An organ culture system to model early degenerative changes of the intervertebral disc

ABSTRACT: INTRODUCTION: Back pain, a significant source of morbidity in our society, is related to the degenerative changes of the intervertebral disc. At present, the treatment of disc disease consists of therapies that are aimed at symptomatic relief. This shortcoming stems in large part from our lack of understanding of the biochemical and molecular events that drive the disease process. The goal of this study is to develop a model of early disc degeneration using an organ culture. This approach is based on our previous studies that indicate that organ culture closely models molecular events that occur in vivo in an ex vivo setting. METHODS: To mimic a degenerative insult, discs were cultured under low oxygen tension in the presence of TNF-α, IL-1β and serum limiting conditions. RESULTS: Treatment resulted in compromised cell survival and changes in cellular morphology reminiscent of degeneration. There was strong suppression in the expression of matrix proteins including collagen types 1, 2, 6 and 9, proteoglycans, aggrecan and fibromodulin. Moreover, a strong induction in expression of catabolic matrix metalloproteinases (MMP) 3, 9 and 13 with a concomitant increase in aggrecan degradation was seen. An inductive effect on NGF expression was also noticed. Although similar, nucleus pulposus and annulus fibrosus tissues showed some differences in their response to the treatment. CONCLUSIONS: Results of this study show that perturbations in microenvironmental factors result in anatomical and gene expression change within the intervertebral disc that may ultimately compromise cell function and induce pathological deficits. This system would be a valuable screening tool to investigate interventional strategies aimed at restoring disc cell function

Optical spectroscopy of the M15 intermediate velocity cloud

We present echelle spectrograph observations in NaD, at resolutions of 6.2-8.5 km/s, for 11 stars located in the line-of-sight to the M15 intermediate velocity cloud, which has a radial velocity of 70 km/s. This cloud is a part of IVC Complex gp. The targets range in magnitude from V=13.3-14.8. Seven of the observed stars are in the M15 globular cluster, the remaining four being field stars. Column density ratios of log(N cm^-2)=11.8-12.5 are derived. Combining the current sightlines with previously-existing data, we find the NaD/HI ratio in the IVC varies by upto a factor of 25. One cluster star, M15 ZNG-1, was also observed in Calcium. We find N(CaI)/N(CaII)<0.03 and NaI/CaII=0.25, similar to values seen in the local ISM. Finally, we detect tentative evidence for IV absorption in KI towards 3 cluster stars.Comment: A&A, in pres

Backreaction from non-conformal quantum fields in de Sitter spacetime

We study the backreaction on the mean field geometry due to a non-conformal quantum field in a Robertson-Walker background. In the regime of small mass and small deviation from conformal coupling, we compute perturbatively the expectation value of the stress tensor of the field for a variety of vacuum states, and use it to obtain explicitly the semiclassical gravity solutions for isotropic perturbations around de Sitter spacetime, which is found to be stable. Our results show clearly the crucial role of the non-local terms that appear in the effective action: they cancel the contribution from local terms proportional to the logarithm of the scale factor which would otherwise become dominant at late times and prevent the existence of a stable self-consistent de Sitter solution. Finally, the opposite regime of a strongly non-conformal field with a large mass is also considered.Comment: 31 page

Multi-Messenger Gravitational Wave Searches with Pulsar Timing Arrays: Application to 3C66B Using the NANOGrav 11-year Data Set

When galaxies merge, the supermassive black holes in their centers may form binaries and, during the process of merger, emit low-frequency gravitational radiation in the process. In this paper we consider the galaxy 3C66B, which was used as the target of the first multi-messenger search for gravitational waves. Due to the observed periodicities present in the photometric and astrometric data of the source of the source, it has been theorized to contain a supermassive black hole binary. Its apparent 1.05-year orbital period would place the gravitational wave emission directly in the pulsar timing band. Since the first pulsar timing array study of 3C66B, revised models of the source have been published, and timing array sensitivities and techniques have improved dramatically. With these advances, we further constrain the chirp mass of the potential supermassive black hole binary in 3C66B to less than $(1.65\pm0.02) \times 10^9~{M_\odot}$ using data from the NANOGrav 11-year data set. This upper limit provides a factor of 1.6 improvement over previous limits, and a factor of 4.3 over the first search done. Nevertheless, the most recent orbital model for the source is still consistent with our limit from pulsar timing array data. In addition, we are able to quantify the improvement made by the inclusion of source properties gleaned from electromagnetic data to `blind' pulsar timing array searches. With these methods, it is apparent that it is not necessary to obtain exact a priori knowledge of the period of a binary to gain meaningful astrophysical inferences.Comment: 14 pages, 6 figures. Accepted by Ap

