Digital transformation in bio manufacturing

This presentation describes ways to leverage and implement digitalization technologies in biopharmaceutical manufacturing. An accelerated process development workflow is described that employs micro-scale technologies, modular unit operations with integrated process control and monitoring systems, systems integration, and full plant automation. The presentation describes how to best develop and transfer knowledge between steps in the workflow via first-principles models, data analytics, and machine learning. Case studies are described that illustrate the application of each of the above methods, including where process equipment was designed digitally by using first-principles models first, then the process equipment was constructed and implemented experimentally, with the experimental results confirming model predictions

The Discovery of Water Maser Emission from Eight Nearby Galaxies

Using the Green Bank Telescope, we conducted a ``snapshot'' survey for water maser emission toward the nuclei of 611 galaxies and detected eight new sources. The sample consisted of nearby (v < 5000 km/s) and luminous (M_B < -19.5) galaxies, some with known nuclear activity but most not previously known to host AGNs. Our detections include both megamasers associated with AGNs and relatively low luminosity masers probably associated with star formation. The detection in UGC 3789 is particularly intriguing because the spectrum shows both systemic and high-velocity lines indicative of emission from an AGN accretion disk seen edge-on. Based on six months of monitoring, we detected accelerations among the systemic features ranging from 2 to 8 km/s/yr, the larger values belonging to the most redshifted systemic components. High-velocity maser lines in UGC 3789 show no detectable drift over the same period. Although UGC 3789 was not known to be an AGN prior to this survey, the presence of a disk maser is strong evidence for nuclear activity, and an optical spectrum obtained later has confirmed it. With follow up observations, it may be possible to measure a geometric distance to UGC 3789.Comment: to appear in Astrophysical Journal, 1 May 200

Towards Precision Supermassive Black Hole Masses using Megamaser Disks

Megamaser disks provide the most precise and accurate extragalactic supermassive black hole masses. Here we describe a search for megamasers in nearby galaxies using the Green Bank Telescope (GBT). We focus on galaxies where we believe that we can resolve the gravitational sphere of influence of the black hole and derive a stellar or gas dynamical measurement with optical or NIR observations. Since there are only a handful of super massive black holes (SMBH) that have direct black hole mass measurements from more than one method, even a single galaxy with a megamaser disk and a stellar dynamical black hole mass would provide necessary checks on the stellar dynamical methods. We targeted 87 objects from the Hobby-Eberly Telescope Massive Galaxy Survey, and detected no new maser disks. Most of the targeted objects are elliptical galaxies with typical stellar velocity dispersions of 250 km/s and distances within 130 Mpc. We discuss the implications of our non-detections, whether they imply a threshold X-ray luminosity required for masing, or possibly reflect the difficulty of maintaining a masing disk around much more massive (>10^8 Msun) black holes at low Eddington ratio. Given the power of maser disks at probing black hole accretion and demographics, we suggest that future maser searches should endeavour to remove remaining sample biases, in order to sort out the importance of these covariant effects.Comment: 9 pages, 5 figures, Apj, updated to match the accepted versio

Refining the M_BH-V_c scaling relation with HI rotation curves of water megamaser galaxies

Black hole - galaxy scaling relations provide information about the coevolution of supermassive black holes and their host galaxies. We compare the black hole mass - circular velocity (MBH - Vc) relation with the black hole mass - bulge stellar velocity dispersion (MBH - sigma) relation, to see whether the scaling relations can passively emerge from a large number of mergers, or require a physical mechanism, such as feedback from an active nucleus. We present VLA H I observations of five galaxies, including three water megamaser galaxies, to measure the circular velocity. Using twenty-two galaxies with dynamical MBH measurements and Vc measurements extending to large radius, our best-fit MBH - Vc relation, log MBH = alpha + beta log(Vc /200 km s^-1), yields alpha = 7.43+/-0.13, beta = 3.68+1.23/-1.20, and intrinsic scatter epsilon_int = 0.51+0.11/-0.09. The intrinsic scatter may well be higher than 0.51, as we take great care to ascribe conservatively large observational errors. We find comparable scatter in the MBH - sigma relations, epsilon_int = 0.48+0.10/-0.08, while pure merging scenarios would likely result in a tighter scaling with the dark halo (as traced by Vc) than baryonic (sigma) properties. Instead, feedback from the active nucleus may act on bulge scales to tighten the MBH - sigma relation with respect to the MBH - Vc relation, as observed.Comment: 27 pages, 15 figures, ApJ accepte

Circumnuclear Structures in Megamaser Host Galaxies

Using HST, we identify circumnuclear ($100$-$500$ pc scale) structures in nine new H$_2$O megamaser host galaxies to understand the flow of matter from kpc-scale galactic structures down to the supermassive black holes (SMBHs) at galactic centers. We double the sample analyzed in a similar way by Greene et al. (2013) and consider the properties of the combined sample of 18 sources. We find that disk-like structure is virtually ubiquitous when we can resolve $<200$ pc scales, in support of the notion that non-axisymmetries on these scales are a necessary condition for SMBH fueling. We perform an analysis of the orientation of our identified nuclear regions and compare it with the orientation of megamaser disks and the kpc-scale disks of the hosts. We find marginal evidence that the disk-like nuclear structures show increasing misalignment from the kpc-scale host galaxy disk as the scale of the structure decreases. In turn, we find that the orientation of both the $\sim100$ pc scale nuclear structures and their host galaxy large-scale disks is consistent with random with respect to the orientation of their respective megamaser disks.Comment: 24 pages, 16 figures, 4 tables; Resubmitted to ApJ after referee's comment

Plug-and-play software for mechanistic modelling of end-to-end continuous manufacturing of monoclonal antibodies

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21cm Absorption by Compact Hydrogen Disks Around Black Holes in Radio-Loud Nuclei of Galaxies

The clumpy maser disks observed in some galactic nuclei mark the outskirts of the accretion disk that fuels the central black hole and provide a potential site of nuclear star formation. Unfortunately, most of the gas in maser disks is currently not being probed; large maser gains favor paths that are characterized by a small velocity gradient and require rare edge-on orientations of the disk. Here we propose a method for mapping the atomic hydrogen distribution in nuclear disks through its 21cm absorption against the radio continuum glow around the central black hole. In NGC 4258, the 21cm optical depth may approach unity for high angular-resolution (VLBI) imaging of coherent clumps which are dominated by thermal broadening and have the column density inferred from X-ray absorption data, ~10^{23}/cm^2. Spreading the 21cm absorption over the full rotation velocity width of the material in front of the narrow radio jets gives a mean optical depth of ~0.1. Spectroscopic searches for the 21cm absorption feature in other galaxies can be used to identify the large population of inclined gaseous disks which are not masing in our direction. Follow-up imaging of 21cm silhouettes of accelerating clumps within these disks can in turn be used to measure cosmological distances.Comment: 4 page