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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 109 records · Page 6

Discovery of Pyridopyrimidinones that Selectively Inhibit the H1047R PI3Kα Mutant Protein

The H1047R mutation of PIK3CA is highly prevalent in breast cancers and other solid tumors. Selectively targeting PI3Kα H1047R over PI3Kα WT is crucial due to the role that PI3Kα WT plays in normal cellular processes, including glucose homeostasis. Currently, only one PI3Kα H1047R -selective inhibitor has progressed into clinical trials, while three pan mutant (H1047R, H1047L, H1047Y, E542K, and E545K) selective PI3Kα inhibitors have also reached the clinical stage. Herein, we report the design and discovery of a series of pyridopyrimidinones that inhibit PI3Kα H1047R with high selectivity over PI3Kα WT , resulting in the discovery of compound 17. When dosed in the HCC1954 tumor model in mice, 17 provided tumor regressions and a clear pharmacodynamic response. X-ray cocrystal structures from several PI3Kα inhibitors were obtained, revealing three distinct binding modes within PI3Kα H1047R including a previously reported cryptic pocket in the C-terminus of the kinase domain wherein we observe a ligand-induced interaction with Arg1047.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

A Review of the Recent NASA Long-Term Orbital Debris Environment Projection and Active Debris Removal Modeling Activities

The NASA Orbital Debris Program Office (ODPO) developed a high fidelity debris evolutionary model, LEGEND (a LEO-to-GEO Environment Debris model), in 2004 to enhance its capability to better model the near-Earth environment. LEGEND can mimic the growth of the historical debris population and project it into the future based on user-defined scenarios. The first major LEGEND study concluded that even without any future launches, the LEO population would continue to increase due to mutual collisions among existing objects. In reality, the increase will be worse than this prediction because of ongoing satellite launches and unexpected major breakups. Even with a full implementation of the commonly-adopted mitigation measures, the LEO population growth is inevitable. To preserve the near-Earth environment for future generations, active debris removal (ADR) must be considered. A follow-up LEGEND ADR study was completed recently. The main results indicate that (1) the mass and collision probability of each object can be used to establish an effective removal selection criterion and (2) a removal rate of ~5 objects per year is sufficient to stabilize the LEO environment. Due to the limitation of removal techniques, however, different target selection criteria (in size, altitude, inclination, etc.) may be more practical. A careful evaluation of the effectiveness of different proposed techniques must be carried out to maximize the long-term benefit to the environment.

Liou, J.C.↗

Controlling Selectivity in Plasmonic Catalysis: Switching Reaction Pathway from Hydrogenation to Homocoupling Under Visible–Light Irradiation

Plasmonic catalysis enables the use of light to accelerate molecular transformations. Its application to the control reaction selectivity is highly attractive but remains challenging. Here, we have found that the plasmonic properties in AgPd nanoparticles allowed different reaction pathways for tunable product formation under visible-light irradiation. By employing the hydrogenation of phenylacetylene as a model transformation, we demonstrate that visible-light irradiation can be employed to steer the reaction pathway from hydrogenation to homocoupling. Our data showed that the decrease in the concentration of H species at the surface due to plasmon-enhanced H2 desorption led to the control in selectivity. Furthermore, these results provide important insights into the understanding of reaction selectivity with light, paving the way for the application of plasmonic catalysis to the synthesis of 1,3-diynes, and bringing the vision of light-driven transformations with target selectivity one step closer to reality.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

REP Concept Feasibility Study

Radioisotope Electric Propulsion (REP) may have the potential to provide certain advantages, over conventional chemical propulsion, for outer planetary exploration involving small bodies and long term investigations for medium class missions requiring power comparable to past outer planetary exploration missions. This paper describes a study that investigates the concept s feasibility by performing a preliminary conceptual design of an REP-based spacecraft for a design reference mission. The mission utilizes a spacecraft with a radioisotope power supply less than one kilowatt while operating for a minimum of 10-years. A key element of the REP spacecraft is to ensure sustained science return by orbiting or flying in formation with selected targets. Utilizing current and impending technological advances, this study finds that at a conceptual design level a small body REP orbiter/explorer appears to be feasible for the design reference mission selected for this study.

