Asymptotic Spectrum of Kerr Black Holes in the Small Angular Momentum Limit

We study analytically the highly damped quasinormal modes of Kerr black holes in the small angular momentum limit. To check the previous analytic calculations in the literature, which use a combination of radial and tortoise coordinates, we reproduce all the results using the radial coordinate only. According to the earlier calculations, the real part of the highly damped quasinormal mode frequency of Kerr black holes approaches zero in the limit where the angular momentum goes to zero. This result is not consistent with the Schwarzschild limit where the real part of the highly damped quasinormal mode frequency is equal to c^3 ln(3)/(8 pi G M). In this paper, our calculations suggest that the highly damped quasinormal modes of Kerr black holes in the zero angular momentum limit make a continuous transition from the Kerr value to the Schwarzschild value. We explore the nature of this transition using a combination of analytical and numerical techniques. Finally, we calculate the highly damped quasinormal modes of the extremal case in which the topology of Stokes/anti-Stokes lines takes a different form.Comment: 13 pages, 6 figure

Wolf 1130: A Nearby Triple System Containing a Cool, Ultramassive White Dwarf

Following the discovery of the T8 subdwarf WISEJ200520.38+542433.9 (Wolf 1130C), with common proper motion to a binary (Wolf 1130AB) consisting of an M subdwarf and a white dwarf, we set out to learn more about the old binary in the system. We find that the A and B components of Wolf 1130 are tidally locked, which is revealed by the coherence of more than a year of V band photometry phase folded to the derived orbital period of 0.4967 days. Forty new high-resolution, near-infrared spectra obtained with the Immersion Grating Infrared Spectrometer (IGRINS) provide radial velocities and a projected rotational velocity (v sin i) of 14.7 +/- 0.7 km/s for the M subdwarf. In tandem with a Gaia parallax-derived radius and verified tidal-locking, we calculate an inclination of i=29 +/- 2 degrees. From the single-lined orbital solution and the inclination we derive an absolute mass for the unseen primary (1.24+0.19-0.15 Msun). Its non-detection between 0.2 and 2.5 microns implies that it is an old (>3.7 Gyr) and cool (Teff<7000K) ONe white dwarf. This is the first ultramassive white dwarf within 25pc. The evolution of Wolf 1130AB into a cataclysmic variable is inevitable, making it a potential Type Ia supernova progenitor. The formation of a triple system with a primary mass >100 times the tertiary mass and the survival of the system through the common-envelope phase, where ~80% of the system mass was lost, is remarkable. Our analysis of Wolf 1130 allows us to infer its formation and evolutionary history, which has unique implications for understanding low-mass star and brown dwarf formation around intermediate mass stars.Comment: 37 pages, 9 Figures, 5 Table

High-Velocity Features of Calcium and Silicon in the Spectra of Type Ia Supernovae

"High-velocity features" (HVFs) are spectral features in Type Ia supernovae (SNe Ia) that have minima indicating significantly higher (by greater than about 6000 km/s) velocities than typical "photospheric-velocity features" (PVFs). The PVFs are absorption features with minima indicating typical photospheric (i.e., bulk ejecta) velocities (usually ~9000-15,000 km/s near B-band maximum brightness). In this work we undertake the most in-depth study of HVFs ever performed. The dataset used herein consists of 445 low-resolution optical and near-infrared (NIR) spectra (at epochs up to 5 d past maximum brightness) of 210 low-redshift SNe Ia that follow the "Phillips relation." A series of Gaussian functions is fit to the data in order to characterise possible HVFs of Ca II H&K, Si II {\lambda}6355, and the Ca II NIR triplet. The temporal evolution of the velocities and strengths of the PVFs and HVFs of these three spectral features is investigated, as are possible correlations with other SN Ia observables. We find that while HVFs of Ca II are regularly observed (except in underluminous SNe Ia, where they are never found), HVFs of Si II {\lambda}6355 are significantly rarer, and they tend to exist at the earliest epochs and mostly in objects with large photospheric velocities. It is also shown that stronger HVFs of Si II {\lambda}6355 are found in objects that lack C II absorption at early times and that have red ultraviolet/optical colours near maximum brightness. These results lead to a self-consistent connection between the presence and strength of HVFs of Si II {\lambda}6355 and many other mutually correlated SN~Ia observables, including photospheric velocity.Comment: 48 pages (22 of which are tables), 15 figures, 5 tables, re-submitted to MNRAS (after first referee report

