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At least 595 records · Page 33

DMTN-165: A Hybrid Notification and Alert Retrieval Service

We consider the implications of providing a subset of alert packet contents in the alert stream, with the full alert packets available for rate-limited retrieval using an identifier included in the "lightweight" alert. This hybrid approach would enable much wider dissemination of the complete lightweight alert stream, potentially to thousands more users than is possible in the current baseline. In turn this "alerts on your laptop" access would allow users to conduct more sophisticated filtering and analysis than the current Alert Filtering Service, increasing the overall scientific returns of the alert stream. Community brokers would still be able to retrieve all of the contents of the full alert stream within the 60 second latency window and would gain greater control over their ingestion of the bulk alert data. Technically, this hybrid system may represent a modest increase in complexity over the current baseline but is likely to be more operationally robust.

79 ASTRONOMY AND ASTROPHYSICS↗

Gating interactions steer loop conformational changes in the active site of the L1 metallo-β-lactamase

β-Lactam antibiotics are the most important and widely used antibacterial agents across the world. However, the widespread dissemination of β-lactamases among pathogenic bacteria limits the efficacy of β-lactam antibiotics. This has created a major public health crisis. The use of β-lactamase inhibitors has proven useful in restoring the activity of β-lactam antibiotics, yet, effective clinically approved inhibitors against class B metallo-β-lactamases are not available. L1, a class B3 enzyme expressed by Stenotrophomonas maltophilia , is a significant contributor to the β-lactam resistance displayed by this opportunistic pathogen. Structurally, L1 is a tetramer with two elongated loops, α3-β7 and β12-α5, present around the active site of each monomer. Residues in these two loops influence substrate/inhibitor binding. To study how the conformational changes of the elongated loops affect the active site in each monomer, enhanced sampling molecular dynamics simulations were performed, Markov State Models were built, and convolutional variational autoencoder-based deep learning was applied. The key identified residues (D150a, H151, P225, Y227, and R236) were mutated and the activity of the generated L1 variants was evaluated in cell-based experiments. The results demonstrate that there are extremely significant gating interactions between α3-β7 and β12-α5 loops. Taken together, the gating interactions with the conformational changes of the key residues play an important role in the structural remodeling of the active site. These observations offer insights into the potential for novel drug development exploiting these gating interactions.

59 BASIC BIOLOGICAL SCIENCES↗

VirION2: a short- and long-read sequencing and informatics workflow to study the genomic diversity of viruses in nature

Microbes play fundamental roles in shaping natural ecosystem properties and functions, but do so under constraints imposed by their viral predators. However, studying viruses in nature can be challenging due to low biomass and the lack of universal gene markers. Though metagenomic short-read sequencing has greatly improved our virus ecology toolkit—and revealed many critical ecosystem roles for viruses—microdiverse populations and fine-scale genomic traits are missed. Some of these microdiverse populations are abundant and the missed regions may be of interest for identifying selection pressures that underpin evolutionary constraints associated with hosts and environments. Though long-read sequencing promises complete virus genomes on single reads, it currently suffers from high DNA requirements and sequencing errors that limit accurate gene prediction. Here we introduce VirION2, an integrated short- and long-read metagenomic wet-lab and informatics pipeline that updates our previous method (VirION) to further enhance the utility of long-read viral metagenomics. Using a viral mock community, we first optimized laboratory protocols (polymerase choice, DNA shearing size, PCR cycling) to enable 76% longer reads (now median length of 6,965 bp) from 100-fold less input DNA (now 1 nanogram). Using a virome from a natural seawater sample, we compared viromes generated with VirION2 against other library preparation options (unamplified, original VirION, and short-read), and optimized downstream informatics for improved long-read error correction and assembly. VirION2 assemblies combined with short-read based data (‘enhanced’ viromes), provided significant improvements over VirION libraries in the recovery of longer and more complete viral genomes, and our optimized error-correction strategy using long- and short-read data achieved 99.97% accuracy. In the seawater virome, VirION2 assemblies captured 5,161 viral populations (including all of the virus populations observed in the other assemblies), 30% of which were uniquely assembled through inclusion of long-reads, and 22% of the top 10% most abundant virus populations derived from assembly of long-reads. Viral populations unique to VirION2 assemblies had significantly higher microdiversity means, which may explain why short-read virome approaches failed to capture them. These findings suggest the VirION2 sample prep and workflow can help researchers better investigate the virosphere, even from challenging low-biomass samples. Our new protocols are available to the research community on protocols.io as a ‘living document’ to facilitate dissemination of updates to keep pace with the rapid evolution of long-read sequencing technology.

