5632 research outputs found
Sort by
Metadata retrieval from sequence databases with ffq
No full textMotivation: Several genomic databases host data and metadata for an ever-growing collection of sequence datasets. While these databases have a shared hierarchical structure, there are no tools specifically designed to leverage it for metadata extraction.
Results: We present a command-line tool, called ffq, for querying user-generated data and metadata from sequence databases. Given an accession or a paper’s DOI, ffq efficiently fetches metadata and links to raw data in JSON format. ffq’s modularity and simplicity make it extensible to any genomic database exposing its data for programmatic access.
Availability and implementation: ffq is free and open source, and the code can be found here: https://github.com/pachterlab/ffq
An Energy Sharing Mechanism Considering Network Constraints and Market Power Limitation
No full textAs the number of prosumers with distributed energy resources (DERs) grows, the conventional centralized operation scheme may suffer from conflicting interests, privacy concerns, and incentive inadequacy. In this paper, we propose an energy sharing mechanism to address the above challenges. It takes into account network constraints and fairness among prosumers. In the proposed energy sharing market, all prosumers play a generalized Nash game. The market equilibrium is proved to have nice features in a large market or when it is a variational equilibrium. To deal with the possible market failure, inefficiency, or instability in general cases, we introduce a price regulation policy to avoid market power exploitation. The improved energy sharing mechanism with price regulation can guarantee the existence and uniqueness of a socially near-optimal market equilibrium. Some advantageous properties are proved, such as the prosumer’s individual rationality, a sharing price structure similar to the locational marginal price, and the tendency towards social optimum with an increasing number of prosumers. For implementation, a practical bidding algorithm is developed with a convergence condition. Experimental results validate the theoretical outcomes and show the practicability of our model and method
Mechanical basis and topological routes to cell elimination
No full textCell layers eliminate unwanted cells through the extrusion process, which underlines healthy versus flawed tissue behaviors. Although several biochemical pathways have been identified, the underlying mechanical basis including the forces involved in cellular extrusion remains largely unexplored. Utilizing a phase-field model of a three-dimensional cell layer, we study the interplay of cell extrusion with cell–cell and cell–substrate interactions in a flat monolayer. Independent tuning of cell–cell versus cell–substrate adhesion forces reveals that extrusion events can be distinctly linked to defects in nematic and hexatic orders associated with cellular arrangements. Specifically, we show that by increasing relative cell–cell adhesion forces the cell monolayer can switch between the collective tendency towards fivefold, hexatic, disclinations relative to half-integer, nematic, defects for extruding a cell. We unify our findings by accessing three-dimensional mechanical stress fields to show that an extrusion event acts as a mechanism to relieve localized stress concentration
Debris disk color with the Hubble Space Telescope
No full textContext. Multiwavelength scattered light imaging of debris disks may inform dust properties including typical size and mineral composition. Existing studies have investigated a small set of individual systems across a variety of imaging instruments and filters, calling for uniform comparison studies to systematically investigate dust properties.
Aims. We obtain the surface brightness of dust particles in debris disks by post-processing coronagraphic imaging observations, and compare the multiwavelength reflectance of dust. For a sample of resolved debris disks, we perform a systematic analysis on the reflectance properties of their birth rings.
Methods. We reduced the visible and near-infrared images of 23 debris disk systems hosted by A through M stars using two coronagraphs on board the Hubble Space Telescope: the STIS instrument observations centered at 0.58 µm, and the NICMOS instrument at 1.12 µm or 1.60 µm. For proper recovery of debris disks, we used classical reference differential imaging for STIS, and adopted non-negative matrix factorization with forward modeling for NICMOS. By dividing disk signals by stellar signals to take into account intrinsic stellar color effects, we systematically obtained and compared the reflectance of debris birth rings at ≈90º scattering angle.
Results. Debris birth rings typically exhibit a blue color at ≈90º scattering angle. As the stellar luminosity increases, the color tends to be more neutral. A likely L-shaped color–albedo distribution indicates a clustering of scatterer properties.
