We have completed two years of photometric and spectroscopic monitoring of a large number of active galactic nuclei (AGNs) with very high accretion rates. In this paper, we report on the result of the second phase of the campaign, during 2013-2014, and the measurements of five new Hβ time lags out of eight monitored AGNs. All five objects were identified as super-Eddington accreting massive black holes (SEAMBHs). The highest measured accretion rates for the objects in this campaign areṀ 200, wherė M =Ṁ • /L Edd c −2 ,Ṁ • is the mass accretion rates, L Edd is the Eddington luminosity and c is the speed of light. We find that the Hβ time lags in SEAMBHs are significantly shorter than those measured in sub-Eddington AGNs, and the deviations increase with increasing accretion rates. Thus, the relationship between broad-line region size (R Hβ ) and optical luminosity at 5100Å, R Hβ − L 5100 , requires accretion rate as an additional parameter. We propose that much of the effect may be due to the strong anisotropy of the emitted slim-disk radiation. Scaling R Hβ by the gravitational radius of the black hole, we define a new radius-mass parameter (Y ) and show that it saturates at a critical accretion rate ofṀ c = 6 ∼ 30, indicating a transition from thin to slim accretion disk and a saturated luminosity of the slim disks. The parameter Y is a very useful probe -2for understanding the various types of accretion onto massive black holes. We briefly comment on implications to the general population of super-Eddington AGNs in the universe and applications to cosmology.
Background & Aims Constitutive activation of NF-κB and STAT3 pathways in human colorectal cancers links inflammation to CRC development and progression. However, the underlying mechanisms remain to be elucidated. Here we investigated the roles of miR-221 and miR-222 in regulating both NF-κB and STAT3 activities and colorectal tumorigenesis. Methods miR-221/222 mimics and their inhibitors/sponges were transiently or stably transfected into cells. Dual luciferase reporter assays were utilized to examine the activation of both NF-κB and STAT3 signaling, as well as the regulation of miR-221/222. Quantitative PCR and immunoblot analysis were employed to examine the mRNA and protein expression. MTT assay, flow cytometric analysis and xenotransplant of tumor cells were performed to investigate the CRC cell growth in vitro and in vivo. Results miR-221 and miR-222 positively regulate both NF-κB and STAT3 activities, which in return induce miR-221/222 expression, creating a positive feedback loop in human CRCs. miR-221/222 directly bind to the coding region of RelA, leading to increased RelA mRNA stability. In addition, miR-221/222 reduce ubiquitination of RelA and STAT3 proteins by directly targeting the 3′ UTR of PDLIM2, an E3 ligase for both RelA and STAT3. We demonstrate that disruption of the positive feedback loop suppresses human CRC cell growth in vitro and in vivo. The expression of miR-221/222 correlates with the expression of RelA, STAT3 and PDLIM2 in human CRC clinical samples. Conclusions Our findings define a novel miR-221/222 mediated mechanism underlying constitutive activation of NF-κB and STAT3 pathways in human CRCs and provide a promising therapeutic target for human CRCs.
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