Using binary stars to bound the mass of the graviton

Interacting white dwarf binary star systems, including helium cataclysmic variable (HeCV) systems, are expected to be strong sources of gravitational radiation, and should be detectable by proposed space-based laser interferometer gravitational wave observatories such as LISA. Several HeCV star systems are presently known and can be studied optically, which will allow electromagnetic and gravitational wave observations to be correlated. Comparisons of the phases of a gravitational wave signal and the orbital light curve from an interacting binary white dwarf star system can be used to bound the mass of the graviton. Observations of typical HeCV systems by LISA could potentially yield an upper bound on the inverse mass of the graviton as strong as $h/m_{g} = \lambda_{g} > 1 \times 10^{15}$ km ($m_{g} < 1 \times 10^{-24}$ eV), more than two orders of magnitude better than present solar system derived bounds.Comment: 21 pages plus 4 figures; ReVTe

Bounding the mass of the graviton using gravitional-wave observations of inspiralling compact binaries

If gravitation is propagated by a massive field, then the velocity of gravitational waves (gravitons) will depend upon their frequency and the effective Newtonian potential will have a Yukawa form. In the case of inspiralling compact binaries, gravitational waves emitted at low frequency early in the inspiral will travel slightly slower than those emitted at high frequency later, modifying the phase evolution of the observed inspiral gravitational waveform, similar to that caused by post-Newtonian corrections to quadrupole phasing. Matched filtering of the waveforms can bound such frequency-dependent variations in propagation speed, and thereby bound the graviton mass. The bound depends on the mass of the source and on noise characteristics of the detector, but is independent of the distance to the source, except for weak cosmological redshift effects. For observations of stellar-mass compact inspiral using ground-based interferometers of the LIGO/VIRGO type, the bound on the graviton Compton wavelength is of the order of $6 \times 10^{12}$ km, about double that from solar-system tests of Yukawa modifications of Newtonian gravity. For observations of super-massive black hole binary inspiral at cosmological distances using the proposed laser interferometer space antenna (LISA), the bound can be as large as $6 \times 10^{16}$ km. This is three orders of magnitude weaker than model-dependent bounds from galactic cluster dynamics.Comment: 8 pages, RevTeX, submitted to Phys. Rev.

Homeostatic competition drives tumor growth and metastasis nucleation

We propose a mechanism for tumor growth emphasizing the role of homeostatic regulation and tissue stability. We show that competition between surface and bulk effects leads to the existence of a critical size that must be overcome by metastases to reach macroscopic sizes. This property can qualitatively explain the observed size distributions of metastases, while size-independent growth rates cannot account for clinical and experimental data. In addition, it potentially explains the observed preferential growth of metastases on tissue surfaces and membranes such as the pleural and peritoneal layers, suggests a mechanism underlying the seed and soil hypothesis introduced by Stephen Paget in 1889 and yields realistic values for metastatic inefficiency. We propose a number of key experiments to test these concepts. The homeostatic pressure as introduced in this work could constitute a quantitative, experimentally accessible measure for the metastatic potential of early malignant growths.Comment: 13 pages, 11 figures, to be published in the HFSP Journa

Post-Einsteinian tests of gravitation

Einstein gravitation theory can be extended by preserving its geometrical nature but changing the relation between curvature and energy-momentum tensors. This change accounts for radiative corrections, replacing the Newton gravitation constant by two running couplings which depend on scale and differ in the two sectors of traceless and traced tensors. The metric and curvature tensors in the field of the Sun, which were obtained in previous papers within a linearized approximation, are then calculated without this restriction. Modifications of gravitational effects on geodesics are then studied, allowing one to explore phenomenological consequences of extensions lying in the vicinity of general relativity. Some of these extended theories are able to account for the Pioneer anomaly while remaining compatible with tests involving the motion of planets. The PPN Ansatz corresponds to peculiar extensions of general relativity which do not have the ability to meet this compatibility challenge.Comment: 19 pages Corrected typo

Loss of Cbl and Cbl-b ubiquitin ligases abrogates hematopoietic stem cell quiescence and sensitizes leukemic disease to chemotherapy.

Cbl and Cbl-b are tyrosine kinase-directed RING finger type ubiquitin ligases (E3s) that negatively regulate cellular activation pathways. E3 activity-disrupting human Cbl mutations are associated with myeloproliferative disorders (MPD) that are reproduced in mice with Cbl RING finger mutant knock-in or hematopoietic Cbl and Cbl-b double knockout. However, the role of Cbl proteins in hematopoietic stem cell (HSC) homeostasis, especially in the context of MPD is unclear. Here we demonstrate that HSC expansion and MPD development upon combined Cbl and Cbl-b deletion are dependent on HSCs. Cell cycle analysis demonstrated that DKO HSCs exhibit reduced quiescence associated with compromised reconstitution ability and propensity to undergo exhaustion. We show that sustained c-Kit and FLT3 signaling in DKO HSCs promotes loss of colony-forming potential, and c-Kit or FLT3 inhibition in vitro protects HSCs from exhaustion. In vivo, treatment with 5-fluorouracil hastens DKO HSC exhaustion and protects mice from death due to MPD. Our data reveal a novel and leukemia therapy-relevant role of Cbl and Cbl-b in the maintenance of HSC quiescence and protection against exhaustion, through negative regulation of tyrosine kinase-coupled receptor signaling

