Flow cytometric detection of gamma interferon can effectively discriminate Mycobacterium bovis BCG-vaccinated cattle from M. bovis-infected cattle

Mycobacterium bovis is the causative agent of bovine tuberculosis, a disease that is increasing in incidence in United Kingdom cattle herds. In addition to increasing economic losses, the rise in bovine tuberculosis poses a human health risk. There is an urgent requirement for effective strategies for disease eradication; this will likely involve vaccination in conjunction with current test and slaughter policies. A policy involving vaccination would require an accurate diagnosis of M. bovis-infected animals and the potential to distinguish these animals from vaccinates. Currently used diagnostic tests, the skin test and gamma interferon (IFN-γ) blood test, have a sensitivity of up to 95%. A further complication is that M. bovis BCG-vaccinated animals are also scored positive by these tests. We tested the hypothesis that the quantification of IFN-γ-producing lymphocytes by flow cytometric analysis of intracellular IFN-γ expression would provide a more accurate discrimination of M. bovis-infected animals from BCG vaccinates. Significant numbers of IFN-γ-expressing CD4(+) T cells were detected following culture of heparinized blood from M. bovis-infected animals, but not from BCG vaccinates, with purified protein derived from M. bovis (PPD-B) or live mycobacteria. Only 1 of 17 BCG-vaccinated animals had a significant number of CD4(+) T lymphocytes expressing IFN-γ, compared with 21/22 M. bovis-infected animals. This assay could allow an accurate diagnosis of M. bovis and allow the discrimination of BCG-vaccinated cattle from infected cattle

Probing Cool and Warm Infrared Galaxies using Photometric and Structural Measures

We have analyzed a sample of nearby cool and warm infrared (IR) galaxies using photometric and structural parameters. The set of measures include far-infrared color ($C = \log_{10}[S_{60\mu m}/S_{100\mu m}]$), total IR luminosity ($L_{TIR}$), radio surface brightness as well as radio, near-infrared, and optical sizes. In a given luminosity range cool and warm galaxies are considered as those sources that are found approximately $1 \sigma$ below and above the mean color in the far-infrared $C - L_{TIR}$ diagram. We find that galaxy radio surface brightness is well correlated with color whereas size is less well correlated with color. Our analysis indicates that IR galaxies that are dominated by cool dust are large, massive spirals that are not strongly interacting or merging and presumably the ones with the least active star formation. Dust in these cool objects is less centrally concentrated than in the more typical luminous and ultra-luminous IR galaxies that are dominated by warm dust. Our study also shows that low luminosity early type unbarred and transitional spirals are responsible for the large scatter in the $C - L_{TIR}$ diagram. Among highly luminous galaxies, late type unbarred spirals are predominately warm, and early type unbarred and barred are systematically cooler. We highlight the significance of $C - L_{TIR}$ diagram in terms of local and high redshifts sub-millimeter galaxies.Comment: Accepted for publication in ApJ, 2006, 23 pages, 3 postscript figures, 1 table. The table can be obtained on request from the author

Interferometric Observations of the Nuclear Region of Arp220 at Submillimeter Wavelengths

We report the first submillimeter interferometric observations of an ultraluminous infrared galaxy. We observed Arp220 in the CO J=3-2 line and 342GHz continuum with the single baseline CSO-JCMT interferometer consisting of the Caltech Submillimeter Observatory (CSO) and the James Clerk Maxwell Telescope (JCMT). Models were fit to the measured visibilities to constrain the structure of the source. The morphologies of the CO J=3-2 line and 342GHz continuum emission are similar to those seen in published maps at 230 and 110GHz. We clearly detect a binary source separated by about 1 arcsec in the east-west direction in the 342GHz continuum. The CO J=3-2 visibility amplitudes, however, indicate a more complicated structure, with evidence for a compact binary at some velocities and rather more extended structure at others. Less than 30% of the total CO J=3-2 emission is detected by the interferometer, which implies the presence of significant quantities of extended gas. We also obtained single-dish CO J=2-1, CO J=3-2 and HCN J=4-3 spectra. The HCN J=4-3 spectrum, unlike the CO spectra, is dominated by a single redshifted peak. The HCN J=4-3/CO J=3-2, HCN J=4-3/HCN J=1-0 and CO J=3-2/2-1 line ratios are larger in the redshifted (eastern) source, which suggests that the two sources may have different physical conditions. This result might be explained by the presence of an intense starburst that has begun to deplete or disperse the densest gas in the western source, while the eastern source harbors undispersed high density gas.Comment: 17 pages, 9 figures, 4 Tables. accepted by Ap