Wolf 1130: A Nearby Triple System Containing a Cool, Ultramassive White Dwarf

Following the discovery of the T8 subdwarf WISE J200520.38+542433.9 (Wolf 1130C), which has a proper motion in common with a binary (Wolf 1130AB) consisting of an M subdwarf and a white dwarf, we set out to learn more about the old binary in the system. We find that the A and B components of Wolf 1130 are tidally locked, which is revealed by the coherence of more than a year of V-band photometry phase-folded to the derived orbital period of 0.4967 days. Forty new high-resolution, near-infrared spectra obtained with the Immersion Grating Infrared Spectrometer provide radial velocities and a projected rotational velocity (v sin i) of 14.7 ± 0.7 km s^(-1) for the M subdwarf. In tandem with a Gaia parallax-derived radius and verified tidal locking, we calculate an inclination of i = 29° ± 2°. From the single-lined orbital solution and the inclination we derive an absolute mass for the unseen primary (1.24^(+0.19)_(-0.15) M ⊙). Its non-detection between 0.2 and 2.5 μm implies that it is an old (>3.7 Gyr) and cool (T_(eff) 100 times the tertiary mass and the survival of the system through the common-envelope phase, where ~80% of the system mass was lost, is remarkable. Our analysis of Wolf 1130 allows us to infer its formation and evolutionary history, which has unique implications for understanding low-mass star and brown dwarf formation around intermediate-mass stars

Cancer-Associated Fibroblasts Neutralize the Anti-tumor Effect of CSF1 Receptor Blockade by Inducing PMN-MDSC Infiltration of Tumors.

Tumor-associated macrophages (TAM) contribute to all aspects of tumor progression. Use of CSF1R inhibitors to target TAM is therapeutically appealing, but has had very limited anti-tumor effects. Here, we have identified the mechanism that limited the effect of CSF1R targeted therapy. We demonstrated that carcinoma-associated fibroblasts (CAF) are major sources of chemokines that recruit granulocytes to tumors. CSF1 produced by tumor cells caused HDAC2-mediated downregulation of granulocyte-specific chemokine expression in CAF, which limited migration of these cells to tumors. Treatment with CSF1R inhibitors disrupted this crosstalk and triggered a profound increase in granulocyte recruitment to tumors. Combining CSF1R inhibitor with a CXCR2 antagonist blocked granulocyte infiltration of tumors and showed strong anti-tumor effects

Genetic predisposition to in situ and invasive lobular carcinoma of the breast.

Invasive lobular breast cancer (ILC) accounts for 10-15% of all invasive breast carcinomas. It is generally ER positive (ER+) and often associated with lobular carcinoma in situ (LCIS). Genome-wide association studies have identified more than 70 common polymorphisms that predispose to breast cancer, but these studies included predominantly ductal (IDC) carcinomas. To identify novel common polymorphisms that predispose to ILC and LCIS, we pooled data from 6,023 cases (5,622 ILC, 401 pure LCIS) and 34,271 controls from 36 studies genotyped using the iCOGS chip. Six novel SNPs most strongly associated with ILC/LCIS in the pooled analysis were genotyped in a further 516 lobular cases (482 ILC, 36 LCIS) and 1,467 controls. These analyses identified a lobular-specific SNP at 7q34 (rs11977670, OR (95%CI) for ILC = 1.13 (1.09-1.18), P = 6.0 × 10(-10); P-het for ILC vs IDC ER+ tumors = 1.8 × 10(-4)). Of the 75 known breast cancer polymorphisms that were genotyped, 56 were associated with ILC and 15 with LCIS at P<0.05. Two SNPs showed significantly stronger associations for ILC than LCIS (rs2981579/10q26/FGFR2, P-het = 0.04 and rs889312/5q11/MAP3K1, P-het = 0.03); and two showed stronger associations for LCIS than ILC (rs6678914/1q32/LGR6, P-het = 0.001 and rs1752911/6q14, P-het = 0.04). In addition, seven of the 75 known loci showed significant differences between ER+ tumors with IDC and ILC histology, three of these showing stronger associations for ILC (rs11249433/1p11, rs2981579/10q26/FGFR2 and rs10995190/10q21/ZNF365) and four associated only with IDC (5p12/rs10941679; rs2588809/14q24/RAD51L1, rs6472903/8q21 and rs1550623/2q31/CDCA7). In conclusion, we have identified one novel lobular breast cancer specific predisposition polymorphism at 7q34, and shown for the first time that common breast cancer polymorphisms predispose to LCIS. We have shown that many of the ER+ breast cancer predisposition loci also predispose to ILC, although there is some heterogeneity between ER+ lobular and ER+ IDC tumors. These data provide evidence for overlapping, but distinct etiological pathways within ER+ breast cancer between morphological subtypes

