Simulation of Lunar Surface Communications Network Exploration Scenarios

Simulations and modeling of surface-based communications networks provides a rapid and cost effective means of requirement analysis, protocol assessments, and tradeoff studies. Robust testing in especially important for exploration systems, where the cost of deployment is high and systems cannot be easily replaced or repaired. However, simulation of the envisioned exploration networks cannot be achieved using commercial off the shelf network simulation software. Models for the nonstandard, non-COTS protocols used aboard space systems are not readily available. This paper will address the simulation of realistic scenarios representative of the activities which will take place on the surface of the Moon, including selection of candidate network architectures, and the development of an integrated simulation tool using OPNET modeler capable of faithfully modeling those communications scenarios in the variable delay, dynamic surface environments. Scenarios for exploration missions, OPNET development, limitations, and simulations results will be provided and discussed

Promiscuous Partitioning of a Covalent Intermediate Common in the Pentein Superfamily

SummaryMany enzymes in the pentein superfamily use a transient covalent intermediate in their catalytic mechanisms. Here we trap and determine the structure of a stable covalent adduct that mimics this intermediate using a mutant dimethylarginine dimethylaminohydrolase and an alternative substrate. The interactions observed between the enzyme and trapped adduct suggest an altered angle of attack between the nucleophiles of the first and second half-reactions of normal catalysis. The stable covalent adduct is also capable of further reaction. Addition of imidazole rescues the original hydrolytic activity. Notably, addition of other amines instead yields substituted arginine products, which arise from partitioning of the intermediate into the evolutionarily related amidinotransferase reaction pathway. The enzyme provides both selectivity and catalysis for the amidinotransferase reaction, underscoring commonalities among the reaction pathways in this mechanistically diverse enzyme superfamily. The promiscuous partitioning of this intermediate may also help to illuminate the evolutionary history of these enzymes

Surface Communications Network Architectures for Exploration Missions

contents include the following: 1. Requirements: Missions. Infrastructure. End-to-End. 2. Operational View: System View. Nodes. Interfaces. Links. Network Design. Technologies

First detection of ND in the solar-mass protostar IRAS16293-2422

In the past decade, much progress has been made in characterising the processes leading to the enhanced deuterium fractionation observed in the ISM and in particular in the cold, dense parts of star forming regions such as protostellar envelopes. Very high molecular D/H ratios have been found for saturated molecules and ions. However, little is known about the deuterium fractionation in radicals, even though simple radicals often represent an intermediate stage in the formation of more complex, saturated molecules. The imidogen radical NH is such an intermediate species for the ammonia synthesis in the gas phase. Herschel/HIFI represents a unique opportunity to study the deuteration and formation mechanisms of such species, which are not observable from the ground. We searched here for the deuterated radical ND in order to determine the deuterium fractionation of imidogen and constrain the deuteration mechanism of this species. We observed the solar-mass Class 0 protostar IRAS16293-2422 with the heterodyne instrument HIFI as part of the Herschel key programme CHESS (Chemical HErschel Surveys of Star forming regions). The deuterated form of the imidogen radical ND was detected and securely identified with 2 hyperfine component groups of its fundamental transition in absorption against the continuum background emitted from the nascent protostar. The 3 groups of hyperfine components of its hydrogenated counterpart NH were also detected in absorption. We derive a very high deuterium fractionation with an [ND]/[NH] ratio of between 30 and 100%. The deuterium fractionation of imidogen is of the same order of magnitude as that in other molecules, which suggests that an efficient deuterium fractionation mechanism is at play. We discuss two possible formation pathways for ND, by means of either the reaction of N+ with HD, or deuteron/proton exchange with NH.Comment: Accepted; To appear in A&A Herschel/HIFI Special Issu