The Sunyaev-Zel'dovich Effect by Cocoons of Radio Galaxies

We estimate the deformation of the cosmic microwave background radiation by the hot region (``cocoon'') around a radio galaxy. A simple model is adopted for cocoon evolution while the jet is on, and a model of evolution is constructed after the jet is off. It is found that at low redshift the phase after the jet is off is longer than the lifetime of the jets. The Compton y-parameter generated by cocoons is calculated with a Press-Schechter number density evolution. The resultant value of y is of the same order as the COBE constraint. The Sunyaev-Zeldovich effect due to cocoons could therefore be a significant foreground source of small angular scale anisotropies in the cosmic microwave background radiation.Comment: Published version, 23 pages with 5 figure

Sensitive observations at 1.4 and 250 GHz of z > 5 QSOs

We present 1.4 and 5 GHz observations taken with the Very Large Array (VLA), and observations at 250 GHz obtained with the Max-Planck millimeter bolometer (MAMBO) at the IRAM 30~m telescope, of ten optically selected Quasi-stellar Objects (QSOs) at 5.0 < z < 6.28. Four sources are detected at 1.4 GHz two of which are radio loud and are also detected at 5 GHz. These results are roughly consistent with there being no evolution of the radio-loud QSO fraction out to z~6. Three sources have been detected at 250 GHz or 350 GHz at much higher levels than their 1.4 GHz flux densities suggesting that the observed mm emission is likely thermal emission from warm dust, although more exotic possibilities cannot be precluded. The highest redshift source in our sample (J1030+0524 at z=6.28) is not detected at 1.4 or 250 GHz, but four fairly bright radio sources (flux density at 1.4GHz > 0.2 mJy) are detected in a 2' field centered on the QSO, including an edge-brightened ('FRII') double radio source with an extent of about 1'. A similar over-density of radio sources is seen in the field of the highest redshift QSO J1148+5251. We speculate that these over-densities of radio sources may indicate clusters along the lines-of-sight, in which case gravitational lensing by the cluster could magnify the QSO emission by a factor 2 or so without giving rise to arcsecond-scale distortions in the optical images of the QSOs.Comment: 25 pages, 12 figures. accepted by A

Rotating Nuclear Rings and Extreme Starbursts in Ultraluminous Galaxies

New high resolution interferometer data of 10 IR ultraluminous galaxies shows the molecular gas is in rotating nuclear rings or disks with radii 300 to 800 pc. Most of the CO flux comes from a moderate-density, warm, intercloud medium rather than self-gravitating clouds. Gas masses of ~ 5 x 10^9 Msun, 5 times lower than the standard method are derived from a model of the molecular disks. The ratio of molecular gas to dynamical mass, is M_gas/M_dyn ~ 1/6 with a maximum ratio of gas to total mass surface density of 1/3. For the galaxies VIIZw31, Arp193, and IRAS 10565+24, there is good evidence for rotating molecular rings with a central gap. In addition to the rotating rings a new class of star formation region is identified which we call an Extreme Starburst. They have a characteristic size of only 100 pc., about 10^9 Msun of gas and an IR luminosity of ~3 x 10^11 Lsun. Four extreme starbursts are identified in the 3 closest galaxies in the sample Arp220, Arp193 and Mrk273. They are the most prodigious star formation events in the local universe, each representing about 1000 times as many OB stars as 30 Doradus. In Arp220, the CO and 1.3 mm continuum maps show the two ``nuclei'' embedded in a central ring or disk and a fainter structure extending 3 kpc to the east, normal to the nuclear disk. There is no evidence that these sources really are the pre-merger nuclei. They are compact, extreme starburst regions containing 10^9 Msun of dense molecular gas and new stars, but no old stars. Most of the dust emission and HCN emission arises in the two extreme starbursts. The entire bolometric luminosity of Arp~220 comes from starbursts, not an AGN. In Mrk231, the disk geometry shows that the molecular disk cannot be heated by the AGN; the far IR luminosity of Mrk~231 is powered by a starburst, not the AGN. (Abridged)Comment: 97 pages Latex with aasms.sty, including 29 encapsulated Postscript figures. Figs 18 and 23 are GIFs. 31 figures total. Text and higher quality versions of figures available at http://sbastk.ess.sunysb.edu/www/RINGS_ESB_PREPRINT.html To be published in Ap. J., 10 Nov. 199

Radio-Excess IRAS Galaxies: PMN/FSC Sample Selection

A sample of 178 extragalactic objects is defined by correlating the 60 micron IRAS FSC with the 5 GHz PMN catalog. Of these, 98 objects lie above the radio/far-infrared relation for radio-quiet objects. These radio-excess galaxies and quasars have a uniform distribution of radio excesses and appear to be a new population of active galaxies not present in previous radio/far-infrared samples. The radio-excess objects extend over the full range of far-infrared luminosities seen in extragalactic objects. Objects with small radio excesses are more likely to have far-infrared colors similar to starbursts, while objects with large radio excesses have far-infrared colors typical of pure AGN. Some of the most far-infrared luminous radio-excess objects have the highest far-infrared optical depths. These are good candidates to search for hidden broad line regions in polarized light or via near-infrared spectroscopy. Some low far-infrared luminosity radio-excess objects appear to derive a dominant fraction of their far-infrared emission from star formation, despite the dominance of the AGN at radio wavelengths. Many of the radio-excess objects have sizes likely to be smaller than the optical host, but show optically thin radio emission. We draw parallels between these objects and high radio luminosity Compact Steep-Spectrum (CSS) and GigaHertz Peaked-Spectrum (GPS) objects. Radio sources with these characteristics may be young AGN in which the radio activity has begun only recently. Alternatively, high central densities in the host galaxies may be confining the radio sources to compact sizes. We discuss future observations required to distinguish between these possibilities and determine the nature of radio-excess objects.Comment: Submitted to AJ. 44 pages, 11 figures. A version of the paper with higher quality figures is available from http://www.mso.anu.edu.au/~cdrake/PMNFSC/paperI

