Pilot scale hybrid fed batch and continuous processing of biologics

Pfizer Bioprocessing R&D is focused on developing enabling technologies that will reduce capital and operational expenses, decrease equipment scale, increase automation and utilize fewer FTEs. To realize this vision, our Pilot Facility has partnered with our cell culture process development colleagues to adapt a fed batch platform 150L stainless steel bioreactor to run in hybrid perfusion, standard perfusion, low volume cell controlled perfusion, and continuous stirred tank modes. Through adjustments to impeller configuration, sparging strategy, and addition ports the bioreactor was able to deliver multiple batches that produced ~3X gains in cell density and volumetric productivity versus conventional fed batch platform methods

GRID INTEGRATION OF WAVE AND TIDAL ENERGY

International audienceWave and tidal energy provide a renewable source of electricity. However, their inherent fluctuations may have a negative impact on the power quality of a local electrical network. Grid operators assess this impact through the use of dynamic models of the generation units, which are inserted into the overall power system model. Providing these models is a compulsory step for any power generator to procure a grid connection above a specified power capacity. Significant issues were encountered in the wind energy industry regarding the dynamic modelling of devices, among which were model numerical instability, poor dynamic model quality and model incompatibility. Considering the large diversity of device types in the emerging ocean energy industry, these problems are considered as a major barrier to the larger scale grid-integration of marine energy converters. Dynamic models must clearly demonstrate the compliance of the actual power generation device and array of devices to the grid code requirements for grid-connection to be allowed. A further barrier to grid connection of ocean energy devices is that existing grid codes – mainly written in the context of wind energy-may be irrelevant or inadequate for ocean energy devices. This paper presents an overview of these issues, and details a radically different approach to the dynamic modelling of ocean energy devices that will assist in overcoming the issues previously encountered in the development of wind turbine models. It also highlights the gaps and inadequacy regarding grid code requirements for ocean energy devices, and provides some recommendations for a new ocean energy grid code

Being Even Slightly Shallow Makes Life Hard

We study the computational complexity of identifying dense substructures, namely r/2-shallow topological minors and r-subdivisions. Of particular interest is the case r = 1, when these substructures correspond to very localized relaxations of subgraphs. Since Densest Subgraph can be solved in polynomial time, we ask whether these slight relaxations also admit efficient algorithms. In the following, we provide a negative answer: Dense r/2-Shallow Topological Minor and Dense r-Subdivsion are already NP-hard for r = 1 in very sparse graphs. Further, they do not admit algorithms with running time 2^(o(tw^2)) n^O(1) when parameterized by the treewidth of the input graph for r > 2 unless ETH fails

Structured sedation programs in the emergency department, hospital and other acute settings: protocol for systematic review of effects and events.

BACKGROUND: The use of procedural sedation outside the operating theatre has increased in hospital settings and has gained popularity among non-anesthesiologists. Sedative agents used for procedural pain, although effective, also pose significant risks to the patient if used incorrectly. There is currently no universally accepted program of education for practitioners using or introducing procedural sedation into their practice. There is emerging literature identifying structured procedural sedation programs (PSPs) as a method of ensuring a standardized level of competency among staff and reducing risks to the patient. We hypothesize that programs of education for healthcare professionals using procedural sedation outside the operating theatre are beneficial in improving patient care, safety, practitioner competence and reducing adverse event rates. METHODS: Electronic databases will be systematically searched for studies (randomized and non-randomized) examining the effectiveness of structured PSPs from 1966 to present. Database searches will be supplemented by contact with experts, reference and citation checking, and a grey literature search. No language restriction will be imposed. Screening of titles and abstracts, and data extraction will be performed by two independent reviewers. All disagreements will be resolved by discussion with an independent third party. Data analysis will be completed adhering to procedures outlined in the Cochrane Handbook of Systematic Reviews of Interventions. If the data allows, a meta-analysis will be performed. DISCUSSION: This review will cohere evidence on the effectiveness of structured PSPs on sedation events and patient outcomes within the hospital and other acute care settings. In addition, it will examine key components identified within a PSP associated with patient safety and improved patient outcomes.Trial registration: PROSPERO registration number: CRD42013003851

