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At least 847 records · Page 47

Issues and Methods Concerning the Evaluation of Hypersingular and Near-Hypersingular Integrals in BEM Formulations

It is known that higher order modeling of the sources and the geometry in Boundary Element Modeling (BEM) formulations is essential to highly efficient computational electromagnetics. However, in order to achieve the benefits of hIgher order basis and geometry modeling, the singular and near-singular terms arising in BEM formulations must be integrated accurately. In particular, the accurate integration of near-singular terms, which occur when observation points are near but not on source regions of the scattering object, has been considered one of the remaining limitations on the computational efficiency of integral equation methods. The method of singularity subtraction has been used extensively for the evaluation of singular and near-singular terms. Piecewise integration of the source terms in this manner, while manageable for bases of constant and linear orders, becomes unwieldy and prone to error for bases of higher order. Furthermore, we find that the singularity subtraction method is not conducive to object-oriented programming practices, particularly in the context of multiple operators. To extend the capabilities, accuracy, and maintainability of general-purpose codes, the subtraction method is being replaced in favor of the purely numerical quadrature schemes. These schemes employ singularity cancellation methods in which a change of variables is chosen such that the Jacobian of the transformation cancels the singularity. An example of the sin,oularity cancellation approach is the Duffy method, which has two major drawbacks: 1) In the resulting integrand, it produces an angular variation about the singular point that becomes nearly-singular for observation points close to an edge of the parent element, and 2) it appears not to work well when applied to nearly-singular integrals. Recently, the authors have introduced the transformation u(x(prime))= sinh (exp -1) x(prime)/Square root of ((y prime (exp 2))+ z(exp 2) for integrating functions of the form I = Integral of (lambda(r(prime))((e(exp -jkR))/(4 pi R) d D where A (r (prime)) is a vector or scalar basis function and R = Square root of( (x(prime)(exp2) + (y(prime)(exp2) + z(exp 2)) is the distance between source and observation points. This scheme has all of the advantages of the Duffy method while avoiding the disadvantages listed above. In this presentation we will survey similar approaches for handling singular and near-singular terms for kernels with 1/R(exp 2) type behavior, addressing potential pitfalls and offering techniques to efficiently handle special cases.

Fink, P. W.↗

Celestial Mapping System for Lunar Surface Mapping and Analytics

Celestial Mapping System (CMS) is a software platform to generate virtual 3D globe for celestial bodies within our solar system. Various layers are built on top of the virtual globe to provide visualization of high resolution imagery, enable precise measurements, build analytical capabilities and broad range of functionalities to assist planetary scientists and mission planners. CMS is built using OpenJDK 11 and will run on a wide variety of platforms such as Linux, Windows, OSX, etc. It has a thick client with less overhead to access hardware resources. This allows features such as terrain profiling and distance calculations to be performed on the client and on the fly. The present focus of CMS is on developing lunar mapping tool kits to provide features such as - 3D first person view with zoom and navigational capabilities, realistic terrain visualization based on LRO data, measurement tools, Apollo landing site annotations, stereoscopic view, elevation profiles, line of sight analysis and many more. The application is developed to provide situational and domain awareness on Lunar surface, planning capabilities for equipment placements and traverse path optimization. As data becomes available, CMS has the capabilities to integrate data sets that change dynamically in real-time, which will be useful for monitoring satellites and remotely-sensed data on Lunar surface. CMS utilizes NASA WorldWind Java library and OpenGL to achieve high-performance rendering of data and measurements, and also adheres to OGC standards. CMS supports importing synthetic features in a variety of 3D, 2D, vector and raster formats. Nomenclature is pulled from USGS Moon IAU2000 database, and lunar parameters are based of the standardized IAU2000 Moon ellipsoid. GDAL (Geospatial Data Abstraction Library) was used to modify and test the accuracy of datasets before integrating into the application. Our high-resolution global elevation model was compared with the LRO LOLA DEM elevation values and tested to ensure accuracy. Celestial Mapping System has several potential use cases for NASA including subsurface lava tubes visualization and analysis, soil analysis, resource visualization and representation on 3D globe.

