clearance in naïve mice. These features guide efforts to target the 45 Ti isotope to prostate cancer tissue through the design, synthesis, and evaluation of Ent‐DUPA, a small molecule conjugate composed of a prostate specific membrane antigen (PSMA) targeting peptide and a monofunctionalized Ent scaffold. The [ 45 Ti][Ti(Ent‐DUPA)] 2− complex forms readily at room temperature. In a tumor xenograft model in mice, selective tumor tissue accumulation (8±5 %, n =5), and low off‐target uptake in other organs is observed. Overall, this work demonstrates targeted imaging with 45 Ti (IV) , provides a foundation for advancing the application of 45 Ti in nuclear medicine, and reveals that Ent can be repurposed as a 45 Ti‐complexing cargo for targeted nuclear imaging applications.

Koller, Angus J.↗
DOE OSTI2024

Optimization of neutron chopper and optics for CENTAUR, the SANS/WANS diffractometer at the spallation neutron source second target station

Herein this report presents the physics design and optimization of the neutron chopper and optics systems for the CENTAUR instrument, a multifunctional small-angle and wide-angle neutron scattering diffractometer for the Spallation Neutron Source Second Target Station. This instrument will offer a wide range of capabilities, including small-angle neutron scattering with wide Q coverage (e.g., 0.001–20 Å –1 ), providing a tool to investigate structures from atomic to mesoscopic scales simultaneously. To efficiently transport desired neutrons from the compact high-brightness cold source, several innovative designs are utilized: a time-zero chopper with a straight guide system for short-wavelength neutrons, octagonal guides for higher flux, and a correlation chopper to reduce inelastic scattering. The optimization process considers factors such as useable time-integrated flux, instrument resolution, brilliance transfer, divergence, and acceptance diagram uniformity. The overall design prioritizes flexibility to accommodate diverse user requirements.

46 INSTRUMENTATION RELATED TO NUCLEAR SCIENCE AND ↗
DOE OSTI2024

A phosphorylation-deficient ribosomal protein eS6 is largely functional in Arabidopsis thaliana , rescuing mutant defects from global translation and gene expression to photosynthesis and growth

The eukaryote-specific ribosomal protein of the small subunit eS6 is phosphorylated through the target of rapamycin (TOR) kinase pathway. Although this phosphorylation event responds dynamically to environmental conditions and has been studied for over 50 years, its biochemical and physiological significance remains controversial and poorly understood. Here, we report data from Arabidopsis thaliana, which indicate that plants expressing only a phospho-deficient isoform of eS6 grow essentially normally under laboratory conditions. The eS6z (RPS6A) paralog of eS6 functionally rescued a double mutant in both rps6a and rps6b genes when expressed at approximately twice the wild-type dosage. A mutant isoform of eS6z lacking the major six phosphorylatable serine and threonine residues in its carboxyl-terminal tail also rescued the lethality, rosette growth, and polyribosome loading of the double mutant. This isoform also complemented many mutant phenotypes of rps6 that were newly characterized here, including photosynthetic efficiency, and most of the gene expression defects that were measured by transcriptomics and proteomics. However, compared with plants rescued with a phospho-enabled version of eS6z, the phospho-deficient seedlings retained a mild pointed-leaf phenotype, root growth was reduced, and certain cell cycle-related mRNAs and ribosome biogenesis proteins were misexpressed. The residual defects of the phospho-deficient seedlings could be understood as an incomplete rescue of the rps6 mutant defects. There was little or no evidence for gain-of-function defects. As previously published, the phospho-deficient eS6z also rescued the rps6a and rps6b single mutants; however, phosphorylation of the eS6y (RPS6B) paralog remained lower than predicted, further underscoring that plants can tolerate phospho-deficiency of eS6 well. Our data also yield new insights into how plants cope with mutations in essential, duplicated ribosomal protein isoforms.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2024

Plastic additives in the ocean: Use of a comprehensive dataset for meta-analysis and method development