Eddington-limited accretion and the black hole mass function at redshift 6

We present discovery observations of a quasar in the Canada-France High-z Quasar Survey (CFHQS) at redshift z=6.44. We also use near-IR spectroscopy of nine CFHQS quasars at z~6 to determine black hole masses. These are compared with similar estimates for more luminous Sloan Digital Sky Survey (SDSS) quasars to investigate the relationship between black hole mass and quasar luminosity. We find a strong correlation between MgII FWHM and UV luminosity and that most quasars at this early epoch are accreting close to the Eddington limit. Thus these quasars appear to be in an early stage of their life cycle where they are building up their black hole mass exponentially. Combining these results with the quasar luminosity function, we derive the black hole mass function at z=6. Our black hole mass function is ~10^4 times lower than at z=0 and substantially below estimates from previous studies. The main uncertainties which could increase the black hole mass function are a larger population of obscured quasars at high-redshift than is observed at low-redshift and/or a low quasar duty cycle at z=6. In comparison, the global stellar mass function is only ~10^2 times lower at z=6 than at z=0. The difference between the black hole and stellar mass function evolution is due to either rapid early star formation which is not limited by radiation pressure as is the case for black hole growth or inefficient black hole seeding. Our work predicts that the black hole mass - stellar mass relation for a volume-limited sample of galaxies declines rapidly at very high redshift. This is in contrast to the observed increase at 4<z<6 from the local relation if one just studies the most massive black holes.Comment: 16 pages, 10 figures, AJ in pres

Improving the sensitivity to gravitational-wave sources by modifying the input-output optics of advanced interferometers

We study frequency dependent (FD) input-output schemes for signal-recycling interferometers, the baseline design of Advanced LIGO and the current configuration of GEO 600. Complementary to a recent proposal by Harms et al. to use FD input squeezing and ordinary homodyne detection, we explore a scheme which uses ordinary squeezed vacuum, but FD readout. Both schemes, which are sub-optimal among all possible input-output schemes, provide a global noise suppression by the power squeeze factor, while being realizable by using detuned Fabry-Perot cavities as input/output filters. At high frequencies, the two schemes are shown to be equivalent, while at low frequencies our scheme gives better performance than that of Harms et al., and is nearly fully optimal. We then study the sensitivity improvement achievable by these schemes in Advanced LIGO era (with 30-m filter cavities and current estimates of filter-mirror losses and thermal noise), for neutron star binary inspirals, and for narrowband GW sources such as low-mass X-ray binaries and known radio pulsars. Optical losses are shown to be a major obstacle for the actual implementation of these techniques in Advanced LIGO. On time scales of third-generation interferometers, like EURO/LIGO-III (~2012), with kilometer-scale filter cavities, a signal-recycling interferometer with the FD readout scheme explored in this paper can have performances comparable to existing proposals. [abridged]Comment: Figs. 9 and 12 corrected; Appendix added for narrowband data analysi

Upper limits on the strength of periodic gravitational waves from PSR J1939+2134

The first science run of the LIGO and GEO gravitational wave detectors presented the opportunity to test methods of searching for gravitational waves from known pulsars. Here we present new direct upper limits on the strength of waves from the pulsar PSR J1939+2134 using two independent analysis methods, one in the frequency domain using frequentist statistics and one in the time domain using Bayesian inference. Both methods show that the strain amplitude at Earth from this pulsar is less than a few times $10^{-22}$.Comment: 7 pages, 1 figure, to appear in the Proceedings of the 5th Edoardo Amaldi Conference on Gravitational Waves, Tirrenia, Pisa, Italy, 6-11 July 200