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At least 1,261 records · Page 70

Sputtering of silicon and its compounds in the electronic stopping region

Silicon, silicon dioxide, and silicon nitride have been sputtered with chlorine ions at 5 MeV and 20 MeV. While the yield from the silicon target was unmeasurably low, the insulating compounds exhibited the enhanced yields observed in other insulating targets. The yield follows the electronic stopping power and seems to be independent of the target's thermal properties. Some of the data suggest that the enhanced sputtering mechanism may be active in extremely thin films (not less than 3 monolayers).

Qiu, Y.↗

Deposition of adherent Ag-Ti duplex films on ceramics in a multiple-cathode sputter deposition system

The adhesion of Ag films deposited on oxide ceramics can be increased by first depositing intermediate films of active metals such as Ti. Such duplex coatings can be fabricated in a widely used three target sputter deposition system. It is shown here that the beneficial effect of the intermediate Ti film can be defeated by commonly used in situ target and substrate sputter cleaning procedures which result in Ag under the Ti. Auger electron spectroscopy and wear testing of the coatings are used to develop a cleaning strategy resulting in an adherent film system.

Honecy, Frank S.↗

Branch strategies - Modeling and optimization

The authors provide a common platform for modeling different schemes for reducing the branch-delay penalty in pipelined processors as well as evaluating the associated increased instruction bandwidth. Their objective is twofold: to develop a model for different approaches to the branch problem and to help select an optimal strategy after taking into account additional i-traffic generated by branch strategies. The model presented provides a flexible tool for comparing different branch strategies in terms of the reduction it offers in average branch delay and also in terms of the associated cost of wasted instruction fetches. This additional criterion turns out to be a valuable consideration in choosing between two strategies that perform almost equally. More importantly, it provides a better insight into the expected overall system performance. Simple compiler-support-based low-implementation-cost strategies can be very effective under certain conditions. An active branch prediction scheme based on loop buffers can be as competitive as a branch-target-buffer based strategy.

Dubey, Pradeep K.↗

Mechanisms test bed math model modification and simulation support

This report summarizes the work performed under contract NAS8-38771 in support of the Marshall Space Flight Center Six Degree of Freedom Motion Facility and Flight Robotics Laboratory. The contract activities included the development of the two flexible body and Remote Manipulator System simulations, Dynamic Overhead Target Simulator control system and operating software, Global Positioning System simulation, and Manipulator Coupled Spacecraft Controls Testbed. Technical support was also provided for the Lightning Imaging Sensor and Solar X-Ray Imaging programs. The cover sheets and introductory sections for the documentation written under this contract are provided as an appendix.

Gilchrist, Andrea C.↗

Wind Variability of B Supergiants: The Rapid Rotator HD 64760 (B0.5 Ib) - No. 1

We present the results of a 6 day time series of observations of the rapidly rotating B0.5 Ib star HD 64760. We point out several reasons why such intermediate luminosity B supergiants are ideal targets for wind variability studies and then present our results that show the following: continuous wind activity throughout the 6 day run with the wind never in steady state for more than a few hr; wind variability very near nu = 0 km sec(exp -1) in the resonance lines from the lower ionization stages (Al III and C II); a distinct correlation between variability in the Si III ; lambda(lambda)1300 triplets, the strong C III (lambda)1247 singlet, and the onset of extremely strong wind activity, suggesting a connection between photospheric and wind activity; long temporal coherence in the behavior of the strong absorption events; evidence for large-scale spatial coherence, implied by a whole scale, simultaneous weakening in the wind absorption over a wide range in velocities; and ionization variability in the wind accompanying the largest changes in the absorption strengths of the wind lines. In addition, modeling of the wind lines provides the following information about the state the wind in HD 64760. The number of structures on the portion of a constant velocity surface occulting the stellar disk at a particular time must be quite small, while the number on the entire constant velocity surface throughout the wind must be large. The escape probability at low velocity is overestimated by a normal beta approx. 1 velocity law, perhaps due to the presence of low-velocity shocks deep in the wind or a shallow velocity gradient at low velocity. Estimates of the ionization structure in the wind indicate that the ionization ratios are not those expected from thermal equilibrium wind models or from an extrapolation of previous O star results. The large observed q(N V)/q(Si IV) ratio is almost certainly due to distributed X-rays, but the level of ionization predicted by distributed X-ray wind models is inconsistent with the predicted mass-loss rate. Thus, it is impossible to reconcile the observed ionization ratios and the predicted mass-loss rate within the framework of the available models.