Edwards, Daryl A.↗

Mechanism of selective recognition of Lys48-linked polyubiquitin by macrocyclic peptide inhibitors of proteasomal degradation

Post-translational modification of proteins with polyubiquitin chains is a critical cellular signaling mechanism in eukaryotes with implications in various cellular states and processes. Unregulated ubiquitin-mediated protein degradation can be detrimental to cellular homeostasis, causing numerous diseases including cancers. Recently, macrocyclic peptides were developed that selectively target long Lysine-48-linked polyubiquitin chains (tetra-ubiquitin) to inhibit ubiquitin-proteasome system, leading to attenuation of tumor growth in vivo. However, structural determinants of the chain length and linkage selectivity by these cyclic peptides remained unclear. Here, we uncover the mechanism underlying cyclic peptide’s affinity and binding selectivity by combining X-ray crystallography, solution NMR, and biochemical studies. We found that the peptide engages three consecutive ubiquitins that form a ring around the peptide and determined requirements for preferential selection of a specific trimer moiety in longer polyubiquitin chains. The structural insights gained from this work will guide the development of next-generation cyclic peptides with enhanced anti-cancer activity.

59 BASIC BIOLOGICAL SCIENCES↗

Active/Passive Control of Sound Radiation from Panels using Constrained Layer Damping

A hybrid passive/active noise control system utilizing constrained layer damping and model predictive feedback control is presented. This system is used to control the sound radiation of panels due to broadband disturbances. To facilitate the hybrid system design, a methodology for placement of constrained layer damping which targets selected modes based on their relative radiated sound power is developed. The placement methodology is utilized to determine two constrained layer damping configurations for experimental evaluation of a hybrid system. The first configuration targets the (4,1) panel mode which is not controllable by the piezoelectric control actuator, and the (2,3) and (5,2) panel modes. The second configuration targets the (1,1) and (3,1) modes. The experimental results demonstrate the improved reduction of radiated sound power using the hybrid passive/active control system as compared to the active control system alone.

Gibbs, Gary P.↗

Finding Near-Earth Asteroid (NEA) Destinations for Human Exploration: Implications for Astrobiology

The current number of known potential NEA targets for HSF is limited to those objects whose orbital characteristics are similar to that of the Earth. This is due to the projected capabilities of the exploration systems currently under consideration and development at NASA. However, NEAs with such orbital characteristics often have viewing geometries that place them at low solar elongations and thus are difficult to detect from the vicinity of Earth. While ongoing ground-based surveys and data archives maintained by the NEO Program Observation Program Office and the Minor Planet Center (MPC) have provided a solid basis upon which to build, a more complete catalog of the NEO population is required to inform a robust and sustainable HSF exploration program. Since all the present NEO observing assets are currently confined to the vicinity of the Earth, additional effort must be made to provide capabilities for detection of additional HSF targets via assets beyond Earth orbit. A space-based NEO survey telescope located beyond the vicinity of the Earth, has considerable implications for planetary science and astrobiology. Such a telescope will provide foundational knowledge of our Solar System small body population and detect targets of interest for both the HSF and scientific communities. Data from this asset will yield basic characterization data on the NEOs observed (i.e., albedo, size determination, potential for volatiles and organics, etc.) and help down select targets for future HSF missions. Ideally, the most attractive targets from both HSF and astrobiology perspectives are those NEAs that may contain organic and volatile materials, and which could be effectively sampled at a variety of locations and depths. Presented here is an overview of four space-based survey concepts; any one of which after just a few years of operation will discover many highly accessible NEO targets suitable for robotic and human exploration. Such a space-based survey mission will reveal incredible returns for several disciplines including: exploration, in situ resource utilization, planetary defense, and science. Of particular, interest to the scientific

