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At least 73 records · Page 4

C6 Hydroxymethyl-Substituted Carbapenem MA-1-206 Inhibits the Major Acinetobacter baumannii Carbapenemase OXA-23 by Impeding Deacylation

Acinetobacter baumannii has become a major nosocomial pathogen, as it is often multidrug-resistant, which results in infections characterized by high mortality rates. The bacterium achieves high levels of resistance to β-lactam antibiotics by producing β-lactamases, enzymes which destroy these valuable agents. Historically, the carbapenem family of b-lactam antibiotics have been the drugs of choice for treating A. baumannii infections. However, their effectiveness has been significantly diminished due to the pathogen’s production of carbapenem-hydrolyzing class D β-lactamases (CHDLs); thus, new antibiotics and inhibitors of these enzymes are urgently needed. Here, we describe a new carbapenem antibiotic, MA-1-206, in which the canonical C6 hydroxyethyl group has been replaced with hydroxymethyl. The antimicrobial susceptibility studies presented here demonstrated that this compound is more potent than meropenem and imipenem against A. baumannii producing OXA-23, the most prevalent CHDL of this pathogen, and also against strains producing the CHDL OXA-24/40 and the class B metallo-β-lactamase VIM-2. Our kinetic and mass spectrometry studies revealed that this drug is a reversible inhibitor of OXA-23, where inhibition takes place through a branched pathway. X-ray crystallographic studies, molecular docking, and molecular dynamics simulations of the OXA-23-MA-1-206 complex show that the C6 hydroxymethyl group forms a hydrogen bond with the carboxylated catalytic lysine of OXA-23, effectively preventing deacylation. These results provide a promising strategy for designing a new generation of CHDL-resistant carbapenems to restore their efficacy against deadly A. baumannii infections. Carbapenem antibiotics are the drugs of choice for treatment of deadly infections caused by Gram-negative bacteria. However, their efficacy is severely compromised by the wide spread of carbapenem-hydrolyzing class D β-lactamases (CHDLs). The importance of this research is the discovery that substitution of the canonical hydroxyethyl group of carbapenems by a hydroxymethyl significantly enhances stability against inactivation by the major CHDL of Acinetobacter baumannii, OXA-23. These results provide a novel strategy for designing next-generation, carbapenemase-stable carbapenems to fight multidrug-resistant infections caused by Gram-negative pathogens

59 BASIC BIOLOGICAL SCIENCES↗

Prediction of intrinsic topological superconductivity in Mn-doped GeTe monolayer from first-principles

The recent discovery of topological superconductors (TSCs) has sparked enormous interest. The realization of TSC requires a delicate tuning of multiple microscopic parameters, which remains a great challenge. Here, we develop a first-principles approach to quantify realistic conditions of TSC by solving self-consistently Bogoliubov-de Gennes equation based on a Wannier function construction of band structure, in presence of Rashba spin-orbit coupling, Zeeman splitting and electron-phonon coupling. We further demonstrate the power of this method by predicting the Mn-doped GeTe (Ge 1- x Mn x Te) monolayer—a well-known dilute magnetic semiconductor showing superconductivity under hole doping—to be a Class D TSC with Chern number of -1 and chiral Majorana edge modes. By constructing a first-principles phase diagram in the parameter space of temperature and Mn concentration, we propose the TSC phase can be induced at a lower-limit transition temperature of ~40 mK and the Mn concentration of x ~0.015%. Our approach can be generally applied to TSCs with a phonon-mediated pairing, providing useful guidance for future experiments.