In excess of 13,000 chemicals are added to plastics (‘additives’) to improve performance, durability, and production of plastic products. They are categorized into numerous chemical classes including flame retardants, light stabilizers, antioxidants, and plasticizers. While research on plastic additives in the marine environment has increased over the past decade, there is a lack of methodological standardization. To direct future measurement of plastic additives, we compiled a first-of-its-kind dataset of literature assessing plastic additives in marine environments, delineated by sample type (plastic debris, seawater, sediment, biota). Using this dataset, we performed a meta-analysis to summarize the state of the science. Currently, our dataset includes 217 publications published between 1978 and May 2023. The majority of publications analyzed plastic additives in biota collected from Europe and Asia. Analyses concentrated on plasticizers, brominated flame retardants, and bisphenols. Common sample preparation techniques included Solvent - Agitation extraction for plastic, sediment, and biota samples, and Solid Phase Extraction for seawater samples with dichloromethane and solvent mixtures including dichloromethane as the organic extraction solvent. Finally, most analyses were performed utilizing gas chromatography/mass spectrometry. There are a variety of data gaps illuminated by this meta-analysis, most notably the small number of compounds that have been targeted for detection compared to the large number of additives used in plastic production. The provided dataset facilitates future investigation of trends in plastic additive concentration data in the marine environment (allowing for comparison to toxicity thresholds) and acts as a starting point for optimizing and harmonizing plastic additive analytical methods.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2023

Molecular Transformation of Dissolved Organic Matter during the Processes of Wildfire, Alum Coagulation, and Disinfection Using ESI(-) and ESI(+) FT-ICR MS

Forest fires alter the quality of terrestrial dissolved organic matter (DOM) flushed into source water, which could be further changed during alum coagulation and serve as potential disinfection byproduct (DBP) precursors in water facilities. To unveil this molecular transformation, we applied 12T Fourier transform ion cyclotron resonance mass spectrometry on a controlled study which used the leachates of black and white ashes (collected immediately after the 2013 Rim Fire, CA) along with unburned white fir (Abies concolor) and ponderosa pine (Pinus ponderosa). Here, results showed that the assigned features in DOM from burned ashes had a smaller molecular weight (MW), contained more unsaturated, aromatic, and oxidized and less fraction of labile compounds, and were enriched with nitrogen, relative to unburned litters. After alum coagulation, we observed the disappeared features with higher MW and S/C and N/C atom ratios than the resistant features. During the following disinfections, the disappeared features serving as the potential DBP precursors had higher MW and unsaturation degree, contained more S- and N-containing functionalities, and were more aromatic, compared to the resistant features. Our study suggested organic compounds with small MW and high aromaticity as the targets for water facilities to improve post-fire drinking water quality.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2021

Mechanistic Duality of Bacterial Efflux Substrates and Inhibitors: Example of Simple Substituted Cinnamoyl and Naphthyl Amides

Antibiotic resistance poses an immediate and growing threat to human health. Multidrug efflux pumps are promising targets for overcoming antibiotic resistance with small-molecule therapeutics. Previously, we identified a diaminoquinoline acrylamide, NSC-33353, as a potent inhibitor of the AcrAB–TolC efflux pump in Escherichia coli. This inhibitor potentiates the antibacterial activities of novobiocin and erythromycin upon binding to the membrane fusion protein AcrA. It is also a substrate for efflux and lacks appreciable intrinsic antibacterial activity of its own in wild-type cells. Here, we have modified the substituents of the cinnamoyl group of NSC-33353, giving rise to analogs that retain the ability to inhibit efflux, lost the features of the efflux substrates, and gained antibacterial activity in wild-type cells. The replacement of the cinnamoyl group with naphthyl isosteres generated compounds that lack antibacterial activity but are both excellent efflux pump inhibitors and substrates. Surprisingly, these inhibitors potentiate the antibacterial activity of novobiocin but not erythromycin. Surface plasmon resonance experiments and molecular docking suggest that the replacement of the cinnamoyl group with naphthyl shifts the affinity of the compounds away from AcrA to the AcrB transporter, making them better efflux substrates and changing their mechanism of inhibition. These results provide new insights into the duality of efflux substrate/inhibitor features in chemical scaffolds that will facilitate the development of new efflux pump inhibitors.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2021

Structural Characterization of the Human Cytosolic Malate Dehydrogenase I

The first crystal structure of the human cytosolic malate dehydrogenase I (MDH1) is described. Structure determination at a high resolution (1.65 Å) followed production, isolation, and purification of human MDH1 using a bacterial expression system. The structure is a binary complex of MDH1 with only a bound malonate molecule in the substrate binding site. Comparisons of this structure with malate dehydrogenase enzymes from other species confirm that the human enzyme adopts similar secondary, tertiary, and quaternary structures and that the enzyme retains a similar conformation even when nicotinamide adenine dinucleotide (NAD + ) is not bound. A comparison to the highly homologous porcine (sus scrofa) MDH1 ternary structures leads to the conclusion that only small conformational differences are needed to accommodate binding by NAD + or other NAD + mimetics. Conformational differences observed in the second subunit show that the NAD + binding elements are nevertheless quite flexible. Comparison of hMDH1 to the human mitochondrial malate dehydrogenase (hMDH2) reveals some key differences in the α7–α8 loop, which lies directly beneath the substrate binding pocket. These differences might be exploited in the structure-assisted design of selective small molecule inhibitors of hMDH1, an emerging target for the development of anticancer therapeutics.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2020

