Enhancement of vaccinia virus based oncolysis with histone deacetylase inhibitors

Histone deacetylase inhibitors (HDI) dampen cellular innate immune response by decreasing interferon production and have been shown to increase the growth of vesicular stomatitis virus and HSV. As attenuated tumour-selective oncolytic vaccinia viruses (VV) are already undergoing clinical evaluation, the goal of this study is to determine whether HDI can also enhance the potency of these poxviruses in infection-resistant cancer cell lines. Multiple HDIs were tested and Trichostatin A (TSA) was found to potently enhance the spread and replication of a tumour selective vaccinia virus in several infection-resistant cancer cell lines. TSA significantly decreased the number of lung metastases in a syngeneic B16F10LacZ lung metastasis model yet did not increase the replication of vaccinia in normal tissues. The combination of TSA and VV increased survival of mice harbouring human HCT116 colon tumour xenografts as compared to mice treated with either agent alone. We conclude that TSA can selectively and effectively enhance the replication and spread of oncolytic vaccinia virus in cancer cells. © 2010 MacTavish et al

“Working the system”: The experience of being a primary care patient

Health care providers and system administrators are in the midst of a paradigm shift; moving from paternalism toward an egalitarian approach. For patient centred care to occur, health care providers must prioritize patient needs; provide information regarding treatments while taking patient preferences and expectations into account. While there is literature regarding patient centredness, there is less information from the patient perspective about the experience of being a patient and the influence on behaviour. Using phenomenological research methods and the theory of planned behaviour as a theoretical framework, this study addressed the questions, a) what is the essence of being a primary health care patient, and b) what influence do beliefs, attitudes, and experience have on people’s behaviour as a patient? Nineteen individuals participated. Seven shared elements of being a primary health care patient were identified and contributed to the development of a composite vignette. The patient experience was a socially oriented, governed and reinforced cyclical process. Patients described themselves as actively engaged in their health care – “working the system” to get what they needed, when they needed it. Patients changed their beliefs, attitudes and behaviour as a result of experiences with their physicians, and their perceived success or failure in acquiring the best health care possible. Being a patient was not a single, observable behaviour, but rather a set of contextually dependent strategies patients’ directed at the specific goal of getting the best healthcare possible. The theory of planned behaviour was unsuitable for understanding patients’ beliefs, attitudes and behaviour

EChOSim: The Exoplanet Characterisation Observatory software simulator

EChOSim is the end-to-end time-domain simulator of the Exoplanet Characterisation Observatory (EChO) space mission. EChOSim has been developed to assess the capability EChO has to detect and characterize the atmospheres of transiting exoplanets, and through this revolutionize the knowledge we have of the Milky Way and of our place in the Galaxy. Here we discuss the details of the EChOSim implementation and describe the models used to represent the instrument and to simulate the detection. Software simulators have assumed a central role in the design of new instrumentation and in assessing the level of systematics affecting the measurements of existing experiments. Thanks to its high modularity, EChOSim can simulate basic aspects of several existing and proposed spectrometers for exoplanet transits, including instruments on the Hubble Space Telescope and Spitzer, or ground-based and balloon borne experiments. A discussion of different uses of EChOSim is given, including examples of simulations performed to assess the EChO mission

Cosmic Microwave Background Polarization

Cosmic microwave background (CMB) anisotropy is our richest source of cosmological information; the standard cosmological model was largely established thanks to study of the temperature anisotropies. By the end of the decade, the Planck satellite will close this important chapter and move us deeper into the new frontier of polarization measurements. Numerous ground--based and balloon--borne experiments are already forging into this new territory. Besides providing new and independent information on the primordial density perturbations and cosmological parameters, polarization measurements offer the potential to detect primordial gravity waves, constrain dark energy and measure the neutrino mass scale. A vigorous experimental program is underway worldwide and heading towards a new satellite mission dedicated to CMB polarization.Comment: Review given at TAUP 2005; References added; Additional reference

Instrumental and Analytic Methods for Bolometric Polarimetry

We discuss instrumental and analytic methods that have been developed for the first generation of bolometric cosmic microwave background (CMB) polarimeters. The design, characterization, and analysis of data obtained using Polarization Sensitive Bolometers (PSBs) are described in detail. This is followed by a brief study of the effect of various polarization modulation techniques on the recovery of sky polarization from scanning polarimeter data. Having been successfully implemented on the sub-orbital Boomerang experiment, PSBs are currently operational in two terrestrial CMB polarization experiments (QUaD and the Robinson Telescope). We investigate two approaches to the analysis of data from these experiments, using realistic simulations of time ordered data to illustrate the impact of instrumental effects on the fidelity of the recovered polarization signal. We find that the analysis of difference time streams takes full advantage of the high degree of common mode rejection afforded by the PSB design. In addition to the observational efforts currently underway, this discussion is directly applicable to the PSBs that constitute the polarized capability of the Planck HFI instrument.Comment: 23 pages, 11 figures. for submission to A&

