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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 91 records · Page 5

Characterization of two affinity matured Anti-Yersinia pestis F1 human antibodies with medical countermeasure potential

Yersinia pestis , the causative agent of plague and a biological threat agent, presents an urgent need for novel medical countermeasures due to documented cases of naturally acquired antibiotic resistance and potential person-to-person spread during a pneumonic infection. Immunotherapy has been proposed as a way to circumvent current and future antibiotic resistance. Here, we describe the development and characterization of two affinity matured human antibodies (αF1Ig AM2 and αF1Ig AM8) that promote survival of mice after exposure to aerosolized Y . pestis . We share details of the error prone PCR and yeast display technology-based affinity maturation process that we used. The resultant matured antibodies have nanomolar affinity for Y . pestis F1 antigen, are produced in high yield, and are resilient to 37°C stress for up to 6 months. Importantly, in vitro assays using a murine macrophage cell line demonstrated that αF1Ig AM2 and αF1Ig AM8 are opsonic. Even more importantly, in vivo studies using pneumonic plague mouse models showed that 100% of the mice receiving 500 μg of IgGs αF1Ig AM2 and αF1Ig AM8 survived lethal challenge with aerosolized Y . pestis CO92. Combined, these results provide evidence of the quality and robustness of αF1Ig AM2 and αF1Ig AM8 and support their development as potential medical countermeasures against plague.

59 BASIC BIOLOGICAL SCIENCES↗

A Portfolio Approach to Massively Parallel Bayesian Optimization

One way to reduce the time of conducting optimization studies is to evaluate designs in parallel rather than just one-at-a-time. For expensive-to-evaluate black-boxes, batch versions of Bayesian optimization have been proposed. They work by building a surrogate model of the black-box to simultaneously select multiple designs via an infill criterion. Still, despite the increased availability of computing resources that enable large-scale parallelism, the strategies that work for selecting a few tens of parallel designs for evaluations become limiting due to the complexity of selecting more designs. It is even more crucial when the black-box is noisy, necessitating more evaluations as well as repeating experiments. Here we propose a scalable strategy that can keep up with massive batching natively, focused on the exploration/exploitation trade-off and a portfolio allocation. We compare the approach with related methods on noisy functions, for mono and multi-objective optimization tasks. These experiments show orders of magnitude speed improvements over existing methods with similar or better performance.

97 MATHEMATICS AND COMPUTING↗

Insights into Slip-Rate Time Functions, Rupture Parameter Correlations, and Ground Motions from Validated Multicycle Earthquake Ruptures

Earthquake strong-motion predictions using kinematic source modeling require knowledge of the slip-rate functions (SRFs) along the rupture and their distinct characteristics in asperities, background (off-asperity) areas and near the surface. Here, in this study we analyzed SRFs from well-validated, self-consistent, and fully dynamic rupture models from earthquake cycles obeying a rate-and-state friction law, from our companion study (Galvez et al., 2021). The shapes of SRFs in asperities are well described by the regularized Yoffe function (RYF), which has only two parameters: rise time T r and smoothing time T s , which control the generation of long- and short-period ground motions, respectively. In background areas, we demonstrate that, in addition to the primary rupture, multiple secondary ruptures may also nucleate from rupture heterogeneities related to asperities, resulting in SRFs with multiple peaks. Because it is impossible to fit a multiple-peak SRF by the single-peak RYF, we describe SRFs in background areas in an effective way by fitting their amplitude spectra with the RYF spectra. Such spectrally effective RYFs capture salient aspects of seismic-wave generation and can be used in rupture generators for strong motion prediction. We found that small T s values correlate with small characteristic weakening distances, large peak slip rates (PSRs), and large rupture velocities. T r values are larger in background areas and smaller in asperities. Within the shallow aseismic zone, T s values approximately quadruple whereas T r values approximately double. Because of this dominant T s increase, PSR values decrease in the near-surface zone. These features indicate that the generation of strong motions by the near-surface portions of the rupture is negligible in the studied scenarios.

Geosciences↗

OPEXatLANL Survey Results [Slides]

The survey was open online July 19-August 4, 2021. It was open to all employees with LANL email addresses, Google access. It was used to measure OPEXatLANL awareness, usage. It consisted of 7 multiple-choice questions, 3 short-answer questions. A total of 383 responses were collected (55 managers, 328 non-managers).