Massa, Derck↗

NASA Goddard Giovanni Support for YOTC

The fundamental challenges to overcoming our shortcomings in understanding and modeling/predicting tropical convection have been twofold: I) the need to represent the broad range of scales applicable to the tropical organization problem (i.e. cumulus to planetary), and II) the lack of observations that adequately and simultaneously characterize this broad range of scales and that also provide three-dimensional information on thermodynamic, radiative and dynamical interactions, including cloud microphysical processes. In regards to the second challenge, it should be stressed that this problem will not be solved through the production and examination of one or a few high quality long-term records of fundamental quantities (e.g., SST, water vapor, cloud fraction). Rather, an alternative and more comprehensive paradigm is needed, one that integrates the multitude of applicable resources and measures of tropical convection in a manner that that can be better utilized by the diagnostic, modeling and forecasting communities to more completely and coherently focus on the problem.Because the goal of YOTC involves examining a scientifically complex, multi-scale process , rather than documenting the characteristics of a single parameter (e.g., SST, cloud cover), YOTC has an IOP perspective that targets a period, May 2008 April 2010, long enough to encompass many cases of tropical convection activity in many of its most challenging yet influential forms. This includes mesoscale and synoptic variability, easterly waves and hurricanes, convectively coupled waves, the MJO and the culmination of these in terms of the monsoon, their interactions with the extra-tropics, and mean characteristics such as tropical-to-subtropical transitions. The YOTC time period and length are driven in part by the following: 1) keeping the multi-sensor/multi-platform and model-analyses data sets and associated infrastructure manageable, 2) facilitating a focused effort by the research and operational communities on a specific scientific problem, and 3) capitalizing on the recent key additions to the armada of satellites (e.g., CloudSat and CALIPSO). The proposed dissemination framework for the YOTC satellite data archive is based on the Giovanni system. Giovanni is a web-based application developed by the NASA Goddard Earth Science (GES) Data and Information Service Center (DISC) that provides a simple and intuitive way to visualize, analyze, and access/download vast amounts of Earth science remote sensing data. A prototype YOTC Giovanni System (hereafter YOTC-GS) is in the process of being developed. YOTC-GS will provide access to level 2 (i.e. swath level data) and/or level 3 (i.e. gridded/mapped data) forms of satellite data, the choice or both depending on what is appropriate and relevant. The former is needed and better suited for detailed process examination, exploiting the highest temporal-spatial resolutions available and comparison to regional cloud-system resolving model / cloud resolving model (CSRM/CRM) model output. The latter is needed and more well suited for examination of phenomena, conditions and processes on large to global scales, and for comparisons to global model analyses, prediction and simulation output.

Ostrenga, Dana↗

NASA Giovanni Tool for Visualization and Analysis Support for the YOTC Program

The fundamental challenges to overcoming our shortcomings in understanding and modeling/predicting tropical convection have been two folds: I) the need to represent the broad range of scales applicable to the tropical organization problem (i.e. cumulus to planetary), and II) the lack of observations that adequately and simultaneously characterize this broad range of scales and that also provide three-dimensional information on thermodynamic, radiative and dynamical interactions, including cloud microphysical processes. Because the goal of Overview of Year Of Tropical Convection (YOTC) involves examining a scientifically complex, multi-scale "process", rather than documenting the characteristics of a single parameter (e.g., SST, cloud cover), YOTC has an IOP perspective that targets a period, May 2008 - April 2010, long enough to encompass many cases of tropical convection activity in many of its most challenging yet influential forms. This includes mesoscale and synoptic variability, easterly waves and hurricanes, convectively coupled waves, the MJO, and the culmination of these in terms of the monsoon, their interactions with the extra-tropics, and mean characteristics such as tropical-to-subtropical transitions. The YOTC time period and length are driven in part by the following: 1) keeping the multi-sensor/multi-platform and model-analyses data sets and associated infrastructure manageable, 2) facilitating a focused effort by the research and operational communities on a specific scientific problem, and 3) capitalizing on the recent key additions to the armada of satellites (e.g., CloudSat and CALIPSO).

