The Contribution Of Outer HI Disks To The Merging Binary Black Hole Population

We investigate the contribution of outer HI disks to the observable population of merging black hole binaries. Like dwarf galaxies, the outer HI disks of spirals have low star formation rates and lower metallicities than the inner disks of spirals. Since low-metallicity star formation can produce more detectable compact binaries than typical star formation, the environments in the outskirts of spiral galaxies may be conducive to producing a rich population of massive binary black holes. We consider here both detailed controlled simulations of spirals and cosmological simulations, as well as the current range of observed values for metallicity and star formation in outer disks. We find that outer HI disks contribute at least as much as dwarf galaxies do to the observed LIGO/Virgo detection rates. Identifying the host galaxies of merging massive black holes should provide constraints on cosmological parameters and insights into the formation channels of binary mergers.Comment: accepted to ApJL, 5 pages, 2 figure

The First Massive Black Hole Seeds and Their Hosts

We investigate the formation of the first massive black holes (MBHs) in high redshift galaxies, with the goal of providing insights to which galaxies do or do not host MBHs. We adopt a novel approach to forming seed black holes in galaxy halos in cosmological SPH+ N -body simulations. The formation of MBH seeds is dictated directly by the local gas density, temperature, and metallicity, and motivated by physical models of MBH formation. We explore seed black hole populations as a function of halo mass and redshift, and examine how varying the efficiency of MBH seed formation affects the relationship between black holes and their hosts. Seed black holes tend to form in halos with mass between 10 7 and 10 9 M _ , and the formation rate is suppressed around z = 5 due to the diffusion of metals throughout the intergalactic medium. We find that the time of MBH formation and the occupation fraction of black holes are a function of the host halo mass. By z = 5, halos with mass M halo > 3 _ 10 9 M _ host MBHs regardless of the efficiency of seed formation, while the occupation fraction for smaller halos increases with black hole formation efficiency. Our simulations explain why MBHs are found in some bulgeless and dwarf galaxies, but we also predict that their occurrence becomes rarer and rarer in low-mass systems.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/90769/1/0004-637X_742_1_13.pd

Bicultural Competence and the Latino 2.5 Generation: The Acculturative Advantages and Challenges of Having One Foreign-Born and One U.S.-Born Parent

The 2.5 generation refers to individuals who have one parent born in the United States and one born in another country. The presence of both native-born and foreign-born parents has the potential to enhance bicultural adaptation. Across two studies with Latino young adults, we examine the extent to which the 2.5 generation is distinct from members of other generations with regard to cultural orientation, acculturative stress, and parent ethnic socialization. Results suggest that the 2.5-generation individuals report greater native cultural orientation, ethnic identity, and parental socialization compared with third-generation individuals, along with greater American orientation than first-generation individuals. The 2.5 generation also reports less language use and more acculturative stress due to Spanish competency pressures than firstand second-generation individuals. These results demonstrate that the 2.5-generation individuals may have some bicultural advantages compared with third-generation individuals; however, they may also experience similar challenges with regard to language maintenance

Bicultural Competence and the Latino 2.5 Generation: The Acculturative Advantages and Challenges of Having One Foreign-Born and One U.S.-Born Parent

The 2.5 generation refers to individuals who have one parent born in the United States and one born in another country. The presence of both native-born and foreign-born parents has the potential to enhance bicultural adaptation. Across two studies with Latino young adults, we examine the extent to which the 2.5 generation is distinct from members of other generations with regard to cultural orientation, acculturative stress, and parent ethnic socialization. Results suggest that the 2.5-generation individuals report greater native cultural orientation, ethnic identity, and parental socialization compared with third-generation individuals, along with greater American orientation than first-generation individuals. The 2.5 generation also reports less language use and more acculturative stress due to Spanish competency pressures than firstand second-generation individuals. These results demonstrate that the 2.5-generation individuals may have some bicultural advantages compared with third-generation individuals; however, they may also experience similar challenges with regard to language maintenance

Dwarf AGNs from Variability for the Origins of Seeds (DAVOS): Intermediate-mass black hole demographics from optical synoptic surveys

We present a phenomenological forward Monte Carlo model for forecasting the population of active galactic nuclei (AGNs) in dwarf galaxies observable via their optical variability. Our model accounts for expected changes in the spectral energy distribution of AGNs in the intermediate-mass black hole (IMBH) mass range and uses observational constraints on optical variability as a function of black hole (BH) mass to generate mock light curves. Adopting several different models for the BH occupation function, including one for off-nuclear IMBHs, we quantify differences in the predicted local AGN mass and luminosity functions in dwarf galaxies. As a result, we are able to model the variable fraction of AGNs as a function of physical host properties, such as host galaxy stellar mass, in the presence of complex selection effects. We find that our adopted occupation fractions for the "heavy" and "light" initial BH seeding scenarios can be distinguished with variability data at the $2-3 \sigma$ level for galaxy host stellar masses below $\sim 10^8 M_\odot$ with the Vera C. Rubin Observatory. We demonstrate the prevalence of a selection bias whereby recovered IMBH masses fall, on average, above the predicted value from the local host galaxy - BH mass scaling relation with the strength of the bias dependent on the survey sensitivity. The methodology developed in this work can be used more broadly to forecast and correct for selection effects for AGN demographic studies in synoptic surveys. Finally, we show that a targeted $\sim$ hourly cadence program over a few nights with the Rubin Observatory can provide strong constraints on IMBH masses given their expected rapid variability timescales.Comment: 26 pages, 16 figures incl. 5 appendices; re-submitted to MNRAS following referee repor

