Extrapolating SMBH correlations down the mass scale: the case for IMBHs in globular clusters

Empirical evidence for both stellar mass black holes M_bh<10^2 M_sun) and supermassive black holes (SMBHs, M_bh>10^5 M_sun) is well established. Moreover, every galaxy with a bulge appears to host a SMBH, whose mass is correlated with the bulge mass, and even more strongly with the central stellar velocity dispersion sigma_c, the `M-sigma' relation. On the other hand, evidence for "intermediate-mass" black holes (IMBHs, with masses in the range 1^2 - 10^5 M_sun) is relatively sparse, with only a few mass measurements reported in globular clusters (GCs), dwarf galaxies and low-mass AGNs. We explore the question of whether globular clusters extend the M-sigma relationship for galaxies to lower black hole masses and find that available data for globular clusters are consistent with the extrapolation of this relationship. We use this extrapolated M-sigma relationship to predict the putative black hole masses of those globular clusters where existence of central IMBH was proposed. We discuss how globular clusters can be used as a constraint on theories making specific predictions for the low-mass end of the M-sigma relation.Comment: 14 pages, 3 figures, accepted for publication in Astrophysics and Space Science; fixed typos and a quote in Sec.

Track E Implementation Science, Health Systems and Economics

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/138412/1/jia218443.pd

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

X-ray induced fluorescence measurement of segregation in a DyI3–Hg metal-halide lamp

Segregation of elemental Dy in a DyI3–Hg metal-halide high-intensity discharge lamp has been observed with x-ray induced fluorescence. Significant radial and axial Dy segregation are seen, with the axial segregation characterized by a Fischer parameter value of λ = 0.215 ± 0.002mm−1. This is within 7% of the value (λ = 0.20±0.01mm−1) obtained by Flikweert et al (2005 J. Appl. Phys. 98 073301) based on laser absorption by neutral Dy atoms. Elemental I is seento exhibit considerably less axial and radial segregation. Some aspects of the observed radial segregation are compatible with a simplified fluid picture describing two main transition regions in the radial coordinate. The first transition occurs in the region where DyI3 molecules are in equilibrium with neutral Dy atoms. The second transition occurs where neutral Dy atoms are in equilibrium with ionized Dy. These measurements are part of a larger study on segregation in metal-halide lamps under a variety of conditions

Genome-wide study identifies association between HLA-B∗55:01 and Self-Reported Penicillin Allergy

Hypersensitivity reactions to drugs are often unpredictable and can be life threatening, underscoring a need for understanding their underlying mechanisms and risk factors. The extent to which germline genetic variation influences the risk of commonly reported drug allergies such as penicillin allergy remains largely unknown. We extracted data from the electronic health records of more than 600,000 participants from the UK, Estonian, and Vanderbilt University Medical Center’s BioVU biobanks to study the role of genetic variation in the occurrence of self-reported penicillin hypersensitivity reactions. We used imputed SNP to HLA typing data from these cohorts to further fine map the human leukocyte antigen (HLA) association and replicated our results in 23andMe’s research cohort involving a total of 1.12 million individuals. Genome-wide meta-analysis of penicillin allergy revealed two loci, including one located in the HLA region on chromosome 6. This signal was further fine-mapped to the HLA-B∗55:01 allele (OR 1.41 95% CI 1.33–1.49, p value 2.04 × 10−31) and confirmed by independent replication in 23andMe’s research cohort (OR 1.30 95% CI 1.25–1.34, p value 1.00 × 10−47). The lead SNP was also associated with lower lymphocyte counts and in silico follow-up suggests a potential effect on T-lymphocytes at HLA-B∗55:01. We also observed a significant hit in PTPN22 and the GWAS results correlated with the genetics of rheumatoid arthritis and psoriasis. We present robust evidence for the role of an allele of the major histocompatibility complex (MHC) I gene HLA-B in the occurrence of penicillin allergy