Modeling reverberation mapping data II: dynamical modeling of the Lick AGN Monitoring Project 2008 dataset

We present dynamical modeling of the broad line region (BLR) for a sample of five Seyfert 1 galaxies using reverberation mapping data taken by the Lick AGN Monitoring Project in 2008. By modeling the AGN continuum light curve and H$\beta$ line profiles directly we are able to constrain the geometry and kinematics of the BLR and make a measurement of the black hole mass that does not depend upon the virial factor, $f$, needed in traditional reverberation mapping analysis. We find that the geometry of the BLR is generally a thick disk viewed close to face-on. While the H$\beta$ emission is found to come preferentially from the far side of the BLR, the mean size of the BLR is consistent with the lags measured with cross-correlation analysis. The BLR kinematics are found to be consistent with either inflowing motions or elliptical orbits, often with some combination of the two. We measure black hole masses of $\log_{10}(M_{\rm\,BH}/M_\odot)=6.62^{+0.10}_{-0.13}$ for Arp 151, $7.42^{+0.26}_{-0.27}$ for Mrk 1310, $7.51^{+0.23}_{-0.14}$ for NGC 5548, $6.42^{+0.24}_{-0.18}$ for NGC 6814, and $6.99^{+0.32}_{-0.25}$ for SBS 1116+583A. The $f$ factors measured individually for each AGN are found to correlate with inclination angle, although not with $M_{\rm\,BH}$, $L_{5100}$, or FWHM/$\sigma$ of the emission line profile.Comment: 21 pages, 24 figures, 3 tables, Accepted for publication in MNRAS, corrected masses for NGC 5548 and NGC 6814 in the abstrac

Positron emission tomography imaging of endometrial cancer using engineered anti-EMP2 antibody fragments.

PurposeAs imaging of the cell surface tetraspan protein epithelial membrane protein-2 (EMP2) expression in malignant tumors may provide important prognostic and predictive diagnostic information, the goal of this study is to determine if antibody fragments to EMP2 may be useful for imaging EMP2 positive tumors.ProceduresThe normal tissue distribution of EMP2 protein expression was evaluated by immunohistochemistry and found to be discretely expressed in both mouse and human tissues. To detect EMP2 in tumors, a recombinant human anti-EMP2 minibody (scFv-hinge-C(H)3 dimer; 80 kDa) was designed to recognize a common epitope in mice and humans and characterized. In human tumor cell lines, the antibody binding induced EMP2 internalization and degradation, prompting the need for a residualizing imaging strategy. Following conjugation to DOTA (1,4,7,10-tetraazacyclododecane-N,N',N',N'″-tetraacetic acid), the minibody was radiolabeled with (64)Cu (t (1/2) = 12.7 h) and evaluated in mice as a positron emission tomography (PET) imaging agent for human EMP2-expressing endometrial tumor xenografts.ResultsThe residualizing agent, (64)Cu-DOTA anti-EMP2 minibody, achieved high uptake in endometrial cancer xenografts overexpressing EMP2 (10.2 ± 2.6, percent injected dose per gram (%ID/g) ± SD) with moderate uptake in wild-type HEC1A tumors (6.0 ± 0.1). In both cases, precise tumor delineation was observed from the PET images. In contrast, low uptake was observed with anti-EMP2 minibodies in EMP2-negative tumors (1.9 ± 0.5).ConclusionsThis new immune-PET agent may be useful for preclinical assessment of anti-EMP2 targeting in vivo. It may also have value for imaging of tumor localization and therapeutic response in patients with EMP2-positive malignancies

The Lick AGN Monitoring Project 2011: Dynamical Modeling of the Broad Line Region in Mrk 50

We present dynamical modeling of the broad line region (BLR) in the Seyfert 1 galaxy Mrk 50 using reverberation mapping data taken as part of the Lick AGN Monitoring Project (LAMP) 2011. We model the reverberation mapping data directly, constraining the geometry and kinematics of the BLR, as well as deriving a black hole mass estimate that does not depend on a normalizing factor or virial coefficient. We find that the geometry of the BLR in Mrk 50 is a nearly face-on thick disk, with a mean radius of 9.6(+1.2,-0.9) light days, a width of the BLR of 6.9(+1.2,-1.1) light days, and a disk opening angle of 25\pm10 degrees above the plane. We also constrain the inclination angle to be 9(+7,-5) degrees, close to face-on. Finally, the black hole mass of Mrk 50 is inferred to be log10(M(BH)/Msun) = 7.57(+0.44,-0.27). By comparison to the virial black hole mass estimate from traditional reverberation mapping analysis, we find the normalizing constant (virial coefficient) to be log10(f) = 0.78(+0.44,-0.27), consistent with the commonly adopted mean value of 0.74 based on aligning the M(BH)-{\sigma}* relation for AGN and quiescent galaxies. While our dynamical model includes the possibility of a net inflow or outflow in the BLR, we cannot distinguish between these two scenarios.Comment: Accepted for publication in ApJ. 8 pages, 6 figure

