Obscured Active Galactic Nuclei Hickox, Ryan C; Alexander, David M
Annual review of astronomy and astrophysics,
09/2018, Letnik:
56, Številka:
1
Journal Article
Recenzirano
Active galactic nuclei (AGN) are powered by the accretion of material onto a supermassive black hole (SMBH) and are among the most luminous objects in the Universe. However, the huge radiative power ...of most AGN cannot be seen directly, as the accretion is hidden behind gas and dust that absorb many of the characteristic observational signatures. This obscuration presents an important challenge for uncovering the complete AGN population and understanding the cosmic evolution of SMBHs. In this review, we describe a broad range of multiwavelength techniques that are currently being employed to identify obscured AGN, and we assess the reliability and completeness of each technique. We follow with a discussion of the demographics of obscured AGN activity, explore the nature and physical scales of the obscuring material, and assess the implications of obscured AGN for observational cosmology. We conclude with an outline of the prospects for future progress from both observations and theoretical models, and we highlight some of the key outstanding questions.
Alzheimer's disease (AD) is associated with extensive alterations in grey matter microstructure, but our ability to quantify this in vivo is limited. Neurite orientation dispersion and density ...imaging (NODDI) is a multi‐shell diffusion MRI technique that estimates neuritic microstructure in the form of orientation dispersion and neurite density indices (ODI/NDI). Mean values for cortical thickness, ODI, and NDI were extracted from predefined regions of interest in the cortical grey matter of 38 patients with young onset AD and 22 healthy controls. Five cortical regions associated with early atrophy in AD (entorhinal cortex, inferior temporal gyrus, middle temporal gyrus, fusiform gyrus, and precuneus) and one region relatively spared from atrophy in AD (precentral gyrus) were investigated. ODI, NDI, and cortical thickness values were compared between controls and patients for each region, and their associations with MMSE score were assessed. NDI values of all regions were significantly lower in patients. Cortical thickness measurements were significantly lower in patients in regions associated with early atrophy in AD, but not in the precentral gyrus. Decreased ODI was evident in patients in the inferior and middle temporal gyri, fusiform gyrus, and precuneus. The majority of AD‐related decreases in cortical ODI and NDI persisted following adjustment for cortical thickness, as well as each other. There was evidence in the patient group that cortical NDI was associated with MMSE performance. These data suggest distinct differences in cortical NDI and ODI occur in AD and these metrics provide pathologically relevant information beyond that of cortical thinning.
Patients with diffuse large B cell lymphoma (DLBCL) exhibit marked diversity in tumor behavior and outcomes, yet the identification of poor-risk groups remains challenging. In addition, the biology ...underlying these differences is incompletely understood. We hypothesized that characterization of mutational heterogeneity and genomic evolution using circulating tumor DNA (ctDNA) profiling could reveal molecular determinants of adverse outcomes. To address this hypothesis, we applied cancer personalized profiling by deep sequencing (CAPP-Seq) analysis to tumor biopsies and cell-free DNA samples from 92 lymphoma patients and 24 healthy subjects. At diagnosis, the amount of ctDNA was found to strongly correlate with clinical indices and was independently predictive of patient outcomes. We demonstrate that ctDNA genotyping can classify transcriptionally defined tumor subtypes, including DLBCL cell of origin, directly from plasma. By simultaneously tracking multiple somatic mutations in ctDNA, our approach outperformed immunoglobulin sequencing and radiographic imaging for the detection of minimal residual disease and facilitated noninvasive identification of emergent resistance mutations to targeted therapies. In addition, we identified distinct patterns of clonal evolution distinguishing indolent follicular lymphomas from those that transformed into DLBCL, allowing for potential noninvasive prediction of histological transformation. Collectively, our results demonstrate that ctDNA analysis reveals biological factors that underlie lymphoma clinical outcomes and could facilitate individualized therapy.
The United Kingdom's COVID-19 epidemic during early 2020 was one of world's largest and was unusually well represented by virus genomic sampling. We determined the fine-scale genetic lineage ...structure of this epidemic through analysis of 50,887 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genomes, including 26,181 from the UK sampled throughout the country's first wave of infection. Using large-scale phylogenetic analyses combined with epidemiological and travel data, we quantified the size, spatiotemporal origins, and persistence of genetically distinct UK transmission lineages. Rapid fluctuations in virus importation rates resulted in >1000 lineages; those introduced prior to national lockdown tended to be larger and more dispersed. Lineage importation and regional lineage diversity declined after lockdown, whereas lineage elimination was size-dependent. We discuss the implications of our genetic perspective on transmission dynamics for COVID-19 epidemiology and control.
