Assessment of treatment response in tuberculosis

Antibiotic treatment of tuberculosis has a duration of several months. There is significant variability of the host immune response and the pharmacokinetic-pharmacodynamic properties of Mycobacterium tuberculosis sub-populations at the site of disease. A limitation of sputum-based measures of treatment response may be sub-optimal detection and monitoring of Mycobacterium tuberculosis sub-populations. Potential biomarkers and surrogate endpoints should be benchmarked against hard clinical outcomes (failure/relapse/death) and may need tailoring to specific patient populations. Here, we assess the evidence supporting currently utilized and future potential host and pathogen-based models and biomarkers for monitoring treatment response in active and latent tuberculosis. Biomarkers for monitoring treatment response in extrapulmonary, pediatric and drug resistant tuberculosis are research priorities

Energy absorption by "sparse" systems: beyond linear response theory

The analysis of the response to driving in the case of weakly chaotic or weakly interacting systems should go beyond linear response theory. Due to the "sparsity" of the perturbation matrix, a resistor network picture of transitions between energy levels is essential. The Kubo formula is modified, replacing the "algebraic" average over the squared matrix elements by a "resistor network" average. Consequently the response becomes semi-linear rather than linear. Some novel results have been obtained in the context of two prototype problems: the heating rate of particles in Billiards with vibrating walls; and the Ohmic Joule conductance of mesoscopic rings driven by electromotive force. Respectively, the obtained results are contrasted with the "Wall formula" and the "Drude formula".Comment: 8 pages, 7 figures, short pedagogical review. Proceedings of FQMT conference (Prague, 2011). Ref correcte

The mass of dwarf spheroidal galaxies and the missing satellite problem

We present the results from a suite of N-body simulations of the tidal stripping of two-component dwarf galaxies comprising some stars and dark matter. We show that recent kinematic data from the local group dwarf spheroidal (dSph) galaxies suggests that dSph galaxies must be sufficiently massive ($10^9 - 10^{10}$M$_\odot$) that tidal stripping is of little importance for the stars. We discuss the implications of these massive dSph galaxies for cosmology and galaxy formation.Comment: 4 pages, 1 figure, to appear in the proceedings of the IAUC198 "Near-Field Cosmology with Dwarf Elliptical Galaxies", H. Jerjen & B. Binggeli (eds.). Comments welcom

The tidal stripping of satellites

We present an improved analytic calculation for the tidal radius of satellites and test our results against N-body simulations. The tidal radius in general depends upon four factors: the potential of the host galaxy, the potential of the satellite, the orbit of the satellite and {\it the orbit of the star within the satellite}. We demonstrate that this last point is critical and suggest using {\it three tidal radii} to cover the range of orbits of stars within the satellite. In this way we show explicitly that prograde star orbits will be more easily stripped than radial orbits; while radial orbits are more easily stripped than retrograde ones. This result has previously been established by several authors numerically, but can now be understood analytically. For point mass, power-law (which includes the isothermal sphere), and a restricted class of split power law potentials our solution is fully analytic. For more general potentials, we provide an equation which may be rapidly solved numerically. Over short times (\simlt 1-2 Gyrs $\sim 1$ satellite orbit), we find excellent agreement between our analytic and numerical models. Over longer times, star orbits within the satellite are transformed by the tidal field of the host galaxy. In a Hubble time, this causes a convergence of the three limiting tidal radii towards the prograde stripping radius. Beyond the prograde stripping radius, the velocity dispersion will be tangentially anisotropic.Comment: 10 pages, 5 figures. Final version accepted for publication in MNRAS. Some new fully analytic tidal radii have been added for power law density profiles (including the isothermal sphere) and some split power law

A survey of polarization in the JVAS/CLASS flat-spectrum radio source surveys: I. The data and catalogue production

We have used the very large JVAS/CLASS 8.4-GHz surveys of flat-spectrum radio sources to obtain a large, uniformly observed and calibrated, sample of radio source polarizations. These are useful for many investigations of the properties of radio sources and the interstellar medium. We discuss comparisons with polarization measurements from this survey and from other large-scale surveys of polarization in flat-spectrum sources.Comment: Accepted by MNRAS. 8 pages, 5 figures. Full version of Table 2 available at http://www.jb.man.ac.uk/~njj/classqu_po