GIS system↗

Supersonic airfoil optimization

A procedure for the optimization of supersonic airfoils is presented. A nonlinear, full-potential solver (NCOREL) is coupled with a numerical optimizer (CONMIN). The NCOREL code is a three-dimensional supersonic marching method, however, only two-dimensional (conical) results are used for the airfoil problem. Each airfoil evaluated in the NCOREL aerodynamic code is composed of a linear combination of user-specified basis airfoils. The weighting factors of the basis airfoils plus the angle of attack form the design variable vector. The inviscid drag coefficient is minimized subject to lift and crossflow Mach number gradient constraints. The optimization strategy is found to be extremely important for the efficient determination of an optimum airfoil.

Pittman, J. L.↗

Wildfire Segmentation From Remotely Sensed Data Using Quantum-Compatible Conditional Vector Quantized-Variational Autoencoders

Wildfires represent a critical environmental hazard with multifaceted implications for ecosystems, communities, and public health [1]. The escalating frequency and intensity of wildfires globally have intensified the urgency for robust segmentation methodologies to facilitate effective mitigation, response, and recovery strategies [2]. Accurate wildfire segmentation is pivotal for delineating fire boundaries, assessing progression patterns, and prioritizing resource allocation during emergency scenarios. Furthermore, precise segmentation enables stakeholders, including policymakers, environmental scientists, and emergency responders, to formulate evidence-based strategies, thereby minimizing socio-economic disruptions and ecological degradation. Consequently, advancing wildfire segmentation techniques through innovative technological interventions remains a paramount research imperative. Although foundational in wildfire segmentation, traditional deterministic models exhibit inherent limitations that compromise their efficacy in dynamic and uncertain environments. These models often operate on rigid algorithms prioritizing deterministic classifications, thereby overlooking the inherent complexities and uncertainties associated with wildfire behavior and satellite data variability. Such deterministic frameworks tend to produce oversimplified representations that fail to capture the intricate nuances of evolving fire dynamics, spatial heterogeneity, and environmental interactions [1]. Consequently, the deterministic approach’s propensity for uncertainty collapsing [1, 3] hampers the accuracy, reliability, and applicability of segmentation outcomes in real-world scenarios. Contrastingly, stochastic models offer a more nuanced and adaptable framework for wildfire segmentation. By integrating probabilistic elements into the modeling paradigm, stochastic approaches, particularly probabilistic approaches such as variational auto encoders (VAEs) [4], facilitate comprehensive uncertainty assessment, enabling researchers to quantify and incorporate uncertainties into segmentation outcomes effectively. This probabilistic nature empowers stochastic models to encapsulate variability, account for data inconsistencies, and adapt to evolving environmental conditions, enhancing segmentation accuracy, reliability, and robustness. Embracing stochastic methodologies thus catalyzes advancements in wildfire science by fostering a more holistic, adaptive, and resilient segmentation framework. Despite VAEs demonstrating significant promise in various applications, they come with inherent limitations that have garnered attention within the machine learning community. One of the primary drawbacks lies in their reliance on static priors, which essentially assume a fixed distribution for latent variables, thereby limiting the model’s flexibility to capture complex data structures effectively [5]. This static nature leads to suboptimal representations, especially when dealing with complex and high-dimensional data. Additionally, VAEs often struggle with generating sharp and realistic samples, a phenomenon commonly referred to as mode collapse [5, 7, 6]. Furthermore, the optimization process in VAEs, which involves balancing the reconstruction loss and the regularization term, can sometimes be challenging to fine-tune [7]. In recent efforts to address these shortcomings, alternative approaches like Vector Quantized Variational Auto encoders(VQ-VAEs) [7], address the challenges by incorporating discrete latent variables and leveraging techniques that enhance the quality and diversity of generated samples while maintaining efficient training dynamics. VQ-VAEs propose a dynamic prior distribution generation mechanism that diverges from the static priors commonly associated with traditional VAEs. This dynamic approach allows for more adaptive and context-aware latent variable representations, thereby potentially capturing complex data structures more effectively. Unlike autoregressive prior models such as PixelCNN, which, despite their ability to model dependencies across data dimensions, suffer from significant computational inefficiencies and lack flexibility in handling diverse datasets. In our work, we propose to use a generative quantum-compatible approach to help alleviate the shortcomings of autoregressive prior model in VQ-VAEs. Restricted Boltzmann Machines (RBMs) are a viable alternative prior model that can learn prior distributions in a faster and more flexible manner. In this research endeavor, we meticulously curate a state-of-the-art dataset leveraging satellite MODIS data in conjunction with VIIRS fire masks, derived from Fire Radiative Power (FRP), thereby encapsulating diverse wildfire scenarios and environmental contexts. We developed a conditional VQ-VAE architecture with the RBM prior model that is trained in a supervised manner for segmenting wildfire masks. This innovative approach synergistically harnesses deep learning capabilities, enabling the generation of segmentation maps characterized by heightened precision, granularity, and contextual relevance. Furthermore, replacing the autoregressive prior learning method proposed by the original VQ-VAE with a prior density approximation via quantum-compatible RBM facilitates expedited inference processes, augments flexibility in prior sampling, optimizes computational efficiency and establishes a groundbreaking benchmark in wildfire segmentation methodologies.

