Testing of molded high temperature plastic actuator road seals for use in advanced aircraft hydraulic systems

Molded high temperature plastic first and second stage rod seal elements were evaluated in seal assemblies to determine performance characteristics. These characteristics were compared with the performance of machined seal elements. The 6.35 cm second stage Chevron seal assembly was tested using molded Chevrons fabricated from five molding materials. Impulse screening tests conducted over a range of 311 K to 478 K revealed thermal setting deficiencies in the aromatic polyimide molding materials. Seal elements fabricated from aromatic copolyester materials structurally failed during impulse cycle calibration. Endurance testing of 3.85 million cycles at 450 K using MIL-H-83283 fluid showed poorer seal performance with the unfilled aromatic polyimide material than had been attained with seals machined from Vespel SP-21 material. The 6.35 cm first stage step-cut compression loaded seal ring fabricated from copolyester injection molding material failed structurally during impulse cycle calibration. Molding of complex shape rod seals was shown to be a potentially controllable technique, but additional molding material property testing is recommended

Lipid-coated nanoscale coordination polymers for targeted cisplatin delivery

Nanoscale coordination polymers (NCPs) containing a Pt(IV) cisplatin prodrug, disuccinatocisplatin, were formed by a surfactant-templated synthesis and were shown to have a prodrug loading of 8.2 wt% and a diameter of ~133 nm by dynamic light scattering. These NCPs were stabilized by coating with a DOPC/cholesterol/DSPE-Peg2K lipid layer; a release profile in phosphate buffered saline showed an initial drug release of ~25% within the first hour and no more release observed up to 192 h. The NCP was rendered target-specific for sigma receptors by addition of an AA-DSPE-Peg2K conjugate (AA = anisamide) in the lipid formulation. The AA-containing NCP showed a statistically significant decrease in IC50 (inhibitory concentration, 50%) compared to the non-targeted NCP. Enhanced uptake of the AA-containing NCP was further supported by confocal microscopy and competitive binding assays

A Horizon Study for Cosmic Explorer: Science, Observatories, and Community

Gravitational-wave astronomy has revolutionized humanity's view of the universe. Investment in the field has rewarded the scientific community with the first direct detection of a binary black hole merger and the multimessenger observation of a neutron-star merger. Each of these was a watershed moment in astronomy, made possible because gravitational waves reveal the cosmos in a way that no other probe can. Since the first detection of gravitational waves in 2015, the National Science Foundation's LIGO and its partner observatory, the European Union's Virgo, have detected over fifty binary black hole mergers and a second neutron star merger -- a rate of discovery that has amazed even the most optimistic scientists.This Horizon Study describes a next-generation ground-based gravitational-wave observatory: Cosmic Explorer. With ten times the sensitivity of Advanced LIGO, Cosmic Explorer will push the gravitational-wave astronomy towards the edge of the observable universe ($z \sim 100$). This Horizon Study presents the science objective for Cosmic Explorer, and describes and evaluates its design concepts for. Cosmic Explorer will continue the United States' leadership in gravitational-wave astronomy in the international effort to build a "Third-Generation" (3G) observatory network that will make discoveries transformative across astronomy, physics, and cosmology

Structural basis of SETD6-mediated regulation of the NF-kB network via methyl-lysine signaling

SET domain containing 6 (SETD6) monomethylates the RelA subunit of nuclear factor kappa B (NF-κB). The ankyrin repeats of G9a-like protein (GLP) recognizes RelA monomethylated at Lys310. Adjacent to Lys310 is Ser311, a known phosphorylation site of RelA. Ser311 phosphorylation inhibits Lys310 methylation by SETD6 as well as binding of Lys310me1 by GLP. The structure of SETD6 in complex with RelA peptide containing the methylation site, in the presence of S-adenosyl-l-methionine, reveals a V-like protein structure and suggests a model for NF-κB binding to SETD6. In addition, structural modeling of the GLP ankyrin repeats bound to Lys310me1 peptide provides insight into the molecular basis for inhibition of Lys310me1 binding by Ser311 phosphorylation. Together, these findings provide a structural explanation for a key cellular signaling pathway centered on RelA Lys310 methylation, which is generated by SETD6 and recognized by GLP, and incorporate a methylation–phosphorylation switch of adjacent lysine and serine residues. Finally, SETD6 is structurally similar to the Rubisco large subunit methyltransferase. Given the restriction of Rubisco to plant species, this particular appearance of the protein lysine methyltransferase has been evolutionarily well conserved

A facility design for repackaging ORNL CH-TRU legacy waste in Building 3525

For the last 25 years, the Oak Ridge National Laboratory (ORNL) has conducted operations which have generated solid, contact-handled transuranic (CH-TRU) waste. At present the CH-TRU waste inventory at ORNL is about 3400 55-gal drums retrievably stored in RCRA-permitted, aboveground facilities. Of the 3400 drums, approximately 2600 drums will need to be repackaged. The current US Department of Energy (DOE) strategy for disposal of these drums is to transport them to the Waste Isolation Pilot Plant (WIPP) in New Mexico which only accepts TRU waste that meets a very specific set of criteria documented in the WIPP-WAC (waste acceptance criteria). This report describes activities that were performed from January 1994 to May 1995 associated with the design and preparation of an existing facility for repackaging and certifying some or all of the CH-TRU drums at ORNL to meet the WIPP-WAC. For this study, the Irradiated Fuel Examination Laboratory (IFEL) in Building 3525 was selected as the reference facility for modification. These design activities were terminated in May 1995 as more attractive options for CH-TRU waste repackaging were considered to be available. As a result, this document serves as a final report of those design activities

