Extreme Mass-Ratio Inspirals in the Effective-One-Body Approach: Quasi-Circular, Equatorial Orbits around a Spinning Black Hole

We construct effective-one-body waveform models suitable for data analysis with LISA for extreme-mass ratio inspirals in quasi-circular, equatorial orbits about a spinning supermassive black hole. The accuracy of our model is established through comparisons against frequency-domain, Teukolsky-based waveforms in the radiative approximation. The calibration of eight high-order post-Newtonian parameters in the energy flux suffices to obtain a phase and fractional amplitude agreement of better than 1 radian and 1 % respectively over a period between 2 and 6 months depending on the system considered. This agreement translates into matches higher than 97 % over a period between 4 and 9 months, depending on the system. Better agreements can be obtained if a larger number of calibration parameters are included. Higher-order mass ratio terms in the effective-one-body Hamiltonian and radiation-reaction introduce phase corrections of at most 30 radians in a one year evolution. These corrections are usually one order of magnitude larger than those introduced by the spin of the small object in a one year evolution. These results suggest that the effective-one-body approach for extreme mass ratio inspirals is a good compromise between accuracy and computational price for LISA data analysis purposes.Comment: 21 pages, 8 figures, submitted to Phys. Rev.

Seeking the Loop Quantum Gravity Barbero-Immirzi Parameter and Field in 4D, N\cal N = 1 Supergravity

We embed the Loop Quantum Gravity Barbero-Immirzi parameter and field within an action describing 4D, $\cal N$ = 1 supergravity and thus within a Low Energy Effective Action of Superstring/M-Theory. We use the fully gauge-covariant description of supergravity in (curved) superspace. The gravitational constant is replaced with the vacuum expectation value of a scalar field, which in local supersymmetry is promoted to a complex, covariantly chiral scalar superfield. The imaginary part of this superfield couples to a supersymmetric Holst term. The Holst term also serves as a starting point in the Loop Quantum Gravity action. This suggest the possibility of a relation between Loop Quantum Gravity and supersymmetric string theory, where the Barbero-Immirzi parameter and field of the former play the role of the supersymmetric axion in the latter. Adding matter fermions in Loop Quantum Gravity may require the extension of the Holst action through the Nieh-Yan topological invariant, while in pure, matter-free supergravity their supersymmetric extensions are the same. We show that, when the Barbero-Immirzi parameter is promoted to a field in the context of 4D supergravity, it is equivalent to adding a dynamical complex chiral (dilaton-axion) superfield with a non-trivial kinetic term (or K\"ahler potential), coupled to supergravity.Comment: 20 pages, 1 figure. Replaced with accepted version in Phys. Rev.

Small molecule inhibitors of Late SV40 Factor (LSF) abrogate hepatocellular carcinoma (HCC): evaluation using an endogenous HCC model

Hepatocellular carcinoma (HCC) is a lethal malignancy with high mortality and poor prognosis. Oncogenic transcription factor Late SV40 Factor (LSF) plays an important role in promoting HCC. A small molecule inhibitor of LSF, Factor Quinolinone Inhibitor 1 (FQI1), significantly inhibited human HCC xenografts in nude mice without harming normal cells. Here we evaluated the efficacy of FQI1 and another inhibitor, FQI2, in inhibiting endogenous hepatocarcinogenesis. HCC was induced in a transgenic mouse with hepatocyte-specific overexpression of c-myc (Alb/c-myc) by injecting N-nitrosodiethylamine (DEN) followed by FQI1 or FQI2 treatment after tumor development. LSF inhibitors markedly decreased tumor burden in Alb/c-myc mice with a corresponding decrease in proliferation and angiogenesis. Interestingly, in vitro treatment of human HCC cells with LSF inhibitors resulted in mitotic arrest with an accompanying increase in CyclinB1. Inhibition of CyclinB1 induction by Cycloheximide or CDK1 activity by Roscovitine significantly prevented FQI-induced mitotic arrest. A significant induction of apoptosis was also observed upon treatment with FQI. These effects of LSF inhibition, mitotic arrest and induction of apoptosis by FQI1s provide multiple avenues by which these inhibitors eliminate HCC cells. LSF inhibitors might be highly potent and effective therapeutics for HCC either alone or in combination with currently existing therapies.The present study was supported in part by grants from The James S. McDonnell Foundation, National Cancer Institute Grant R01 CA138540-01A1 (DS), National Institutes of Health Grant R01 CA134721 (PBF), the Samuel Waxman Cancer Research Foundation (SWCRF) (DS and PBF), National Institutes of Health Grants R01 GM078240 and P50 GM67041 (SES), the Johnson and Johnson Clinical Innovation Award (UH), and the Boston University Ignition Award (UH). JLSW was supported by Alnylam Pharmaceuticals, Inc. DS is the Harrison Endowed Scholar in Cancer Research and Blick scholar. PBF holds the Thelma Newmeyer Corman Chair in Cancer Research. The authors acknowledge Dr. Lauren E. Brown (Dept. Chemistry, Boston University) for the synthesis of FQI1 and FQI2, and Lucy Flynn (Dept. Biology, Boston University) for initially identifying G2/M effects caused by FQI1. (James S. McDonnell Foundation; R01 CA138540-01A1 - National Cancer Institute; R01 CA134721 - National Institutes of Health; R01 GM078240 - National Institutes of Health; P50 GM67041 - National Institutes of Health; Samuel Waxman Cancer Research Foundation (SWCRF); Johnson and Johnson Clinical Innovation Award; Boston University Ignition Award; Alnylam Pharmaceuticals, Inc.)Published versio

