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The variable continuum emission of an active galactic nucleus (AGN) produces corresponding responses in the broad emission lines, which are modulated by light travel delays, and contain information on the physical properties, structure, and kinematics of the emitting gas region. The reverberation mapping technique, a time series analysis of the driving light curve and response, can recover some of this information, including the size and velocity field of the broad-line region (BLR). Here we introduce a new forward-modeling tool, the Broad Emission Line MApping Code, which simulates the velocity-resolved reverberation response of the BLR to any given input light curve by setting up a 3D ensemble of gas clouds for various specified geometries, velocity fields, and cloud properties. In this work, we present numerical approximations to the transfer function by simulating the velocity-resolved responses to a single continuum pulse for sets of models representing a spherical BLR with a radiatively driven outflow and a disklike BLR with Keplerian rotation. We explore how the structure, velocity field, and other BLR properties affect the transfer function. We calculate the response-weighted time delay (reverberation “lag”), which is considered to be a proxy for the luminosity-weighted radius of the BLR. We investigate the effects of anisotropic cloud emission and matter-bounded (completely ionized) clouds and find the response-weighted delay is only equivalent to the luminosity-weighted radius when clouds emit isotropically and are radiation-bounded (partially ionized). Otherwise, the luminosity-weighted radius can be overestimated by up to a factor of 2.

 

Homologs of the mutagenic Escherichia coli DNA polymerase V (pol V) are encoded by numerous pathogens and mobile elements. We have used Rum pol (RumA′2B), from the integrative conjugative element (ICE), R391, as a model mobile element-encoded polymerase (MEPol). The highly mutagenic Rum pol is transferred horizontally into a variety of recipient cells, including many pathogens. Moving between species, it is unclear if Rum pol can function on its own or requires activation by host factors. Here, we show that Rum pol biochemical activity requires the formation of a physical mutasomal complex, Rum Mut, containing RumA′2B-RecA-ATP, with RecA being donated by each recipient bacteria. For R391, Rum Mut specific activities in vitro and mutagenesis rates in vivo depend on the phylogenetic distance of host-cell RecA from E. coli RecA. Rum pol is a highly conserved and effective mobile catalyst of rapid evolution, with the potential to generate a broad mutational landscape that could serve to ensure bacterial adaptation in antibiotic-rich environments leading to the establishment of antibiotic resistance.

 

Amyloid beta (Aβ) is thought to play a critical role in the pathogenesis of Alzheimer’s disease (AD). Prion-like Aβ polymorphs, or “strains”, can have varying pathogenicity and may underlie the phenotypic heterogeneity of the disease. In order to develop effective AD therapies, it is critical to identify the strains of Aβ that might arise prior to the onset of clinical symptoms and understand how they may change with progressing disease. Down syndrome (DS), as the most common genetic cause of AD, presents promising opportunities to compare such features between early and advanced AD. In this work, we evaluate the neuropathology and Aβ strain profile in the post-mortem brain tissues of 210 DS, AD, and control individuals. We assayed the levels of various Aβ and tau species and used conformation-sensitive fluorescent probes to detect differences in Aβ strains among individuals and populations. We found that these cohorts have some common but also some distinct strains from one another, with the most heterogeneous populations of Aβ emerging in subjects with high levels of AD pathology. The emergence of distinct strains in DS at these later stages of disease suggests that the confluence of aging, pathology, and other DS-linked factors may favor conditions that generate strains that are unique from sporadic AD.

 

The size and structure of the dusty circumnuclear torus in active galactic nuclei (AGNs) can be investigated by analyzing the temporal response of the torus's infrared (IR) dust emission to variations in the AGN ultraviolet/optical luminosity. This method, reverberation mapping, is applicable over a wide redshift range, but the IR response is sensitive to several poorly constrained variables relating to the dust distribution and its illumination, complicating the interpretation of measured reverberation lags. We have used an enhanced version of our torus reverberation mapping code (TORMAC) to conduct a comprehensive exploration of the torus response functions at selected wavelengths, for the standard interstellar medium grain composition. The shapes of the response functions vary widely over the parameter range covered by our models, with the largest variations occurring at shorter wavelengths (≤4.5 μm). The reverberation lag, quantified as the response-weighted delay (RWD), is most affected by the radial depth of the torus, the steepness of the radial cloud distribution, the degree of anisotropy of the AGN radiation field, and the volume filling factor. Nevertheless, we find that the RWD provides a reasonably robust estimate, to within a factor of ~3, of the luminosity-weighted torus radius, confirming the basic assumption underlying reverberation mapping. However, overall, the models predict radii at 2.2 μm that are typically a factor of ~2 larger than those derived from K-band reverberation mapping. This is likely an indication that the innermost region of the torus is populated by clouds dominated by large graphite grains. 

The ability to direct cell behavior has been central to the success of numerous therapeutics to regenerate tissue or facilitate device integration. Biomaterial scientists are challenged to understand and modulate the interactions of biomaterials with biological systems in order to achieve effective tissue repair. One key area of research investigates the use of extracellular matrix‐derived ligands to target specific integrin interactions and induce cellular responses, such as increased cell migration, proliferation, and differentiation of mesenchymal stem cells. These integrin‐targeting proteins and peptides have been implemented in a variety of different polymeric scaffolds and devices to enhance tissue regeneration and integration. This review first presents an overview of integrin‐mediated cellular processes that have been identified in angiogenesis, wound healing, and bone regeneration. Then, research utilizing biomaterials are highlighted with integrin‐targeting motifs as a means to direct these cellular processes to enhance tissue regeneration. In addition to providing improved materials for tissue repair and device integration, these innovative biomaterials provide new tools to probe the complex processes of tissue remodeling in order to enhance the rational design of biomaterial scaffolds and guide tissue regeneration strategies.