SEARCH · Engineering Papers
Results for “DISCOVERIES”
Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.
Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.
Discovery of a chemical probe for PRDM9
PRDM9 is a PR domain containing protein which trimethylates histone 3 on lysine 4 and 36. Its normal expression is restricted to germ cells and attenuation of its activity results in altered meiotic gene transcription, impairment of double-stranded breaks and pairing between homologous chromosomes. There is growing evidence for a role of aberrant expression of PRDM9 in oncogenesis and genome instability. Here we report the discovery of MRK-740, a potent (IC 50 : 80 ± 16 nM), selective and cell-active PRDM9 inhibitor (Chemical Probe). MRK-740 binds in the substrate-binding pocket, with unusually extensive interactions with the cofactor S-adenosylmethionine (SAM), conferring SAM-dependent substrate-competitive inhibition. In cells, MRK-740 specifically and directly inhibits H3K4 methylation at endogenous PRDM9 target loci, whereas the closely related inactive control compound, MRK-740-NC, does not. The discovery of MRK-740 as a chemical probe for the PRDM subfamily of methyltransferases highlights the potential for exploiting SAM in targeting SAM-dependent methyltransferases.
Discovery and biological characterization of potent myeloid cell leukemia-1 inhibitors
Abstract not provided
Accelerating Discovery of Solid‐State Thin‐Film Metal Dealloying for 3D Nanoarchitecture Materials Design through Laser Thermal Gradient Treatment
Thin‐film solid‐state metal dealloying (thin‐film SSMD) is a promising method for fabricating nanostructures with controlled morphology and efficiency, offering advantages over conventional bulk materials processing methods for integration into practical applications. Although machine learning (ML) has facilitated the design of dealloying systems, the selection of key thermal treatment parameters for nanostructure formation remains largely unknown and dependent on experimental trial and error. To overcome this challenge, a workflow enabling high‐throughput characterization of thermal treatment parameters is demonstrated using a laser‐based thermal treatment to create temperature gradients on single thin‐film samples of Nb‐Al/Sc and Nb‐Al/Cu. This continuous thermal space enables observation of dealloying transitions and the resulting nanostructures of interest. Through synchrotron X‐ray multimodal and high‐throughput characterization, critical transitions and nanostructures can be rapidly captured and subsequently verified using electron microscopy. The key temperatures driving chemical reactions and morphological evolutions are clearly identified. While the oxidation may influence nanostructure formation during thin‐film treatment, the dealloying process at the dealloying front involves interactions solely between the dealloying elements, highlighting the availability and viability of the selected systems. Further, this approach enables efficient exploration of the dealloying process and validation of ML predictions, thereby accelerating the discovery of thin‐film SSMD systems with targeted nanostructures.
Supercomputer-Based Ensemble Docking Drug Discovery Pipeline with Application to Covid-19
In this work, we present a supercomputer-driven pipeline for in silico drug discovery using enhanced sampling molecular dynamics (MD) and ensemble docking. Ensemble docking makes use of MD results by docking compound databases into representative protein binding-site conformations, thus taking into account the dynamic properties of the binding sites. We also describe preliminary results obtained for 24 systems involving eight proteins of the proteome of SARS-CoV-2. The MD involves temperature replica exchange enhanced sampling, making use of massively parallel supercomputing to quickly sample the configurational space of protein drug targets. Using the Summit supercomputer at the Oak Ridge National Laboratory, more than 1 ms of enhanced sampling MD can be generated per day. We have ensemble docked repurposing databases to 10 configurations of each of the 24 SARS-CoV-2 systems using AutoDock Vina. Comparison to experiment demonstrates remarkably high hit rates for the top scoring tranches of compounds identified by our ensemble approach. We also demonstrate that, using Autodock-GPU on Summit, it is possible to perform exhaustive docking of one billion compounds in under 24 h. Finally, we discuss preliminary results and planned improvements to the pipeline, including the use of quantum mechanical (QM), machine learning, and artificial intelligence (AI) methods to cluster MD trajectories and rescore docking poses.
Electron Density Guided Fragment-Based Lead Discovery of Ketohexokinase Inhibitors
Abstract not provided
Carrier density control in Cu 2 HgGeTe 4 and discovery of Hg 2 GeTe 4 via phase boundary mapping
Phase boundary mapping in Cu 2 HgGeTe 4 allows discovery of Hg 2 GeTe 4 and further enables carrier density control over 4 orders of magnitude.
