TGFβ inhibition stimulates collagen maturation to enhance bone repair and fracture resistance in a murine myeloma model

Multiple myeloma is a plasma cell malignancy that causes debilitating bone disease and fractures, in which TGFβ plays a central role. Current treatments do not repair existing damage and fractures remain a common occurrence. We developed a novel low tumour phase murine model mimicking the plateau phase in patients, as we hypothesized this would be an ideal time to treat with a bone anabolic. Using in vivo microCT we show substantial and rapid bone lesion repair (and prevention) driven by SD‐208 (TGFβ receptor I kinase inhibitor) and chemotherapy (bortezomib and lenalidomide) in mice with human U266‐GFP‐luc myeloma. We discovered that lesion repair occurred via an intramembranous fracture repair‐like mechanism and that SD‐208 enhanced collagen matrix maturation to significantly improve fracture resistance. Lesion healing was associated with VEGFA expression in woven bone, reduced osteocyte‐derived PTHrP, increased osteoblasts, decreased osteoclasts and lower serum TRACP‐5b. SD‐208 also completely prevented bone lesion development mice with aggressive JJN3 tumors, and was more effective than an anti‐TGFβ neutralizing antibody (1D11). We also discovered that SD‐208 promoted osteoblastic differentiation (and overcame the TGFβ‐induced block in osteoblastogenesis) in myeloma patient bone marrow stromal cells in vitro, comparable to normal donors. The improved bone quality and fracture‐resistance with SD‐208 provides incentive for clinical translation to improve myeloma patient quality of life by reducing fracture risk and fatality

LOCV calculation for Beta-stable matter at finite temperature

The method of lowest-order constrained variational, which predicts reasonably the nuclear matter semi-empirical data is used to calculate the equation of state of beta-stable matter at finite temperature. The Reid soft-core with and without the N-$\Delta$ interactions which fits the N-N scattering data as well as the $UV_{14}$ potential plus the three-nucleon interaction are considered in the nuclear many-body Hamiltonian. The electron and muon are treated relativistically in the total Hamiltonian at given temperature, to make the fluid electrically neutral and stable against beta decay. The calculation is performed for a wide range of baryon density and temperature which are of interest in the astrophysics. The free energy, entropy, proton abundance, etc. of nuclear beta-stable matter are calculated. It is shown that by increasing the temperature, the maximum proton abundance is pushed to the lower density while the maximum itself increases as we increase the temperature. The proton fraction is not enough to see any gas-liquid phase transition. Finally we get an overall agreement with other many-body techniques, which are available only at zero temperature.Comment: LaTex, 20 page

The rotational modes of relativistic stars: Numerical results

We study the inertial modes of slowly rotating, fully relativistic compact stars. The equations that govern perturbations of both barotropic and non-barotropic models are discussed, but we present numerical results only for the barotropic case. For barotropic stars all inertial modes are a hybrid mixture of axial and polar perturbations. We use a spectral method to solve for such modes of various polytropic models. Our main attention is on modes that can be driven unstable by the emission of gravitational waves. Hence, we calculate the gravitational-wave growth timescale for these unstable modes and compare the results to previous estimates obtained in Newtonian gravity (i.e. using post-Newtonian radiation formulas). We find that the inertial modes are slightly stabilized by relativistic effects, but that previous conclusions concerning eg. the unstable r-modes remain essentially unaltered when the problem is studied in full general relativity.Comment: RevTeX, 29 pages, 31 eps figure

R-mode oscillations of differentially and rapidly rotating Newtonian polytropic stars

For the analysis of the r-mode oscillation of hot young neutron stars, it is necessary to consider the effect of it differential rotation, because viscosity is not strong enough for differentially rotating young neutron stars to be lead to uniformly rotating configurations on a very short time scale after their birth. In this paper, we have developed a numerical scheme to solve r-mode oscillations of differentially rotating polytropic inviscid stars. This is the extended version of the method which was applied to compute r-mode oscillations of uniformly rotating Newtonian polytropic stars. By using this new method, we have succeeded in obtaining eigenvalues and eigenfunctions of r-mode oscillations of differentially rotating polytropic stars. Our numerical results show that as the degree of differential rotation is increased, it becomes more difficult to solve r-mode oscillations for slightly deformed configurations from sphere compared to solving r-mode oscillations of considerably deformed stars. One reason for it seems that for slightly deformed stars corotation points appear near the surface region if the degree of differential rotation is strong enough. This is similar to the situation that the perturbational approach of r-mode oscillations for it slowly rotating stars in general relativity results in a singular eigenvalue problem.Comment: including 7 figures. submitted to PR

Active Galactic Nuclei at the Crossroads of Astrophysics

Over the last five decades, AGN studies have produced a number of spectacular examples of synergies and multifaceted approaches in astrophysics. The field of AGN research now spans the entire spectral range and covers more than twelve orders of magnitude in the spatial and temporal domains. The next generation of astrophysical facilities will open up new possibilities for AGN studies, especially in the areas of high-resolution and high-fidelity imaging and spectroscopy of nuclear regions in the X-ray, optical, and radio bands. These studies will address in detail a number of critical issues in AGN research such as processes in the immediate vicinity of supermassive black holes, physical conditions of broad-line and narrow-line regions, formation and evolution of accretion disks and relativistic outflows, and the connection between nuclear activity and galaxy evolution.Comment: 16 pages, 5 figures; review contribution; "Exploring the Cosmic Frontier: Astrophysical Instruments for the 21st Century", ESO Astrophysical Symposia Serie

