Building population models for large-scale neural recordings: opportunities and pitfalls

Modern recording technologies now enable simultaneous recording from large numbers of neurons. This has driven the development of new statistical models for analyzing and interpreting neural population activity. Here we provide a broad overview of recent developments in this area. We compare and contrast different approaches, highlight strengths and limitations, and discuss biological and mechanistic insights that these methods provide

Metastatic model of HPV+ oropharyngeal squamous cell carcinoma demonstrates heterogeneity in tumor metastasis

Human papillomavirus induced (HPV+) cancer incidence is rapidly rising, comprising 60–80% of oropharyngeal squamous cell carcinomas (OPSCCs); while rare, recurrent/metastatic disease accounts for nearly all related deaths. An in vivo pre-clinical model for these invasive cancers is necessary for testing new therapies. We characterize an immune competent recurrent/metastatic HPV+ murine model of OPSSC which consists of four lung metastatic (MLM) cell lines isolated from an animal with HPV+ OPSCC that failed cisplatin/radiation treatment. These individual metastatic clonal cell lines were tested to verify their origin (parental transgene expression and define their physiological properties: proliferation, metastatic potential, heterogeneity and sensitivity/resistance to cisplatin and radiation. All MLMs retain expression of parental HPV16 E6 and E7 and degrade P53 yet are heterogeneous from one another and from the parental cell line as defined by Illumina expression microarray. Consistent with this, reverse phase protein array defines differences in protein expression/activation between MLMs as well as the parental line. While in vitro growth rates of MLMs are slower than the parental line, in vivo growth of MLM clones is greatly enhanced. Moreover, in vivo resistance to standard therapies is dramatically increased in 3 of the 4 MLMs. Lymphatic and/or lung metastasis occurs 100% of the time in one MLM line. This recurrent/metastatic model of HPV+ OPSCC retains the characteristics evident in refractory human disease (heterogeneity, resistance to therapy, metastasis in lymph nodes/lungs) thus serving as an ideal translational system to test novel therapeutics. Moreover, this system may provide insights into the molecular mechanisms of metastasis

History of Hydrogen Reionization in the Cold Dark Matter Model

We calculate the reionization history in Cold Dark Matter (CDM) models. The epoch of the end of reionization and the Thomson scattering optical depth to the cosmic microwave background depend on the power spectrum amplitude on small scales and on the ionizing photon emissivity per unit mass in collapsed halos. We calibrate the emissivity to reproduce the measured ionizing background intensity at z=4. Models in which all CDM halos have either a constant emissivity or a constant energy emitted per Hubble time, per unit mass, predict that reionization ends near z~6 and the optical depth is in the range 0.05 < tau_e < 0.09, consistent with WMAP results at the 1 to 2 sigma level. If the optical depth is as high as 0.17 (as suggested by WMAP), halos of velocity dispersion ~ 3-30 km/s at z>15 must have ionizing emissivities per unit mass larger by a factor >~ 50 compared to the more massive halos that produce the ionizing emissivity at z=4. This factor increases to 100 if the CDM power spectrum amplitude is required to agree with the Croft et al. (2002) measurement from the Lyman alpha forest. If tau_e >~ 0.17 were confirmed, a higher ionizing emissivity at z>15 compared to z=4 might arise from an enhanced star formation rate or quasar abundance per unit mass and an increased escape fraction for ionizing photons; the end of reionization could have been delayed to z~6 because of the suppression of gas accretion and star formation in low-mass halos as the medium was reionized.Comment: 19 pages, 4 figues, submitted to Ap

The Mass of the Central Black Hole in the Seyfert Galaxy NGC 4151

In order to improve the reverberation-mapping based estimate of the mass of the central supermassive black hole in the Seyfert 1 galaxy NGC 4151, we have reanalyzed archival ultraviolet monitoring spectra from two campaigns undertaken with the International Ultraviolet Explorer. We measure emission-line time delays for four lines, C IV 1549, He II 1640, C III] 1909, and Mg II 2798, from both campaigns. We combine these measurements with the dispersion of the variable part of each respective emission line to obtain the mass of the central object. Despite the problematic nature of some of the data, we are able to measure a mass of 41.1 (+/- 7.3) million solar masses, although this, like all reverberation-based masses, is probably systematically uncertain by a factor of 3-4.Comment: 25 pages, 5 figures. Accepted for publication in The Astrophysical Journa