99 GENERAL AND MISCELLANEOUS↗

Nanolipoprotein particle (NLP) vaccine confers protection against Yersinia pestis aerosol challenge in a BALB/c mouse model

Introduction: Yersinia pestis is the etiological agent of plague, a disease that remains a concern as demonstrated by recent outbreaks in Madagascar. Infection with Y. pestis results in a rapidly progressing illness that can only be successfully treated with antibiotics given shortly after symptom onset. Live attenuated or whole cell inactivated vaccines confer protection against bubonic plague, but pneumonic plague has been more difficult to prevent. Novel effective subunit vaccine formulations may circumvent some of these shortfalls. Here, we compare the immunogenicity generated by an advanced subunit vaccine (F1V fusion protein) and a nanolipoprotein particle (NLP)-based vaccine. Methods: The NLP, a high-density lipoprotein mimetic, provides a nanoscale delivery platform for recombinant Y. pestis antigens LcrV (V) and F1. BALB/c mice were immunized via subcutaneous injection twice, three or four weeks apart. Four weeks later, splenocytes and sera were collected for immune profiling, and mice were challenged with aerosolized Y. pestis CO92. Results: Both formulations induced a strong IgG response against the F1 and V proteins, along with a robust memory B cell response and a balanced cell-mediated immune response as evidenced by both Th1- and Th2-related cytokines. The NLP-based vaccine induced a stronger cytokine response against F1, V, and F1V proteins relative to the F1V vaccine. As with F1V, the inclusion of Alhydrogel (Alu) in NLP vaccine formulations was critical for enhanced immunogenicity and protective efficacy. Mice that received two doses of F1:V:NLP + Alu and CpG were completely protected from a challenge with approximately eight median lethal doses of aerosolized Y. pestis CO92 and this protection confirmed the well-documented synergy between the F1 and V antigens in context of pneumonic plague. The NLPs have defined regions of polarity that facilitates the incorporation of a wide range of adjuvants and antigens with distinct physicochemical properties and are an excellent candidate platform for the development of multi-antigen vaccines.

F1↗

Origin of Plutonium-244 in the Early Solar System

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

79 ASTRONOMY AND ASTROPHYSICS↗

Dimorphos’s Material Properties and Estimates of Crater Size from the DART Impact

On 2022 September 26, the Double Asteroid Redirection Test (DART) spacecraft intentionally collided with Dimorphos, the moon of the binary asteroid system 65803 Didymos. This collision provided the first full-scale test of a kinetic impactor for planetary defense. Images from DART’s DRACO camera revealed Dimorphos to be an oblate spheroid covered in boulders of varying sizes and shapes. Very little was known about Dimorphos prior to DART’s impact, including its shape, structure, and material properties. Approach observations and those following the DART impact have provided crucial knowledge that narrows the parameter space relevant to modeling the impact into Dimorphos. Here we present the results of a suite of hydrocode simulations of the DART impact on Dimorphos. Despite remaining uncertainties, initial models of DART’s kinetic impact provide important information about the results of DART (e.g., potential crater size and morphology, ejecta mass) and the properties of Dimorphos. Simulations here suggest that Dimorphos has near-surface strength ranging from a few Pascals to tens of kPa, which corresponds to crater sizes of ~40–60 m. Simulated crater sizes provide a crucial comparison metric for the European Space Agency Hera mission when it arrives at the Didymos system. Hera’s measurement of crater size in combination with measurement of Dimorphos’s mass will allow us to assess our simulations and provide the information needed to make the DART impact experiment both the first test of a planetary defense mitigation mission and the first full-scale planetary defense simulation validation exercise.

36 MATERIALS SCIENCE↗

Evidence of Recent Material Transport within a Binary Asteroid System

Images acquired by the Double Asteroid Redirection Test (DART) before its impact into Dimorphos—the moon of the Didymos binary asteroid system—unexpectedly reveal a set of discontinuous rays spanning the imaged surface. These albedo features are visible only after correcting for lighting differences, which normalize the effects of the pervasive boulders that cover the surface. Comparison to physical experiments and numerical simulations shows that these bright, fan-shaped albedo features are consistent with the aftermath of a low-velocity impact into a field of boulders and provide our first direct evidence for the transfer of material in a binary asteroid system due to the shedding material from radiative torques. Parts of these and possible additional albedo markings from the reentry of boulders after the DART impact may be visible to the Hera mission when it explores the post-DART Didymos system.

Astronomy and AstroPhysics↗

Numerical data frame readout system used in testing telemetry systems

Digital telemetry systems are treated by a display system that offers direct readout as high data rates. The rates appear in numerical format and are adaptable to photographic recording techniques. The system can show bit dropouts at a memory output or locate a malfunction in a system.

Cote, C. E.↗