402 research outputs found
Sequence selective binding of ditrisarubicin B to DNA: comparison with daunomycin
AbstractDNase I footprinting has been used to examine the sequence selective binding of ditrisarubicin B, novel anthracycline antibiotic, to DNA. At 37°C no footprinting pattern is observed, the drug protects all sites from enzymic cleavage with equal efficiency. At 4°C a footprinting pattern is induced with low drug concentrations which is different from that produced by daunomycin. The best binding sites contain the dinucleotide step GpT (ApC) and are located in regions of alternating purines and pyrimidines
Identifying Exoplanets with Deep Learning. V. Improved Light Curve Classification for TESS Full Frame Image Observations
The TESS mission produces a large amount of time series data, only a small
fraction of which contain detectable exoplanetary transit signals. Deep
learning techniques such as neural networks have proved effective at
differentiating promising astrophysical eclipsing candidates from other
phenomena such as stellar variability and systematic instrumental effects in an
efficient, unbiased and sustainable manner. This paper presents a high quality
dataset containing light curves from the Primary Mission and 1st Extended
Mission full frame images and periodic signals detected via Box Least Squares
(Kov\'acs et al. 2002; Hartman 2012). The dataset was curated using a thorough
manual review process then used to train a neural network called
Astronet-Triage-v2. On our test set, for transiting/eclipsing events we achieve
a 99.6% recall (true positives over all data with positive labels) at a
precision of 75.7% (true positives over all predicted positives). Since 90% of
our training data is from the Primary Mission, we also test our ability to
generalize on held-out 1st Extended Mission data. Here, we find an area under
the precision-recall curve of 0.965, a 4% improvement over Astronet-Triage (Yu
et al. 2019). On the TESS Object of Interest (TOI) Catalog through April 2022,
a shortlist of planets and planet candidates, Astronet-Triage-v2 is able to
recover 3577 out of 4140 TOIs, while Astronet-Triage only recovers 3349 targets
at an equal level of precision. In other words, upgrading to Astronet-Triage-v2
helps save at least 200 planet candidates from being lost. The new model is
currently used for planet candidate triage in the Quick-Look Pipeline (Huang et
al. 2020a,b; Kunimoto et al. 2021).Comment: accepted for publication in AJ. code can be found at:
https://github.com/mdanatg/Astronet-Triage and data can be found at:
https://zenodo.org/record/741157
Phonons in random alloys: the itinerant coherent-potential approximation
We present the itinerant coherent-potential approximation(ICPA), an analytic,
translationally invariant and tractable form of augmented-space-based,
multiple-scattering theory in a single-site approximation for harmonic phonons
in realistic random binary alloys with mass and force-constant disorder.
We provide expressions for quantities needed for comparison with experimental
structure factors such as partial and average spectral functions and derive the
sum rules associated with them. Numerical results are presented for Ni_{55}
Pd_{45} and Ni_{50} Pt_{50} alloys which serve as test cases, the former for
weak force-constant disorder and the latter for strong. We present results on
dispersion curves and disorder-induced widths. Direct comparisons with the
single-site coherent potential approximation(CPA) and experiment are made which
provide insight into the physics of force-constant changes in random alloys.
The CPA accounts well for the weak force-constant disorder case but fails for
strong force-constant disorder where the ICPA succeeds.Comment: 19 pages, 12 eps figures, uses RevTex
GLIDA: GPCR—ligand database for chemical genomics drug discovery—database and tools update
G-protein coupled receptors (GPCRs) represent one of the most important families of drug targets in pharmaceutical development. GLIDA is a public GPCR-related Chemical Genomics database that is primarily focused on the integration of information between GPCRs and their ligands. It provides interaction data between GPCRs and their ligands, along with chemical information on the ligands, as well as biological information regarding GPCRs. These data are connected with each other in a relational database, allowing users in the field of Chemical Genomics research to easily retrieve such information from either biological or chemical starting points. GLIDA includes a variety of similarity search functions for the GPCRs and for their ligands. Thus, GLIDA can provide correlation maps linking the searched homologous GPCRs (or ligands) with their ligands (or GPCRs). By analyzing the correlation patterns between GPCRs and ligands, we can gain more detailed knowledge about their conserved molecular recognition patterns and improve drug design efforts by focusing on inferred candidates for GPCR-specific drugs. This article provides a summary of the GLIDA database and user facilities, and describes recent improvements to database design, data contents, ligand classification programs, similarity search options and graphical interfaces. GLIDA is publicly available at http://pharminfo.pharm.kyoto-u.ac.jp/services/glida/. We hope that it will prove very useful for Chemical Genomics research and GPCR-related drug discovery
Unstable chromosome rearrangements in Staphylococcus aureus cause phenotype switching associated with persistent infections
