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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.

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At least 541 records · Page 30

Profile Generation for GPU Targets

GPU accelerators are ubiquitous, but their ecosystem is far less evolved than the host one. Compiler heuristics are often tuned for CPUs and reused for GPU. Similarly, tooling and more evolved optimization techniques are historically not available on GPU targets. In this work, we address one of these shortcomings and enable profile generation and profile-guided optimizations (PGO) for GPU targets. While this is only a single step towards a CPU equivalent ecosystem for offload devices, it shows how old misconceptions on the limitations of GPUs are often not warranted anymore. Through our implementation in LLVM/Offload, we enable device-side PGO for full scientific applications and open up tooling opportunities, including code coverage analysis and compiler-built-in roofline analysis. Our evaluation highlights the performance implications of profile generation, the insights gained from these profiles, and the (missed) opportunities in utilizing the information for GPU compilation.

McDonough, Ethan Luis [Lawrence Livermore National↗

Processing iridium foil targets for the production of radioplatinum isotopes

Dissolving noble metals remains challenging because of their high reduction potentials and tendency to passivate as oxides. This barrier is acute for iridium metal targets used to produce platinum radioisotopes, where post-irradiation processing is costly and hazardous with conventional routes. Here, we report a rapid alkali-fusion method that converts Ir metal directly into chloride media compatible with downstream separations. In the process, an Ir foil is fused with Na 2 O 2 and KCl at temperatures above the KCl melting point; the molten salt enhances heat transfer and facilitates O 2− /Na + transport to the Ir surface, overcoming Ir's oxidation resistance. The fused cake is then cooled and leached in 10 M HCl, yielding Ir in solution without specialized microwave digestion or HF. Pt separation from bulk Ir was evaluated using extraction-chromatography resins. A newly formulated ionic-liquid resin containing Cyphos IL 104 (E104) was compared with two commercial resins (TrisKem TK200 and TK201). All resins achieved >90 % Ir recovery. Pt co-recovery depended on resin chemistry: TK200 recovered 85.9 % Pt, TK201 recovered 54.1 % Pt, and E104 recovered 72.9 % Pt. This study introduces a fast, scalable dissolution route for solid Ir targets and demonstrates resin choices that tune Ir/Pt separation, lowering the barrier to routine production and purification of Pt radioisotopes.

07 ISOTOPE AND RADIATION SOURCES↗

Analysis of strategies to meet ASHRAE S241 infectious aerosol control targets by space type and region using EnergyPlus™ simulations

Professional organizations, such as ASHRAE, have recently proposed new voluntary standards for controlling infectious aerosols. Specifically, ASHRAE Standard 241 (S241) defines equivalent clean air targets for a range of space types that can be met through combinations of mitigation measures. This paper seeks to inform the selection of measures by space type and climate zone through building simulations that quantify the impacts of increased outdoor air ventilation; increasing filtration and/or adding germicidal ultraviolet (GUV) in the central heating, ventilation, and air-conditioning (HVAC) systems; or using portable air cleaners (PACs), upper room GUV, or whole room GUV approaches to increase equivalent clean air delivery. The measures are assessed individually and in practical combinations for their ability to meet S241 in four space types (offices, classrooms, dining areas, and healthcare waiting rooms) using prototype buildings modeled using EnergyPlus. The mitigation measures are compared holistically against baseline building operations using metrics for equivalent clean air, energy, and comfort. The results in this study show that single measures can meet S241 for offices with minimal impacts on energy and comfort, while either upper room GUV systems or combinations of measures such as MERV 13 HVAC filtration with PACs are needed to meet S241 for classrooms. The dining area and healthcare waiting room targets cannot be met in this study when assuming design occupancy and MS2 as the challenge agent, even when combining multiple measures together. This paper provides valuable considerations when designing measures to meet S241 for a range of spaces and scenarios.