Single-cell transcriptomics uncovers distinct molecular signatures of stem cells in chronic myeloid leukemia

Recent advances in single-cell transcriptomics are ideally placed to unravel intratumoral heterogeneity and selective resistance of cancer stem cell (SC) subpopulations to molecularly targeted cancer therapies. However, current single-cell RNA-sequencing approaches lack the sensitivity required to reliably detect somatic mutations. We developed a method that combines high-sensitivity mutation detection with whole-transcriptome analysis of the same single cell. We applied this technique to analyze more than 2,000 SCs from patients with chronic myeloid leukemia (CML) throughout the disease course, revealing heterogeneity of CML-SCs, including the identification of a subgroup of CML-SCs with a distinct molecular signature that selectively persisted during prolonged therapy. Analysis of nonleukemic SCs from patients with CML also provided new insights into cell-extrinsic disruption of hematopoiesis in CML associated with clinical outcome. Furthermore, we used this single-cell approach to identify a blast-crisis-specific SC population, which was also present in a subclone of CML-SCs during the chronic phase in a patient who subsequently developed blast crisis. This approach, which might be broadly applied to any malignancy, illustrates how single-cell analysis can identify subpopulations of therapy-resistant SCs that are not apparent through cell-population analysis

Single-cell transcriptomics uncovers distinct molecular signatures of stem cells in chronic myeloid leukemia

Recent advances in single-cell transcriptomics are ideally placed to unravel intratumoral heterogeneity and selective resistance of cancer stem cell (SC) subpopulations to molecularly targeted cancer therapies. However, current single-cell RNA-sequencing approaches lack the sensitivity required to reliably detect somatic mutations. We developed a method that combines high-sensitivity mutation detection with whole-transcriptome analysis of the same single cell. We applied this technique to analyze more than 2,000 SCs from patients with chronic myeloid leukemia (CML) throughout the disease course, revealing heterogeneity of CML-SCs, including the identification of a subgroup of CML-SCs with a distinct molecular signature that selectively persisted during prolonged therapy. Analysis of nonleukemic SCs from patients with CML also provided new insights into cell-extrinsic disruption of hematopoiesis in CML associated with clinical outcome. Furthermore, we used this single-cell approach to identify a blast-crisis-specific SC population, which was also present in a subclone of CML-SCs during the chronic phase in a patient who subsequently developed blast crisis. This approach, which might be broadly applied to any malignancy, illustrates how single-cell analysis can identify subpopulations of therapy-resistant SCs that are not apparent through cell-population analysis

Modeling the spectral energy distribution of ULIRGs I: the radio spectra

As a constraint for new starburst/AGN models of IRAS bright galaxies we determine the radio spectra of 31 luminous and ultraluminous IRAS galaxies (LIRGs/ULIRGs). We construct the radio spectra using both new and archival data. From our sample of radio spectra we find that very few have a straight power-law slope. Although some sources show a flattening of the radio spectral slope at high frequencies the average spectrum shows a steepening of the radio spectrum from 1.4 to 22.5 GHz. This is unexpected because in sources with high rates of star formation we expect flat spectrum, free-free emission to make a significant contribution to the radio flux at higher radio frequencies. Despite this trend the radio spectral indices between 8.4 and 22.5 GHz are flatter for sources with higher values of the FIR-radio flux density ratio q, when this is calculated at 8.4 GHz. Therefore, sources that are deficient in radio emission relative to FIR emission (presumably younger sources) have a larger thermal component to their radio emission. However, we find no correlation between the radio spectral index between 1.4 and 4.8 GHz and q at 8.4 GHz. Because the low frequency spectral index is affected by free-free absorption, and this is a function of source size for a given mass of ionized gas, this is evidence that the ionized gas in ULIRGs shows a range of densities. The youngest LIRGs and ULIRGs are characterized by a larger contribution to their high-frequency radio spectra from free-free emission. However, the youngest sources are not those that have the greatest free-free absorption at low radio frequencies. The sources in which the effects of free-free absorption are strongest are instead the most compact sources. Although these have the warmest FIR colours, they are not necessarily the youngest sources.Comment: 16 pages. Submitted to A&A Re-submitted, with aesthetic improvements to the text and figure