De novo design of potent and resilient hACE2 decoys to neutralize SARS-CoV-2

We developed a de novo protein design strategy to swiftly engineer decoys for neutralizing pathogens that exploit extracellular host proteins to infect the cell. Our pipeline allowed the design, validation, and optimization of de novo hACE2 decoys to neutralize SARS-CoV-2. The best decoy, CTC-445.2, binds with low nanomolar affinity and high specificity to the RBD of the spike protein. Cryo-EM shows that the design is accurate and can simultaneously bind to all three RBDs of a single spike protein. Because the decoy replicates the spike protein target interface in hACE2, it is intrinsically resilient to viral mutational escape. A bivalent decoy, CTC-445.2d, shows ~10-fold improvement in binding. CTC-445.2d potently neutralizes SARS-CoV-2 infection of cells in vitro and a single intranasal prophylactic dose of decoy protected Syrian hamsters from a subsequent lethal SARS-CoV-2 challenge

Big-bang Nucleosynthesis Enters the Precision Era

The last parameter of big-bang nucleosynthesis, the baryon density, is being pinned down by measurements of the deuterium abundance in high-redshift hydrogen clouds. When it is determined, it will fix the primeval light-element abundances. D, ^3He and ^7Li will become ``tracers'' for the study of Galactic and stellar chemical evolution, and big-bang nucleosynthesis will become an even sharper probe of particle physics, e.g., the bound to the number of light neutrino species will be tightened significantly. Two key tests of the consistency of the standard theory are on the horizon: an independent, high-precision determination of the baryon density from anisotropy of the cosmic background radiation and a precision determination of the primeval $^4$He abundance.Comment: 19 pages Latex; 8 eps figures; submitted to Rev Mod Phys (Colloquia

De novo design of potent and resilient hACE2 decoys to neutralize SARS-CoV-2

We developed a de novo protein design strategy to swiftly engineer decoys for neutralizing pathogens that exploit extracellular host proteins to infect the cell. Our pipeline allowed the design, validation, and optimization of de novo hACE2 decoys to neutralize SARS-CoV-2. The best decoy, CTC-445.2, binds with low nanomolar affinity and high specificity to the RBD of the spike protein. Cryo-EM shows that the design is accurate and can simultaneously bind to all three RBDs of a single spike protein. Because the decoy replicates the spike protein target interface in hACE2, it is intrinsically resilient to viral mutational escape. A bivalent decoy, CTC-445.2d, shows ~10-fold improvement in binding. CTC-445.2d potently neutralizes SARS-CoV-2 infection of cells in vitro and a single intranasal prophylactic dose of decoy protected Syrian hamsters from a subsequent lethal SARS-CoV-2 challenge

Studies on the mechanism and inhibition of enzymes in the pentein superfamily

textDimethylarginine dimethylaminohydrolase (DDAH) indirectly regulates nitric oxide production by hydrolyzing methylated arginines, which are endogenous nitric oxide synthase inhibitors. This enzyme is a member of the mechanistically diverse pentein superfamily, which contains hydrolase, dihydrolase, and amidinotransferase enzymes. These enzymes are proposed to use the same first catalytic step, followed by partitioning into their respective activities. Here, variants of DDAH that can catalyze the dihydrolase and amidinotransfer reactions are presented, as well as a variant of succinylarginine dihydrolase which catalyzes a single hydrolysis reaction. The results experimentally demonstrate that the proposed common catalytic intermediate can be used for several different reactions. The results suggest that enzymes in the pentein superfamily may have evolved divergently from a catalytically promiscuous ancestor. The control DDAH asserts over nitric oxide production makes it an attractive drug target for disease states marked by pathological overproduction of nitric oxide. Only a limited number of inhibitors different from substrate are reported, due in part to lack of robust assays for high-throughput screening of compound libraries. Therefore, high-throughput assays were developed, optimized, and validated to screen for inhibitors of Pseudomonas aeruginosa DDAH and human DDAH-1. These assays were used to screen three commercial libraries totaling 6,466 compounds. One drug in phase III clinical trials, ebselen, was identified and characterized as a bioavailable, rapid covalent inactivator of DDAH both in vitro and in cultured cells. Four "fragment-sized" inhibitors were also identified and characterized in the screening, including 4-halopyridines and benzimidazole-like compounds. The 4-halopyridines, not previously known to modify proteins, act as quiescent affinity labels to selectively inactivate DDAH, and the benzimidazole-like compounds are competitive, rapidly reversible inhibitors of DDAH. These diverse molecules serve as starting points for the development of molecular probes and therapeutic drugs to reduce pathological overproduction of nitric oxide.Biochemistr