Ostrenga, Dana↗

Assessing Ceres’ Past and Current Habitability

Dwarf planet Ceres is a compelling target as an evolved ocean world with, at least, regional brine reservoirs and potentially ongoing geological activity. Situated in the Main Belt of asteroids, Ceres is the most water-rich body in the inner solar system (in relative abundance) and is accessible enough for a sample return with the resources of a typical medium-class (New Frontiers) NASA mission. NASA’s Dawn mission at Ceres revealed the presence of liquid, brine-driven activity, organic matter, and a rich salt chemistry. With this evidence, the overarching goals of the mission concept presented herein are to quantify Ceres’ current habitability potential and origin. A sample return from young evaporite deposits in Occator crater offers greater science return than an in situ exploration mission by enabling high-resolution analysis of (1) organic matter expected from terrestrial and chondritic analogs that are trapped in salt minerals and (2) isotopes of refractory elements for a similar cost and less science risk. The sample return concept would be executed with a single flight system due to Ceres’ relative proximity to Earth and low gravity. Solar electric propulsion was identified as the most cost-effective approach for getting to Ceres and back. De-orbiting, landing, and takeoff are performed with a throttleable monopropellant hydrazine system. The solar arrays are stowed prior to landing and takeoff. Sample acquisition builds on the pneumatic system designed by Honeybee Robotics. The sample return mission concept relies on the availability of key technologies: an enhanced landing vision system leveraging investments from Mars 2020; retractable/redeployable solar arrays, which have been demonstrated on the International Space Station but not at Ceres’ gravity; and an emerging design from upcoming missions for sample transfer from the pneumatic sampling system to the sample return capsule. Return of a sample of mass ~100 g from Ceres, maintained at ≤ -20°C, is without precedent for any currently advocated Ocean World mission, enabling a vast range of experimental techniques back on Earth with sensitivities and accuracies far beyond those feasible with in situ instruments. A sample of this size also enables analyses to benefit from techniques that will become available in the future.

Casillas, Raul Polit↗

Hydrogen Storage System Modeling: Public Access, Maintenance, and Enhancements

The hydrogen storage system modeling project aims to develop new and enhance existing material-based hydrogen storage system models and make them accessible to the research community through a public web page. Updating existing storage systems models supports material developers in evaluating the performance of their new materials in mobile and stationary applications relative to the available DOE Technical Targets. Developing new tools helps researchers evaluate the performance of hydrogen storage materials developed under HyMARC activities or other fundamental hydrogen storage materials discovery research. New models will also work for validating alternatives to material-based systems (liquefied & gaseous hydrogen), comparing various mobile and stationary use cases, and expand to include medium-, heavy-duty, and mining vehicles and stationary application(s).

AMR↗

Modeling the Influenza A NP-vRNA-Polymerase Complex in Atomic Detail

Seasonal flu is an acute respiratory disease that exacts a massive toll on human populations, healthcare systems and economies. The disease is caused by an enveloped Influenza virus containing eight ribonucleoprotein (RNP) complexes. Each RNP incorporates multiple copies of nucleoprotein (NP), a fragment of the viral genome (vRNA), and a viral RNA-dependent RNA polymerase (POL), and is responsible for packaging the viral genome and performing critical functions including replication and transcription. A complete model of an Influenza RNP in atomic detail can elucidate the structural basis for viral genome functions, and identify potential targets for viral therapeutics. In this work we construct a model of a complete Influenza A RNP complex in atomic detail using multiple sources of structural and sequence information and a series of homology-modeling techniques, including a motif-matching fragment assembly method. Our final model provides a rationale for experimentally-observed changes to viral polymerase activity in numerous mutational assays. Further, our model reveals specific interactions between the three primary structural components of the RNP, including potential targets for blocking POL-binding to the NP-vRNA complex. The methods developed in this work open the possibility of elucidating other functionally-relevant atomic-scale interactions in additional RNP structures and other biomolecular complexes.