quantum machine learning↗

Application of a vectorized particle simulation in high-speed near-continuum flow

An efficient particle simulation technique, developed for use on vector architecture based supercomputers for studying hypersonic rarefied gas flows is employed to simulate the complex wake generated by Mach six flow over a 10 deg half-angle wedge for freestream Reynolds numbers of 1780 and 3560. Data obtained are compared against higher Reynolds number experimental results. Simulations utilized as many as 10 to the 5th computational cells and 10 to the 7th simulated particles having power-law interaction potentials. A code performance of 1.8-2.4 microsec of Cray-2 CPU time to process a single particle per timestep is achieved. Diffuse adiabatic and isothermal wedge surface models are used in this investigation. Although the wedge geometry is two-dimensional, the simulation incorporates a width-wise direction, resulting in a three-dimensional computation.

Woronowicz, Michael S.↗

Optical laboratory solution and error model simulation of a linear time-varying finite element equation

The use of simplified error models to accurately simulate and evaluate the performance of an optical linear-algebra processor is described. The optical architecture used to perform banded matrix-vector products is reviewed, along with a linear dynamic finite-element case study. The laboratory hardware and ac-modulation technique used are presented. The individual processor error-source models and their simulator implementation are detailed. Several significant simplifications are introduced to ease the computational requirements and complexity of the simulations. The error models are verified with a laboratory implementation of the processor, and are used to evaluate its potential performance.

Taylor, B. K.↗

Update on the Juncture Flow PIV Results and Future Plans

A novel, embedded, 2D Particle Image Velocimetry system has been developed and implemented to obtain off-body velocity measurements in the junction of an 8% wing-body configuration in the NASA Langley Research Center 14- by 22-Foot Subsonic Tunnel. Although the initial purpose for implementing the system during this test was to evaluate system performance and identify potential risks, a considerable amount of data were obtained in the wing-fuselage junction near the trailing edge at a Reynolds Number of 2.4 Million and angle of attack of 5 degrees. In addition to providing notable efficiencies with regard to image acquisition and test operations, the PIV system captured unique details of the flow separation to complement the extensive suite of measurement techniques applied during the test. Instantaneous PIV vector fields reveal that the flow separation is not stationary but rather highly dynamic. Mean flow statistics calculated from the PIV measurements highlight where reverse flow and Reynolds stresses are concentrated in the separated region and agree well with results from the embedded Laser Doppler Velocimeter system and Computational Fluid Dynamics. The comparisons and ional insight gained during this effort will help guide system improvements for the upcoming entry in 2020.

Jenkins, Luther N.↗

Lower-Hybrid Wave Structures and Interactions With Electrons Observed in Magnetotail Reconnection Diffusion Regions

We investigate waves close to the lower-hybrid frequency in 12 magnetotail reconnection electron diffusion region (EDR) events with guide field levels of near-zero to 30%. In about half of the events, the wave vector has a small component along the current sheet normal, consistent with known lower-hybrid drift wave properties, but the perpendicular magnetic field fluctuations can be comparable or greater than the parallel component, a feature unique to the waves inside and adjacent to EDRs. Another new wave property is that the wave vector has a significant component along the current sheet normal in some events and completely along the normal for one event. In 1/4of the events, the ∇∙𝑷(sub 𝑒) term has a significant contribution to the wave electric field, possibly a feature of lower-hybrid waves more likely to exist in the diffusion region than further away from the X-line. Electron temperature variations are correlated with the wave potential, due to wave electric field acceleration and crossings at the corrugated separatrix region with different amounts of mixing between reconnection inflowing and outflowing populations. The latter also leads to the anti-correlation between parallel and perpendicular temperature components. Using four-spacecraft measurements, the magnetic field line twisting is demonstrated by the correlated fluctuations in (∇×𝑽(sub 𝐸×𝐵))||and (∇×𝐁)||. The lower-hybrid wave in the EDR of weak guide field reconnection may be generated near separatrices and penetrate to the mid-plane or locally generated, and the latter possibility is beyond the prediction of previous reconnection simulations.

