Cosmic Evolution of Stellar-mass Black Hole Merger Rate in Active Galactic Nuclei

Binary black hole mergers encode information about their environment and the astrophysical processes that led to their formation. Measuring the redshift dependence of their merger rate will help probe the formation and evolution of galaxies and the evolution of the star formation rate. Here we compute the cosmic evolution of the merger rate for stellar-mass binaries in the disks of Active Galactic Nuclei (AGNs). We focus on recent evolution out to redshift $z=2$, covering the accessible range of current Earth-based gravitational-wave observatories. On this scale, the AGN population density is the main contributor to redshift-dependence. We find that the AGN-assisted merger rate does not meaningfully evolve with redshift, differentiating this channel from field binaries and some other dynamical formation scenarios.Comment: 6 pages, 2 figure

Gravitational wave source populations: Disentangling an AGN component

The astrophysical origin of the over 90 compact binary mergers discovered by the LIGO and Virgo gravitational wave observatories is an open question. While the unusual mass and spin of some of the discovered objects constrain progenitor scenarios, the observed mergers are consistent with multiple interpretations. A promising approach to solve this question is to consider the observed distributions of binary properties and compare them to expectations from different origin scenarios. Here we describe a new hierarchical population analysis framework to assess the relative contribution of different formation channels simultaneously. For this study we considered binary formation in AGN disks along with phenomenological models, but the same framework can be extended to other models. We find that high-mass and high-mass-ratio binaries appear more likely to have an AGN origin compared to the same origin as lower-mass events. Future observations of high-mass black hole mergers could further disentangle the AGN component from other channels.Comment: 7 pages, 4 figures, and 1 tabl

Synthetic DNA immunotherapy in biochemically relapsed prostate cancer

Background: INO-5150 (PSA and PSMA) +/- INO-9012 (IL-12), a synthetic DNA immunotherapy, was assessed for safety, immunogenicity and efficacy in biochemically recurrent prostate cancer patients (pts). Methods: Phase I, open-label, multi-center study in the US included pts with rising PSA after surgery and/or RT, PSA doubling time (PSADT) \u3e3 months (mos), testosterone \u3e150 ng/dL and no concurrent ADT. Safety, immunogenicity and efficacy (PSA kinetics, PFS) were evaluated in 4 treatment arms of 15 pts each. Arms A: 2mg INO-5150, B: 8.5 mg INO-5150, C: 2mg INO-5150 + 1mg INO-9012 and D: 8.5mg INO-5150 + 1mg INO-9012. Pts received 4 IM doses of vaccine followed by electroporation on day 0, wks 3, 12 and 24 and were followed for 72 wks. Results: 50/61 (82%) pts completed all visits and treatments were well tolerated with no safety concerns. Median PFS for overall population [N = 61, baseline (D0) PSADT range (mos) 1.5-217.1, median 9.8] and for a subset of pts with D0 PSADT ≤12mos (N = 36) has not yet been reached (FU 3-19 mos). 86% of pts with D0 PSADT ≤12 mos were progression free through 19mos FU. 27 out of 36 (75%) pts with D0 PSADT≤ 12 mos had disease stabilization at wks 27 evidenced by significant improvement in log2PSA change over time (slope) and PSADT from D0 (Slope=0.19 declined to 0.1, PSADT=5.3 improved to 10.1 mos, p = \u3c0.0001). This effect was maintained at wk 72 (Slope=0.09, PSADT=10.6, p = \u3c0.0001). Immunogenicity was observed in 77% (47/61) of pts by multiple immunologic assessments. Patient immunogenicity to INO-5150 as determined by CD38 and Perforin + CD8 T cell immune reactivity correlated with attenuated % PSA rise compared to pts without reactivity (p = 0.05, n = 50). Conclusions: INO-5150 +/- INO-9012 was safe, well tolerated and immunogenic. Clinical efficacy was observed in the patients with D0 PSADT≤ 12 mos as evidenced by a significant dampening of log2PSA change over time and increased PSADT up to 72 weeks FU. Additional genomic analyses are ongoing to further elucidate the correlation of immunologic efficacy and clinical benefit. (NCT02514213)

The induction levels of heat shock protein 70 differentiate the vulnerabilities to mutant huntingtin among neuronal subtypes