59 BASIC BIOLOGICAL SCIENCES↗

Advanced PGM-free Cathode Engineering for High Power Density and Durability

Polymer electrolyte fuel cells (PEFCs) are among the most promising technologies for future electric vehicles by using clean H2 with much-improved energy conversion efficiency, longer range, and rapid refueling. However, due to a large amount of platinum group metal (PGM) catalyst used in their electrodes, their prohibitively high cost hinders broad commercialization of PEFCs for transportation. Therefore, there is a critical need to develop low-cost, high-performance PGM-free cathode catalysts that have the potential to dramatically transform the economics of PEFC commercialization by reducing catalyst costs by one to two orders of magnitude. However, before PGM-free cathodes become viable, several technical challenges associated with PGM-free cathodes must be addressed, including insufficient activity and stability of the catalysts, as well as severe water flooding and large transport losses in the electrodes. Overcoming those barriers and ultimately meeting the challenging automotive PEFC performance targets was the focus of this comprehensive research and development effort on new PGM-free cathodes. To this end, we assembled a team including leading researchers from universities and industry with different but complementary expertise and capabilities. The project combined three novel and promising approaches: Advanced metal-organic framework (MOF)-derived M-N-C catalysts with a high activity and impressive durability, Novel PGM-free specific cathode architectures and fabrication strategies capable of addressing the substantial flooding and transport resistances in thicker cathodes by introducing engineered hydrophobicity through additives and support layers, and Advanced electrode ionomers with high proton conductivity for low ohmic losses across the electrode and more uniform catalyst utilization. The implementation of these new materials and electrode designs was supported by a suite of advanced experimental and simulation tools that allows us to identify performance and durability bottlenecks, devise solutions, and establish rational material design and synthesis targets. These methods include advanced electrochemical characterization, high-resolution imaging, and multi-scale modeling. In addition, the project team leveraged a broad cross-section of the ElectroCat consortium’s national laboratory facilities and expertise in advancing these materials and design strategies. Finally, the industry partners on the project facilitated the evaluation of scaled-up synthesis and manufacturing in the United States. Over its four-year period, the project made significant year-over-year advances in PGM-free cathode performance and viability. A combination of high activity and highly durable catalysts were developed through novel catalyst synthesis strategies, which met several performance and durability targets. More specifically, a catalyst prepared from MOFs and Fe2O3 nanoparticles with ammonium chloride and chemical vapor deposition treatments yielded a significant advancement in PGM-free cathode durability. Several novel strategies for fabricating cathodes were demonstrated, including those designed to reduce flooding and thickness of the cells for significantly increased volumetric power density. An optimized cathode with high conductivity ionomer and tuned ink processing for hydrophobicity yielded high fuel cell performance with new levels power density and maximum current. The scientific studies and modeling assessment also provided an outlook for future efforts, including a focus on catalysts with an increased density of the highly stable active sites developed in this project.

08 HYDROGEN↗

Crystal structure of dihydrofolate reductase from the filarial nematode W. bancrofti in complex with NADPH and folate

Lymphatic filariasis is a debilitating illness with an estimated 50 million cases as of 2018. The majority of cases are caused by the parasitic worm W. bancrofti and additional cases by the worms B. malayi and B. timori. Dihydrofolate reductase (DHFR) is an established target in the treatment of cancer, bacterial, and protozoal infections and may be a potential target for drugs targeting parasitic worm infections, including filariasis. Recent studies have shown that known antifolate compounds, including methotrexate, inhibit the activity of W. bancrofti DHFR (WbDHFR). However, the absence of structural information for filarial DHFRs has limited the study of more in-depth structure-function relationships. We report the structure of WbDHFR complexed with NADPH and folate using X-ray diffraction data measured to 2.47 Å resolution. The structure of WbDHFR reveals the usual DHFR fold and is currently only the second nematode DHFR structure in the Protein Data Bank. The equilibrium dissociation constants for NADPH (90 ± 29 nM) and folate (23 ± 4 nM) were determined by equilibrium titrations. The interactions of known antifolates with WbDHFR were analyzed using molecular docking programs and molecular dynamics simulations. Antifolates with a hydrophobic core and extended linker formed favorable interactions with WbDHFR. These combined data should now facilitate the rational design of filarial DHFR inhibitors, which in turn can be used to determine whether DHFR is a viable drug target for filariasis and whether existing antifolates may be repurposed for its treatment.