GUV↗

Crimean-Congo hemorrhagic fever survivors elicit protective non-neutralizing antibodies that target 11 overlapping regions on glycoprotein GP38

Crimean-Congo hemorrhagic fever virus can cause lethal disease in humans yet there are no approved medical countermeasures. Viral glycoprotein GP38, exclusive to Nairoviridae , is a target of protective antibodies and is a key antigen in preclinical vaccine candidates. Here, we isolate 188 GP38-specific antibodies from human survivors of infection. Competition experiments show that these antibodies bind across 5 distinct antigenic sites, encompassing 11 overlapping regions. Additionally, we show structures of GP38 bound with 9 of these antibodies targeting different antigenic sites. Although these GP38-specific antibodies are non-neutralizing, several display protective efficacy equal to or better than murine antibody 13G8 in two highly stringent rodent models of infection. Together, these data expand our understanding regarding this important viral protein and may inform the development of broadly effective CCHFV antibody therapeutics.

59 BASIC BIOLOGICAL SCIENCES↗

How ignition and target gain > 1 were achieved in inertial fusion

For many decades the running joke in fusion research has been that “fusion” is twenty years away and always will be. Yet, in 2023 we find ourselves in a position where we can talk about the milestones of burning plasmas, fusion ignition, and target energy gain greater than unity in the past tense – a situation that is remarkable! Herein this paper tells some of the story of the applied physics challenges that needed to be overcome to achieve these milestones and the strategy our team followed. Things did not always go well and some practical lessons learned are part of this story. The data shows, getting to a burning plasma in late 2020 and early 2021 was a key tipping-point, after which ignition (August 8, 2021) and target gain (December 5, 2022) were rapidly achieved.

70 PLASMA PHYSICS AND FUSION TECHNOLOGY↗

Remeasurement of the 239 Pu(n,f)/ 235 U(n,f) Cross-Section Ratio with the NIFFTE fission Time Projection Chamber Using Vapor-deposited Targets

The NIFFTE fission Time Projection Chamber (fissionTPC) has been used to measure the 239 Pu(n,f)/ 235 U(n,f) cross-section ratio for neutron-induced fission in the range of 0.1–100 MeV, with high precision. A white neutron source was provided by the Los Alamos Neutron Science Center, where the experiment was conducted as a remeasurement to evaluate a roughly 2% discrepancy of the previous fissionTPC results with ENDF/B-VIII.0. Further, a detailed accounting of measurement uncertainties was performed, based on the fissionTPC's novel ability to provide three-dimensional reconstruction of fission-fragment ionization profiles. Current results obtained using a vapor-deposited, highly uniform 239 Pu target, in comparison to the measurement published in 2021, where a 239 Pu electroplated target was used, are presented and discussed. The remeasurement presented here is in agreement with the previous fissionTPC result within measurement uncertainties.

235U↗

Reducing waste of the hydride-dehydride process for U-6 wt% Nb spherical powders through lower impact and targeted milling

The breakdown of solid metal into powder during the hydride-dehydride process is commercially important for the formation of titanium and other metal powders. Typically, the milling of the brittle hydride powder occurs in a ball mill, where milling media impacts powder particles to break them down. The milling media can impact particles that are larger than desired, as desired, or smaller than desired, indiscriminately making all particles smaller. In this work, we investigate how to minimize waste powder production during milling using two different milling methods, planetary ball milling and milling in a sieve shaker (sieve-milling). Both processes yielded similar amounts of 20–75 μm diameter powder (the target size range); however, sieve-milling generated a significantly smaller amount of undersized waste powder. The powders were characterized by X-ray diffraction, SEM/STEM, and magnetic susceptibility. Several differences between ball milling and sieve-milling processes are discussed. We then conclude that the decreased yield of undersized powder in sieve-milling was due to a combination of lower impact energy in sieve-milling, unreacted metallic cores in the hydride flakes, and the ability to mill target particle sizes during sieve-milling. While these results are from the milling of brittle hydride powder, similar methods may be applicable to other brittle powders, including ceramics or salts.

Chemistry↗

Pareto-optimal target definition for multi-axis random vibration testing

In random vibration testing with multiple control channels, existing control laws require specification of a complete spectral density matrix at each control frequency. Spectral density matrices include autospectral densities on the diagonal and cross-spectral densities on the off-diagonal. In practice, the off-diagonal terms are often unknown, and recent vibration testing research has focused on fixing the diagonal and specifying the off-diagonal to minimize the required control energy, subject to a constraint that the target matrix is positive semidefinite. This paper shows that, even with a fixed diagonal, off-diagonal terms strongly affect control residuals. This overlooked effect occurs in both square and rectangular systems. By jointly considering input energy and control residuals, open-loop inputs are derived directly from the diagonal without specifying the off-diagonal terms. Vibration targets that can be used in closed-loop control are then derived using the optimal inputs, with positive semidefinite constraints applied during the derivation. The result is a set of Pareto-optimal control solutions. For each solution in the set, any other possible solution produces greater control error, greater input energy, or both. A balanced solution is selected automatically, though others can be chosen based on test needs. Simulations and experiments show that the proposed method outperforms state-of-the-art energy-minimizing approaches, achieving significant reductions in both control error and input energy.