Constraints on the Neutrino Mass from SZ Surveys

Statistical measures of galaxy clusters are sensitive to neutrino masses in the sub-eV range. We explore the possibility of using cluster number counts from the ongoing PLANCK/SZ and future cosmic-variance-limited surveys to constrain neutrino masses from CMB data alone. The precision with which the total neutrino mass can be determined from SZ number counts is limited mostly by uncertainties in the cluster mass function and intracluster gas evolution; these are explicitly accounted for in our analysis. We find that projected results from the PLANCK/SZ survey can be used to determine the total neutrino mass with a (1\sigma) uncertainty of 0.06 eV, assuming it is in the range 0.1-0.3 eV, and the survey detection limit is set at the 5\sigma significance level. Our results constitute a significant improvement on the limits expected from PLANCK/CMB lensing measurements, 0.15 eV. Based on expected results from future cosmic-variance-limited (CVL) SZ survey we predict a 1\sigma uncertainty of 0.04 eV, a level comparable to that expected when CMB lensing extraction is carried out with the same experiment. A few percent uncertainty in the mass function parameters could result in up to a factor \sim 2-3 degradation of our PLANCK and CVL forecasts. Our analysis shows that cluster number counts provide a viable complementary cosmological probe to CMB lensing constraints on the total neutrino mass.Comment: Replaced with a revised version to match the MNRAS accepted version. arXiv admin note: text overlap with arXiv:1009.411

Enhancing the tensor-to-scalar ratio in simple inflation

We show that in theories with a nontrivial kinetic term the contribution of the gravitational waves to the CMB fluctuations can be substantially larger than that is naively expected in simple inflationary models. This increase of the tensor-to-scalar perturbation ratio leads to a larger B-component of the CMB polarization, thus making the prospects for future detection much more promising. The other important consequence of the considered model is a higher energy scale of inflation and hence higher reheating temperature compared to a simple inflation.Comment: 9 pages, 1 figure and references are added, discussion is slightly extended, published versio

Early Dark Energy Cosmologies

We propose a novel parameterization of the dark energy density. It is particularly well suited to describe a non-negligible contribution of dark energy at early times and contains only three parameters, which are all physically meaningful: the fractional dark energy density today, the equation of state today and the fractional dark energy density at early times. As we parameterize Omega_d(a) directly instead of the equation of state, we can give analytic expressions for the Hubble parameter, the conformal horizon today and at last scattering, the sound horizon at last scattering, the acoustic scale as well as the luminosity distance. For an equation of state today w_0 < -1, our model crosses the cosmological constant boundary. We perform numerical studies to constrain the parameters of our model by using Cosmic Microwave Background, Large Scale Structure and Supernovae Ia data. At 95% confidence, we find that the fractional dark energy density at early times Omega_early < 0.06. This bound tightens considerably to Omega_early < 0.04 when the latest Boomerang data is included. We find that both the gold sample of Riess et. al. and the SNLS data by Astier et. al. when combined with CMB and LSS data mildly prefer w_0 < -1, but are well compatible with a cosmological constant.Comment: 6 pages, 3 figures; references added, matches published versio

Fast and precise map-making for massively multi-detector CMB experiments

Future cosmic microwave background (CMB) polarisation experiments aim to measure an unprecedentedly small signal - the primordial gravity wave component of the polarisation field B-mode. To achieve this, they will analyse huge datasets, involving years worth of time-ordered data (TOD) from massively multi-detector focal planes. This creates the need for fast and precise methods to complement the M-L approach in analysis pipelines. In this paper, we investigate fast map-making methods as applied to long duration, massively multi-detector, ground-based experiments, in the context of the search for B-modes. We focus on two alternative map-making approaches: destriping and TOD filtering, comparing their performance on simulated multi-detector polarisation data. We have written an optimised, parallel destriping code, the DEStriping CARTographer DESCART, that is generalised for massive focal planes, including the potential effect of cross-correlated TOD 1/f noise. We also determine the scaling of computing time for destriping as applied to a simulated full-season data-set for a realistic experiment. We find that destriping can out-perform filtering in estimating both the large-scale E and B-mode angular power spectra. In particular, filtering can produce significant spurious B-mode power via EB mixing. Whilst this can be removed, it contributes to the variance of B-mode bandpower estimates at scales near the primordial B-mode peak. For the experimental configuration we simulate, this has an effect on the possible detection significance for primordial B-modes. Destriping is a viable alternative fast method to the full M-L approach that does not cause the problems associated with filtering, and is flexible enough to fit into both M-L and Monte-Carlo pseudo-Cl pipelines.Comment: 16 pages, 14 figures. MNRAS accepted. Typos corrected and computing time/memory requirement orders-of-magnitude numbers in section 4 replaced by precise number

Probing for cosmological parameters with LAMOST measurement

In this paper we study the sensitivity of the Large Sky Area Multi-Object Fiber Spectroscopic Telescope (LAMOST) project to the determination of cosmological parameters, employing the Monte Carlo Markov Chains (MCMC) method. For comparison, we first analyze the constraints on cosmological parameters from current observational data, including WMAP, SDSS and SN Ia. We then simulate the 3D matter power spectrum data expected from LAMOST, together with the simulated CMB data for PLANCK and the SN Ia from 5-year Supernovae Legacy Survey (SNLS). With the simulated data, we investigate the future improvement on cosmological parameter constraints, emphasizing the role of LAMOST. Our results show the potential of LAMOST in probing for the cosmological parameters, especially in constraining the equation-of-state (EoS) of the dark energy and the neutrino mass.Comment: 7 pages and 3 figures. Replaced with version accepted for publication in JCA