Chemistry↗

Safety Case for Small Uncrewed Aircraft Systems (sUAS) Beyond Visual Line of Sight (BVLOS) Operations at NASA Langley Research Center

This Technical Memorandum (TM) is written to provide for dissemination of the methods and safety considerations for operations of small Uncrewed Aerial Systems (sUAS) Beyond Visual Line-of-Sight (BVLOS)at NASA Langley Research Center. It includes the Safety Case used to acquire a BVLOS Certificate of Authorization (COA) from the FAA and is being published to enable others to benefit from this work. The intended operations, subject to approval from the Federal Aviation Administration (FAA) and the National Aeronautics and Space Administration (NASA), will include a combination of Within Visual Line of Sight (WVLOS) and Beyond Visual Line of Sight (BVLOS) flights, comprising of at most five sUAS operating concurrently, with no more than three operating BVLOS. Flights will occur in a subset of the Langley Air Force Base (LAFB) Class D airspace (KLFI) at a maximum altitude of 400 ft AGL. Most operations within this subset will take place in the City Environment Range Testing for Autonomous Integrated Navigation (CERTAIN) Range. The CERTAIN Range includes airspace inside the borders of NASA Langley Research Center (LaRC). Additional airspace over the northern section of CERTAIN will be requested as part of the Certificate of Authorization (COA). NASA LaRC BVLOS operations on the CERTAIN Range can be broken down into five critical components needed to meet the 14 CFR § 91.113 see and avoid requirement: 1) procedural deconfliction with LAFB for UAS operations at or below 400 ft and manned aircraft at or above 900’ AGL; 2) ground equipment for detection of intruder aircraft and to support communications between crewmembers ; 3) sUAS vehicles with advanced onboard automation capable of autonomously maintaining safe separation; 4) BVLOS standardized operating procedures (SOPs); 5) and personnel to execute the flight operations in accordance with the SOPs and respond to airborne contingencies. The introduction of new ground equipment includes the use of the Remote Operations for Autonomous Missions (ROAM) UAS Operations Center, development and use of an Integrated Airspace Display (IAD), use of the L-STAR and GA-9120 radars, and the incorporation of standardized Vertiports. The ROAM Operations Center will be the central point for all BVLOS sUAS operations. All command and control (C2), voice communications and airspace awareness displays will reside inside ROAM. The IAD will provide raw data from ADS-B, FLARM, radar tracks and telemetered GPS vehicle positions for interpretation by an Airspace Monitor. The radars will search the class D airspace around the CERTAIN Range and serve as a backup to procedural deconfliction procedures coordinated with LAFB. In the event of a procedural deconfliction breakdown, radar detections of non-participating aircraft will be available so that the 91.113 see and avoid requirement can still be safely met. Finally, the incorporation of Vertiports will have video and network connectivity that enables large numbers of sUAS launches and recoveries from a single location. This is a continuation of the remote command and control of unpiloted aircraft component focused on evaluating unpiloted aircraft flight crew roles and responsibilities, control interfaces and the associated data links needed to operate a fleet of aircraft within a UAM Ecosystem. This work supports the development of future aviation operational concepts based on an Urban Air Mobility Maturity Level (UML) 4 environment (Patterson, 2020). It is assumed that future airspace will include hundreds of simultaneous aircraft operations within the airspace, therefore scalable operations are essential for enabling this future airspace to become a reality. Follow on work includes envisioned flights that expand operations beyond the CERTAIN range and lead to an effective Maritime Surveillance capability.

Matthew W Coldsnow↗

SMA for Highly Constrained Projects

This is a collection of presentation elements into a consolidated presentation on overall safety and mission assurance practices for highly constrained projects, such as Class D, 7120.8, or Do No Harm.

safety and mission assurance↗

Development of a Nitrogen and Magnesium Oxide based Class A, B & D Suffocating Fire System (SFSS) for Gloveboxes