Machine detector interface for the e+e−e^+e^- future circular collider

The international Future Circular Collider (FCC) study aims at a design of $pp$, $e^+e^-$, $ep$ colliders to be built in a new 100 km tunnel in the Geneva region. The $e^+e^-$ collider (FCC-ee) has a centre of mass energy range between 90 (Z-pole) and 375 GeV (tt_bar). To reach such unprecedented energies and luminosities, the design of the interaction region is crucial. The crab-waist collision scheme has been chosen for the design and it will be compatible with all beam energies. In this paper we will describe the machine detector interface layout including the solenoid compensation scheme. We will describe how this layout fulfills all the requirements set by the parameters table and by the physical constraints. We will summarize the studies of the impact of the synchrotron radiation, the analysis of trapped modes and of the backgrounds induced by single beam and luminosity effects giving an estimate of the losses in the interaction region and in the detector.Comment: 6 pages, 7 figures, 62th ICFA ABDW on High Luminosity Circular $e^+e^-$ Colliders, eeFACT2018, Hong Kong, Chin

Investigation and management of an outbreak of Salmonella Typhimurium DT8 associated with duck eggs, Ireland 2009 to 2011.

Salmonella Typhimurium DT8 was a very rare cause of human illness in Ireland between 2000 and 2008, with only four human isolates from three patients being identified. Over a 19-month period between August 2009 and February 2011, 34 confirmed cases and one probable case of Salmonella Typhimurium DT8 were detected, all of which had an MLVA pattern 2-10-NA-12-212 or a closely related pattern. The epidemiological investigations strongly supported a linkbetween illness and exposure to duck eggs. Moreover, S. Typhimurium with an MLVA pattern indistinguishable (or closely related) to the isolates from human cases, was identified in 22 commercial and backyard duck flocks, twelve of which were linked with known human cases. A range of control measures were taken at farm level, and advice was provided to consumers on the hygienic handling and cooking of duck eggs. Although no definitive link was established with a concurrent duck egg-related outbreak of S. Typhimurium DT8 in the United Kingdom, it seems likely that the two events were related. It may be appropriate for other countries with a tradition of consuming duck eggs to consider the need for measures to reduce the risk of similar outbreaks

Early Radio and X-Ray Observations of the Youngest Nearby Type Ia Supernova PTF 11kly (SN 2011fe)

On 2011 August 24 (UT) the Palomar Transient Factory (PTF) discovered PTF11kly (SN 2011fe), the youngest and most nearby Type Ia supernova (SN Ia) in decades. We followed this event up in the radio (centimeter and millimeter bands) and X-ray bands, starting about a day after the estimated explosion time.We present our analysis of the radio and X-ray observations, yielding the tightest constraints yet placed on the pre-explosion mass-loss rate from the progenitor system of this supernova. We find a robust limit of Ṁ ≾ 10^(−8)(w/100 km s^(−1))M_☉ yr^(−1) from sensitive X-ray non-detections, as well as a similar limit from radio data, which depends, however, on assumptions about microphysical parameters. We discuss our results in the context of single-degenerate models for SNe Ia and find that our observations modestly disfavor symbiotic progenitor models involving a red giant donor, but cannot constrain systems accreting from main-sequence or sub-giant stars, including the popular supersoft channel. In view of the proximity of PTF11kly and the sensitivity of our prompt observations, we would have to wait for a long time (a decade or longer) in order to more meaningfully probe the circumstellar matter of SNe Ia

Exploring the Optical Transient Sky with the Palomar Transient Factory

The Palomar Transient Factory (PTF) is a wide-field experiment designed to investigate the optical transient and variable sky on time scales from minutes to years. PTF uses the CFH12k mosaic camera, with a field of view of 7.9 deg^2 and a plate scale of 1 asec/pixel, mounted on the the Palomar Observatory 48-inch Samuel Oschin Telescope. The PTF operation strategy is devised to probe the existing gaps in the transient phase space and to search for theoretically predicted, but not yet detected, phenomena, such as fallback supernovae, macronovae, .Ia supernovae and the orphan afterglows of gamma-ray bursts. PTF will also discover many new members of known source classes, from cataclysmic variables in their various avatars to supernovae and active galactic nuclei, and will provide important insights into understanding galactic dynamics (through RR Lyrae stars) and the Solar system (asteroids and near-Earth objects). The lessons that can be learned from PTF will be essential for the preparation of future large synoptic sky surveys like the Large Synoptic Survey Telescope. In this paper we present the scientific motivation for PTF and describe in detail the goals and expectations for this experiment.Comment: 15 pages, 6 figures, submitted to PAS