Staphylococcus aureus small-colony variants (SCVs) are associated with unusually chronic and persistent infections despite active antibiotic treatment. The molecular basis for this clinically important phenomenon is poorly understood, hampered by the instability of the SCV phenotype. Here we investigated the genetic basis for an unstable S. aureus SCV that arose spontaneously while studying rifampicin resistance. This SCV showed no nucleotide differences across its genome compared with a normal-colony variant (NCV) revertant, yet the SCV presented the hallmarks of S. aureus linked to persistent infection: down-regulation of virulence genes and reduced hemolysis and neutrophil chemotaxis, while exhibiting increased survival in blood and ability to invade host cells. Further genome analysis revealed chromosome structural variation uniquely associated with the SCV. These variations included an asymmetric inversion across half of the S. aureus chromosome via recombination between type I restriction modification system (T1RMS) genes, and the activation of a conserved prophage harboring the immune evasion cluster (IEC). Phenotypic reversion to the wild-type–like NCV state correlated with reversal of the chromosomal inversion (CI) and with prophage stabilization. Further analysis of 29 complete S. aureus genomes showed strong signatures of recombination between hsdMS genes, suggesting that analogous CI has repeatedly occurred during S. aureus evolution. Using qPCR and long-read amplicon deep sequencing, we detected subpopulations with T1RMS rearrangements causing CIs and prophage activation across major S. aureus lineages. Here, we have discovered a previously unrecognized and widespread mechanism of reversible genomic instability in S. aureus associated with SCV generation and persistent infections.A.H. is supported by the H2020-MSCA-Global Fellowship (Grant 657766). Doherty Applied Microbial Genomics is funded by the Department of Microbiology and Immunology at The University of Melbourn
The Spatial and Temporal Construction of Confidence in the Visual Scene
Human subjects can report many items of a cluttered field a few hundred milliseconds after stimulus presentation. This memory decays rapidly and after a second only 3 or 4 items can be stored in working memory. Here we compared the dynamics of objective performance with a measure of subjective report and we observed that 1) Objective performance beyond explicit subjective reports (blindsight) was significantly more pronounced within a short temporal interval and within specific locations of the visual field which were robust across sessions 2) High confidence errors (false beliefs) were largely confined to a small spatial window neighboring the cue. The size of this window did not change in time 3) Subjective confidence showed a moderate but consistent decrease with time, independent of all other experimental factors. Our study allowed us to asses quantitatively the temporal and spatial access to an objective response and to subjective reports
TOI-5126: A hot super-Neptune and warm Neptune pair discovered by and
We present the confirmation of a hot super-Neptune with an exterior Neptune
companion orbiting a bright (V = 10.1 mag) F-dwarf identified by the
(). The two
planets, observed in sectors 45, 46 and 48 of the extended
mission, are and
with d and
d orbital periods, respectively. We also obtained
precise space based photometric follow-up of the system with ESAs
() to constrain
the radius and ephemeris of TOI-5126 b. TOI 5126 b is located in the "hot
Neptune Desert" and is an ideal candidate for follow-up transmission
spectroscopy due to its high predicted equilibrium temperature ( K) implying a cloud-free atmosphere. TOI-5126 c is a warm
Neptune ( K) also suitable for follow-up. Tentative
transit timing variations (TTVs) have also been identified in analysis,
suggesting the presence of at least one additional planet, however this signal
may be caused by spot-crossing events, necessitating further precise
photometric follow-up to confirm these signals.Comment: Accepted in MNRAS, 18 pages, 14 figure
TESS Hunt for Young and Maturing Exoplanets (THYME). X. A Two-planet System in the 210 Myr MELANGE-5 Association
Young (<500 Myr) planets are critical to studying how planets form and evolve. Among these young planetary systems, multiplanet configurations are particularly useful, as they provide a means to control for variables within a system. Here, we report the discovery and characterization of a young planetary system, TOI-1224. We show that the planet host resides within a young population we denote as MELANGE-5. By employing a range of age-dating methods—isochrone fitting, lithium abundance analysis, gyrochronology, and Gaia excess variability—we estimate the age of MELANGE-5 to be 210 ± 27 Myr. MELANGE-5 is situated in close proximity to previously identified younger (80–110 Myr) associations, Crius 221 and Theia 424/Volans-Carina, motivating further work to map out the group boundaries. In addition to a planet candidate detected by the TESS pipeline and alerted as a TESS object of interest, TOI-1224 b, we identify a second planet, TOI-1224 c, using custom search tools optimized for young stars (Notch and LOCoR). We find that the planets are 2.10 ± 0.09 R⊕ and 2.88 ± 0.10 R⊕ and orbit their host star every 4.18 and 17.95 days, respectively. With their bright (K = 9.1 mag), small (R* = 0.44 R⊙), and cool (Teff = 3326 K) host star, these planets represent excellent candidates for atmospheric characterization with JWST
TESS Discovery of Twin Planets near 2:1 Resonance around Early M-Dwarf TOI 4342
With data from the Transiting Exoplanet Survey Satellite (TESS), we showcase
improvements to the MIT Quick-Look Pipeline (QLP) through the discovery and
validation of a multi-planet system around M-dwarf TOI 4342 (,
, , K,
pc). With updates to QLP, including a new multi-planet search, as well as
faster cadence data from TESS' First Extended Mission, we discovered two
sub-Neptunes ( and ; = 5.538 days and = 10.689 days)
and validated them with ground-based photometry, spectra, and speckle imaging.
Both planets notably have high transmission spectroscopy metrics (TSMs) of 36
and 32, making TOI 4342 one of the best systems for comparative atmospheric
studies. This system demonstrates how improvements to QLP, along with faster
cadence Full-Frame Images (FFIs), can lead to the discovery of new multi-planet
systems.Comment: accepted for publication in A
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