Testing related to the development and performance of a “Proof of Concept” Nitrogen/Magnesium Oxide Suffocating Fire System (SFSS) was conducted at Fire and Pump Service Group (FPSG) located in Rancho Dominguez, California. The SFSS Engineering Team (SFSSET), consisting of FPSG and Los Alamos National Laboratory (LANL) personnel researched, developed a prototype, and conducted testing to determine effective means to deliver magnesium oxide (MgO) sand into a glovebox (GB) in a class D fire event. The prototypes development also established the effective coverage area of a magnesium oxide suppression system as well as demonstrated that the GB inert atmosphere could be maintained during and after the release of the MgO sand to control Class A, B and D fires. Previous testing conducted on nitrogen based SFSS provided evidence that the nitrogen based SFSS controlled Class A and B fires (Ralph Clayton, Los Alamos National Laboratory, Brandon Troc and Frank Broidy, Fire and Pump Service Group 2020).Final testing was conducted within a mock GB capable of simulating an inert glovebox atmosphere. Testing demonstrated that the inert atmosphere can be maintained during and after discharge of the MgO sand over a coverage area.

98 NUCLEAR DISARMAMENT, SAFEGUARDS, AND PHYSICAL P↗

Spectroscopy and Photometry of Mars Trojans

Mars is the only terrestrial planet known to have co-orbiting "Trojan" asteroids. We have obtained visible and near-IR reflectance spectra of three of these objects: 5261 Eureka and 1998 VF31 in the L5 region and 1999 UJ7 in the L4 region. We also obtained JHK spectrophotometry and a visible lightcurve for 5261 Eureka. The asteroid 5261 Eureka has a visible spectrum that is classified as Sr in the Bus taxonomy, and has infrared colors consistent with the A-class asteroids. The data for 1998 VF31 have a restricted wavelength range, but are most consistent with the Sr or Sa class, though we note a marginal consistency with the D class. We can rule out a C-class classification. 1999 UJ7 has an X-class or T-class spectrum, which is unlike that of the other two Mars Trojans. The photometric data for Eureka are limited, but we can constrain the period to longer than 5 hours (likely 5.556 hours) and lightcurve amplitude of at least 0.15 magnitude at this viewing geometry. The spectral differences among the Mars Trojans suggests that either they did not all form at their present solar distances or that they have not always been at their present sizes. 0 2003 Elsevier Inc. All rights reserved. Keywords: Asteroids; Asteroids, composition; Spectroscopy; Satellites of Mars

Rivkin, A. S.↗

Spectroscopy and Photometry of Mars Trojans

Mars is the only terrestrial planet known to have co-orbiting Trojan asteroids. We have obtained visible and near-IR reflectance spectra of three of these objects: 5261 Eureka and 1998 VF31 in the L5 region and 1999 UJ7 in the LA region. We also obtained JHK spectrophotometry and a visible lightcurve for 5261 Eureka. The asteroid 5261 Eureka has a visible spectrum that is classified as Sr in the Bus taxonomy, and has infrared colors consistent with the A-class asteroids. The data for 1998 VF31 have a restricted wavelength range, but are most consistent with the Sr or Sa class, though we note a marginal consistency with the D class. We can rule out a C-class classification. 1999 UJ7 has an X-class or T-class spectrum, which is unlike that of the other two Mars Trojans. The photometric data for Eureka are limited, but we can constrain the period to longer than 5 hours (likely 5.5-6 hours) and lightcurve amplitude of at least 0.15 magnitude at this viewing geometry. The spectral differences among the Mars Trojans suggests that either they did not all form at their present solar distances or that they have not always been at their present sizes.

Rivkin, A. S.↗

Effect of density gradients in confined supersonic shear layers. Part 2: 3-D modes

The effect of basic flow density gradients on the supersonic wall modes were investigated in Part 1 of this analysis. In that investigation only the 2-D modes were studied. Tam and Hu investigated the 3-D modes in a confined vortex sheet and reported that the first 2-D Class A mode (A01) had the highest growth rate compared to all other 2-D and 3-D modes present in the vortex sheet for that particular set of flow patterns. They also showed that this result also held true for finite thickness shear layers with delta(sub w) less than 0.125. For free shear layers, Sandham and Reynolds showed that the 3-D K-H mode became the dominant mode for M(sub c) greater than 0.6. Jackson and Grosch investigated the effect of crossflow and obliqueness on the slow and fast odes present in a M(sub c) greater than 1 environment and showed that for certain combination of crossflow and wave angles the growth rates could be increased by up to a factor of 2 with respect to the 2-D case. The case studied here is a confined shear layer shown in Part 1. All solution procedures and basic low profiles are the same as in Part 1. The effect of density gradients on the 3-D modes present in the density ratios considered in Part 1 are investigated.

