ALMA Observations of Circumnuclear Disks in Early Type Galaxies: 12CO(2-1) and Continuum Properties

We present results from an Atacama Large Millimeter/submillimeter Array (ALMA) Cycle 2 program to map CO(2-1) emission in nearby early-type galaxies (ETGs) that host circumnuclear gas disks. We obtained $\sim0.3''-$resolution Band 6 observations of seven ETGs selected on the basis of dust disks in Hubble Space Telescope images. We detect CO emission in five at high signal-to-noise ratio with the remaining two only faintly detected. All CO emission is coincident with the dust and is in dynamically cold rotation. Four ETGs show evidence of rapid central rotation; these are prime candidates for higher-resolution ALMA observations to measure the black hole masses. In this paper we focus on the molecular gas and continuum properties. Total gas masses and H$_2$ column densities for our five CO-bright galaxies are on average $\sim10^8$ $M_\odot$ and $\sim10^{22.5}$ cm$^{-2}$ over the $\sim$kpc-scale disks, and analysis suggests that these disks are stabilized against gravitational fragmentation. The continuum emission of all seven galaxies is dominated by a central, unresolved source, and in five we also detect a spatially extended component. The $\sim$230 GHz nuclear continua are modeled as power laws ranging from $S_\nu \sim \nu^{-0.4}$ to $\nu^{1.6}$ within the observed frequency band. The extended continuum profiles of the two radio-bright (and CO-faint) galaxies are roughly aligned with their radio jet and suggests resolved synchrotron jets. The extended continua of the CO-bright disks are coincident with optically thick dust absorption and have spectral slopes that are consistent with thermal dust emission.Comment: 20 pages, 10 figures; accepted for publication in Ap

A Precision Measurement of the Mass of the Black Hole in NGC 3258 from High-Resolution ALMA Observations of its Circumnuclear Disk

We present $\sim0.10^{\prime\prime}-$resolution Atacama Large Millimeter/submillimeter Array (ALMA) CO(2$-$1) imaging of the arcsecond-scale ($r \approx 150$ pc) dusty molecular disk in the giant elliptical galaxy NGC 3258. The data provide unprecedented resolution of cold gas disk kinematics within the dynamical sphere of influence of a supermassive black hole, revealing a quasi-Keplerian central increase in projected rotation speed rising from 280 km s$^{-1}$ at the disk's outer edge to $>400$ km s$^{-1}$ near the disk center. We construct dynamical models for the rotating disk and fit beam-smeared model CO line profiles directly to the ALMA data cube. Our models incorporate both flat disks and tilted-ring disks that provide a better fit of the mildly warped structure in NGC 3258. We show that the exceptional angular resolution of the ALMA data makes it possible to infer the host galaxy's mass profile within $r=150$ pc solely from the ALMA CO kinematics, without relying on optical or near-infrared imaging data to determine the stellar mass profile. Our model therefore circumvents any uncertainty in the black hole mass that would result from the substantial dust extinction in the galaxy's central region. The best model fit yields $M_\mathrm{BH} = 2.249\times10^9$ $M_\odot$ with a statistical model-fitting uncertainty of just 0.18\%, and systematic uncertainties of 0.62\% from various aspects of the model construction and 12\% from uncertainty in the distance to NGC 3258. This observation demonstrates the full potential of ALMA for carrying out highly precise measurements of $M_\mathrm{BH}$ in early-type galaxies containing circumnuclear gas disksComment: Accepted for publication in ApJ. 32 pages, 22 figure

MEASUREMENT OF THE BLACK HOLE MASS IN NGC 1332 FROM ALMA OBSERVATIONS AT 0.044 ARCSECOND RESOLUTION

We present Atacama Large Millimeter/submillimeter Array (ALMA) Cycle 3 observations of CO(2-1) emission from the circumnuclear disk in the E/S0 galaxy NGC 1332 at 0.″044 resolution. The disk exhibits regular rotational kinematics and central high-velocity emission (±500 km s ) consistent with the presence of a compact central mass. We construct models for a thin, dynamically cold disk in the gravitational potential of the host galaxy and black hole and fit the beam-smeared model line profiles directly to the ALMA data cube. Model fits successfully reproduce the disk kinematics out to r = 200 pc. Fitting models just to spatial pixels within projected r = 50 pc of the nucleus (two times larger than the black hole's gravitational radius of influence), we find M =(6.64 ) × 10 M . This observation demonstrates ALMA's powerful capability to determine the masses of supermassive black holes by resolving gas kinematics on small angular scales in galaxy nuclei. -1 +0.65 8 BH -0.63

Predicting the initial spread of novel Asian origin influenza A viruses in the continental USA by wild waterfowl

Using data on waterfowl band recoveries, we identified spatially explicit hotspots of concentrated waterfowl movement to predict occurrence and spatial spread of a novel influenza A virus (clade 2.3.4.4) introduced from Asia by waterfowl from an initial outbreak in North America in November 2014. In response to the outbreak, the hotspots of waterfowl movement were used to help guide sampling for clade 2.3.4.4 viruses in waterfowl as an early warning for the US poultry industry during the outbreak. After surveillance sampling of waterfowl, we tested whether there was greater detection of clade 2.3.4.4 viruses inside hotspots. We found that hotspots defined using kernel density estimates of waterfowl band recoveries worked well in predicting areas with higher prevalence of the viruses in waterfowl. This approach exemplifies the value of ecological knowledge in predicting risk to agricultural security