Autospectral density↗

Suppression and enhancement of electromagnetic pulses from laser–target interactions by strong magnetic fields

Laser–target interactions generate intense electromagnetic pulses (EMPs) that can interfere with measurements and damage equipment. In this paper we show that applying a magnetic field to nanosecond pulse laser–target interactions decreases the magnitude of EMPs. We demonstrate this effect in two experiments with different geometries (spherical versus planar), laser intensities ( ∼10 13 versus ∼10 15 W/cm 2 ) and applied field strength (12 versus 0.1 T) that both observed suppression of EMPs in approximately the 1 GHz band (by factors of 0.65× and 0.32×, respectively). We then observe the opposite effect at high intensities with a picosecond pulse: for planar experiments with laser intensities of approximately 10 19 W/cm 2 and magnetic fields of 6–10 T, the magnitude of EMPs is increased by a factor of 1.75×. These results provide a benchmark for models of EMP generation, but suggest that magnetic fields are not a viable solution for mitigating EMPs in the high-intensity laser facilities where they are most damaging.

electromagnetic pulse↗

Discovery and Development of a Small-Molecule Inhibitor Targeting the GAS41 YEATS Domain in Nonsmall Cell Lung Cancer

Abstract GAS41 is frequently overexpressed in Non-Small Cell Lung Cancer (NSCLC). GAS41 contains a YEATS domain, which recognizes acetylated lysine residues on histones to recruit protein complexes and facilitate transcription. Suppression of GAS41 in NSCLC models inhibits cellular proliferation and markedly reduces tumor growth in mouse xenografts, justifying the development of small-molecule inhibitors. We have employed structure-based design and medicinal chemistry optimization to discover DLG-41, a submicromolar inhibitor binding to the GAS41 YEATS domain. DLG-41 potently disrupts the association of GAS41 YEATS with chromatin in mammalian cells and inhibits the proliferation of NSCLC cell lines with submicromolar potency without significantly affecting normal lung fibroblasts. DLG-41 induces more effective growth inhibition in A549 versus GAS41-knockout cells, demonstrating on-target activity. DLG-41 treatment upregulates the CDKN1A gene and downregulates pathways associated with lung cancer cell identity, tumor migration, and invasion. DLG-41 is a promising chemical probe for targeting GAS41 protein in NSCLC models and has potential for future development.

Listunov, Dymytrii [University of Michigan , , , ,↗

Inverse Thermodynamics: Designing Interactions for Targeted Phase Behavior

The traditional goal of inverse self-assembly is to design interactions that drive particles toward a desired target structure. However, achieving successful self-assembly also requires tuning the thermodynamic conditions under which the structure is stable. In this work, we extend the inverse design paradigm to explicitly address this challenge by developing a framework for inverse thermodynamics, i.e., the design of interaction potentials that realize specific thermodynamic behavior. As a step in this direction, using patchy particle mixtures as a model system, we demonstrate how precise control over both bonding topology and bond energetics enables the programming of targeted phase behavior. In particular, we establish design principles for azeotropic demixing and show how to create mixtures that exhibit azeotropy at any prescribed composition. Our predictions are validated through Gibbs-ensemble simulations [Panagiotopoulos, Mol. Phys. 1987, 61, 813−826]. These results highlight the necessity of coupling structural design with thermodynamic engineering, and provide a blueprint for controlling complex phase behavior in multicomponent systems.