Determination of the Deep Inelastic Contribution to the Generalised Gerasimov-Drell-Hearn Integral for the Proton and Neutron

The virtual photon absorption cross section differences [sigma_1/2-sigma_3/2] for the proton and neutron have been determined from measurements of polarised cross section asymmetries in deep inelastic scattering of 27.5 GeV longitudinally polarised positrons from polarised 1H and 3He internal gas targets. The data were collected in the region above the nucleon resonances in the kinematic range nu < 23.5 GeV and 0.8 GeV**2 < Q**2 < 12 GeV**2. For the proton the contribution to the generalised Gerasimov-Drell-Hearn integral was found to be substantial and must be included for an accurate determination of the full integral. Furthermore the data are consistent with a QCD next-to-leading order fit based on previous deep inelastic scattering data. Therefore higher twist effects do not appear significant.Comment: 6 pages, 3 figures, 1 table, revte

Observation of a Coherence Length Effect in Exclusive Rho^0 Electroproduction

Exclusive incoherent electroproduction of the rho^0(770) meson from 1H, 2H, 3He, and 14N targets has been studied by the HERMES experiment at squared four-momentum transfer Q**2>0.4 GeV**2 and positron energy loss nu from 9 to 20 GeV. The ratio of the 14N to 1H cross sections per nucleon, known as the nuclear transparency, was found to decrease with increasing coherence length of quark-antiquark fluctuations of the virtual photon. The data provide clear evidence of the interaction of the quark- antiquark fluctuations with the nuclear medium.Comment: RevTeX, 5 pages, 3 figure

Flavor Decomposition of the Polarized Quark Distributions in the Nucleon from Inclusive and Semi-inclusive Deep-inelastic Scattering

Spin asymmetries of semi-inclusive cross sections for the production of positively and negatively charged hadrons have been measured in deep-inelastic scattering of polarized positrons on polarized hydrogen and 3He targets, in the kinematic range 0.023<x<0.6 and 1 GeV^2<Q^2<10 GeV^2. Polarized quark distributions are extracted as a function of x for up $(u+u_bar) and down (d+d_bar) flavors. The up quark polarization is positive and the down quark polarization is negative in the measured range. The polarization of the sea is compatible with zero. The first moments of the polarized quark distributions are presented. The isospin non-singlet combination Delta_q_3 is consistent with the prediction based on the Bjorken sum rule. The moments of the polarized quark distributions are compared to predictions based on SU(3)_f flavor symmetry and to a prediction from lattice QCD.Comment: 14 pages, 6 figures (eps format), 10 tables in Latex New version contains tables of asymmetries and correlation matri

Contribution of copy number variants to schizophrenia from a genome-wide study of 41,321 subjects

Copy number variants (CNVs) have been strongly implicated in the genetic etiology of schizophrenia (SCZ). However, genome-wide investigation of the contribution of CNV to risk has been hampered by limited sample sizes. We sought to address this obstacle by applying a centralized analysis pipeline to a SCZ cohort of 21,094 cases and 20,227 controls. A global enrichment of CNV burden was observed in cases (OR=1.11, P=5.7×10−15), which persisted after excluding loci implicated in previous studies (OR=1.07, P=1.7 ×10−6). CNV burden was enriched for genes associated with synaptic function (OR = 1.68, P = 2.8 ×10−11) and neurobehavioral phenotypes in mouse (OR = 1.18, P= 7.3 ×10−5). Genome-wide significant evidence was obtained for eight loci, including 1q21.1, 2p16.3 (NRXN1), 3q29, 7q11.2, 15q13.3, distal 16p11.2, proximal 16p11.2 and 22q11.2. Suggestive support was found for eight additional candidate susceptibility and protective loci, which consisted predominantly of CNVs mediated by non-allelic homologous recombination

All-sky search for long-duration gravitational wave transients with initial LIGO

We present the results of a search for long-duration gravitational wave transients in two sets of data collected by the LIGO Hanford and LIGO Livingston detectors between November 5, 2005 and September 30, 2007, and July 7, 2009 and October 20, 2010, with a total observational time of 283.0 days and 132.9 days, respectively. The search targets gravitational wave transients of duration 10-500 s in a frequency band of 40-1000 Hz, with minimal assumptions about the signal waveform, polarization, source direction, or time of occurrence. All candidate triggers were consistent with the expected background; as a result we set 90% confidence upper limits on the rate of long-duration gravitational wave transients for different types of gravitational wave signals. For signals from black hole accretion disk instabilities, we set upper limits on the source rate density between 3.4×10-5 and 9.4×10-4 Mpc-3 yr-1 at 90% confidence. These are the first results from an all-sky search for unmodeled long-duration transient gravitational waves. © 2016 American Physical Society