Genome-wide association analysis of more than 120,000 individuals identifies 15 new susceptibility loci for breast cancer.

Genome-wide association studies (GWAS) and large-scale replication studies have identified common variants in 79 loci associated with breast cancer, explaining ∼14% of the familial risk of the disease. To identify new susceptibility loci, we performed a meta-analysis of 11 GWAS, comprising 15,748 breast cancer cases and 18,084 controls together with 46,785 cases and 42,892 controls from 41 studies genotyped on a 211,155-marker custom array (iCOGS). Analyses were restricted to women of European ancestry. We generated genotypes for more than 11 million SNPs by imputation using the 1000 Genomes Project reference panel, and we identified 15 new loci associated with breast cancer at P < 5 × 10(-8). Combining association analysis with ChIP-seq chromatin binding data in mammary cell lines and ChIA-PET chromatin interaction data from ENCODE, we identified likely target genes in two regions: SETBP1 at 18q12.3 and RNF115 and PDZK1 at 1q21.1. One association appears to be driven by an amino acid substitution encoded in EXO1.BCAC is funded by Cancer Research UK (C1287/A10118, C1287/A12014) and by the European Community's Seventh Framework Programme under grant agreement 223175 (HEALTH-F2-2009-223175) (COGS). Meetings of the BCAC have been funded by the European Union COST programme (BM0606). Genotyping on the iCOGS array was funded by the European Union (HEALTH-F2-2009-223175), Cancer Research UK (C1287/A10710, C8197/A16565), the Canadian Institutes of Health Research (CIHR) for the CIHR Team in Familial Risks of Breast Cancer program and the Ministry of Economic Development, Innovation and Export Trade of Quebec, grant PSR-SIIRI-701. Combination of the GWAS data was supported in part by the US National Institutes of Health (NIH) Cancer Post-Cancer GWAS initiative, grant 1 U19 CA148065-01 (DRIVE, part of the GAME-ON initiative). For a full description of funding and acknowledgments, see the Supplementary Note.This is the author accepted manuscript. The final version is available from NPG via http://dx.doi.org/10.1038/ng.324

Breast cancer risk variants at 6q25 display different phenotype associations and regulate ESR1, RMND1 and CCDC170.

We analyzed 3,872 common genetic variants across the ESR1 locus (encoding estrogen receptor α) in 118,816 subjects from three international consortia. We found evidence for at least five independent causal variants, each associated with different phenotype sets, including estrogen receptor (ER(+) or ER(-)) and human ERBB2 (HER2(+) or HER2(-)) tumor subtypes, mammographic density and tumor grade. The best candidate causal variants for ER(-) tumors lie in four separate enhancer elements, and their risk alleles reduce expression of ESR1, RMND1 and CCDC170, whereas the risk alleles of the strongest candidates for the remaining independent causal variant disrupt a silencer element and putatively increase ESR1 and RMND1 expression.This is the author accepted manuscript. The final version is available from Nature Publishing Group via http://dx.doi.org/10.1038/ng.352