Conclusions. The observed color trend correlates with the expected blow-out size of dust particles. The color-albedo clustering likely suggests different populations of dust in these systems. More detailed radiative transfer models with realistic dust morphology will contribute to explaining the observed color and color–albedo distribution of debris systems
Analysis of shock wave acceleration from normal detonation reflection
No full textNormal detonation reflection generates a shock wave that exhibits complicated dynamics as it propagates through the incident detonation and post-detonation flow. Ideal models have historically neglected the influence of a finite detonation thickness on the reflected shock due to its small size relative to laboratory scales. However, one-dimensional numerical simulations show that the reflected shock accelerates to a large shock speed not predicted by ideal theory as it propagates through the incident detonation. Analysis with a derived shock-change equation identifies the principal role of the highly nonuniform upstream flow on producing the large shock acceleration. Simulations of detonation reflection show how a finite detonation thickness affects the entire trajectory of the reflected shock
Sodium Brightening of (3200) Phaethon near Perihelion
No full textSunskirting asteroid (3200) Phaethon has been repeatedly observed in Solar Terrestrial Relations Observatory (STEREO) Heliospheric Imager 1 (HI1) imagery to anomalously brighten and produce an antisunward tail for a few days near each perihelion passage, phenomena previously attributed to the ejection of micron-sized dust grains. Color imaging by the Solar and Heliospheric Observatory (SOHO) Large Angle Spectrometric Coronagraph (LASCO) during the 2022 May apparition indicates that the observed brightening and tail development instead capture the release of sodium atoms, which resonantly fluoresce at the 589.0/589.6 nm D lines. While HI1's design bandpass nominally excludes the D lines, filter degradation has substantially increased its D line sensitivity, as quantified by the brightness of Mercury’s sodium tail in HI1 imagery. Furthermore, the expected fluorescence efficiency and acceleration of sodium atoms under solar radiation readily reproduce both the photometric and morphological behaviors observed by LASCO and HI1 during the 2022 apparition and the 17 earlier apparitions since 1997. This finding connects Phaethon to the broader population of sunskirting and sungrazing comets observed by SOHO, which often also exhibit bright sodium emission with minimal visible dust, but distinguishes it from other sunskirting asteroids without detectable sodium production under comparable solar heating. These differences may reflect variations in the degree of sodium depletion of near-surface material and thus the extent and/or timing of any past or present resurfacing activity
The role of conformational change and key glutamic acid residues in the ClC-ec1 antiporter
No full textThe triple glutamine (Q) mutant (QQQ) structure of a Cl⁻/H⁺ antiporter from Escherichia coli (ClC-ec1) displaying a novel backbone arrangement has been used to challenge the long-held notion that Cl⁻/H⁺ antiporters do not operate through large conformational motions. The QQQ mutant substitutes the glutamine residue for an external glutamate E148, an internal glutamate E203, and a third glutamate E113 that hydrogen-bonds with E203. However, it is unknown if QQQ represents a physiologically relevant state, as well as how the protonation of the wild-type glutamates relates to the global dynamics. We herein apply continuous constant-pH molecular dynamics to investigate the H⁺-coupled dynamics of ClC-ec1. Although any large-scale conformational rearrangement upon acidification would be due to the accumulation of excess charge within the protein, protonation of the glutamates significantly impacts mainly the local structure and dynamics. Despite the fact that the extracellular pore enlarges at acidic pHs, an occluded ClC-ec1 within the active pH range of 3.5–7.5 requires a protonated E148 to facilitate extracellular Cl⁻ release. E203 is also involved in the intracellular H⁺ transfer as an H⁺ acceptor. The water wire connection of E148 with the intracellular solution is regulated by the charge states of the E113/E203 dyad with coupled proton titration. However, the dynamics extracted from our simulations are not QQQ-like, indicating that the QQQ mutant does not represent the behavior of the wild-type ClC-ec1. These findings reinforce the necessity of having a protonatable residue at the E203 position in ClC-ec1 and suggest that a higher level of complexity exists for the intracellular H⁺ transfer in Cl⁻/H⁺ antiporters
Germline-encoded amino acid–binding motifs drive immunodominant public antibody responses
No full textINTRODUCTION. Antibodies are generated by a DNA recombination mechanism occurring in the immunoglobulin heavy and light chain genes in which modular VDJ (for heavy) and VJ (for light) gene segments are combinatorially assembled. The vast complexity of the antibody repertoire allows many species to generate antibodies against virtually any protein. However, when different individuals are exposed to a given pathogen they often mount antibody responses to the same precise protein regions—or epitopes—from the pathogen. The mechanisms underlying these recurrent antibody responses to immunodominant “public epitopes” are not well understood.