Peroomian, Oshin↗

Resource Prospector (RP): A Cost-Effective Lunar Resource Pathfinder

Resource Prospector (RP) is an in-situ resource utilization (ISRU) technology demonstration mission under study by the NASA Human Exploration and Operations Mission Directorates (HEOMD). This clever mission is currently planned to launch in 2020 and will demonstrate extraction of oxygen, water and other volatiles, as well measure mineralogical content such as silicon and light metals, like aluminum and titanium, from lunar regolith. Expanding human presence beyond low-Earth orbit to asteroids and Mars will require the maximum possible use of local materials, so-called in-situ resources, and the moon presents a unique destination to conduct robotic investigations that advance ISRU capabilities, as well as providing significant exploration and science value. This mission is equally important; however, for how it executes as a risk-tolerant, cost-effective mission. RP follows on the path-finding approaches of the Lunar Crater Observation and Sensing Satellite (LCROSS) mission. The LCROSS mission confirmed the presence of water-ice on the moon, but also established a new lightweight-approach to project and mission execution which was considerably cheaper and faster than traditional NASA missions. RP has been designated as a Class D mission, just as LCROSS. This mission classification is the most risk-tolerant class of mission within the NASA risk framework and as such, is given more latitude to accept higher-levels of residual risk. The intention is that by saving monies normally spent attempting to assure a single missions success, more missions can be funded. A well-designed portfolio can accept occasional mission failure, as it still gets more done for the same investment of resources. This classification enables tailoring the NASA Policy Requirements (NPRs) to lighter-weight approaches to mission management and execution. RP is also studying both international and commercial partnerships as a means to maximize return on the investment. International partnerships provide both capabilities synergies and cost-sharing opportunities, while the evolving new space commercial options are revealing new approaches to acquiring cost-effective services, including the benefits of bundling services. Even the world of launch vehicles is changing, offering much less expensive access to space, especially if NASA is able to be flexible in how it approaches mission assurance. Finally, leveraging investments being made elsewhere within a program portfolio, can enable cost-savings by enabling two applications with one investment. RP will be the next pathfinder mission to both enable exploration capabilities for future missions, and continue to evolve cost-effective approaches for NASA.

Lunar↗

Multicolor photometry of outer Jovian satellites

Multicolor photometry was obtained of satellites J6 Himalia, J7 Elara, and J10 Lysithea in the prograde cloud of outer Jovian satellites, and of J8 Pasiphae, J9 Sinope, and J11 Carme in the retrograde cloud. The data for J9 are fragmentary; otherwise, the satellites all look like C-class asteroids, except J11, which shows a remarkable brightness in the ultraviolet. The absence of D-class spectra among the outer Jovian satellites suggests that they were not derived from the same population as the outer-belt and Trojan asteroid populations.

Tholen, D. J.↗

Hydrovolcanic Astromaterials in the Lab

Zag and Monahans (1998) are H chondrite regolith breccias that contain 4.5 GY old halite crystals which in turn contain abundant inclusions of aqueous fluids, solids and organics. We have previously proposed that these halites originated on a hydrovolcanically-active C class asteroid, probably Ceres, or a trans-neptunian object (TNO - or P- or D-class asteroid) injected into the inner solar system during giant planet migration. We have begun a detailed analysis of organics and other solids trapped within the halite, which we hypothesize sample the mantle of the halite parent object, and are examining a halite-bearing C1 chondrite clast also found in Zag, which is similar to the solids in the halite. These investigations will reveal the water-rock interactions on the hydrovolcanically-active parent world.