The Lick AGN Monitoring Project 2011: Dynamical Modeling of the Broad-Line Region

We present models of the H$\beta$-emitting broad-line region (BLR) in seven Seyfert 1 galaxies from the Lick AGN (Active Galactic Nucleus) Monitoring Project 2011 sample, drawing inferences on the BLR structure and dynamics as well as the mass of the central supermassive black hole. We find that the BLR is generally a thick disk, viewed close to face-on, with preferential emission back toward the ionizing source. The dynamics in our sample range from near-circular elliptical orbits to inflowing or outflowing trajectories. We measure black hole masses of $\log_{10}(M_{\rm BH}/M_\odot) = 6.48^{+0.21}_{-0.18}$ for PG 1310$-$108, $7.50^{+0.25}_{-0.18}$ for Mrk 50, $7.46^{+0.15}_{-0.21}$ for Mrk 141, $7.58^{+0.08}_{-0.08}$ for Mrk 279, $7.11^{+0.20}_{-0.17}$ for Mrk 1511, $6.65^{+0.27}_{-0.15}$ for NGC 4593, and $6.94^{+0.14}_{-0.14}$ for Zw 229$-$015. We use these black hole mass measurements along with cross-correlation time lags and line widths to recover the scale factor $f$ used in traditional reverberation mapping measurements. Combining our results with other studies that use this modeling technique, bringing our sample size to 16, we calculate a scale factor that can be used for measuring black hole masses in other reverberation mapping campaigns. When using the root-mean-square (rms) spectrum and using the line dispersion to measure the line width, we find $\log_{10}(f_{{\rm rms},\sigma})_{\rm pred} = 0.57 \pm 0.19$. Finally, we search for correlations between $f$ and other AGN and BLR parameters and find marginal evidence that $f$ is correlated with $M_{\rm BH}$ and the BLR inclination angle, but no significant evidence of a correlation with the AGN luminosity or Eddington ratio.Comment: 26 pages, 14 figures. Accepted for publication in Ap

Early-branching gut fungi possess a large, comprehensive array of biomass-degrading enzymes

available in PMC 2016 November 07The fungal kingdom is the source of almost all industrial enzymes in use for lignocellulose bioprocessing. We developed a systems-level approach that integrates transcriptomic sequencing, proteomics, phenotype, and biochemical studies of relatively unexplored basal fungi. Anaerobic gut fungi isolated from herbivores produce a large array of biomass-degrading enzymes that synergistically degrade crude, untreated plant biomass and are competitive with optimized commercial preparations from Aspergillus and Trichoderma. Compared to these model platforms, gut fungal enzymes are unbiased in substrate preference due to a wealth of xylan-degrading enzymes. These enzymes are universally catabolite-repressed and are further regulated by a rich landscape of noncoding regulatory RNAs. Additionally, we identified several promising sequence-divergent enzyme candidates for lignocellulosic bioprocessing.United States. Dept. of Energy. Office of Science (Biological and Environmental Research (BER) program)United States. Department of Energy (DOE Grant DE-SC0010352)United States. Department of Agriculture (Award 2011-67017-20459)Institute for Collaborative Biotechnologies (grant W911NF-09-0001

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

Development and Validation of the Behavioral Tendencies Questionnaire

At a fundamental level, taxonomy of behavior and behavioral tendencies can be described in terms of approach, avoid, or equivocate (i.e., neither approach nor avoid). While there are numerous theories of personality, temperament, and character, few seem to take advantage of parsimonious taxonomy. The present study sought to implement this taxonomy by creating a questionnaire based on a categorization of behavioral temperaments/tendencies first identified in Buddhist accounts over fifteen hundred years ago. Items were developed using historical and contemporary texts of the behavioral temperaments, described as “Greedy/Faithful”, “Aversive/Discerning”, and “Deluded/Speculative”. To both maintain this categorical typology and benefit from the advantageous properties of forced-choice response format (e.g., reduction of response biases), binary pairwise preferences for items were modeled using Latent Class Analysis (LCA). One sample (n1 = 394) was used to estimate the item parameters, and the second sample (n2 = 504) was used to classify the participants using the established parameters and cross-validate the classification against multiple other measures. The cross-validated measure exhibited good nomothetic span (construct-consistent relationships with related measures) that seemed to corroborate the ideas present in the original Buddhist source documents. The final 13-block questionnaire created from the best performing items (the Behavioral Tendencies Questionnaire or BTQ) is a psychometrically valid questionnaire that is historically consistent, based in behavioral tendencies, and promises practical and clinical utility particularly in settings that teach and study meditation practices such as Mindfulness Based Stress Reduction (MBSR)