Landis, Rob↗

Small-molecule modulation of β-arrestins

β-Arrestins are multifunctional regulators of G-protein-coupled receptor (GPCR) signalling and orchestrate diverse downstream signalling events and physiological responses across the GPCR superfamily. Although GPCR pharmacology has advanced to target orthosteric and allosteric sites, as well as G proteins and GPCR kinases, direct chemical tools to modulate β-arrestin activities have remained conspicuously absent. Here we report the identification of small-molecule inhibitors that selectively target β-arrestins and delineate their mechanism of action through integrated pharmacological, biochemical, biophysical and structural analyses. These inhibitors disrupt β-arrestin engagement with agonist-activated GPCRs, impairing desensitization, internalization and β-arrestin-dependent physiological functions while sparing G protein–receptor coupling. Cryo-electron microscopy, molecular dynamics simulations and structure-guided mutagenesis reveal that one modulator, Cmpd-5, engages a pocket within the central crest of β-arrestin1 formed by the middle, C and lariat loops, a critical receptor-binding interface, stabilizing a distinct conformation that is incompatible with full β-arrestin–receptor engagement. Together, these findings establish a mechanistic framework for β-arrestin modulation, reveal a novel allosteric site for structure-based drug design, and open new avenues for transducer-targeted, pathway-specific GPCR therapeutic agents.

Kahsai, Alem W. [Duke University, Durham, NC (Unit↗

Development of a bench-scale dissolution concept for the direct extraction of nuclear fuel

Current used nuclear fuel reprocessing efforts utilize a hydrometallurgical approach in which the UNF is dissolved in hot nitric acid followed by solvent extraction into an organic solvent to harvest target nuclides. Previous studies have shown that the dissolution and loading process could be combined into a single organic dissolution/extraction step, producing loaded organic in a single step process. This single step process also includes the advantage of selectively targeting key nuclides in the dissolution while leaving undesirable constituents as part of the undissolved solids. This process is referred to hereafter as direct extraction. Ongoing research from multiple national labs has proven the effectiveness of this technique at research scale. Therefore, potential methods to implement direct extraction at both bench and industrial scale have been developed. The key features of potential dissolver system designs were identified via the team at Pacific Northwest National Laboratory and several designs based on industrial counterparts were assessed for feasibility. This report summarizes the advantages and disadvantages of multiple methods, concluding with a path forward to create multiple unique dissolver designs. The first design will be a single stage recirculating eductor mixer. The second design recommendation is a stator rotor static mixing flow loop design. Each dissolver could be utilized separately, simultaneously, or in series to answer questions surrounding reaction kinetics including residence time, provide a proof of concept for targeted extractions of specific nuclides, and inform needs for industrial scale implementation

11 NUCLEAR FUEL CYCLE AND FUEL MATERIALS↗

On modeling performance of open-loop mechanisms

A technique is presented for modeling the performance of open-loop mechanisms or systems, where performance is measured by success or failure as a function of the selected target for movement along a constrained trajectory and without corrective feedback. A modification of signal detection theory is used, which normalizes dissimilar data and indicates two independent parameters of performance: (1) discriminability and (2) optimality of the distribution of selected moves. An illustrative application is made to experimental data.

Sheridan, T. B.↗

Methods and systems for producing nanolipoprotein particles

Provided herein are methods and systems for the production of a nanolipoprotein particle (NLP) that includes a scaffold protein a membrane forming lipid and optionally a target protein. At least one of the scaffold protein and target protein can be provided through an IVT system. The membrane forming lipid, scaffold protein and optionally the target protein can be assembled for a time and under conditions that allow obtaining high yield NLPs, NPLs with an increased solubility, an NLP of a controlled size, and/or an NLP having a size predetermined to include a pre-selected target protein.

Coleman, Matthew A.↗

Feedback on Forty-year Long Clean-up Operations of a Contaminated Soil for Environmental Purpose - 20026