Azeotropes↗

Photothermal Properties of Nanostructured Black Titanium Dioxide for Targeted Cellular and Microbial Elimination

Heterophase black titanium dioxide (hB-TiO 2 ), characterized by broadened near-infrared (NIR) absorption, has emerged as a promising photothermally active nanomaterial. This study focused on the synthesis of nanoscale hB-TiO 2 and its evaluation as a multifunctional agent for photothermal therapy (PTT). The purity and composition of the mixed-phase nanoscale hB-TiO 2 were demonstrated by X-ray diffraction, and the morphology of nanoparticles was imaged by transmission electron microscopy. Extensive additional characterization was conducted to validate the optoelectronic properties. The material was further evaluated in biological systems using NIH 3T3-GFP fibroblasts and the fungus Candida albicans. Nanoscale hB-TiO 2 exhibited good biocompatibility in the absence of laser irradiation and effectively ablated both NIH 3T3-GFP cells and C. albicans following 20 min of laser exposure. This noninvasive treatment strategy leverages NIR-responsive materials to induce localized hyperthermia. The findings provide grounds for the use of selectively induced hyperthermia, which could be employed for the targeted destruction of cells or fungi with minimal impact on surrounding tissue if the material is functionalized with specific targeting groups and delivered to cells or fungal infections.

Irradiation↗

The interplay of DNA repair context with target sequence predictably biases Cas9-generated mutations

Abstract Repair of double-stranded breaks generated by CRISPR/Cas9 is highly dependent on the flanking DNA sequence. To learn about interactions between DNA repair and target sequence, we measure frequencies of over 236,000 distinct Cas9-generated mutational outcomes at over 2800 synthetic target sequences in 18 DNA repair deficient mouse embryonic stem cells lines. We classify the outcomes in an unbiased way, finding a specialised role forPrkdc(DNA-PKcs protein) andPolmin creating 1 bp insertions matching the nucleotide on the protospacer-adjacent motif side of the break, a variable involvement ofNbnandPolqin the creation of different deletion outcomes, and uni-directional deletions dependent on both end-protection and end-resection. Using our dataset, we build predictive models of the mutagenic outcomes of Cas9 scission that outperform the current standards. This work improves our understanding of DNA repair gene function, and provides avenues for more precise modulation of Cas9-generated mutations.

Science & Technology - Other Topics↗

Structural and mechanistic insights into protective non-neutralizing antibodies targeting Crimean-Congo hemorrhagic fever virus nucleocapsid protein

Abstract Crimean-Congo Hemorrhagic Fever Virus (CCHFV) is a tick-borne virus endemic to Africa, Asia, and expanding regions within Europe. With mortality rates approaching 40%, rising incidence, and no currently approved countermeasures, CCHFV is recognized as a priority public health threat. CCHFV nucleocapsid protein (NP) has long been a key target for diagnostics. Recently, NP-specific humoral responses have also been correlated with protection conferred by protective vaccines candidates. Additionally, the first non-neutralizing monoclonal antibody (mAb) 9D5 demonstrated protective efficacy against CCHFV challenge, underscoring NP as a viable antiviral target. Here, nine anti-NP mAb were utilized to identify four antigenic sites on NP as well as localize these sites to the head or stalk domains. These mAb also revealed variable levels of in vivo protection, independent from whether the epitope site is located in the head or stalk regions. Additionally, three X-ray crystallography structures were obtained that included CCHFV NP from strain Afg09-2990 in complex with the most potent mAb (9D5). This, along with additional structures of two unbound NPs, revealed structural elements critical for mAb-9D5 broad-spectrum protective characteristics. These findings provide a path towards the rapid identification of broadly protective anti-NP mAb countermeasures.

Moresco, Vanessa↗

Cross sections of 147–149 Sm( 6 Li,x) reactions for the production of 149 Tb for targeted alpha therapy

Terbium-149g (t 1/2 = 4.12 h) is of particular interest for targeted alpha therapy cancer treatment due to its ability to decay via both alpha and positron emission, making it a potential theranostic nuclide. Due to many challenges facing its production, there are limited facilities worldwide that have demonstrated the ability to produce this nuclide in quantities sufficient for medical research. Since the Cyclotron Institute at Texas A&M University is a specialized accelerator facility capable of accelerating a wide variety of ions, we are investigating production pathway options. One of the major challenges facing its production is the known co-production of the excited isomeric state, 149m Tb (t 1/2 = 4.1 min). However, this state does not decay to the ground state of 149g Tb, negating any potential contribution to its yield. Due to its short-half life, the cross section for the population of this state has never been measured. After calculating several potential reaction yields using predictive models, the reactions of 147–149 Sm( 6 Li,xn) 149 Tb were identified as candidates. Lithium-6 beams of varied energies between 45-65 MeV were impinged on enriched 147 Sm, 148 Sm, and 149 Sm targets at the Cyclotron Institute at Texas A&M University, and the reaction products were measured immediately following irradiation using high-purity germanium detectors, enabling detection of both 149m Tb and 149g Tb. Cross sections for all nuclides produced in sufficient activity in these reactions were also measured and reported here. We conclude that the population of 149m Tb is much preferred over population of the ground state for these 6 Li-induced reactions, and it is necessary to explore other options for 149g Tb production.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Structural and biophysical insights into targeting of claudin-4 by a synthetic antibody fragment