Principal factors in performance of indirect-drive laser fusion experiments

Progress in inertial confinement fusion depends on the accurate interpretation of experiments that are complex and difficult to explain with simulations. Results could depend on small changes in the laser pulse or target or physics that are not fully understood or characterized. In this paper we discuss an x-ray-driven platform with fewer sources of degradation, and find the fusion yield can be described as a physically motivated function of laser energy, target scale, and implosion symmetry. Furthermore, this platform and analysis could enable a more experimental approach to the study and optimization of implosion physics.

70 PLASMA PHYSICS AND FUSION TECHNOLOGY↗
DOE OSTI2022

Non-linear MHD modelling of edge localized modes suppression by resonant magnetic perturbations in ITER

Edge localized modes (ELMs) suppression by resonant magnetic perturbations (RMPs) was studied with the non-linear magneto-hydro-dynamic (MHD) code JOREK for the ITER H-mode scenarios at 15 MA, 12.5 MA, 10 MA/5.3 T. In this study, the main aim was to demonstrate that ELMs can be suppressed by RMPs while the divertor 3D footprints of heat and particle fluxes remain within divertor material limits. The unstable peeling–ballooning modes responsible for ELMs without RMPs were modelled first for each scenario using numerically accessible parameters for ITER. Then the stabilization of ELMs by RMPs was modelled with the same parameters. RMP spectra, optimized by the linear MHD MARS-F code, with main toroidal harmonics N = 2, N = 3, N = 4 have been used as boundary conditions of the computational domain of JOREK, including realistic RMP coils, main plasma, scrape off layer (SOL) divertor and realistic first wall. The model includes all relevant plasma flows: toroidal rotation, two fluid diamagnetic effects and neoclassical poloidal friction. With RMPs, the main toroidal harmonic and the non-linearly coupled harmonics remain dominant at the plasma edge, producing saturated modes and a continuous MHD turbulent transport thereby avoiding ELM crashes in all scenarios considered here. The threshold for ELM suppression was found at a maximum RMP coils current of 45 kAt–60 kAt compared to the coils maximum capability of 90 kAt. In the high beta poloidal steady-state 10 MA/5.3 T scenario, a rotating QH-mode without ELMs was observed even without RMPs. In this scenario with RMPs N = 3, N = 4 at 20 kAt maximum current in RMP coils, similar QH-mode behaviour was observed however with dominant edge harmonic corresponding to the main toroidal number of RMPs. The present MHD modelling was limited in time by few tens of ms after RMPs were switched on until the magnetic energy of the modes saturates. As a consequence the thermal energy was still evolving on this time scale, far from the ITER confinement time scale and hence only the form of 3D footprints on the divertor targets can be indicated within this set-up. Also note, that the divertor physics was missing in this model, so realistic values of fluxes are out of reach in this modelling. However the stationary 3D divertor and particle fluxes could be simply extrapolated from these results to the stationary situation considering that a large power fraction should be radiated in the core and SOL and only about 50 MW power is going to the divertor, which is an arbitrary, but reasonable number used here. The 3D footprints with RMPs show the characteristic splitting with the main RMP toroidal symmetry. The maximum radial extension of the footprints typically was ~20 cm in inner divertor and ~40 cm in outer divertor with stationary heat fluxes decreasing further out from the initial strike point from ~5 MW m ₋2 to ~1 MW m ₋2 assuming a total power in the divertor and walls is 50 MW. The heat fluxes remain within the divertor target and baffle areas, however with rather small margin in the outer divertor which could be an issue for the first wall especially in transient regimes when part of the plasma thermal energy is released due to switching on the RMP coils. This fact should be considered when RMPs are applied with a more favorable application before or soon after the L–H transition, although optimization is required to avoid increasing the L–H power threshold with RMPs.

70 PLASMA PHYSICS AND FUSION TECHNOLOGY↗