H-beta Line Width and the UV-X-ray Spectra of Luminous AGN

The width of the broad H-beta emission line is the primary defining characteristic of the NLS1 class. This parameter is also an important component of Boroson and Green's optical Eigenvector 1 (EV1), which links steeper soft X-ray spectra with narrower H-beta emission, stronger H-beta blue wing, stronger optical Fe II emission, and weaker [O III] lambda 5007. Potentially, EV1 represents a fundamental physical process linking the dynamics of fueling and outflow with the accretion rate. We attempted to understand these relationships by extending the optical spectra into the UV for a sample of 22 QSOs with high quality soft-X-ray spectra, and discovered a whole new set of UV relationships that suggest that high accretion rates are linked to dense gas and perhaps nuclear starbursts. While it has been argued that narrow (BLR) H-beta means low Black Hole mass in luminous NLS1s, the C IV, lambda 1549 and Ly alpha emission lines are broader, perhaps the result of outflows driven by their high Eddington accretion rates. We present some new trends of optical-UV with X-ray spectral energy distributions. Steeper X-ray spectra appear associated with stronger UV relative to optical continua, but the presence of strong UV absorption lines is associated with depressed soft X-rays and redder optical-UV continua.Comment: Invited talk presented at the Joint MPE,AIP,ESO workshop on NLS1s, Bad Honnef, Dec. 1999, to appear in New Astronomy Reviews; also available at http://wave.xray.mpe.mpg.de/conferences/nls1-worksho

Tonicity-responsive microRNAs contribute to the maximal induction of osmoregulatory transcription factor OREBP in response to high-NaCl hypertonicity

Osmotic response element binding protein (OREBP) is a Rel-like transcription factor critical for cellular osmoresponses. Previous studies suggest that hypertonicity-induced accumulation of OREBP protein might be mediated by transcription activation as well as posttranscriptional mRNA stabilization or increased translation. However, the underlying mechanisms remain incompletely elucidated. Here, we report that microRNAs (miRNAs) play critical regulatory roles in hypertonicity-induced induction of OREBP. In renal medullary epithelial mIMCD3 cells, hypertonicity greatly stimulates the activity of the 3′-untranslated region of OREBP (OREBP-3′UTR). Furthermore, overexpression of OREBP-3′UTR or depletion of miRNAs by knocking-down Dicer greatly increases OREBP protein expression. On the other hand, significant alterations in miRNA expression occur rapidly in response to high NaCl exposure, with miR-200b and miR-717 being most significantly down-regulated. Moreover, increased miR-200b or miR-717 causes significant down-regulation of mRNA, protein and transcription activity of OREBP, whereas inhibition of miRNAs or disruption of the miRNA–3′UTR interactions abrogates the silencing effects. In vivo in mouse renal medulla, miR-200b and miR-717 are found to function to tune OREBP in response to renal tonicity alterations. Together, our results support the notion that miRNAs contribute to the maximal induction of OREBP to participate in cellular responses to osmotic stress in mammalian renal cells

Strategic Learning for Active, Adaptive, and Autonomous Cyber Defense

The increasing instances of advanced attacks call for a new defense paradigm that is active, autonomous, and adaptive, named as the \texttt{`3A'} defense paradigm. This chapter introduces three defense schemes that actively interact with attackers to increase the attack cost and gather threat information, i.e., defensive deception for detection and counter-deception, feedback-driven Moving Target Defense (MTD), and adaptive honeypot engagement. Due to the cyber deception, external noise, and the absent knowledge of the other players' behaviors and goals, these schemes possess three progressive levels of information restrictions, i.e., from the parameter uncertainty, the payoff uncertainty, to the environmental uncertainty. To estimate the unknown and reduce uncertainty, we adopt three different strategic learning schemes that fit the associated information restrictions. All three learning schemes share the same feedback structure of sensation, estimation, and actions so that the most rewarding policies get reinforced and converge to the optimal ones in autonomous and adaptive fashions. This work aims to shed lights on proactive defense strategies, lay a solid foundation for strategic learning under incomplete information, and quantify the tradeoff between the security and costs.Comment: arXiv admin note: text overlap with arXiv:1906.1218

Strong protective effect of the APOL1 p.N264K variant against G2-associated focal segmental glomerulosclerosis and kidney disease

Abstract African Americans have a significantly higher risk of developing chronic kidney disease, especially focal segmental glomerulosclerosis -, than European Americans. Two coding variants (G1 and G2) in the APOL1 gene play a major role in this disparity. While 13% of African Americans carry the high-risk recessive genotypes, only a fraction of these individuals develops FSGS or kidney failure, indicating the involvement of additional disease modifiers. Here, we show that the presence of the APOL1 p.N264K missense variant, when co-inherited with the G2 APOL1 risk allele, substantially reduces the penetrance of the G1G2 and G2G2 high-risk genotypes by rendering these genotypes low-risk. These results align with prior functional evidence showing that the p.N264K variant reduces the toxicity of the APOL1 high-risk alleles. These findings have important implications for our understanding of the mechanisms of APOL1-associated nephropathy, as well as for the clinical management of individuals with high-risk genotypes that include the G2 allele