The Power of Brane-Induced Gravity

We study the role of the brane-induced graviton kinetic term in theories with large extra dimensions. In five dimensions we construct a model with a TeV-scale fundamental Planck mass and a {\it flat} extra dimension the size of which can be astronomically large. 4D gravity on the brane is mediated by a massless zero-mode, whereas the couplings of the heavy Kaluza-Klein modes to ordinary matter are suppressed. The model can manifest itself through the predicted deviations from Einstein theory in long distance precision measurements of the planetary orbits. The bulk states can be a rather exotic form of dark matter, which at sub-solar distances interact via strong 5D gravitational force. We show that the induced term changes dramatically the phenomenology of sub-millimeter extra dimensions. For instance, high-energy constraints from star cooling or cosmology can be substantially relaxed.Comment: 24 pages, 4 eps figures; v2 typos corrected; v3 1 ref. added; PRD versio

Constraints from orbital motions around the Earth of the environmental fifth-force hypothesis for the OPERA superluminal neutrino phenomenology

It has been recently suggested by Dvali and Vikman that the superluminal neutrino phenomenology of the OPERA experiment may be due to an environmental feature of the Earth, naturally yielding a long-range fifth force of gravitational origin whose coupling with the neutrino is set by the scale M_*, in units of reduced Planck mass. Its characteristic length lambda should not be smaller than one Earth's radius R_e, while its upper bound is expected to be slightly smaller than the Earth-Moon distance (60 R_e). We analytically work out some orbital effects of a Yukawa-type fifth force for a test particle moving in the modified field of a central body. Our results are quite general since they are not restricted to any particular size of lambda; moreover, they are valid for an arbitrary orbital configuration of the particle, i.e. for any value of its eccentricity $e$. We find that the dimensionless strength coupling parameter alpha is constrained to |alpha| <= 1 10^-10-4 10^-9 for 1 R_e <= lambda <= 10 R_e by the laser data of the Earth's artificial satellite LAGEOS II, corresponding to M_* >= 4 10^9 -1.6 10^10. The Moon perigee allows to obtain |alpha| <= 3 10^-11 for the Earth-Moon pair in the range 15 R_e <= lambda = 3 10^10 - 4.5 10^10. Our results are neither necessarily limited to the superluminal OPERA scenario nor to the Dvali-Vikman model, in which it is M_* = 10^-6 at lambda = 1 R_e, in contrast with our bounds: they generally extend to any theoretical scenario implying a fifth-force of Yukawa-type.Comment: LaTex2e, 18 pages, 4 figures, 1 table, 81 reference

Post-Einsteinian tests of linearized gravitation

The general relativistic treatment of gravitation can be extended by preserving the geometrical nature of the theory but modifying the form of the coupling between curvature and stress tensors. The gravitation constant is thus replaced by two running coupling constants which depend on scale and differ in the sectors of traceless and traced tensors. When calculated in the solar system in a linearized approximation, the metric is described by two gravitation potentials. This extends the parametrized post-Newtonian (PPN) phenomenological framework while allowing one to preserve compatibility with gravity tests performed in the solar system. Consequences of this extension are drawn here for phenomena correctly treated in the linear approximation. We obtain a Pioneer-like anomaly for probes with an eccentric motion as well as a range dependence of Eddington parameter $\gamma$ to be seen in light deflection experiments.Comment: 15 pages. Accepted version, to appear in Classical and Quantum Gravit

The Behaviour Of Cosmological Models With Varying-G

We provide a detailed analysis of Friedmann-Robertson-Walker universes in a wide range of scalar-tensor theories of gravity. We apply solution-generating methods to three parametrised classes of scalar-tensor theory which lead naturally to general relativity in the weak-field limit. We restrict the parameters which specify these theories by the requirements imposed by the weak-field tests of gravitation theories in the solar system and by the requirement that viable cosmological solutions be obtained. We construct a range of exact solutions for open, closed, and flat isotropic universes containing matter with equation of state $p\leq \frac{1}{3}\rho$ and in vacuum. We study the range of early and late-time behaviours displayed, examine when there is a `bounce' at early times, and expansion maxima in closed models.Comment: 58 pages LaTeX, 6 postscript figures, uses eps

A Phase Ib dose-escalation study to evaluate safety and tolerability of the addition of the aminopeptidase inhibitor tosedostat (CHR-2797) to paclitaxel in patients with advanced solid tumours

Contains fulltext : 89517timmer-bonte.pdf (publisher's version ) (Closed access)BACKGROUND: This Phase Ib dose-escalating study investigated safety, maximum tolerated dose (MTD), dose-limiting toxicity (DLT), pharmacokinetics (PK) and clinical antitumour activity of tosedostat (CHR-2797), an orally bioavailable aminopeptidase inhibitor, in combination with paclitaxel. METHODS: A total of 22 patients received paclitaxel (135-175 mg m(-2)) intravenously, administered once every three weeks for up to six cycles, with oral tosedostat (90-240 mg) daily. RESULTS: One DLT (grade 3 dyspnoea) was observed in one patient with tosedostat 180 mg combined with paclitaxel 175 mg m(-2). A high number of paclitaxel infusion reactions was noted during the second administration (59%) and this prompted interruption of tosedostat dosing for 5 days around every second and subsequent paclitaxel infusion. No formal MTD was determined because of the high frequency of paclitaxel infusion reactions that may have been influenced by tosedostat. Most frequently observed drug-related adverse events were alopecia, fatigue (95% each), peripheral sensory neuropathy (59%), paclitaxel hypersensitivity (59%) and rash (55%). One patient died because of eosinophilic myocarditis, possibly related to study medication. There was no PK interaction between tosedostat and paclitaxel. In all, 3 patients had a partial response and 12 patients had stable disease lasting >3 months. CONCLUSION: The combination of tosedostat with paclitaxel was well tolerated except for the high incidence of paclitaxel-related infusion reactions