Biases in Virial Black Hole Masses: An SDSS Perspective

We compile black hole (BH) masses for $\sim 60,000$ quasars in the redshift range $0.1 \lesssim z \lesssim 4.5$ included in the Fifth Data Release of the Sloan Digital Sky Survey (SDSS), using virial BH mass estimators based on the \hbeta, \MgII, and \CIV emission lines. We find that: (1) within our sample, the widths of the three lines follow log-normal distributions, with means and dispersions that do not depend strongly on luminosity or redshift;(2) the \MgII- and \hbeta-estimated BH masses are consistent with one another; and (3) the \CIV BH mass estimator may be more severely affected by a disk wind component than the \MgII and \hbeta estimators, giving a positive bias in mass correlated with the \CIV-\MgII blueshift. Most SDSS quasars have virial BH masses in the range $10^8-10^9 M_\odot$. There is a clear upper mass limit of $\sim 10^{10} M_\odot$ for active BHs at $z \gtrsim 2$, decreasing at lower redshifts. Making the reasonable assumptions that the underlying BH mass distribution decreases with mass and that the Eddington ratio distribution at fixed BH mass has non-zero width, we show that the measured virial BH mass distribution and Eddington ratio distribution are subject to Malmquist bias. A radio quasar subsample (with $1.5\lesssim z\lesssim 2.3$) has mean virial BH mass larger by $\sim 0.12$ dex than the whole sample. A broad absorption line (BAL) quasar subsample (with $1.7\lesssim z\lesssim 2.2$) has identical virial mass distribution as the nonBAL sample, with no mean offset. (Abridged)Comment: Updated virial mass measurements; improved presentation of the MC simulation; added new discussion sections; conclusions unchanged. The full table1 is available at http://www.astro.princeton.edu/~yshen/BH_mass/datafile1.txt.tar.g

Analysis of the Murine Immune Response to Pulmonary Delivery of Precisely Fabricated Nano- and Microscale Particles

Nanomedicine has the potential to transform clinical care in the 21st century. However, a precise understanding of how nanomaterial design parameters such as size, shape and composition affect the mammalian immune system is a prerequisite for the realization of nanomedicine's translational promise. Herein, we make use of the recently developed Particle Replication in Non-wetting Template (PRINT) fabrication process to precisely fabricate particles across and the nano- and micro-scale with defined shapes and compositions to address the role of particle design parameters on the murine innate immune response in both in vitro and in vivo settings. We find that particles composed of either the biodegradable polymer poly(lactic-co-glycolic acid) (PLGA) or the biocompatible polymer polyethylene glycol (PEG) do not cause release of pro-inflammatory cytokines nor inflammasome activation in bone marrow-derived macrophages. When instilled into the lungs of mice, particle composition and size can augment the number and type of innate immune cells recruited to the lungs without triggering inflammatory responses as assayed by cytokine release and histopathology. Smaller particles (80×320 nm) are more readily taken up in vivo by monocytes and macrophages than larger particles (6 µm diameter), yet particles of all tested sizes remained in the lungs for up to 7 days without clearance or triggering of host immunity. These results suggest rational design of nanoparticle physical parameters can be used for sustained and localized delivery of therapeutics to the lungs

Controlled analysis of nanoparticle charge on mucosal and systemic antibody responses following pulmonary immunization

To our knowledge, no other nano-based vaccine delivery platform has directly assessed the effects of nanoparticle charge on pulmonary vaccination without affecting other physio/chemical particle characteristics and/or antigen loading. The Particle Replication in Non-Wetting Templates nanoparticle fabrication process is unique in that it allows for isolation of charge as the sole variable in these studies while maintaining all other physical and chemical parameters constant. We find that positively charged nanoparticles induce robust mucosal and systemic antibody responses following pulmonary administration, whereas negatively charged nanoparticles fail to do so. Therefore, our studies underscore the importance of considering nanoparticle charge as a critical design parameter when generating pulmonary-based vaccines and may have implications for particulate vaccination through other routes of administration

Precise Black Hole Masses From Megamaser Disks: Black Hole-Bulge Relations at Low Mass