One of the CEA facilities in France is the place of miscellaneous mapping and clean-up operations since the 1980's. The final purpose of the conducted work deals with the environmental remediation of the building. In France, the absence of a regulatory framework for the management of sites polluted by radioactive substances, especially as the lack of release thresholds, has led to develop different approaches of soil radiological characterization. The geostatistical approach is part of them. Preliminary investigations are an unavoidable step prior to clearance and remediation. First, historical analysis enables to define site perimeters to investigate as well as to precisely locate expected contaminated parts. For radioactive pollutants, the media (water, soil, air) and transfer routes participate in the definition of the investigation perimeter and thus also need to be identified through a geological study. At the same time, functional analysis leads to choose the best measurement means which could provide useful information when combined with visual inspection. An equipment well adapted to easy-to-measure radionuclides as gamma emitters, such as gamma probe or on-site gamma spectrometry, is usually selected as a non-destructive assay. Coupled with spatial positions, processed on-site radiological data can be mapped. Data processing consists in mapping and kriging before a geostatistical analysis in order to identify the zones of interest to be targeted. Selected zones are not only linked to high level count rates but also to low level ones so that a pollution-free reference is known in the area. This data processing also enables to categorize waste types according to their origin and contamination levels. An expected volume of different waste then follows as well as the waste characterization equipments. In-depth investigations, e.g. core drillings and samplings, naturally ensue to aim at remediation optimization through the assessment of environmental impact. After clean-up operations, non-destructive assays as well as destructive samplings enable to check the effective clearance. Following this methodology in the present remediation work, results of the first non-destructive assay campaign highlighted a long-lived transuranic radionuclides contamination in the concrete flagstone. Successive non-destructive assays were then performed in the defined zones of interest. Count rates measured with a surface probe were first mapped. The best localization of destructive assays, i.e. core drillings at a 1 meter depth, came from this surface mapping followed by a geostatistical analysis. The concrete flagstone was totally removed. Then, the depth of soil to remove under the flagstone was optimized from the results of radiological activities measured in core drillings samples. A new surface mapping was then drawn after this partial soil excavation. The sand and demolition rubble samples, homogeneously constituted from the flagstone fragments, were analyzed by gamma spectrometry. Meanwhile, waste drums and other containers were also measured by gamma spectrometry and passive neutron measurement devices. All these results have brought miscellaneous pieces of information. In this context, major issues appear in terms of physical constraints such as the premises tininess as well as of soil sampling techniques and in terms of measurement performances assessment and the representativeness of homogeneous samples. The choice of radiological soil and waste characterization devices is described in the light of enhanced performances by keeping in mind radiation protection requirements and a willing to always optimize waste categories (very low level waste) and volume. The improvement of the characterization methods appears through this forty-year long work while sharing the feedback of encountered difficulties. (authors)

12 MANAGEMENT OF RADIOACTIVE AND NON-RADIOACTIVE W↗

Mars 2020 Lander Vision System Flight Performance 1

The Mars 2020 Entry Descent and Landing (EDL) system delivered the Perseverance rover to the surface of Mars on February 18th, 2021. A large fraction of the Jezero Crater landing site was covered with landing hazards including cliffs, inescapable dune fields and rocks. These hazards were identified or inferred using orbital imagery before launch so that they could be avoided using Terrain Relative Navigation (TRN) which was composed of two parts: the Lander Vision System (LVS) and Safe Target Selection (STS). During EDL, the LVS successfully estimated map relative position by fusing landmarks matched between descent imagery and a map of the landing site with Inertial Measurement Unit (IMU) data. This position estimate was used by STS to identify the safest target for landing that was also reachable given fuel and other constraints. The EDL system then used the powered descent phase to retarget to this location and land safely. The overall error between the targeted location and actual landing location was 5m which was an order of magnitude less than the 60m touchdown error requirement. This paper will describe the final tests of the LVS before launch, the checkout of the LVS during operations and the LVS performance during EDL.

Zheng, Jason↗

Clustering analysis of medium-band selected high-redshift galaxies

Next-generation large-scale structure spectroscopic surveys will probe cosmology at high redshifts (2.3 < z < 3.5), relying on abundant galaxy tracers such as Lyα emitters (LAEs) and Lyman break galaxies (LBGs). Medium-band photometry has emerged as a potential technique for efficiently selecting these high-redshift galaxies. In this work, we present clustering analysis of medium-band selected galaxies at high redshift, utilizing photometric data from the Intermediate Band Imaging Survey (IBIS) and spectroscopic data from the Dark Energy Spectroscopic Instrument (DESI). We interpret the clustering of such samples using both Halo Occupation Distribution (HOD) modeling and a perturbation theory description of large-scale structure. Our modeling indicates that the current target sample is composed from an overlapping mixture of LAEs and LBGs with emission lines. Despite differences in target selection, we find that the clustering properties are consistent with previous studies, with correlation lengths r 0 ≃ 3-4 h -1 Mpc and a linear bias of b ∼ 1.8-2.5. Finally, we discuss the simulation requirements implied by these measurements and demonstrate that the properties of the samples would make them excellent targets to enhance our understanding of the high-z universe.