The reason why vulnerabilities to mutant polyglutamine (polyQ) proteins are different among neuronal subtypes is mostly unknown. In this study, we compared the gene expression profiles of three types of primary neurons expressing huntingtin (htt) or ataxin-1. We found that heat shock protein 70 (hsp70), a well known chaperone molecule protecting neurons in the polyQ pathology, was dramatically upregulated only by mutant htt and selectively in the granule cells of the cerebellum. Granule cells, which are insensitive to degeneration in the human Huntington's disease (HD) pathology, lost their resistance by suppressing hsp70 with siRNA, whereas cortical neurons, affected in human HD, gained resistance by overexpressing hsp70. This indicates that induction levels of hsp70 are a critical factor for determining vulnerabilities to mutant htt among neuronal subtypes. CAT (chloramphenicol acetyltransferase) assays showed that CBF (CCAAT box binding factor, CCAAT/enhancer binding protein zeta) activated, but p53 repressed transcription of the hsp70 gene in granule cells. Basal and mutant htt-induced expression levels of p53 were remarkably lower in granule cells than in cortical neurons, suggesting that different magnitudes of p53 are linked to distinct induction levels of hsp70. Surprisingly, however, heat shock factor 1 was not activated in granule cells by mutant htt. Collectively, different levels of hsp70 among neuronal subtypes might be involved in selective neuronal death in the HD pathology

Soliton excitations in halogen-bridged mixed-valence binuclear metal complexes

Motivated by recent stimulative observations in halogen (X)-bridged binuclear transition-metal (M) complexes, which are referred to as MMX chains, we study solitons in a one-dimensional three-quarter-filled charge-density-wave system with both intrasite and intersite electron-lattice couplings. Two distinct ground states of MMX chains are reproduced and the soliton excitations on them are compared. In the weak-coupling region, all the solitons are degenerate to each other and are uniquely scaled by the band gap, whereas in the strong-coupling region, they behave differently deviating from the scenario in the continuum limit. The soliton masses are calculated and compared with those for conventional mononuclear MX chains.Comment: 9 pages, 10 figures embedded, to be published in J. Phys. Soc. Jpn. 71, No. 1 (2002

Effects of single therapeutic doses of promethazine, fexofenadine and olopatadine on psychomotor function and histamine-induced wheal- and flare-responses: a randomized double-blind, placebo-controlled study in healthy volunteers

Since most first-generation antihistamines have undesirable sedative effects on the central nervous systems (CNS), newer (second-generation) antihistamines have been developed to improve patients’ quality of life. However, there are few reports that directly compare the antihistaminic efficacy and impairment of psychomotor functions. We designed a double-blind, placebo controlled, crossover study to concurrently compare the clinical effectiveness of promethazine, a first-generation antihistamine, and fexofenadine and olopatadine, second-generation antihistamines, by measuring their potency as peripheral inhibitors of histamine-induced wheal and flare. Further, we investigated their sedative effects on the CNS using a battery of psychomotor tests. When single therapeutic doses of fexofenadine (60 mg), olopatadine (5 mg) and promethazine (25 mg) were given in a double-blind manner to 24 healthy volunteers, all antihistamines produced a significant reduction in the wheal and flare responses induced by histamine. In the comparison among antihistamines, olopatadine showed a rapid inhibitory effect compared with fexofenadine and promethazine, and had a potent effect compared with promethazine. In a battery of psychomotor assessments using critical flicker fusion, choice reaction time, compensatory tracking, rapid visual information processing and a line analogue rating scale as a subjective assessment of sedation, promethazine significantly impaired psychomotor function. Fexofenadine and olopatadine had no significant effect in any of the psychomotor tests. Promethazine, fexofenadine and olopatadine did not affect behavioral activity, as measured by wrist actigraphy. These results suggest that olopatadine at a therapeutic dose has greater antihistaminergic activity than promethazine, and olopatadine and fexofenadine did not cause cognitive or psychomotor impairment

First order reversal curves and intrinsic parameter determination for magnetic materials; Limitations of hysteron-based approaches in correlated systems

The generic problem of extracting information on intrinsic particle properties from the whole class of interacting magnetic fine particle systems is a long standing and difficult inverse problem. As an example, the Switching Field Distribution (SFD) is an important quantity in the characterization of magnetic systems, and its determination in many technological applications, such as recording media, is especially challenging. Techniques such as the first order reversal curve (FORC) methods, were developed to extract the SFD from macroscopic measurements. However, all methods rely on separating the contributions to the measurements of the intrinsic SFD and the extrinsic effects of magnetostatic and exchange interactions. We investigate the underlying physics of the FORC method by applying it to the output predictions of a kinetic Monte-Carlo model with known input parameters. We show that the FORC method is valid only in cases of weak spatial correlation of the magnetisation and suggest a more general approach