Metric Assisted Stochastic Sampling (MASS) search for gravitational waves from binary black hole mergers

We present a novel gravitational wave detection algorithm that conducts amatched filter search stochastically across the compact binary parameter spacerather than relying on a fixed bank of template waveforms. This technique iscompetitive with standard template-bank-driven pipelines in both computationalcost and sensitivity. However, the complexity of the analysis is simplerallowing for easy configuration and horizontal scaling across heterogeneousgrids of computers. To demonstrate the method we analyze approximately onemonth of public LIGO data from July 27 00:00 2017 UTC - Aug 25 22:00 2017 UTCand recover eight known confident gravitational wave candidates. We also injectsimulated binary black hole (BBH) signals to demonstrate the sensitivity.<br

Structure-Function Relationship of Cytoplasmic and Nuclear IκB Proteins: An In Silico Analysis

Cytoplasmic IκB proteins are primary regulators that interact with NF-κB subunits in the cytoplasm of unstimulated cells. Upon stimulation, these IκB proteins are rapidly degraded, thus allowing NF-κB to translocate into the nucleus and activate the transcription of genes encoding various immune mediators. Subsequent to translocation, nuclear IκB proteins play an important role in the regulation of NF-κB transcriptional activity by acting either as activators or inhibitors. To date, molecular basis for the binding of IκBα, IκBβ and IκBζ along with their partners is known; however, the activation and inhibition mechanism of the remaining IκB (IκBNS, IκBε and Bcl-3) proteins remains elusive. Moreover, even though IκB proteins are structurally similar, it is difficult to determine the exact specificities of IκB proteins towards their respective binding partners. The three-dimensional structures of IκBNS, IκBζ and IκBε were modeled. Subsequently, we used an explicit solvent method to perform detailed molecular dynamic simulations of these proteins along with their known crystal structures (IκBα, IκBβ and Bcl-3) in order to investigate the flexibility of the ankyrin repeat domains (ARDs). Furthermore, the refined models of IκBNS, IκBε and Bcl-3 were used for multiple protein-protein docking studies for the identification of IκBNS-p50/p50, IκBε-p50/p65 and Bcl-3-p50/p50 complexes in order to study the structural basis of their activation and inhibition. The docking experiments revealed that IκBε masked the nuclear localization signal (NLS) of the p50/p65 subunits, thereby preventing its translocation into the nucleus. For the Bcl-3- and IκBNS-p50/p50 complexes, the results show that Bcl-3 mediated transcription through its transactivation domain (TAD) while IκBNS inhibited transcription due to its lack of a TAD, which is consistent with biochemical studies. Additionally, the numbers of identified flexible residues were equal in number among all IκB proteins, although they were not conserved. This could be the primary reason for their binding partner specificities

Decontamination Strategy for Large Area and/or Equipment Contaminated with Chemical and Biological Agents using a High Energy Arc Lamp (HEAL)

A strategy for the decontamination of large areas and or equipment contaminated with Biological Warfare Agents (BWAs) and Chemical Warfare Agents (CWAs) was demonstrated using a High Energy Arc Lamp (HEAL) photolysis system. This strategy offers an alternative that is potentially quicker, less hazardous, generates far less waste, and is easier to deploy than those currently fielded by the Department of Defense (DoD). For example, for large frame aircraft the United States Air Force still relies on the combination of weathering (stand alone in environment), air washing (fly aircraft) and finally washing the aircraft with Hot Soapy Water (HSW) in an attempt to remove any remaining contamination. This method is laborious, time consuming (upwards of 12+ hours not including decontamination site preparation), and requires large amounts of water (e.g., 1,600+ gallons for a single large frame aircraft), and generates large amounts of hazardous waste requiring disposal. The efficacy of the HEAL system was demonstrated using diisopropyl methyl phosphonate (DIMP) a G series CWA simulant, and Bacillus globigii (BG) a simulant of Bacillus anthracis. Experiments were designed to simulate the energy flux of a field deployable lamp system that could stand-off 17 meters from a 12m2 target area and uniformly expose a surface at 1360 W/m2. The HEAL system in the absence of a catalyst reduced the amount of B. globigii by five orders of magnitude at a starting concentration of 1.63 x 107 spores. In the case of CWA simulants, the HEAL system in the presence of the catalyst TiO2 effectively degraded DIMP sprayed onto a 100mm diameter Petri dish in 5 minutes

An Early-warning System for Electromagnetic Follow-up of Gravitational-wave Events

Binary neutron stars (BNSs) will spend ≃10–15 minutes in the band of Advanced Laser Interferometer Gravitational-Wave Observatory (LIGO) and Virgo detectors at design sensitivity. Matched-filtering of gravitational-wave (GW) data could in principle accumulate enough signal-to-noise ratio (S/N) to identify a forthcoming event tens of seconds before the companions collide and merge. Here we report on the design and testing of an early-warning GW detection pipeline. Early-warning alerts can be produced for sources that are at low enough redshift so that a large enough S/N accumulates ~10–60 s before merger. We find that about 7% (49%) of the total detectable BNS mergers will be detected 60 s (10 s) before the merger. About 2% of the total detectable BNS mergers will be detected before merger and localized to within 100 deg² (90% credible interval). Coordinated observing by several wide-field telescopes could capture the event seconds before or after the merger. LIGO–Virgo detectors at design sensitivity could facilitate observing at least one event at the onset of merger