Nonexponential decay of an unstable quantum system: Small-QQ-value s-wave decay

We study the decay process of an unstable quantum system, especially the deviation from the exponential decay law. We show that the exponential period no longer exists in the case of the s-wave decay with small $Q$ value, where the $Q$ value is the difference between the energy of the initially prepared state and the minimum energy of the continuous eigenstates in the system. We also derive the quantitative condition that this kind of decay process takes place and discuss what kind of system is suitable to observe the decay.Comment: 17 pages, 6 figure

Membrane Type 1 Matrix Metalloproteinase Regulates Monocyte Migration and Collagen Destruction in Tuberculosis

Tuberculosis (TB) remains a global pandemic and drug resistance is rising. Multicellular granuloma formation is the pathological hallmark of Mycobacterium tuberculosis infection. The membrane type 1 matrix metalloproteinase (MT1-MMP or MMP-14) is a collagenase that is key in leukocyte migration and collagen destruction. In patients with TB, induced sputum MT1-MMP mRNA levels were increased 5.1-fold compared with matched controls and correlated positively with extent of lung infiltration on chest radiographs (r = 0.483; p < 0.05). M. tuberculosis infection of primary human monocytes increased MT1-MMP surface expression 31.7-fold and gene expression 24.5-fold. M. tuberculosis-infected monocytes degraded collagen matrix in an MT1-MMP-dependent manner, and MT1-MMP neutralization decreased collagen degradation by 73%. In human TB granulomas, MT1-MMP immunoreactivity was observed in macrophages throughout the granuloma. Monocyte-monocyte networks caused a 17.5-fold increase in MT1-MMP surface expression dependent on p38 MAPK and G protein-coupled receptor-dependent signaling. Monocytes migrating toward agarose beads impregnated with conditioned media from M. tuberculosis-infected monocytes expressed MT1-MMP. Neutralization of MT1-MMP activity decreased this M. tuberculosis network-dependent monocyte migration by 44%. Taken together, we demonstrate that MT1-MMP is central to two key elements of TB pathogenesis, causing collagen degradation and regulating monocyte migration

A Determination of H_0 with the CLASS Gravitational Lens B1608+656: I. Time Delay Measurements with the VLA

We present the results of a program to monitor the four-image gravitational lens B1608+656 with the VLA. The system was observed over a seven month period from 1996 October to 1997 May. The 64 epochs of observation have an average spacing of 3.6~d. The light curves of the four images of the background source show that the flux density of the background source has varied at the ~5% level. We measure time delays in the system based on common features that are seen in all four light curves. The three independent time delays in the system are found to be Delta t_{BA} = 31 +/- 7~d, Delta t_{BC} = 36 +/- 7~d, and Delta t_{BD} = 76^{+9}_{-10}~d at 95% confidence. This is the first gravitational lens system for which three independent time delays have been measured. A companion paper presents a mass model for the lensing galaxy which correctly reproduces the observed image positions, flux density ratios, and time delay ratios. The last condition is crucial for determining H_0 with a four-image lens. We combine the time delays with the model to obtain a value for the Hubble constant of H_0 = 59^{+8}_{-7} km/s/Mpc at 95% confidence (statistical) for (Omega_M, Omega_{Lambda}) = (1,0). In addition, there is an estimated systematic uncertainty of +/- 15 km/s/Mpc from uncertainties in modeling the radial mass profiles of the lensing galaxies. The value of H_0 presented in this paper is comparable to recent measurements of H_0 from the gravitational lenses 0957+561, PG1115+080, B0218+357, and PKS1830-211.Comment: Accepted for publication in ApJ. 20 pages, 13 figure

Kinematically Cold Populations at Large Radii in the Draco and Ursa Minor Dwarf Spheroidals

We present projected velocity dispersion profiles for the Draco and Ursa Minor (UMi) dwarf spheroidal galaxies based on 207 and 162 discrete stellar velocities, respectively. Both profiles show a sharp decline in the velocity dispersion outside ~30 arcmin (Draco) and ~40 arcmin (UMi). New, deep photometry of Draco reveals a break in the light profile at ~25 arcmin. These data imply the existence of a kinematically cold population in the outer parts of both galaxies. Possible explanations of both the photometric and kinematic data in terms of both equilibrium and non-equilibrium models are discussed in detail. We conclude that these data challenge the picture of dSphs as simple, isolated stellar systems.Comment: 5 pages, accepted for publication in ApJ Letter