The Aerosol Robotic Network (AERONET) Version 3 (V3) aerosol retrieval algorithm is described, which is based on the Version 2 (V2)
algorithm with numerous updates. Comparisons of V3 aerosol ...retrievals to
those of V2 are presented, along with a new approach to estimate
uncertainties in many of the retrieved aerosol parameters. Changes in the V3 aerosol retrieval algorithm include (1) a new polarized radiative transfer code (RTC), which replaced the scalar RTC of V2, (2) detailed
characterization of gas absorption by adding NO2 and H2O to
specify total gas absorption in the atmospheric column, specification of
vertical profiles of all the atmospheric species, (3) new bidirectional reflectance distribution function (BRDF) parameters for land sites adopted
from the MODIS BRDF/Albedo product, (4) a new version of the extraterrestrial
solar flux spectrum, and (5) a new temperature correction procedure of both direct Sun and sky radiance measurements. The potential effect of each change in V3 on single scattering albedo (SSA) retrievals was analyzed. The
operational almucantar retrievals of V2 versus V3 were compared for four AERONET sites: GSFC, Mezaira, Mongu, and Kanpur. Analysis showed very good
agreement in retrieved parameters of the size distributions. Comparisons of
SSA retrievals for dust aerosols (Mezaira) showed a good agreement in 440 nm
SSA, while for longer wavelengths V3 SSAs are systematically higher than those of V2, with the largest mean difference at 675 nm due to cumulative
effects of both extraterrestrial solar flux and BRDF changes. For non-dust
aerosols, the largest SSA deviation is at 675 nm due to differences in
extraterrestrial solar flux spectrums used in each version. Further, the SSA
675 nm mean differences are very different for weakly (GSFC) and strongly
(Mongu) absorbing aerosols, which is explained by the lower sensitivity to a bias in aerosol scattering optical depth by less absorbing aerosols. A new
hybrid (HYB) sky radiance measurement scan is introduced and discussed. The HYB combines features of scans in two different planes to maximize the range
of scattering angles and achieve scan symmetry, thereby allowing for cloud
screening and spatial averaging, which is an advantage over the principal plane scan that lacks robust symmetry. We show that due to an extended range of scattering angles, HYB SSA retrievals for dust aerosols exhibit smaller
variability with solar zenith angles (SZAs) than those of almucantar (ALM), which allows extension of HYB SSA retrievals to SZAs less than 50∘ to as small as 25∘. The comparison of SSA retrievals from closely
time-matched HYB and ALM scans in the 50 to 75∘ SZA range showed good agreement with the differences below ∼0.005. We also present an approach to estimate retrieval uncertainties which
utilizes the variability in retrieved parameters generated by perturbing
both measurements and auxiliary input parameters as a proxy for retrieval uncertainty. The perturbations in measurements and auxiliary inputs are
assumed as estimated biases in aerosol optical depth (AOD), radiometric
calibration of sky radiances combined with solar spectral irradiance, and
surface reflectance. For each set of Level 2 Sun/sky radiometer
observations, 27 inputs corresponding to 27 combinations of biases were
produced and separately inverted to generate the following statistics of
the inversion results: average, standard deviation, minimum and maximum
values. From these statistics, standard deviation (labeled U27) is used as a proxy for estimated uncertainty, and a lookup table (LUT) approach was implemented to reduce the computational time. The U27 climatological LUT was
generated from the entire AERONET almucantar (1993–2018) and hybrid
(2014–2018) scan databases by binning U27s in AOD (440 nm), Angström exponent (AE, 440–870 nm), and SSA (440, 675, 870, 1020 nm). Using this LUT approach, the uncertainty estimates U27 for each individual V3 Level 2 retrieval can
be obtained by interpolation using the corresponding measured and inverted
combination of AOD, AE, and SSA.
Outcomes for patients with diffuse large B-cell lymphoma remain heterogeneous, with existing methods failing to consistently predict treatment failure. We examined the additional prognostic value of ...circulating tumor DNA (ctDNA) before and during therapy for predicting patient outcomes.
We studied the dynamics of ctDNA from 217 patients treated at six centers, using a training and validation framework. We densely characterized early ctDNA dynamics during therapy using cancer personalized profiling by deep sequencing to define response-associated thresholds within a discovery set. These thresholds were assessed in two independent validation sets. Finally, we assessed the prognostic value of ctDNA in the context of established risk factors, including the International Prognostic Index and interim positron emission tomography/computed tomography scans.