Extreme mass ratio inspiral rates: dependence on the massive black hole mass

We study the rate at which stars spiral into a massive black hole (MBH) due to the emission of gravitational waves (GWs), as a function of the mass M of the MBH. In the context of our model, it is shown analytically that the rate approximately depends on the MBH mass as M^{-1/4}. Numerical simulations confirm this result, and show that for all MBH masses, the event rate is highest for stellar black holes, followed by white dwarfs, and lowest for neutron stars. The Laser Interferometer Space Antenna (LISA) is expected to see hundreds of these extreme mass ratio inspirals per year. Since the event rate derived here formally diverges as M->0, the model presented here cannot hold for MBHs of masses that are too low, and we discuss what the limitations of the model are.Comment: Accepted to CQG, special LISA issu

Testing Alternative Theories of Gravity using LISA

We investigate the possible bounds which could be placed on alternative theories of gravity using gravitational wave detection from inspiralling compact binaries with the proposed LISA space interferometer. Specifically, we estimate lower bounds on the coupling parameter \omega of scalar-tensor theories of the Brans-Dicke type and on the Compton wavelength of the graviton \lambda_g in hypothetical massive graviton theories. In these theories, modifications of the gravitational radiation damping formulae or of the propagation of the waves translate into a change in the phase evolution of the observed gravitational waveform. We obtain the bounds through the technique of matched filtering, employing the LISA Sensitivity Curve Generator (SCG), available online. For a neutron star inspiralling into a 10^3 M_sun black hole in the Virgo Cluster, in a two-year integration, we find a lower bound \omega > 3 * 10^5. For lower-mass black holes, the bound could be as large as 2 * 10^6. The bound is independent of LISA arm length, but is inversely proportional to the LISA position noise error. Lower bounds on the graviton Compton wavelength ranging from 10^15 km to 5 * 10^16 km can be obtained from one-year observations of massive binary black hole inspirals at cosmological distances (3 Gpc), for masses ranging from 10^4 to 10^7 M_sun. For the highest-mass systems (10^7 M_sun), the bound is proportional to (LISA arm length)^{1/2} and to (LISA acceleration noise)^{-1/2}. For the others, the bound is independent of these parameters because of the dominance of white-dwarf confusion noise in the relevant part of the frequency spectrum. These bounds improve and extend earlier work which used analytic formulae for the noise curves.Comment: 16 pages, 9 figures, submitted to Classical & Quantum Gravit

Two approaches to testing general relativity in the strong-field regime

Observations of compact objects in the electromagnetic spectrum and the detection of gravitational waves from them can lead to quantitative tests of the theory of general relativity in the strong-field regime following two very different approaches. In the first approach, the general relativistic field equations are modified at a fundamental level and the magnitudes of the potential deviations are constrained by comparison with observations. In the second approach, the exterior spacetimes of compact objects are parametrized in a phenomenological way, the various parameters are measured observationally, and the results are finally compared against the general relativistic predictions. In this article, I discuss the current status of both approaches, focusing on the lessons learned from a large number of recent investigations.Comment: To appear in the proceedings of the conference New Developments in Gravit

SB225002 induces cell death and cell cycle arrest in acute lymphoblastic leukemia cells through the activation of GLIPR1

Acute Lymphoblastic Leukemia (ALL) is the most frequent childhood malignancy. In the effort to find new anti-leukemic agents, we evaluated the small drug SB225002 (N-(2-hydroxy-4-nitrophenyl)-N'-(2-bromophenyl)urea). Although initially described as a selective antagonist of CXCR2, later studies have identified other cellular targets for SB225002, with potential medicinal use in cancer. We found that SB225002 has a significant pro-apoptotic effect against both B- and T-ALL cell lines. Cell cycle analysis demonstrated that treatment with SB225002 induces G2-M cell cycle arrest. Transcriptional profiling revealed that SB225002-mediated apoptosis triggered a transcriptional program typical of tubulin binding agents. Network analysis revealed the activation of genes linked to the JUN and p53 pathways and inhibition of genes linked to the TNF pathway. Early cellular effects activated by SB225002 included the up-regulation of GLIPR1 , a p53-target gene shown to have pro-apoptotic activities in prostate and bladder cancer. Silencing of GLIPR1 in B- and T-ALL cell lines resulted in increased resistance to SB225002. Although SB225002 promoted ROS increase in ALL cells, antioxidant N-Acetyl Cysteine pre-treatment only modestly attenuated cell death, implying that the pro-apoptotic effects of SB225002 are not exclusively mediated by ROS. Moreover, GLIPR1 silencing resulted in increased ROS levels both in untreated and SB225002-treated cells. In conclusion, SB225002 induces cell cycle arrest and apoptosis in different B- and T-ALL cell lines. Inhibition of tubulin function with concurrent activation of the p53 pathway, in particular, its downstream target GLIPR1 , seems to underlie the anti-leukemic effect of SB225002

Renormalized spin coefficients in the accumulated orbital phase for unequal mass black hole binaries

We analyze galactic black hole mergers and their emitted gravitational waves. Such mergers have typically unequal masses with mass ratio of the order 1/10. The emitted gravitational waves carry the inprint of spins and mass quadrupoles of the binary components. Among these contributions, we consider here the quasi-precessional evolution of the spins. A method of taking into account these third post-Newtonian (3PN) effects by renormalizing (redefining) the 1.5 PN and 2PN accurate spin contributions to the accumulated orbital phase is developed.Comment: 10 pages, to appear in Class. Quantum Grav. GWDAW13 Proceedings Special Issue, v2: no typos conjectur