Magnetic reconnection↗

Polarized fusion and potential in situ tests of fuel polarization survival in a tokamak plasma

Abstract The use of spin-polarized fusion fuels would provide a significant boost towards the ignition of a burning plasma. The cross section for D + T → α + n, would be increased by 1.5 if the fuels were injected with parallel polarization. Furthermore, our simulations demonstrate additional non-linear power gains in large-scale machines such as ITER, due to increased alpha heating. Such benefits require the survival of spin polarizations for periods comparable to the particle confinement time. During the 1980s, calculations predicted that polarizations could survive a plasma environment, although concerns persisted regarding the cumulative impacts of wall recycling. In that era, technical challenges prevented direct tests and left the large scale fueling of a power reactor beyond reach. Over the last decades, this situation has changed dramatically. Detailed simulations of ITER have predicted negligible wall recycling in a high-power reactor, and recent advances in laser-driven sources project the capability of producing large quantities of ∼100% polarized D and T. The remaining crucial step is an in-situ demonstration of polarization survival in a plasma. For this, we outline a measurement strategy using the isospin-mirror reaction, D + 3 He → α + p. Polarized 3 He avoids the complexities of handling tritium, while encompassing the same spin-physics. We evaluate two methods of delivering deuterium, using dynamically polarized Lithium-Deuteride (with vector polarization P V D of 70%) or frozen-spin Hydrogen-Deuteride (with P V D of 40%), together with a method of injecting optically-pumped 3 He (with 65% polarization). Pellets of these materials all have long polarization decay times (∼6 min for LiD at 2 K, ∼2 months for HD at 2 K, and ∼3 d for 3 He at 77 K), all far greater than a plasma shot in a research tokamak such as DIII-D (∼20 s). Both species can be propelled from a single cryogenic injection gun. We review plasma requirements and strategies for detecting polarization survival. Polarization alters both fusion yields and the angular distribution of fusion products, and each of these provides a potential signal. In this paper we simulate a selection of shots with similar characteristics in a future high-T ion H plasma, and find ratios of yields from shots with fuel spins parallel and antiparallel reaching 1.3 (HD + 3 He) to 1.6 (LiD + 3 He) over a wide range of poloidal angles. (A companion paper finds sensitivity to fusion product angular distributions as reflected in the pitch angles of protons and alphas reaching the plasma facing wall.)

70 PLASMA PHYSICS AND FUSION TECHNOLOGY↗

A Practical Comparison of Data-Driven Prognostics Methods for Energy Systems

This study explores data-driven prognostics for nuclear power plant (NPP) condensers, focusing on tube fouling. We utilized the Asherah nuclear power plant simulator (ANS) to compare four methods: Random Forest (RF), Support Vector Regressor (SVR), Fully Connected Neural Network (FCNN), and Long Short-Term Memory Neural Network (LSTM). By simulating various fouling scenarios in the ANS, we generated data with different degradation rates under transient operations. The models were trained and tested on these data, with performance evaluated visually and numerically including uncertainty assessment. The LSTM model excelled, exhibiting minimal prediction noise and the most accurate remaining useful life estimates across all degradation levels. Its ability to capture long-term dependencies and produce cleaner outputs makes it a strong candidate, although accurate training data across the entire component lifespan are crucial. The RF model emerged as a robust alternative, providing reliable predictions with high confidence. The FCNN and SVR models, while less effective overall, showed potential under specific conditions. FCNN offers a less complex alternative to LSTM and might benefit from larger datasets. SVR excels in precision when the quality of the training data is high. Furthermore, this study highlights the operational benefits of advanced prognostics in the energy sector and emphasizes the need for further research in NPP condenser health management through real-life experiments.