79 ASTRONOMY AND ASTROPHYSICS↗

Intrinsic alignment as an RSD contaminant in the DESI survey

ABSTRACT We measure the tidal alignment of the major axes of luminous red galaxies (LRGs) from the Legacy Imaging Survey and use it to infer the artificial redshift-space distortion signature that will arise from an orientation-dependent, surface-brightness selection in the Dark Energy Spectroscopic Instrument (DESI) survey. Using photometric redshifts to downweight the shape–density correlations due to weak lensing, we measure the intrinsic tidal alignment of LRGs. Separately, we estimate the net polarization of LRG orientations from DESI’s fibre-magnitude target selection to be of order 10−2 along the line of sight. Using these measurements and a linear tidal model, we forecast a 0.5 per cent fractional decrease on the quadrupole of the two-point correlation function for projected separations of 40–80 h−1 Mpc. We also use a halo catalogue from the Abacussummit cosmological simulation suite to reproduce this false quadrupole.

79 ASTRONOMY AND ASTROPHYSICS↗

S-191 sensor performance evaluation

A final analysis was performed on the Skylab S-191 spectrometer data received from missions SL-2, SL-3, and SL-4. The repeatability and accuracy of the S-191 spectroradiometric internal calibration was determined by correlation to the output obtained from well-defined external targets. These included targets on the moon and earth as well as deep space. In addition, the accuracy of the S-191 short wavelength autocalibration was flight checked by correlation of the earth resources experimental package S-191 outputs and the Backup Unit S-191 outputs after viewing selected targets on the moon.

Hughes, C. L.↗

The Role of Asparagine as a Gatekeeper Residue in the Selective Binding of Rare Earth Elements by Lanthanide‐Binding Peptides

Abstract Lanthanide‐binding tag (LBT) peptides selectively complex lanthanide cations (Ln 3+ ) in their binding pockets and are promising for lanthanide separation. However, designing LBTs that selectively target specific Ln 3+ cations remains a challenge due to limited molecular‐level understanding and control of interactions within the lanthanide‐binding pocket. In this study, we reveal that the N5 asparagine residue acts as a gatekeeper in the binding pocket, resulting in a 100‐fold selectivity for smaller Lu 3+ over larger La 3+ cations. Nuclear magnetic resonance spectroscopy and molecular dynamics simulations show that the N5 residue weakly binds to the larger La 3+ cation, permitting H 2 O molecules inside the pocket. For the smaller Lu 3+ cations, the N5 residue forms an inter‐arm hydrogen bond with the E14 glutamic acid residue, locking the Lu 3+ cation in the pocket and preventing H 2 O infiltration. Mutating the N5 asparagine to a D5 aspartic acid prevents such a hydrogen bond, eliminating the gatekeeping mechanism and precipitously reducing selectivity. The resulting binding affinity to Ln 3+ cations is non‐monotonic but generally increases with cation size. These results suggest a molecular design paradigm: the reduced affinity for larger lanthanides is due to open pocket conformations, while the selectivity of smaller Ln 3+ cations over larger ones is due to the gatekeeping hydrogen bond.

Chemistry↗

Non-Intrusive, Distributed Gas Sensing Technology for Advanced Spacesuits

Chemical sensors for monitoring gas composition, including oxygen, humidity, carbon dioxide, and trace contaminants are needed to characterize and validate spacesuit design and operating parameters. This paper reports on the first prototypes of a non-intrusive gas sensing technology based on flexible sensitive patches positioned inside spacesuit prototypes and interrogated by optical fibers routed outside the suit, taking advantage of the transparent materials of the suit prototypes. The sensitive patches are based on luminescent materials whose emission parameters vary with the partial pressure of a specific gas. Patches sensitive to carbon dioxide, humidity, oxygen, and ammonia have been developed, and their preliminary characterization in the laboratory using Mark III-like helmet parts is described. The first prototype system consists of a four-channel fiber optic luminescent detector that can be used to monitor any of the selected target gases at four locations. To switch from one gas to another we replace the (disposable) sensor patches and adjust the system settings. Repeatability among sensitive patches and of sensor performance from location to location has been confirmed, assuring that suit engineers will have flexibility in selecting multiple sensing points, fitting the sensor elements into the spacesuit, and easily repositioning the sensor elements as desired. The evaluation of the first prototype for monitoring carbon dioxide during washout studies in a space suit prototype is presented.

Delgado, Jesus↗