A high-throughput de novo sequencing approach for shotgun proteomics using high-resolution tandem mass spectrometry

<p>Abstract</p> <p>Background</p> <p>High-resolution tandem mass spectra can now be readily acquired with hybrid instruments, such as LTQ-Orbitrap and LTQ-FT, in high-throughput shotgun proteomics workflows. The improved spectral quality enables more accurate <it>de novo </it>sequencing for identification of post-translational modifications and amino acid polymorphisms.</p> <p>Results</p> <p>In this study, a new <it>de novo </it>sequencing algorithm, called Vonode, has been developed specifically for analysis of such high-resolution tandem mass spectra. To fully exploit the high mass accuracy of these spectra, a unique scoring system is proposed to evaluate sequence tags based primarily on mass accuracy information of fragment ions. Consensus sequence tags were inferred for 11,422 spectra with an average peptide length of 5.5 residues from a total of 40,297 input spectra acquired in a 24-hour proteomics measurement of <it>Rhodopseudomonas palustris</it>. The accuracy of inferred consensus sequence tags was 84%. According to our comparison, the performance of Vonode was shown to be superior to the PepNovo v2.0 algorithm, in terms of the number of <it>de novo </it>sequenced spectra and the sequencing accuracy.</p> <p>Conclusions</p> <p>Here, we improved <it>de novo </it>sequencing performance by developing a new algorithm specifically for high-resolution tandem mass spectral data. The Vonode algorithm is freely available for download at <url>http://compbio.ornl.gov/Vonode</url>.</p

TNK2 preserves epidermal growth factor receptor expression on the cell surface and enhances migration and invasion of human breast cancer cells

Introduction Amplification of the TNK2 gene in primary tumours correlates with poor prognosis. In accordance, TNK2 overexpression was shown to promote invasion of cancer cells - but the mechanism by which TNK2 mediates these effects is unresolved. TNK2 was suggested to regulate Cdc42-driven migration by activation of breast cancer antioestrogen resistance 1 (BCAR1); however, distinct from this effect is evidence for a role of TNK2 in the regulation of epidermal growth factor receptor (EGFR) endocytosis and degradation. In the present study we sought to investigate whether negative targeting of TNK2 by siRNA could be used to inhibit cancer cell invasion, to establish the contribution of its effect on the EGFR and to consequently attempt to resolve the issue of TNK2's mechanism of action. Methods We used siRNA to knockdown expression of TNK2 and its proposed effector BCAR1 in order to analyse the effect of this knockdown on cancer cell behaviour in vitro. We examined morphological changes using phase-contrast microscopy and immunohistochemistry. Functional parameters examined included apoptosis, proliferation, migration and invasion. We also performed flow cytometry analysis to examine EGFR cell surface expression and carried out western blot to examine the total EGFR levels. Results We observed that targeting of TNK2 by siRNA in breast cancer cells resulted in distinct morphological changes characterised by a stellate appearance and an absence of protrusions at membrane edges. These changes were not recapitulated upon siRNA targeting of BCAR1. We thus hypothesised that a component of the effects induced by TNK2 may be independent of BCAR1. Consistent with the idea of an alternative mechanism for TNK2, we observed that TNK2 associates with activated EGFR in breast cancer cells in a TNK2-kinase-independent manner. Furthermore, we demonstrated that TNK2 functions to maintain EGFRs on the cell surface. We could demonstrate that the main functional effect of activating these surface EGFRs in breast cancer cells is stimulation of migration. In accordance, TNK2 silencing by siRNA led to a significant reduction in cell surface EGFR and to a concomitant decrease in the migratory and invasive capacity of breast cancer cells. Conclusion Our data suggest that TNK2 can enhance migration and invasion of breast cancer cells via preservation of EGFR expression, notwithstanding its previously reported signalling via BCAR1, explaining its oncogenic behaviour in vitro and correlation with metastatic human breast cancer in vivo

Identification of 12 new susceptibility loci for different histotypes of epithelial ovarian cancer.