21 SPECIFIC NUCLEAR REACTORS AND ASSOCIATED PLANTS↗

After DART: Using the first full-scale test of a kinetic impactor to inform a future planetary defense mission

NASA’s Double Asteroid Redirection Test (DART) is the first full-scale test of an asteroid deflection technology. Results from the hypervelocity kinetic impact and Earth-based observations, coupled with LICIACube and the later Hera mission, will result in measurement of the momentum transfer efficiency accurate to ~10% and characterization of the Didymos binary system. But DART is a single experiment; how could these results be used in a future planetary defense necessity involving a different asteroid? We examine what aspects of Dimorphos’s response to kinetic impact will be constrained by DART results; how these constraints will help refine knowledge of the physical properties of asteroidal materials and predictive power of impact simulations; what information about a potential Earth impactor could be acquired before a deflection effort; and how design of a deflection mission should be informed by this understanding. We generalize the momentum enhancement factor β, showing that a particular direction-specific β will be directly determined by the DART results, and that a related direction-specific β is a figure of merit for a kinetic impact mission. The DART β determination constrains the ejecta momentum vector, which, with hydrodynamic simulations, constrains the physical properties of Dimorphos’s near-surface. In a hypothetical planetary defense exigency, extrapolating these constraints to a newly discovered asteroid will require Earth-based observations and benefit from in-situ reconnaissance. We show representative predictions for momentum transfer based on different levels of reconnaissance and discuss strategic targeting to optimize the deflection and reduce the risk of a counterproductive deflection in the wrong direction.

Asteroids↗

Ares I-X Ground Diagnostic Prototype

Automating prelaunch diagnostics for launch vehicles offers three potential benefits. First, it potentially improves safety by detecting faults that might otherwise have been missed so that they can be corrected before launch. Second, it potentially reduces launch delays by more quickly diagnosing the cause of anomalies that occur during prelaunch processing. Reducing launch delays will be critical to the success of NASA's planned future missions that require in-orbit rendezvous. Third, it potentially reduces costs by reducing both launch delays and the number of people needed to monitor the prelaunch process. NASA is currently developing the Ares I launch vehicle to bring the Orion capsule and its crew of four astronauts to low-earth orbit on their way to the moon. Ares I-X will be the first unmanned test flight of Ares I. It is scheduled to launch on October 27, 2009. The Ares I-X Ground Diagnostic Prototype is a prototype ground diagnostic system that will provide anomaly detection, fault detection, fault isolation, and diagnostics for the Ares I-X first-stage thrust vector control (TVC) and for the associated ground hydraulics while it is in the Vehicle Assembly Building (VAB) at John F. Kennedy Space Center (KSC) and on the launch pad. It will serve as a prototype for a future operational ground diagnostic system for Ares I. The prototype combines three existing diagnostic tools. The first tool, TEAMS (Testability Engineering and Maintenance System), is a model-based tool that is commercially produced by Qualtech Systems, Inc. It uses a qualitative model of failure propagation to perform fault isolation and diagnostics. We adapted an existing TEAMS model of the TVC to use for diagnostics and developed a TEAMS model of the ground hydraulics. The second tool, Spacecraft Health Inference Engine (SHINE), is a rule-based expert system developed at the NASA Jet Propulsion Laboratory. We developed SHINE rules for fault detection and mode identification. The prototype uses the outputs of SHINE as inputs to TEAMS. The third tool, the Inductive Monitoring System (IMS), is an anomaly detection tool developed at NASA Ames Research Center and is currently used to monitor the International Space Station Control Moment Gyroscopes. IMS automatically "learns" a model of historical nominal data in the form of a set of clusters and signals an alarm when new data fails to match this model. IMS offers the potential to detect faults that have not been modeled. The three tools have been integrated and deployed to Hangar AE at KSC where they interface with live data from the Ares I-X vehicle and from the ground hydraulics. The outputs of the tools are displayed on a console in Hangar AE, one of the locations from which the Ares I-X launch will be monitored. The full paper will describe how the prototype performed before the launch. It will include an analysis of the prototype's accuracy, including false-positive rates, false-negative rates, and receiver operating characteristics (ROC) curves. It will also include a description of the prototype's computational requirements, including CPU usage, main memory usage, and disk usage. If the prototype detects any faults during the prelaunch period then the paper will include a description of those faults. Similarly, if the prototype has any false alarms then the paper will describe them and will attempt to explain their causes.