60 APPLIED LIFE SCIENCES↗

Conceptual Design and Analysis of In-Vessel Components for the Materials Plasma Exposure eXperiment (MPEX)

The materials plasma exposure experiment (MPEX) is a linear plasma divertor simulator currently undergoing conceptual design. The facility will expose material samples to steady-state plasma fluxes to examine plasma–material interactions (PMIs) that are expected in the next generation of fusion devices. The plasmas will be generated by a helicon source, with electron and ion heating sources of up to 800 kW possible. The peak heat fluxes of the target are expected to be up to 10 MW/m 2 . The facility will be capable of handling low-activation neutron-irradiated samples in order to examine the multivariate effects of neutron damage and plasma fluence. Neutron-irradiated samples are planned to be roughly of 10-mm diameter; however, plasma-facing components up to 60×600 mm can be accommodated. The steady-state nature of the device will require the magnetic confinement of the plasma to be achieved with superconducting magnets, with a maximum on-axis field of 2.5 T. In addition, since MPEX will be a steady-state device, in-vessel components need to be water cooled. The primary in-vessel components will be the target, the dump plate, the limiter, the skimmers, and the microwave absorber. The conceptual design of these components is presented here, including analyses that confirm that the designs are adequate to meet the requirements of MPEX operation.

Lumsdaine, Arnold↗

Developing Multi-Gene CRISPRa/I Programs to Accelerate DBTL Cycles in ABF Hosts Engineered for Chemical Production (CRADA 468)

Bacterial metabolism is comprised of large and complex gene networks that can produce valuable chemical products. Sophisticated organism engineering efforts are required to optimize production of high-value compounds from these networks. In principle, synthetic multi-gene transcriptional programs could be constructed to reengineer these networks for efficient industrial chemical production. In practice, however, our incomplete ability to understand and model the underlying networks, combined with our limited ability to predictably control the expression of multiple genes makes achieving this goal difficult. To overcome these challenges, we will combine new CRISPR-Cas multi-gene expression programs with computational modeling, machine learning, and multi-omics data to enhance the efficacy of design-build-test-learn (DBTL) cycles. For industrially promising microorganisms in early stages of development, creating technologies for rapidly engineering complex multi-gene programs could be transformative for accelerating data- and model-driven strain design. New CRISPR-Cas tools allow programmable gene activation (CRISPRa) or repression (CRISPRi) at multiple genes simultaneously, using the catalytically inactive Cas9 protein (dCas9) with guide RNAs that recognize DNA targets through predictable Watson-Crick base pairing. To enable accelerated DBTL cycles, we will combine these technologies with advanced Agile BioFoundry (ABF) capabilities for multi-omics data collection and machine learning. We will demonstrate the immediate applicability of these tools by rapidly improving the production of an industrial aromatic in multiple ABF organisms. We recently identified and optimized new transcriptional activators that can be linked to programmable CRISPR-Cas DNA binding domains to activate gene expression in E. coli. We can now use these CRISPRa tools as generalizable trans-acting regulators for combinatorial multi-gene expression tuning that can be easily transferred to new pathways and networks without additional genome engineering. We anticipate these tools will also transfer to new hosts. We have recently found that CRISPRa systems developed in E. coli can be readily ported to Pseudomonas putida, suggesting that multi-gene CRISPRa/i programs for diverse ABF organisms may be within reach.

59 BASIC BIOLOGICAL SCIENCES↗

Building a Computational and Experimental Rapid Response Pipeline to Counter the Coronavirus Disease 2019 Outbreak and Emerging Biothreats