To identify common alleles associated with different histotypes of epithelial ovarian cancer (EOC), we pooled data from multiple genome-wide genotyping projects totaling 25,509 EOC cases and 40,941 controls. We identified nine new susceptibility loci for different EOC histotypes: six for serous EOC histotypes (3q28, 4q32.3, 8q21.11, 10q24.33, 18q11.2 and 22q12.1), two for mucinous EOC (3q22.3 and 9q31.1) and one for endometrioid EOC (5q12.3). We then performed meta-analysis on the results for high-grade serous ovarian cancer with the results from analysis of 31,448 BRCA1 and BRCA2 mutation carriers, including 3,887 mutation carriers with EOC. This identified three additional susceptibility loci at 2q13, 8q24.1 and 12q24.31. Integrated analyses of genes and regulatory biofeatures at each locus predicted candidate susceptibility genes, including OBFC1, a new candidate susceptibility gene for low-grade and borderline serous EOC

Global, regional, and national under-5 mortality, adult mortality, age-specific mortality, and life expectancy, 1970–2016: a systematic analysis for the Global Burden of Disease Study 2016

BACKGROUND: Detailed assessments of mortality patterns, particularly age-specific mortality, represent a crucial input that enables health systems to target interventions to specific populations. Understanding how all-cause mortality has changed with respect to development status can identify exemplars for best practice. To accomplish this, the Global Burden of Diseases, Injuries, and Risk Factors Study 2016 (GBD 2016) estimated age-specific and sex-specific all-cause mortality between 1970 and 2016 for 195 countries and territories and at the subnational level for the five countries with a population greater than 200 million in 2016. METHODS: We have evaluated how well civil registration systems captured deaths using a set of demographic methods called death distribution methods for adults and from consideration of survey and census data for children younger than 5 years. We generated an overall assessment of completeness of registration of deaths by dividing registered deaths in each location-year by our estimate of all-age deaths generated from our overall estimation process. For 163 locations, including subnational units in countries with a population greater than 200 million with complete vital registration (VR) systems, our estimates were largely driven by the observed data, with corrections for small fluctuations in numbers and estimation for recent years where there were lags in data reporting (lags were variable by location, generally between 1 year and 6 years). For other locations, we took advantage of different data sources available to measure under-5 mortality rates (U5MR) using complete birth histories, summary birth histories, and incomplete VR with adjustments; we measured adult mortality rate (the probability of death in individuals aged 15-60 years) using adjusted incomplete VR, sibling histories, and household death recall. We used the U5MR and adult mortality rate, together with crude death rate due to HIV in the GBD model life table system, to estimate age-specific and sex-specific death rates for each location-year. Using various international databases, we identified fatal discontinuities, which we defined as increases in the death rate of more than one death per million, resulting from conflict and terrorism, natural disasters, major transport or technological accidents, and a subset of epidemic infectious diseases; these were added to estimates in the relevant years. In 47 countries with an identified peak adult prevalence for HIV/AIDS of more than 0·5% and where VR systems were less than 65% complete, we informed our estimates of age-sex-specific mortality using the Estimation and Projection Package (EPP)-Spectrum model fitted to national HIV/AIDS prevalence surveys and antenatal clinic serosurveillance systems. We estimated stillbirths, early neonatal, late neonatal, and childhood mortality using both survey and VR data in spatiotemporal Gaussian process regression models. We estimated abridged life tables for all location-years using age-specific death rates. We grouped locations into development quintiles based on the Socio-demographic Index (SDI) and analysed mortality trends by quintile. Using spline regression, we estimated the expected mortality rate for each age-sex group as a function of SDI. We identified countries with higher life expectancy than expected by comparing observed life expectancy to anticipated life expectancy on the basis of development status alone. FINDINGS: Completeness in the registration of deaths increased from 28% in 1970 to a peak of 45% in 2013; completeness was lower after 2013 because of lags in reporting. Total deaths in children younger than 5 years decreased from 1970 to 2016, and slower decreases occurred at ages 5-24 years. By contrast, numbers of adult deaths increased in each 5-year age bracket above the age of 25 years. The distribution of annualised rates of change in age-specific mortality rate differed over the period 2000 to 2016 compared with earlier decades: increasing annualised rates of change were less frequent, although rising annualised rates of change still occurred in some locations, particularly for adolescent and younger adult age groups. Rates of stillbirths and under-5 mortality both decreased globally from 1970. Evidence for global convergence of death rates was mixed; although the absolute difference between age-standardised death rates narrowed between countries at the lowest and highest levels of SDI, the ratio of these death rates-a measure of relative inequality-increased slightly. There was a strong shift between 1970 and 2016 toward higher life expectancy, most noticeably at higher levels of SDI. Among countries with populations greater than 1 million in 2016, life expectancy at birth was highest for women in Japan, at 86·9 years (95% UI 86·7-87·2), and for men in Singapore, at 81·3 years (78·8-83·7) in 2016. Male life expectancy was generally lower than female life expectancy between 1970 and 2016, an