The black hole (BH)-bulge correlations have greatly influenced the last decade of effort to understand galaxy evolution. Current knowledge of these correlations is limited predominantly to high BH masses (M_BH> 10^8 M_sun) that can be measured using direct stellar, gas, and maser kinematics. These objects, however, do not represent the demographics of more typical L< L* galaxies. This study transcends prior limitations to probe BHs that are an order of magnitude lower in mass, using BH mass measurements derived from the dynamics of H_2O megamasers in circumnuclear disks. The masers trace the Keplerian rotation of circumnuclear molecular disks starting at radii of a few tenths of a pc from the central BH. Modeling of the rotation curves, presented by Kuo et al. (2010), yields BH masses with exquisite precision. We present stellar velocity dispersion measurements for a sample of nine megamaser disk galaxies based on long-slit observations using the B&C spectrograph on the Dupont telescope and the DIS spectrograph on the 3.5m telescope at Apache Point. We also perform bulge-to-disk decomposition of a subset of five of these galaxies with SDSS imaging. The maser galaxies as a group fall below the M_BH-sigma* relation defined by elliptical galaxies. We show, now with very precise BH mass measurements, that the low-scatter power-law relation between M_BH and sigma* seen in elliptical galaxies is not universal. The elliptical galaxy M_BH-sigma* relation cannot be used to derive the BH mass function at low mass or the zeropoint for active BH masses. The processes (perhaps BH self-regulation or minor merging) that operate at higher mass have not effectively established an M_BH-sigma* relation in this low-mass regime.Comment: 21 pages, 14 figures, accepted for publication in the Astrophysical Journa

Analysis of human innate immune responses to PRINT fabricated nanoparticles with cross validation using a humanized mouse model

Ideal nanoparticle (NP)-based drug and vaccine delivery vectors should be free of inherent cytotoxic or immunostimulatory properties. Therefore, determining baseline immune responses to nanomaterials is of utmost importance when designing human therapeutics. We characterized the response of human immune cells to hydrogel NPs fabricated using Particle Replication in Non-wetting Templates (PRINT) technology. We found preferential NP uptake by primary CD14+ monocytes, which was significantly reduced upon PEGylation of the NP surface. Multiplex cytokine analysis of NP treated primary human peripheral blood mononuclear cells (hu-PBMC) suggests that PRINT based hydrogel NPs do not evoke significant inflammatory responses nor do they induce cytotoxicity or complement activation. We furthered these studies using an in vivo humanized mouse model and similarly found preferential NP uptake by human CD14+ monocytes without systemic inflammatory cytokine responses. These studies suggest that PRINT hydrogel particles form a desirable platform for vaccine and drug delivery as they neither induce inflammation nor toxicity

Single Nucleotide Polymorphisms of 8 Inflammation-related Genes and their Associations with Smoking-related Cancers

Tobacco smoke and its metabolites are carcinogens that increase tissue oxidative stress and induce target tissue inflammation. We hypothesized that genetic variation of inflammatory pathway genes plays a role in tobacco-related carcinogenesis and is modified by tobacco smoking. We evaluated the association of 12 single nucleotide polymorphisms of 8 inflammation-related genes with tobacco-related cancers (lung, oropharynx, larynx, esophagus, stomach, liver, bladder, and kidney) using 3 case-control studies from: Los Angeles (population-based; 611 lung and 553 upper aero-digestive tract cancer cases and 1,040 controls), Taixing, China (population-based; 218 esophagus, 206 stomach, 204 liver cancer cases, and 415 controls), and Memorial Sloan-Kettering Cancer Center (hospital-based; 227 bladder cancer cases and 211 controls). After adjusting for age, education, ethnicity, gender, and tobacco smoking, IL10 rs1800871 was inversely associated with oropharyngeal cancer (CT+TT vs. CC adjusted odds ratio [aOR]: 0.69, 95% confidence interval [CI]: 0.50-0.95), and was positively associated with lung cancer among never smokers (TT vs. CT+CC aOR: 2.5, 95% CI: 1.3-5.1) and inversely with oropharyngeal cancer among ever smokers (CT+TT vs. CC aOR: 0.63, 95% CI: 0.41-0.95). Among all pooled never smokers (588 cases and 816 controls), TNF rs1799964 was inversely associated with smoking-related cancer (CC vs. CT+TT aOR: 0.36, 95% CI: 0.17-0.77). Bayesian correction for multiple comparisons suggests that chance is unlikely to explain our findings (although epigenetic mechanisms may be in effect), which support our hypotheses, suggesting that IL10 rs1800871 is a susceptibility marker for oropharyngeal and lung cancers, and that TNF rs1799964 is associated with smoking-related cancers among never smokers. © 2010 UICC

The Sloan Digital Sky Survey Reverberation Mapping Project: Hα and Hβ reverberation measurements from first-year spectroscopy and photometry

Funding: UK Sciences and Technology Facilities Council STFC grant ST/M001296/1 (KH).We present reverberation mapping results from the first year of combined spectroscopic and photometric observations of the Sloan Digital Sky Survey Reverberation Mapping Project. We successfully recover reverberation time delays between the g+i band emission and the broad Hβ emission line for a total of 44 quasars, and for the broad Hα emission line in 18 quasars. Time delays are computed using the JAVELIN and CREAM software and the traditional interpolated cross-correlation function (ICCF): using well-defined criteria, we report measurements of 32 Hβ and 13 Hα lags with JAVELIN, 42 Hβ and 17 Hα lags with CREAM, and 16 Hβ and eight Hα lags with the ICCF. Lag values are generally consistent among the three methods, though we typically measure smaller uncertainties with JAVELIN and CREAM than with the ICCF, given the more physically motivated light curve interpolation and more robust statistical modeling of the former two methods. The median redshift of our Hβ-detected sample of quasars is 0.53, significantly higher than that of the previous reverberation mapping sample. We find that in most objects, the time delay of the Hα emission is consistent with or slightly longer than that of Hβ. We measure black hole masses using our measured time delays and line widths for these quasars. These black hole mass measurements are mostly consistent with expectations based on the local – relationship, and are also consistent with single-epoch black hole mass measurements. This work increases the current sample size of reverberation-mapped active galaxies by about two-thirds and represents the first large sample of reverberation mapping observations beyond the local universe (z < 0.3).PostprintPeer reviewe

