Merger of Multiple Accreting Black Holes Concordant with Gravitational-wave Events

Recently, the advanced Laser Interferometer Gravitational-Wave Observatory (aLIGO) has detected black hole (BH) merger events, most of which are sourced by BHs more massive than 30 M-circle dot. Especially, the observation of GW170104 suggests dynamically assembled binaries favoring a distribution of misaligned spins. It has been argued that mergers of unassociated BHs can be engendered through a chance meeting in a multiple BH system under gas-rich environments. In this paper, we consider the merger of unassociated BHs, concordant with the massive BH merger events. To that end, we simulate a multiple BH system with a post-Newtonian N-body code incorporating gas accretion and general relativistic effects. As a result, we find that gas dynamical friction effectively promotes a three-body interaction of BHs in dense gas of n(gas) greater than or similar to 10(6) cm(-3), so that BH mergers can take place within 30 Myr. This scenario predicts an isotropic distribution of spin tilts. In the concordant models with GW150914, the masses of seed BHs are required to be greater than or similar to 25 M-circle dot. The potential sites of such chance meeting BH mergers are active galactic nucleus (AGN) disks and dense interstellar clouds. Assuming the LIGO O1, we roughly estimate the event rates for PopI BHs and PopIII BHs in AGN disks to be similar or equal to 1-2 yr(-1) and similar or equal to 1 yr(-1), respectively. Multiple episodes of AGNs may enhance the rates by roughly an order of magnitude. For massive PopI BHs in dense interstellar clouds the rate is similar or equal to 0.02 yr(-1). Hence, high-density AGN disks are a more plausible site for mergers of chance meeting BHs

Ku70 alleviates neurodegeneration in drosophila models of Huntington's disease

DNA damage accumulates in genome DNA during the long life of neurons, thus DNA damage repair is indispensable to keep normal functions of neurons. We previously reported that Ku70, a critical molecule for DNA double strand break (DSB) repair, is involved in the pathology of Huntington's disease (HD). Mutant huntingtin (Htt) impaired Ku70 function via direct interaction, and Ku70 supplementation recovered phenotypes of a mouse HD model. In this study, we generate multiple Drosophila HD models that express mutant huntingtin (Htt) in eye or motor neuron by different drivers and show various phenotypes. In such fly models, Ku70 co-expression recovers lifespan, locomotive activity and eye degeneration. In contrast, Ku70 reduction by heterozygous null mutation or siRNA-mediated knock down accelerates lifespan shortening and locomotion disability. These results collectively support that Ku70 is a critical mediator of the HD pathology and a candidate therapeutic target in HD

Gelatine Cavity Dynamics of High-Speed Sphere Impact

We investigate the impact and penetration of a solid sphere passing through gelatine at various impact speeds up to 143.2 m s-1 Tests were performed with several concentrations of gelatine. Impacts for low elastic Froude number Fre a ratio between inertia and gelatine elasticity, resulted in rebound. Higher Fre values resulted in penetration, forming cavities with prominent surface textures. The overall shape of the cavities resembles those observed in water-entry experiments, yet they appear in a different order with respect to increasing inertia: rebound, quasi-seal, deep-seal, shallow-seal and surface-seal. Remarkably, similar to the We – Bo phase diagram in water-entry experiments, the elastic Froude number Fre and elastic Grashof number Gre (a ratio between gravity and gelatine elasticity) classify all five different phenomena into distinguishable regimes. We find that Fre can be a good indicator to describe the cavity length H , particularly in the shallow-seal regime. Finally, the evolution of cavity shape, pinch-off depth, and lower cavity radius are investigated for different Fre values

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)