RATIONALE. We set out to identify a collection of immunodominant public epitopes that would allow us to study mechanisms underlying recurrent antibody responses. We employed VirScan—a phage display platform programmed to display peptides covering the entire human virome—to identify the epitopes of antiviral antibodies from a large cohort of individuals in a high-throughput manner. Additionally, we isolated B cell receptors from different individuals that bound to model public epitopes in order to investigate their determinants of specificity. Finally, we performed a systematic analysis of antibody–antigen structures from the Protein Data Bank (PDB) to search for recurrent modes of antigen recognition.
RESULTS. We mapped 376 immunodominant public epitopes from 51 viral species to single-amino-acid resolution. Antibodies from different individuals that recognized the same public epitope often (i) shared light chain isotype (kappa or lambda) and (ii) bound the same precise critical residues in the epitope. Public epitopes showed biased amino acid composition, including a striking enrichment of lysine at the borders of public epitopes recognized by antibodies with lambda light chains. We examined 50 B cell receptors recognizing three model public epitopes in detail and observed conserved V gene segment usage but almost no conservation of heavy chain CDR3 sequences, indicating that key specificity determinants lay within the V gene segments themselves. Structural analysis of antibody–antigen complexes in the PDB uncovered 18 human V gene segments that harbor germline-encoded amino acid–binding (GRAB) motifs that specifically bind to particular amino acids. Among these were a family of six closely related lambda V gene segments with similar GRAB motifs specific for border lysines. We confirmed that the GRAB motifs we identified were critical for antibody recognition of two model public epitopes. Analysis of murine antibody–antigen structures revealed 21 V gene segment–encoded GRAB motifs that only partially overlapped with the human GRAB motifs, which may explain why there is little overlap between the public epitopes recognized across species. Thus, there appears to be a structural basis underlying the notable convergence in humoral immune responses to immunodominant public epitopes across humans and the differing public epitope selection across species.
CONCLUSION. Recurrent antibody responses to immunodominant public epitopes are a general feature of humoral immunity. We propose that they are driven by GRAB motifs, a germline-encoded component of the architecture of the antibody repertoire that predisposes antibodies to recognize particular structures and thus influences epitope selection and composition. Public epitopes likely arise in part because they are best aligned for recognition by GRAB motifs and can thus be bound by a relatively large precursor pool of B cells. GRAB motifs may have evolved to ensure efficient antibody responses to pathogens; the recurrent responses they engender across populations likely exert selective pressure on pathogens and influence host–pathogen coevolution
Seismic noise characterisation at a potential gravitational wave detector site in Australia
No full textA critical consideration in the design of next-generation gravitational wave detectors is the understanding of the seismic environment that can introduce coherent and incoherent noise of seismic origin at different frequencies. We present detailed low-frequency ambient seismic noise characterisation (0.1–10 Hz) at the Gingin site in Western Australia. Unlike the microseism band (0.06–1 Hz) for which the power shows strong correlations with nearby buoy measurements in the Indian Ocean, the seismic spectrum above 1 Hz is a complex superposition of wind induced seismic noise and anthropogenic seismic noise which can be characterised using beamforming to distinguish between the effects of coherent and incoherent wind induced seismic noise combined with temporal variations in the spatio-spectral properties of seismic noise. This also helps characterise the anthropogenic seismic noise. We show that wind induced seismic noise can either increase or decrease the coherency of background seismic noise for wind speeds above 6 m s−1 due to the interaction of wind with various surface objects. In comparison to the seismic noise at the Virgo site, the secondary microseism (0.2 Hz) noise level is higher in Gingin, but the seismic noise level between 1 and 10 Hz is lower due to the sparse population and absence of nearby road traffic
RNAget: an API to securely retrieve RNA quantifications
No full textLarge-scale sharing of genomic quantification data requires standardized access interfaces. In this Global Alliance for Genomics and Health project, we developed RNAget, an API for secure access to genomic quantification data in matrix form. RNAget provides for slicing matrices to extract desired subsets of data and is applicable to all expression matrix-format data, including RNA sequencing and microarrays. Further, it generalizes to quantification matrices of other sequence-based genomics such as ATAC-seq and ChIP-seq