Zolensky, M. E.↗

Linear Subpixel Learning Algorithm for Land Cover Classification from WELD using High Performance Computing

In this work, we use a Fully Constrained Least Squares Subpixel Learning Algorithm to unmix global WELD (Web Enabled Landsat Data) to obtain fractions or abundances of substrate (S), vegetation (V) and dark objects (D) classes. Because of the sheer nature of data and compute needs, we leveraged the NASA Earth Exchange (NEX) high performance computing architecture to optimize and scale our algorithm for large-scale processing. Subsequently, the S-V-D abundance maps were characterized into 4 classes namely, forest, farmland, water and urban areas (with NPP-VIIRS-national polar orbiting partnership visible infrared imaging radiometer suite nighttime lights data) over California, USA using Random Forest classifier. Validation of these land cover maps with NLCD (National Land Cover Database) 2011 products and NAFD (North American Forest Dynamics) static forest cover maps showed that an overall classification accuracy of over 91 percent was achieved, which is a 6 percent improvement in unmixing based classification relative to per-pixel-based classification. As such, abundance maps continue to offer an useful alternative to high-spatial resolution data derived classification maps for forest inventory analysis, multi-class mapping for eco-climatic models and applications, fast multi-temporal trend analysis and for societal and policy-relevant applications needed at the watershed scale.

Subpixel↗

Near-Infrared Spectrophotometry of Phobos and Deimos

We have observed the leading and trailing hemispheres of Phobos from 1.65 to 3.5 micrometers and Deimos from 1.65 to 3.12 micrometers near opposition. We find the trailing hemisphere of Phobos to be brighter than its leading hemisphere by 0.24 plus or minus 0.06 magnitude at 1.65 micrometers and brighter than Deimos by 0.98 plus or minus 0.07 magnitude at 1.65 micrometers. We see no difference larger than observational uncertainties in spectral slope between the leading and trailing hemispheres when the spectra are normalized to 1.65 micrometers. We find no 3-micrometer absorption feature due to hydrated minerals on either hemisphere to a level of approximately 5-10% on Phobos and approximately 20% on Deimos. When the infrared data are joined to visible and nearby data obtained by previous workers, our data suggest the leading (Stickney-dominated) side of Phobos is best matched by T-class asteroids. The spectral slope of the trailing side of Phobos and leading side of Deimos are bracketed by the D-class asteroids. The best laboratory spectral matches to these parts of Phobos are mature lunar soils and heated carbonaceous chondrites. The lack of 3-micrometer absorption features on either side of Phobos argues against the presence of a large interior reservoir of water ice according to current models of Phobos' interior.

Rivkin, A. S.↗

Near-Infrared Spectrophotometry of Phobos and Deimos

We have observed the leading and trailing hemispheres of Phobos from 1.65 to 3.5 microns and Deimos from 1.65 to 3.12 microns near opposition. We find the trailing hemisphere of Phobos to be brighter than its leading hemisphere by 0.24 +/- 0.06 magnitude at 1.65 microns and brighter than Deimos by 0.98 +/- 0.07 magnitude at 1.65 microns. We see no difference larger than observational uncertainties in spectral slope between the leading and trailing hemispheres when the spectra are normalized to 1.65 microns. We find no 3-micron absorption feature due to hydrated minerals on either hemisphere to a level of approx. 5-10% on Phobos and approx. 20% on Deimos. When the infrared data are joined to visible and near-IR data obtained by previous workers, our data suggest the leading (Stickney-dominated) side of Phobos is best matched by T-class asteroids. The spectral slope of the trailing side of Phobos and leading side of Deimos are bracketed by the D-class asteroids. The best laboratory spectral matches to these parts of Phobos are mature lunar soils and heated carbonaceous chondrites. The lack of 3-micron absorption features on either side of Phobos argues against the presence of a large interior reservoir of water ice according to current models of Phobos' interior.