Accelerated discovery and mechanical property characterization of bioresorbable amorphous alloys in the Mg–Zn–Ca and the Fe–Mg–Zn systems using high-throughput methods
High throughput discovery of amorphous bioresorbable alloys. Top: combinatorial sputtering setup. Bottom: composition of libraries deposited on silicon (Si) wafers for (a) magnesium (Mg)–zinc (Zn)–calcium (Ca) and the (b) iron (Fe)–Mg–Zn systems.
THE DISCOVERY AND NATURE OF THE OPTICAL TRANSIENT CSS100217:102913+404220
We report on the discovery and observations of the extremely luminous optical transient CSS100217:102913+404220 (CSS100217 hereafter). Spectroscopic observations showed that this transient was coincident with a galaxy at redshift z = 0.147 and reached an apparent magnitude of V {approx} 16.3. After correcting for foreground Galactic extinction we determine the absolute magnitude to be M{sub V} = -22.7 approximately 45 days after maximum light. Over a period of 287 rest-frame days, this event had an integrated bolometric luminosity of 1.3 x 10{sup 52} erg based on time-averaged bolometric corrections of {approx}15 from V- and R-band observations. Analysis of the pre-outburst Sloan Digital Sky Survey (SDSS) spectrum of the source shows features consistent with a narrow-line Seyfert 1 galaxy. High-resolution Hubble Space Telescope and Keck follow-up observations show that the event occurred within 150 pc of the nucleus of the galaxy, suggesting a possible link to the active nuclear region. However, the rapid outburst along with photometric and spectroscopic evolution are much more consistent with a luminous supernova. Line diagnostics suggest that the host galaxy is undergoing significant star formation. We use extensive follow-up of the event along with archival Catalina Sky Survey NEO search and SDSS data to investigate the three most likely sources of such an event: (1) an extremely luminous supernova, (2) the tidal disruption of a star by the massive nuclear black hole, and (3) variability of the central active galactic nucleus (AGN). We find that CSS100217 was likely an extremely luminous Type IIn supernova and occurred within the range of the narrow-line region of an AGN. We discuss how similar events may have been missed in past supernova surveys because of confusion with AGN activity.
DISCOVERY OF NINE GAMMA-RAY PULSARS IN FERMI LARGE AREA TELESCOPE DATA USING A NEW BLIND SEARCH METHOD
We report the discovery of nine previously unknown gamma-ray pulsars in a blind search of data from the Fermi Large Area Telescope (LAT). The pulsars were found with a novel hierarchical search method originally developed for detecting continuous gravitational waves from rapidly rotating neutron stars. Designed to find isolated pulsars spinning at up to kHz frequencies, the new method is computationally efficient and incorporates several advances, including a metric-based gridding of the search parameter space (frequency, frequency derivative, and sky location) and the use of photon probability weights. The nine pulsars have spin frequencies between 3 and 12 Hz, and characteristic ages ranging from 17 kyr to 3 Myr. Two of them, PSRs J1803-2149 and J2111+ 4606, are young and energetic Galactic-plane pulsars (spin-down power above 6 Multiplication-Sign 10{sup 35} erg s{sup -1} and ages below 100 kyr). The seven remaining pulsars, PSRs J0106+4855, J0622+3749, J1620-4927, J1746-3239, J2028+3332, J2030+4415, and J2139+4716, are older and less energetic; two of them are located at higher Galactic latitudes (|b| > 10 Degree-Sign ). PSR J0106+4855 has the largest characteristic age (3 Myr) and the smallest surface magnetic field (2 Multiplication-Sign 10{sup 11} G) of all LAT blind-search pulsars. PSR J2139+4716 has the lowest spin-down power (3 Multiplication-Sign 10{sup 33} erg s{sup -1}) among all non-recycled gamma-ray pulsars ever found. Despite extensive multi-frequency observations, only PSR J0106+4855 has detectable pulsations in the radio band. The other eight pulsars belong to the increasing population of radio-quiet gamma-ray pulsars.