Claudins are a 27-member family of ~25 kDa membrane proteins that integrate into tight junctions to form molecular barriers at the paracellular spaces between endothelial and epithelial cells. As the backbone of tight junction structure and function, claudins are attractive targets for modulating tissue permeability to deliver drugs or treat disease. However, structures of claudins are limited due to their small sizes and physicochemical properties—these traits also make therapy development a challenge. Here we report the development of a synthetic antibody fragment (sFab) that binds human claudin-4 and the determination of a high-resolution structure of it bound to claudin-4/enterotoxin complexes using cryogenic electron microscopy. Structural and biophysical results reveal this sFabs mechanism of select binding to human claudin-4 over other homologous claudins and establish the ability of sFabs to bind hard-to-target claudins to probe tight junction structure and function. The findings provide a framework for tight junction modulation by sFabs for tissue-selective therapies.

60 APPLIED LIFE SCIENCES↗

Targeting transcription factors through an IMiD independent zinc finger domain

Abstract Immunomodulatory imide drugs (IMiDs) degrade specific C2H2 zinc finger degrons in transcription factors, making them effective against certain cancers. SALL4, a cancer driver, contains seven C2H2 zinc fingers in three clusters, including an IMiD degron in zinc finger cluster one (ZFC1). Surprisingly, IMiDs do not inhibit the growth of SALL4-expressing cancer cells. To overcome this limit, we focused on a non-IMiD domain, SALL4 zinc finger cluster four (ZFC4). By combining ZFC4-DNA crystal structure and an in silico docking algorithm, in conjunction with cell viability assays, we screened several chemical libraries against a potentially druggable binding pocket, leading to the discovery of SH6, a compound that selectively targets SALL4-expressing cancer cells. Mechanistic studies revealed that SH6 degrades SALL4 protein through the CUL4A/CRBN pathway, while deletion of ZFC4 abolished this activity. Moreover, SH6 treatment led to a significant 87% tumor growth inhibition of SALL4+ patient-derived xenografts and demonstrated good bioavailability in pharmacokinetic studies. In summary, these studies represent a new approach for IMiD independent drug discovery targeting C2H2 transcription factors such as SALL4 in cancer.

Liu, Bee Hui↗

Toward machine-learning-assisted PW-class high-repetition-rate experiments with solid targets

We present progress in utilizing a machine learning (ML) assisted optimization framework to study the trends in a parameter space defined by spectrally shaped, high-intensity, petawatt-class (8 J, 45 fs) laser pulses interacting with solid targets and give the first simulation-based overview of predicted trends. A neural network (NN) incorporating uncertainty quantification is trained to predict the number of hot electrons generated by the laser–target interaction as a function of pulse shaping parameters. The predictions of this NN serve as the basis function for a Bayesian optimization framework to navigate this space. For post-experimental evaluation, we compare two separate neural network (NN) models. One is based solely on data from experiments, and the other is trained only on ensemble particle-in-cell simulations. Reviewing the predicted and observed trends across the experiment-capable laser parameter search space, we find that both ML models predict a maximal increase in hot electron generation at a level of approximately 12%–18%; however, no statistically significant enhancement was observed in experiments. On direct comparison of the NN models, the average discrepancy is 8.5%, with a maximum of 30%. Since shot-to-shot fluctuations in experiments affect the observations, we evaluate the behavior of our optimization framework by performing virtual experiments that vary the number of repeated observations and the noise levels. Here, we discuss the implications of such a framework for future autonomous exploration platforms in high-repetition-rate experiments.

70 PLASMA PHYSICS AND FUSION TECHNOLOGY↗