Rivkin, A. S.↗

Near-Infrared Spectrophotometry of Phobos and Deimos

We have observed the leading and trailing hemispheres of Phobos from 1.65 to 3.5 microns and Deimos from 1.65 to 3.12 microns near opposition. We find the trailing hemisphere of Phobos to be brighter than its leading hemisphere by 0.24 +/- 0.06 magnitude at 1.65 microns and brighter than Deimos by 0.98 +/- 0.07 magnitude at 1.65 microns. We see no difference larger than observational uncertainties in spectral slope between the leading and trailing hemispheres when the spectra are normalized to 1.65 microns. We find no 3-microns absorption feature due to hydrated minerals on either hemisphere to a level of approx. 5 - 10% on Phobos and approx. 20% on Deimos. When the infrared data are joined to visible and near-IR data obtained by previous workers, our data suggest the leading (Stickney-dominated) side of Phobos is best matched by T-class asteroids. The spectral slope of the trailing side of Phobos and leading side of Deimos are bracketed by the D-class asteroids. The best laboratory spectral matches to these parts of Phobos are mature lunar soils and heated carbonaceous chondrites. The lack of 3-microns absorption features on either side of Phobos argues against the presence of a large interior reservoir of water ice according to current models of Phobos' interior.

Rivkin, A. S.↗

NAS Parallel Benchmarks

We describe a new problem size, called Class D, for the NAS Parallel Benchmarks (NPB), whose MPI source code implementation is being released as NPB 2.4. A brief rationale is given for how the new class is derived. We also describe the modifications made to the MPI (Message Passing Interface) implementation to allow the new class to be run on systems with 32-bit integers, and with moderate amounts of memory. Finally, we give the verification values for the new problem size.

VanderWijngaart, Rob↗

NASA's UAS [Unmanned Aircraft Systems] Related Activities

NASA continues to operate all sizes of UAS in all classes of airspace both domestically and internationally. Missions range from highly complex operations in coordination with piloted aircraft, ground, and space systems in support of science objectives to single aircraft operations in support of aeronautics research. One such example is a scaled commercial transport aircraft being used to study recovery techniques due to large upsets. NASA's efforts to support routine UAS operations continued on several fronts last year. At the national level in the United States (U.S.), NASA continued its support of the UAS Executive Committee (ExCom) comprised of the Federal Aviation Administration (FAA), Department of Defense (DoD), Department of Homeland Security (DHS), and NASA. The committee was formed in recognition of the need of UAS operated by these agencies to access to the National Airspace System (NAS) to support operational, training, development and research requirements. Recommendations were received on how to operate both manned and unmanned aircraft in class D airspace and plans are being developed to validate and implement those recommendations. In addition the UAS ExCom has begun developing recommendations for how to achieve routine operations in remote areas as well as for small UAS operations in class G airspace. As well as supporting the UAS ExCom, NASA is a participant in the recently formed Aviation Rule Making Committee for UAS. This committee, established by the FAA, is intended to propose regulatory guidance which would enable routine civil UAS operations. As that effort matures NASA stands ready to supply the necessary technical expertise to help that committee achieve its objectives. By supporting both the UAS ExCom and UAS ARC, NASA is positioned to provide its technical expertise across the full spectrum of UAS airspace access related topic areas. The UAS NAS Access Project got underway this past year under the leadership of NASA s Aeronautics Research Mission Directorate. This project is focused on advancing the state of the art and providing research and analysis results in the areas of Separation Assurance, Communications (non-governmental spectrum allocation for UAS), Certification, and Human System Integration (ground control station design/pilot interfaces). The project is working in close coordination with the FAA and industry standards organizations (e.g. RTCA SC 203). More details on this project are provided in a separate article in this year's yearbook

Bauer, Jeffrey↗