Central Masses and Broad-Line Region Sizes of Active Galactic Nuclei. II. A Homogeneous Analysis of a Large Reverberation-Mapping Database

We present improved black hole masses for 35 active galactic nuclei (AGNs) based on a complete and consistent reanalysis of broad emission-line reverberation-mapping data. From objects with multiple line measurements, we find that the highest precision measure of the virial product is obtained by using the cross-correlation function centroid (as opposed to the cross-correlation function peak) for the time delay and the line dispersion (as opposed to full width half maximum) for the line width and by measuring the line width in the variable part of the spectrum. Accurate line-width measurement depends critically on avoiding contaminating features, in particular the narrow components of the emission lines. We find that the precision (or random component of the error) of reverberation-based black hole mass measurements is typically around 30%, comparable to the precision attained in measurement of black hole masses in quiescent galaxies by gas or stellar dynamical methods. Based on results presented in a companion paper by Onken et al., we provide a zero-point calibration for the reverberation-based black hole mass scale by using the relationship between black hole mass and host-galaxy bulge velocity dispersion. The scatter around this relationship implies that the typical systematic uncertainties in reverberation-based black hole masses are smaller than a factor of three. We present a preliminary version of a mass-luminosity relationship that is much better defined than any previous attempt. Scatter about the mass-luminosity relationship for these AGNs appears to be real and could be correlated with either Eddington ratio or object inclination.Comment: 61 pages, including 8 Tables and 16 Figures. Accepted for publication in The Astrophysical Journa

X-Ray Properties of Narrow-Line Seyfert 1 Galaxies with Very Small Broad-Line Widths

Narrow-line Seyfert\,1 galaxies (NLS1s) with very small broad-line widths (say, FWHM(\hb) \la 1200\,\kms) represent the extreme type of Seyfert\,1 galaxies that have small black hole masses (\mbh) and/or high Eddington ratios (\redd). Here we study the X-ray properties of a homogeneously and optically selected sample of 13 such objects, termed as very narrow line Seyfert\,1 galaxies (VNLS1s), using archival \xmm\ data. It is found that the Fe K$\alpha$ emission line is at most weak in these objects. A soft X-ray excess is ubiquitous, with the thermal temperatures falling within a strict range of 0.1--0.2\,keV. Our result highlights the puzzling independence of the thermal temperature by extending the relations to even smaller FWHM(\hb), i.e., smaller \mbh\ ($\sim 10^6$ \msun) and/or higher \redd. The excess emission can be modeled by a range of viable models, though the disk reflection and Comptonization models generally give somewhat better fits over the smeared absorption and the $p$-free models. At the Eddington ratios around unity and above, the X-ray spectral slopes in the 2--10\,keV band are systematically flatter than the Risaliti et al.'s predictions of the relationship with \redd\ suggested previously. Short timescale (1--2 hours) X-ray variability is common, which, together with the variability amplitude computed for some of the objects, are supportive of the scenario that NLS1s are indeed AGN with relatively small \mbh.Comment: 11 figures and 4 table. Accepted for publication in the Astrophysical Journa

Formation of a galaxy with a central black hole in the Lemaitre-Tolman model

We construct two models of the formation a galaxy with a central black hole, starting from a small initial fluctuation at recombination. This is an application of previously developed methods to find a Lemaitre-Tolman model that evolves from a given initial density or velocity profile to a given final density profile. We show that the black hole itself could be either a collapsed object, or a non-vacuum generalisation of a full Schwarzschild-Kruskal-Szekeres wormhole. Particular attention is paid to the black hole's apparent and event horizons.Comment: REVTeX, 22 pages including 11 figures (25 figure files). Replacement has minor changes in response to the referee, and editorial corrections. To appear in PR

Supermassive Black Holes in Active Galactic Nuclei. II. Calibration of the M-sigma Relationship for AGNs

We calibrate reverberation-based black hole masses in active galactic nuclei (AGNs) by using the correlation between black hole mass, M, and bulge/spheroid stellar velocity dispersion, sigma. We use new measurements of sigma for 6 AGNs and published velocity dispersions for 10 others, in conjunction with improved reverberation mapping results, to determine the scaling factor required to bring reverberation-based black hole masses into agreement with the quiescent galaxy M-sigma relationship. The scatter in the AGN black hole masses is found to be less than a factor of 3. The current observational uncertainties preclude use of the scaling factor to discriminate between broad-line region models.Comment: 16 pages, including 3 figures. Accepted for publication in Ap