The COVID-19 pandemic underscored the promise of monoclonal antibody-based prophylactic and therapeutic drugs, especially where protective candidates can be rapidly identified or developed for emerging biothreats and escape variants. Current cutting-edge technologies for this purpose still rely on pathogen-exposed convalescent volunteers and a large screening effort to find a proverbial needle in a haystack. Computational design of protective antibodies based on pre-existing templates skips those requirements and allows for greater control over the breadth and target epitope, while also co-optimizing for potency and developability or other biophysical characteristics. We approached this problem by building and expanding an in vitro experimental rapid antibody production and characterization pipeline to support development of an autonomous, closed loop, active learning software system based on structural simulation and ground truth experimental data to design and evaluate antibody antigen interactions. Starting from early in the pandemic, we targeted SARS-CoV-2, the causative agent of COVID-19, by re-purposing neutralizing antibodies against SARS-CoV-1 that had been identified in the wake of that outbreak in the early 2000’s. We successfully re-targeted three different anti-SARS-CoV-1 antibodies to neutralize SARS-CoV-2 in vitro, where the antibodies were generated externally and tested through conventional binding and neutralization assays internally or with collaborators. As antibodies were identified from the blood of humans infected with SARS-CoV-2, we shifted to collaborate with academic partners to develop improved versions of their human-derived antibodies. This work reached its most important stage in rapid response to the emergence of the Omicron variant of concern (VOC) in late 2021. In a matter of weeks, enabled by on demand innovation to our screening pipeline, we computationally designed and experimentally characterized derivative antibodies of COV2-2130, one of two antibodies from Vanderbilt that form the basis of the AstraZeneca Evusheld prophylactic drug product. This drug product suffers a serious loss of efficacy against Omicron BA.1 and BA.1.1, the first Omicron strains. Due to tight integration of computational design and experimental evaluation, we were able to identify a pair of designs with potent neutralization of the main targets Omicron BA.1 and BA.1.1; but also the earlier Delta variant, and subsequent Omicron strains including BA.2, BA.4, BA.5, and BA.2.75, demonstrating that our multi-target design process can, by its nature, produce robust antibody designs that strictly improve over the parental antibody. These results, recognized by a 2022 Director’s Science and Technology award, have enabled the follow-on GUIDE program, to commence in FY23. While earlier design campaigns were substantially outsourced, we have engineered better and faster processes internally to better compliment, calibrate, and speed computational designs. As part of the follow-on GUIDE program, we will stand up a rapid and high-throughput antibody production and characterization facility staffed with the expertise and capabilities to foster our current collaboration across PLS and ENG as well as other partnerships toward computational design of biologics.

59 BASIC BIOLOGICAL SCIENCES↗

Directed evolution of a stem-helix–targeting antibody enables MERS-CoV cross-neutralization through enhanced binding affinity

Broadly neutralizing antibodies (bnAbs) targeting conserved regions of the betacoronavirus spike are important for pan-betacoronavirus protection and pandemic preparedness. Here, we report the isolation of a human monoclonal antibody, CC65.1, from a SARS-CoV-2 convalescent donor that targets the conserved S2 stem helix region. CC65.1 neutralizes various sarbecoviruses, including SARS-CoV-2, and binds to the MERS-CoV spike but lacks MERS-CoV-neutralizing activity due to insufficient binding affinity. We utilized directed evolution to enhance the binding affinity of CC65.1 for the MERS-CoV S2 stem helix, yielding engineered antibody variants with newly acquired MERS-CoV-neutralizing activity. High-resolution structural analysis reveals key paratope mutations that enhance binding and stabilize epitope engagement. Our findings demonstrate the potential of in vitro affinity maturation to expand the neutralization breadth of stem-helix-targeting antibodies across divergent betacoronaviruses. This work supports the development of engineered bnAbs for broadly protective betacoronavirus countermeasures and provides a strategy for achieving cross-lineage neutralization.

Zhou, Panpan↗

Progress in understanding and improving oil content and quality in seeds

The world’s population is projected to increase by two billion by 2050, resulting in food and energy insecurity. Oilseed crops have been identified as key to address these challenges: they produce and store lipids in the seeds as triacylglycerols that can serve as a source of food/feed, renewable fuels, and other industrially-relevant chemicals. Therefore, improving seed oil content and composition has generated immense interest. Research efforts aiming to unravel the regulatory pathways involved in fatty acid synthesis and to identify targets for metabolic engineering have made tremendous progress. This review provides a summary of the current knowledge of oil metabolism and discusses how photochemical activity and unconventional pathways can contribute to high carbon conversion efficiency in seeds. It also highlights the importance of 13 C-metabolic flux analysis as a tool to gain insights on the pathways that regulate oil biosynthesis in seeds. Finally, a list of key genes and regulators that have been recently targeted to enhance seed oil production are reviewed and additional possible targets in the metabolic pathways are proposed to achieve desirable oil content and quality.

59 BASIC BIOLOGICAL SCIENCES↗