Black Hole Mass Measurements of Radio Galaxies NGC 315 and NGC 4261 Using ALMA CO Observations

We present Atacama Large Millimeter/submillimeter Array (ALMA) Cycle 5 and Cycle 6 observations of CO(2$-$1) and CO(3$-$2) emission at 0.2''$-$0.3'' resolution in two radio-bright, brightest group/cluster early-type galaxies, NGC 315 and NGC 4261. The data resolve CO emission that extends within their black hole (BH) spheres of influence ($r_\mathrm{g}$), tracing regular Keplerian rotation down to just tens of parsecs from the BHs. The projected molecular gas speeds in the highly inclined ($i>60^\circ$) disks rises at least 500 km s$^{-1}$ near their galaxy centers. We fit dynamical models of thin-disk rotation directly to the ALMA data cubes, and account for the extended stellar mass distributions by constructing galaxy surface brightness profiles corrected for a range of plausible dust extinction values. The best-fit models yield $(M_\mathrm{BH}/10^9\,M_\odot)=2.08\pm0.01(\mathrm{stat})^{+0.32}_{-0.14}(\mathrm{sys})$ for NGC 315 and $(M_\mathrm{BH}/10^9\,M_\odot)=1.67\pm0.10(\mathrm{stat})^{+0.39}_{-0.24}(\mathrm{sys})$ for NGC 4261, the latter of which is larger than previous estimates by a factor of $\sim$3. The BH masses are broadly consistent with the relations between BH masses and host galaxy properties. These are among the first ALMA observations to map dynamically cold gas kinematics well within the BH-dominated regions of radio galaxies, resolving the respective $r_\mathrm{g}$ by factors of $\sim$5$-$10. The observations demonstrate ALMA's ability to precisely measure BH masses in active galaxies, which will enable more confident probes of accretion physics for the most massive galaxies.Comment: 24 pages, 11 figures, 4 tables. Accepted for publication in Ap

Evidence-based selection of theories for designing behaviour change interventions : using methods based on theoretical construct domains to understand clinicians' blood transfusion behaviour

Peer reviewedPostprin

Total synthesis and biological evaluation of simplified aplyronine analogues as synthetically tractable anticancer agents.

The aplyronines are a family of highly cytotoxic marine natural products with potential application in targeted cancer chemotherapy. To address the severe supply issue, function-oriented molecular editing of their macrolactone scaffold led to the design of a series of simplified aplyronine analogues. Enabled by a highly convergent aldol-based route, the total synthesis of four analogues was achieved, with a significant improvement in step economy versus previous compounds, and their cancer cell growth inhibition in the HeLa cell line was determined. The modular strategy presented offers a means for significantly shortening their chemical synthesis to facilitate the continued development of this promising class of anticancer agent

A general approach for the site-selective modification of native proteins, enabling the generation of stable and functional antibody-drug conjugates.

Antibody-drug conjugates (ADCs) are a class of targeted therapeutics that utilize the specificity of antibodies to selectively deliver highly potent cytotoxins to target cells. Although recent years have witnessed significant interest in ADCs, problems remain with the standard linkage chemistries used for cytotoxin-antibody bioconjugation. These typically (1) generate unstable constructs, which may lead to premature cytotoxin release, (2) often give a wide variance in drug-antibody ratios (DAR) and (3) have poor control of attachment location on the antibody, resulting in a variable pharmacokinetic profile. Herein, we report a novel divinylpyrimidine (DVP) linker platform for selective bioconjugation via covalent re-bridging of reduced disulfide bonds on native antibodies. Model studies using the non-engineered trastuzumab antibody validate the utility of this linker platform for the generic generation of highly plasma-stable and functional antibody constructs that incorporate variable biologically relevant payloads (including cytotoxins) in an efficient and site-selective manner with precise control over DAR. DVP linkers were also used to efficiently re-bridge both monomeric and dimeric protein systems, demonstrating their potential utility for general protein modification, protein stabilisation or the development of other protein-conjugate therapeutics.AstraZeneca, Cambridge Trusts, EPSRC, BBSRC, Royal Society, MR

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A Search for 6.7 GHz Methanol Masers in OH Megamaser Galaxies at 0.11<z<0.27

We report the results of a search for 6.7 GHz methanol (CH3OH) maser emission in OH megamaser galaxies at 0.11<z<0.27. No detections were made in the 25 objects observed down to rms noise levels of roughly 0.6 mJy in 150 kHz channels. The OH megamaser sample includes OH emission of all observed types: narrow and broad, physically compact and extended, variable and quiescent, and from simple single lines to multi-component complexes to lines with high velocity wings. Our null result indicates, for the widest possible range of OH megamaser environments, that methanol masing does not scale with OH from Galactic masers to megamasers. These observations, however, are not sensitive enough to rule out methanol masing that scales with star formation from Galactic compact HII regions to starbursts associated with major mergers. This and previous work suggest that OH megamasers do not represent large ensembles of individual masers associated with star forming regions. Maser models combined with observational constraints on the physical settings of OH megamasers indicate that 6.7 GHz methanol megamasers will not be detected by this survey if T(dust) < 100 K or if n(CH3OH) < n(OH).Comment: 5 pages, 1 figure, accepted by A