Gpr124 is essential for blood-brain barrier integrity in central nervous system disease

Although blood-brain barrier (BBB) compromise is central to the etiology of diverse central nervous system (CNS) disorders, endothelial receptor proteins that control BBB function are poorly defined. The endothelial G-protein-coupled receptor (GPCR) Gpr124 has been reported to be required for normal forebrain angiogenesis and BBB function in mouse embryos, but the role of this receptor in adult animals is unknown. Here Gpr124 conditional knockout (CKO) in the endothelia of adult mice did not affect homeostatic BBB integrity, but resulted in BBB disruption and microvascular hemorrhage in mouse models of both ischemic stroke and glioblastoma, accompanied by reduced cerebrovascular canonical Wnt-β-catenin signaling. Constitutive activation of Wnt-β-catenin signaling fully corrected the BBB disruption and hemorrhage defects of Gpr124-CKO mice, with rescue of the endothelial gene tight junction, pericyte coverage and extracellular-matrix deficits. We thus identify Gpr124 as an endothelial GPCR specifically required for endothelial Wnt signaling and BBB integrity under pathological conditions in adult mice. This finding implicates Gpr124 as a potential therapeutic target for human CNS disorders characterized by BBB disruption

iTRAQ Identification of Candidate Serum Biomarkers Associated with Metastatic Progression of Human Prostate Cancer

A major challenge in the management of patients with prostate cancer is identifying those individuals at risk of developing metastatic disease, as in most cases the disease will remain indolent. We analyzed pooled serum samples from 4 groups of patients (n = 5 samples/group), collected prospectively and actively monitored for a minimum of 5 yrs. Patients groups were (i) histological diagnosis of benign prostatic hyperplasia with no evidence of cancer ‘BPH’, (ii) localised cancer with no evidence of progression, ‘non-progressing’ (iii) localised cancer with evidence of biochemical progression, ‘progressing’, and (iv) bone metastasis at presentation ‘metastatic’. Pooled samples were immuno-depleted of the 14 most highly abundant proteins and analysed using a 4-plex iTRAQ approach. Overall 122 proteins were identified and relatively quantified. Comparisons of progressing versus non-progressing groups identified the significant differential expression of 25 proteins (p<0.001). Comparisons of metastatic versus progressing groups identified the significant differential expression of 23 proteins. Mapping the differentially expressed proteins onto the prostate cancer progression pathway revealed the dysregulated expression of individual proteins, pairs of proteins and ‘panels’ of proteins to be associated with particular stages of disease development and progression. The median immunostaining intensity of eukaryotic translation elongation factor 1 alpha 1 (eEF1A1), one of the candidates identified, was significantly higher in osteoblasts in close proximity to metastatic tumour cells compared with osteoblasts in control bone (p = 0.0353, Mann Whitney U). Our proteomic approach has identified leads for potentially useful serum biomarkers associated with the metastatic progression of prostate cancer. The panels identified, including eEF1A1 warrant further investigation and validation

Identification and Molecular Characterization of a New Ovarian Cancer Susceptibility Locus at 17q21.31

Epithelial ovarian cancer (EOC) has a heritable component that remains to be fully characterized. Most identified common susceptibility variants lie in non-protein-coding sequences. We hypothesized that variants in the 3 ′ untranslated region at putative microRNA (miRNA) binding sites represent functional targets that influence EOC susceptibility. Here, we evaluate the association between 767 miRNA binding site single nucleotide polymorphisms (miRSNPs) and EOC risk in 18,174 EOC cases and 26,134 controls from 43 studies genotyped through the Collaborative Oncological Gene-environment Study. We identify several miRSNPs associated with invasive serous EOC risk (OR=1.12, P =10−8 ) mapping to an inversion polymorphism at 17q21.31. Additional genotyping of non-miRSNPs at 17q21.31 reveals stronger signals outside the inversion ( P =10−10 ). Variation at 17q21.31 associates with neurological diseases, and our collaboration is the first to report an association with EOC susceptibility. An integrated molecular analysis in this region provides evidence for ARHGAP27 and PLEKHM1 as candidate EOC susceptibility genes