DISCOVERY OF HIGH-ENERGY AND VERY HIGH ENERGY {gamma}-RAY EMISSION FROM THE BLAZAR RBS 0413
We report on the discovery of high-energy (HE; E > 0.1 GeV) and very high energy (VHE; E > 100 GeV) {gamma}-ray emission from the high-frequency-peaked BL Lac object RBS 0413. VERITAS, a ground-based {gamma}-ray observatory, detected VHE {gamma} rays from RBS 0413 with a statistical significance of 5.5 standard deviations ({sigma}) and a {gamma}-ray flux of (1.5 {+-} 0.6{sub stat} {+-} 0.7{sub syst}) Multiplication-Sign 10{sup -8} photons m{sup -2} s{sup -1} ({approx}1% of the Crab Nebula flux) above 250 GeV. The observed spectrum can be described by a power law with a photon index of 3.18 {+-} 0.68{sub stat} {+-} 0.30{sub syst}. Contemporaneous observations with the Large Area Telescope (LAT) on the Fermi Gamma-ray Space Telescope detected HE {gamma} rays from RBS 0413 with a statistical significance of more than 9{sigma}, a power-law photon index of 1.57 {+-} 0.12{sub stat}+{sup 0.11}{sub -0.12sys}, and a {gamma}-ray flux between 300 MeV and 300 GeV of (1.64 {+-} 0.43{sub stat}{sup +0.31}{sub -0.22sys}) Multiplication-Sign 10{sup -5} photons m{sup -2} s{sup -1}. We present the results from Fermi-LAT and VERITAS, including a spectral energy distribution modeling of the {gamma}-ray, quasi-simultaneous X-ray (Swift-XRT), ultraviolet (Swift-UVOT), and R-band optical (MDM) data. We find that, if conditions close to equipartition are required, both the combined synchrotron self-Compton/external-Compton and the lepto-hadronic models are preferred over a pure synchrotron self-Compton model.
DISCOVERY OF A NEW TeV GAMMA-RAY SOURCE: VER J0521+211
We report the detection of a new TeV gamma-ray source, VER J0521+211, based on observations made with the VERITAS imaging atmospheric Cherenkov Telescope Array. These observations were motivated by the discovery of a cluster of >30 GeV photons in the first year of Fermi Large Area Telescope observations. VER J0521+211 is relatively bright at TeV energies, with a mean photon flux of (1.93 ± 0.13{sub stat} ± 0.78{sub sys}) × 10{sup –11} cm{sup –2} s{sup –1} above 0.2 TeV during the period of the VERITAS observations. The source is strongly variable on a daily timescale across all wavebands, from optical to TeV, with a peak flux corresponding to ∼0.3 times the steady Crab Nebula flux at TeV energies. Follow-up observations in the optical and X-ray bands classify the newly discovered TeV source as a BL Lac-type blazar with uncertain redshift, although recent measurements suggest z = 0.108. VER J0521+211 exhibits all the defining properties of blazars in radio, optical, X-ray, and gamma-ray wavelengths.
Parkes radio searches of Fermi gamma-ray sources and millisecond pulsar discoveries
In a search with the Parkes radio telescope of 56 unidentified Fermi-Large Area Telescope (LAT) gamma-ray sources, we have detected 11 millisecond pulsars (MSPs), 10 of them discoveries, of which five were reported by Kerr et al. We did not detect radio pulsations from six other pulsars now known in these sources. We describe the completed survey, which included multiple observations of many targets conducted to minimize the impact of interstellar scintillation, acceleration effects in binary systems, and eclipses. We consider that 23 of the 39 remaining sources may still be viable pulsar candidates. We present timing solutions and polarimetry for five of the MSPs and gamma-ray pulsations for PSR J1903–7051 (pulsations for five others were reported in the second Fermi-LAT catalog of gamma-ray pulsars). Two of the new MSPs are isolated and five are in >1 day circular orbits with 0.2–0.3 M{sub ⊙} presumed white dwarf companions. PSR J0955–6150, in a 24 day orbit with a ≈0.25 M{sub ⊙} companion but eccentricity of 0.11, belongs to a recently identified class of eccentric MSPs. PSR J1036–8317 is in an 8 hr binary with a >0.14 M{sub ⊙} companion that is probably a white dwarf. PSR J1946–5403 is in a 3 hr orbit with a >0.02 M{sub ⊙} companion with no evidence of radio eclipses.
THE SLOAN BRIGHT ARCS SURVEY: DISCOVERY OF SEVEN NEW STRONGLY LENSED GALAXIES FROM z = 0.66-2.94
We report the discovery of seven new, very bright gravitational lens systems from our ongoing gravitational lens search, the Sloan Bright Arcs Survey (SBAS). Two of the systems are confirmed to have high source redshifts z = 2.19 and z = 2.94. Three other systems lie at intermediate redshift with z = 1.33, 1.82, 1.93 and two systems are at low redshift z = 0.66, 0.86. The lensed source galaxies in all of these systems are bright, with i-band magnitudes ranging from 19.73 to 22.06. We present the spectrum of each of the source galaxies in these systems along with estimates of the Einstein radius for each system. The foreground lens in most systems is identified by a red sequence based cluster finder as a galaxy group; one system is identified as a moderately rich cluster. In total, SBAS has now discovered 19 strong lens systems in the SDSS imaging data, 8 of which are among the highest surface brightness z {approx_equal} 2-3 galaxies known.