Long-reads↗

Collected Papers on Instability of Shell Structures - 1962

Shell structures are important components of airplanes, missiles, and space vehicles, but present capabilities for predicting the local and general instability of many such structures are inadequate. A large effort continues to be devoted to the stability analysis of shell structures, and considerable progress has been made. Results are slowly disseminated, however, and many engaged in research are not fully cognizant of the problems and practices of the vehicle designers who utilize research results. Therefore, an NASA SYMPOSIUM ON INSTABILITY OF SKELL STRUCTURES was organized by the Langley Research Center with sessions held there on October 24 and 25, 1962. Participants were limited to persons contributing papers and to certain officials of the U.S. Government. This symposium was planned to provide those persons concerned with shell instability at research laboratories, at educational institutions, and in the aerospace industry with a comprehensive view of the present state of the art, including the voids in present knowledge, important current problems, and the most fruitful directions for future theoretical and experimental research on the instability of all types of shell structures. Individuals actively engaged in research on shell stability or design were invited to contribute written papers for inclusion in a compilation to be distributed to the participants prior to the symposium. A few papers were selected by a steering committee for oral presentation at the symposium. Provision was made, also, for a discussion of all papers.

MISSILE↗

Technology utilization

Technical and scientific information acquistion, processing, retrieval, and dissemination

INFORMATION RETRIEVAL↗

The Post Office communication system ground station at Goonhilly, Cornwall

The initial purpose of the Post Office satellite system earth station at Goonhilly Downs, Cornwall, is to obtain information on the performance of experimental communication satellite systems; such information will be of great importance to the designers of systems for commercial operation. To facilitate this dissemination the UK and USA Governments prepared and signed, in February 1961, a Memorandum of Understanding regarding collaboration between the British Post Office and the United States National Aeronautics and Space Administration (NASA) on the testing of experimental communication satellites to be launched by NASA. The first phase of the tests covered Projects Telstar and Relay, both active satellites.

COMMUNICATIONS SATELLITE↗

Astronautics and Aeronautics, 1966

At the opening of the tenth year in the era of man’s mobility in outer space, we can look back on 1966 as offering convincing evidence that the United States had gained great competence. This evidence included: five orbital space flights by ten Gemini astronauts; four lunar missions undertaking the orbiting of and soft landing on the moon; numerous contributions to scientific knowledge by unmanned spacecraft and sounding rockets; and further demonstrations of the practical utility of operational space systems, including weather and communications satellites. During 1966, a record 100 American spacecraft were placed into earth orbit or on escape trajectories. Thousands of revealing and useful pictures of the earth were taken from space and of the moon from lunar orbit and on its surface. The Gemini program ended with rendezvous and docking experiments and extravehicular activity by the Gemini test pilots as the Apollo R&D test flights leading to the manned lunar mission came into the schedule. Thirty-five major scientific, technological, and operational milestones were cited for 1966 by the President in his Report to the Congress on aeronautical and space activities of the United States. This was one measure of the American commitment to share in the peaceful exploration of space for all mankind. Another was our support of the final steps toward a United Nations space treaty, undertaken to ensure that the peaceful exploitation of space had juridical basis in international law. Spectacular as some events in the space venture were in 1966, they nonetheless came to have diminished novelty in the eyes of many laymen. The multitude of both important and unspectacular space activities attained almost an accepted and routine place. This volume, as well as its predecessor chronicles, offers a ready reference on the major as well as the less-well known events. Beyond the welter of documented details on the complex nature of aeronautical and space related events and their impact, this volume helps to provide a better perspective upon today as we contemplate tomorrow. Such intent also serves future historians and analysts who cannot be unmindful of what is herein presented. When the Congress created the National Aeronautics and Space Administration in 1958, it charged NASA with the responsibility to “contribute materially to . . . the expansion of human knowledge of phenomena in the atmosphere and space’’ and to “provide for the widest practical and appropriate dissemination of information concerning its activities and results thereof.” NASA has attempted to do this and to include documentation for the historical record. The relating of NASA history begins with this day-by day chronicle and leads to more specialized studies and histories of the unprecedented task of extending man’s mobility and understanding beyond his planet. While a chronology cannot in itself serve as a full-fledged history, the size of this annual volume alone is illustrative of the scope and complexity of the historical task yet to be completed as memories fade and the records disappear.

SPACE PROBE↗