Before therapy, ctDNA was detectable in 98% of patients; pretreatment levels were prognostic in both front-line and salvage settings. In the discovery set, ctDNA levels changed rapidly, with a 2-log decrease after one cycle (early molecular response EMR) and a 2.5-log decrease after two cycles (major molecular response MMR) stratifying outcomes. In the first validation set, patients receiving front-line therapy achieving EMR or MMR had superior outcomes at 24 months (EMR: EFS, 83% v 50%; P = .0015; MMR: EFS, 82% v 46%; P < .001). EMR also predicted superior 24-month outcomes in patients receiving salvage therapy in the first validation set (EFS, 100% v 13%; P = .011). The prognostic value of EMR and MMR was further confirmed in the second validation set. In multivariable analyses including International Prognostic Index and interim positron emission tomography/computed tomography scans across both cohorts, molecular response was independently prognostic of outcomes, including event-free and overall survival.
Pretreatment ctDNA levels and molecular responses are independently prognostic of outcomes in aggressive lymphomas. These risk factors could potentially guide future personalized risk-directed approaches.
The presence of energetically low-lying triplet states is a hallmark of organic semiconductors. Even though they present a wealth of interesting photophysical properties, these optically dark states ...significantly limit optoelectronic device performance. Recent advances in emissive charge-transfer molecules have pioneered routes to reduce the energy gap between triplets and “bright” singlets, allowing thermal population exchange between them and eliminating a significant loss channel in devices. In conjugated polymers, this gap has proved resistant to modification. Here, we introduce a general approach to reduce the singlet–triplet energy gap in fully conjugated polymers, using a donor–orthogonal acceptor motif to spatially separate electron and hole wave functions. This new generation of conjugated polymers allows for a greatly reduced exchange energy, enhancing triplet formation and enabling thermally activated delayed fluorescence. We find that the mechanisms of both processes are driven by excited-state mixing between π–π*and charge-transfer states, affording new insight into reverse intersystem crossing.
Accurate identification of tumor-derived somatic variants in plasma circulating cell-free DNA (cfDNA) requires understanding of the various biological compartments contributing to the cfDNA pool. We ...sought to define the technical feasibility of a high-intensity sequencing assay of cfDNA and matched white blood cell DNA covering a large genomic region (508 genes; 2 megabases; >60,000× raw depth) in a prospective study of 124 patients with metastatic cancer, with contemporaneous matched tumor tissue biopsies, and 47 controls without cancer. The assay displayed high sensitivity and specificity, allowing for de novo detection of tumor-derived mutations and inference of tumor mutational burden, microsatellite instability, mutational signatures and sources of somatic mutations identified in cfDNA. The vast majority of cfDNA mutations (81.6% in controls and 53.2% in patients with cancer) had features consistent with clonal hematopoiesis. This cfDNA sequencing approach revealed that clonal hematopoiesis constitutes a pervasive biological phenomenon, emphasizing the importance of matched cfDNA-white blood cell sequencing for accurate variant interpretation.
Objective There are few studies on the natural history of milk allergy. Most are single-site and not longitudinal, and these have not identified a means for early prediction of outcomes. Methods ...Children aged 3 to 15 months were enrolled in an observational study with either (1) a convincing history of egg allergy, milk allergy, or both with a positive skin prick test (SPT) response to the trigger food and/or (2) moderate-to-severe atopic dermatitis (AD) and a positive SPT response to milk or egg. Children enrolled with a clinical history of milk allergy were followed longitudinally, and resolution was established by means of successful ingestion. Results The cohort consists of 293 children, of whom 244 were given a diagnosis of milk allergy at baseline. Milk allergy has resolved in 154 (52.6%) subjects at a median age of 63 months and a median age at last follow-up of 66 months. Baseline characteristics that were most predictive of resolution included milk-specific IgE level, milk SPT wheal size, and AD severity (all P < .001). Baseline milk-specific IgG4 level and milk IgE/IgG4 ratio were not predictive of resolution and neither was expression of cytokine-inducible SH2-containing protein, forkhead box protein 3, GATA3, IL-10, IL-4, IFN-γ, or T-bet by using real-time PCR in CD25-selected, casein-stimulated mononuclear cells. A calculator to estimate resolution probabilities using baseline milk IgE level, SPT response, and AD severity was devised for use in the clinical setting. Conclusions In this cohort of infants with milk allergy, approximately one half had resolved over 66 months of follow-up. Baseline milk-specific IgE level, SPT wheal size, and AD severity were all important predictors of the likelihood of resolution.
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