Schwabacher, Mark↗

Domain-specific text embedding model for accelerator physics

Accelerator physics presents unique challenges for natural language processing (NLP) due to its specialized terminology and complex concepts. A key component in overcoming these challenges is the development of robust text embedding models that transform textual data into dense vector representations, facilitating efficient information retrieval and semantic understanding. In this work, we introduce AccPhysBERT, a sentence embedding model fine-tuned specifically for accelerator physics. Our model demonstrates superior performance across a range of downstream NLP tasks, surpassing existing models in capturing the domain-specific nuances of the field. We further showcase its practical applications, including semantic paper-reviewer matching and integration into retrieval-augmented generation systems, highlighting its potential to enhance information retrieval and knowledge discovery in accelerator physics. Published by the American Physical Society 2025

Hellert, Thorsten (ORCID:0000000227970926)↗

Quasi drag free gradiometry

Gradiometers are instruments for measuring the gradient of the gravity vector. However, these devices are in varying degrees contaminated by gravity itself or by acceleration. To a large extent these problems are avoidable in orbit, and dramatic improvements in operating accuracy are envisioned. The considered improvements could lead to the possibility of detailed global gravity surveys of the earth, or other planets. An obstacle in the path toward the conduction of such surveys is related to the impossibility to demonstrate an instrument's potential orbital performance in the laboratory. A promising approach for orbital testing is possibly a procedure in which the Shuttle is operated as a drag free satellite. This procedure involves floating the gradiometer in the Shuttle bay. However, certain problems arise in connection with such a procedure. The present investigation is concerned with the possibility that the Shuttle's motion problems can be avoided through the use of a quasi-drag-free magnetic suspension.

Seaman, C. H.↗

Beaconless Pointing for Deep-Space Optical Communication

Free space optical communication is of interest to NASA as a complement to existing radio frequency communication methods. The potential for an increase in science data return capability over current radio-frequency communications is the primary objective. Deep space optical communication requires laser beam pointing accuracy on the order of a few microradians. The laser beam pointing approach discussed here operates without the aid of a terrestrial uplink beacon. Precision pointing is obtained from an on-board star tracker in combination with inertial rate sensors and an outgoing beam reference vector. The beaconless optical pointing system presented in this work is the current approach for the Integrated Radio and Optical Communication (iROC) project.

free-space optical communication↗

Evaluation of 134 Ce/ 134 La as a PET Imaging Theranostic Pair for 225 Ac α-Radiotherapeutics

225 Ac-targeted α-radiotherapy is a promising approach to treating malignancies, including prostate cancer. However, α-emitting isotopes are difficult to image because of low administered activities and a low fraction of suitable γ-emissions. The in vivo generator 134 Ce/ 134 La has been proposed as a potential PET imaging surrogate for the therapeutic nuclides 225 Ac and 227 Th. In this report, we detail efficient radiolabeling methods using the 225 Ac-chelators DOTA and MACROPA. These methods were applied to radiolabeling of prostate cancer imaging agents, including PSMA-617 and MACROPA-PEG 4 -YS5, for evaluation of their in vivo pharmacokinetic characteristics and comparison to the corresponding 225 Ac analogs. Methods: Radiolabeling was performed by mixing DOTA/MACROPA chelates with 134 Ce/ 134 La in NH 4 OAc, pH 8.0, at room temperature, and radiochemical yields were monitored by radio–thin-layer chromatography. In vivo biodistributions of 134 Ce-DOTA/MACROPA.NH 2 complexes were assayed through dynamic small-animal PET/CT imaging and ex vivo biodistribution studies over 1 h in healthy C57BL/6 mice, compared with free 134 CeCl 3 . In vivo, preclinical imaging of 134 Ce-PSMA-617 and 134 Ce-MACROPA-PEG 4 -YS5 was performed on 22Rv1 tumor–bearing male nu/nu-mice. Ex vivo biodistribution was performed for 134 Ce/ 225 Ac-MACROPA-PEG 4 -YS5 conjugates. Results: 134 Ce-MACROPA.NH 2 demonstrated near-quantitative labeling with 1:1 ligand-to-metal ratios at room temperature, whereas a 10:1 ligand-to-metal ratio and elevated temperatures were required for DOTA. Rapid urinary excretion and low liver and bone uptake were seen for 134 Ce/ 225 Ac-DOTA/MACROPA. NH 2 conjugates in comparison to free 134 CeCl 3 confirmed high in vivo stability. An interesting observation during the radiolabeling of tumor-targeting vectors PSMA-617 and MACROPA-PEG 4 -YS5—that the daughter 134 La was expelled from the chelate after the decay of parent 134 Ce—was confirmed through radio–thin-layer chromatography and reverse-phase high-performance liquid chromatography. Both conjugates, 134 Ce-PSMA-617 and 134 Ce-MACROPA-PEG 4 -YS5, displayed tumor uptake in 22Rv1 tumor–bearing mice. The ex vivo biodistribution of 134 Ce-MACROPA.NH 2 , 134 Ce-DOTA and 134 Ce-MACROPA-PEG 4 -YS5 corroborated well with the respective 225 Ac-conjugates. Conclusion: These results demonstrate the PET imaging potential for 134 Ce/ 134 La-labeled small-molecule and antibody agents. The similar 225 Ac and 134 Ce/ 134 La-chemical and pharmacokinetic characteristics suggest that the 134 Ce/ 134 La pair may act as a PET imaging surrogate for 225 Ac-based radioligand therapies.