DISCOVERY OF HIGH-ENERGY GAMMA-RAY EMISSION FROM THE BINARY SYSTEM PSR B1259-63/LS 2883 AROUND PERIASTRON WITH FERMI
We report on the discovery of {>=}100 MeV {gamma}-rays from the binary system PSR B1259-63/LS 2883 using the Large Area Telescope (LAT) on board Fermi. The system comprises a radio pulsar in orbit around a Be star. We report on LAT observations from near apastron to {approx}128 days after the time of periastron, t{sub p} , on 2010 December 15. No {gamma}-ray emission was detected from this source when it was far from periastron. Faint {gamma}-ray emission appeared as the pulsar approached periastron. At {approx}t{sub p} + 30 days, the {>=}100 MeV {gamma}-ray flux increased over a period of a few days to a peak flux 20-30 times that seen during the pre-periastron period, but with a softer spectrum. For the following month, it was seen to be variable on daily timescales, but remained at {approx}(1-4) x 10{sup -6} cm{sup -2} s{sup -1} before starting to fade at {approx}t{sub p} + 57 days. The total {gamma}-ray luminosity observed during this period is comparable to the spin-down power of the pulsar. Simultaneous radio and X-ray observations of the source showed no corresponding dramatic changes in radio and X-ray flux between the pre-periastron and post-periastron flares. We discuss possible explanations for the observed {gamma}-ray-only flaring of the source.
PSR J1838-0537: DISCOVERY OF A YOUNG, ENERGETIC GAMMA-RAY PULSAR
We report the discovery of PSR J1838-0537, a gamma-ray pulsar found through a blind search of data from the Fermi Large Area Telescope (LAT). The pulsar has a spin frequency of 6.9 Hz and a frequency derivative of -2.2 Multiplication-Sign 10{sup -11} Hz s{sup -1}, implying a young characteristic age of 4970 yr and a large spin-down power of 5.9 Multiplication-Sign 10{sup 36} erg s{sup -1}. Follow-up observations with radio telescopes detected no pulsations; thus PSR J1838-0537 appears radio-quiet as viewed from Earth. In 2009 September the pulsar suffered the largest glitch so far seen in any gamma-ray-only pulsar, causing a relative increase in spin frequency of about 5.5 Multiplication-Sign 10{sup -6}. After the glitch, during a putative recovery period, the timing analysis is complicated by the sparsity of the LAT photon data, the weakness of the pulsations, and the reduction in average exposure from a coincidental, contemporaneous change in LAT's sky-survey observing pattern. The pulsar's sky position is coincident with the spatially extended TeV source HESS J1841-055 detected by the High Energy Stereoscopic System (H.E.S.S.). The inferred energetics suggest that HESS J1841-055 contains a pulsar wind nebula powered by the pulsar.
GMRT DISCOVERY OF PSR J1544+4937: AN ECLIPSING BLACK-WIDOW PULSAR IDENTIFIED WITH A FERMI-LAT SOURCE
Using the Giant Metrewave Radio Telescope, we performed deep observations to search for radio pulsations in the directions of unidentified Fermi-Large Area Telescope {gamma}-ray sources. We report the discovery of an eclipsing black-widow millisecond pulsar, PSR J1544+4937, identified with the uncataloged {gamma}-ray source FERMI J1544.2+4941. This 2.16 ms pulsar is in a 2.9 hr compact circular orbit with a very low mass companion (M{sub c} > 0.017M{sub Sun }). At 322 MHz this pulsar is found to be eclipsing for 13% of its orbit, whereas at 607 MHz the pulsar is detected throughout the low-frequency eclipse phase. Variations in the eclipse ingress phase are observed, indicating a clumpy and variable eclipsing medium. Moreover, additional short-duration absorption events are observed around the eclipse boundaries. Using the radio timing ephemeris we were able to detect {gamma}-ray pulsations from this pulsar, confirming it as the source powering the {gamma}-ray emission.
B ′ s with direct decays: Tevatron and LHC discovery prospects in the b b ¯ + E̸ T channel
Not Available