07 ISOTOPE AND RADIATION SOURCES↗

Low-temperature grapho-epitaxial La-substituted BiFeO 3 on metallic perovskite

Bismuth ferrite has garnered considerable attention as a promising candidate for magnetoelectric spin-orbit coupled logic-in-memory. As model systems, epitaxial BiFeO 3 thin films have typically been deposited at relatively high temperatures (650–800 °C), higher than allowed for direct integration with silicon-CMOS platforms. Here, we circumvent this problem by growing lanthanum-substituted BiFeO 3 at 450 °C (which is reasonably compatible with silicon-CMOS integration) on epitaxial BaPb 0.75 Bi 0.25 O 3 electrodes. Notwithstanding the large lattice mismatch between the La-BiFeO 3 , BaPb 0.75 Bi 0.25 O 3 , and SrTiO 3 (001) substrates, all the layers in the heterostructures are well ordered with a [001] texture. Polarization mapping using atomic resolution STEM imaging and vector mapping established the short-range polarization ordering in the low temperature grown La-BiFeO 3 . Current-voltage, pulsed-switching, fatigue, and retention measurements follow the characteristic behavior of high-temperature grown La-BiFeO 3 , where SrRuO 3 typically serves as the metallic electrode. These results provide a possible route for realizing epitaxial multiferroics on complex-oxide buffer layers at low temperatures and opens the door for potential silicon-CMOS integration.

36 MATERIALS SCIENCE↗

Principles of paralog-specific targeted protein degradation engaging the C-degron E3 KLHDC2

Abstract PROTAC® (proteolysis-targeting chimera) molecules induce proximity between an E3 ligase and protein-of-interest (POI) to target the POI for ubiquitin-mediated degradation. Cooperative E3-PROTAC-POI complexes have potential to achieve neo-substrate selectivity beyond that established by POI binding to the ligand alone. Here, we extend the collection of ubiquitin ligases employable for cooperative ternary complex formation to include the C-degron E3 KLHDC2. Ligands were identified that engage the C-degron binding site in KLHDC2, subjected to structure-based improvement, and linked to JQ1 for BET-family neo-substrate recruitment. Consideration of the exit vector emanating from the ligand engaged in KLHDC2’s U-shaped degron-binding pocket enabled generation of SJ46421, which drives formation of a remarkably cooperative, paralog-selective ternary complex with BRD3 BD2 . Meanwhile, screening pro-drug variants enabled surmounting cell permeability limitations imposed by acidic moieties resembling the KLHDC2-binding C-degron. Selectivity for BRD3 compared to other BET-family members is further manifested in ubiquitylation in vitro, and prodrug version SJ46420-mediated degradation in cells. Selectivity is also achieved for the ubiquitin ligase, overcoming E3 auto-inhibition to engage KLHDC2, but not the related KLHDC1, KLHDC3, or KLHDC10 E3s. In sum, our study establishes neo-substrate-specific targeted protein degradation via KLHDC2, and provides a framework for developing selective PROTAC protein degraders employing C-degron E3 ligases.

Science & Technology - Other Topics↗