564 research outputs found

    Critical process parameter identification using the ambr15(tm) for process characterization

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    Process characterization is a critical phase in the development of a commercial process for biotherapeutic production. Knowing the critical quality attributes of your molecule prior to beginning process development and/or characterization is imperative when using a quality by design (QbD) approach. Here we use a (QbD) approach for the characterization of a fed-batch process using an NSO cell line to express an IgG. For this molecule, the glycosylation profile, and in particular, the total fucosylation was identified as a critical quality attribute. After performing a primary hazard analysis, several process inputs were determined to potentially have an impact on this critical quality attribute. These parameters were then studied in a screening DoE using the ambr15™ to model the first and second order effects for each parameter on both the critical quality attributes and process performance. Of the 9 parameters studied, 5 were determined to have a statistically significant effect on the fucosylation of the molecule. In addition, 6 parameters were identified to have a significant impact on process performance. Through process modeling using JMP, a design space was determined for further studies to determine the proven acceptable range (PAR) for each parameter using the 10L, qualified scale down model. An example of the predicted PAR for pH and the timing of the temp shift can be seen in figure 1. Following the 10L studies, a PAR was determined for each parameter and compared with the predicted PAR from ambr. Here we demonstrate the feasibility to use the ambr15™ as a tool for key and even critical process parameter identification to reduce timelines for process characterization

    Intrinsic and extrinsic factors drive ontogeny of early-life at-sea behaviour in a marine top predator

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    Young animals must learn to forage effectively to survive the transition from parental provisioning to independent feeding. Rapid development of successful foraging strategies is particularly important for capital breeders that do not receive parental guidance after weaning. The intrinsic and extrinsic drivers of variation in ontogeny of foraging are poorly understood for many species. Grey seals (Halichoerus grypus) are typical capital breeders; pups are abandoned on the natal site after a brief suckling phase, and must develop foraging skills without external input. We collected location and dive data from recently-weaned grey seal pups from two regions of the United Kingdom (the North Sea and the Celtic and Irish Seas) using animal-borne telemetry devices during their first months of independence at sea. Dive duration, depth, bottom time, and benthic diving increased over the first 40 days. The shape and magnitude of changes differed between regions. Females consistently had longer bottom times, and in the Celtic and Irish Seas they used shallower water than males. Regional sex differences suggest that extrinsic factors, such as water depth, contribute to behavioural sexual segregation. We recommend that conservation strategies consider movements of young naĂŻve animals in addition to those of adults to account for developmental behavioural changes

    Unveiling the nature of the highly obscured AGN in NGC5643 with XMM-Newton

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    We present results from an XMM-Newton observation of the nearby Seyfert 2 galaxy NGC5643. The nucleus exhibits a very flat X-ray continuum above 2 keV, together with a prominent K-alpha fluorescent iron line. This indicates heavy obscuration. We measure an absorbing column density N_H in the range 6-10 x 10^{23} atoms/cm/cm, either directly covering the nuclear emission, or covering its Compton-reflection. In the latter case, we might be observing a rather unusual geometry for the absorber, whereby reflection from the inner far side of a torus is in turn obscured by its near side outer atmosphere. The nuclear emission might be then either covered by a Compton-thick absorber, or undergoing a transient state of low activity. A second source (christened "X-1" in this paper) at the outskirts of NGC5643 optical surface outshines the nucleus in X-rays. If belonging to NGC5643, it is the third brightest (L_X ~ 4 x 10^{40} erg/s) known Ultra Luminous X-ray source. Comparison with past large aperture spectra of NGC 5643 unveils dramatic X-ray spectral changes above 1 keV. We interpret them as due to variability of the active nucleus and of source X-1 intrinsic X-ray powers by a factor >10 and 5, respectively.Comment: 11 LATEX pages, 12 figures, to appear in Monthly Notices of the Royal Astronomical Societ

    Dynamic Performance of Cantilevered Sign Trusses for Fatigue

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    Cantilevered overhead sign structures (COSS) experience cyclic loading due to stochastic loads such as natural wind gusts (NWG). Wind loading can produce large deflections in the cantilever and large-magnitude stresses can develop at the box-type connection between the cantilevered arm and mast where fatigue performance is a concern. Modifications to the sign structures pose further concerns as changes to the aerodynamic properties could have unintended consequences. A design consideration of COSS is serviceability of the sign through use of a steel grate walkway that workers can use for maintenance on the sign. The steel grate walkways on COSS are rarely used for maintenance anymore, hence are being removed by multiple state DOTs to prevent vandalism. However, the impact on COSS with the removal of the walkways is unknown. This report describes an investigation in which the dynamic and aerodynamic properties of COSS was studied, and the effect of the walkway presence on structural response was explored. Computer simulations of 32 different COSS configurations were carried out to see the effect of the grate removal on the natural frequency and the mass of the overall structural system. Aerodynamic performance was considered through the use of computational fluid dynamics (CFD) and experimental testing, where wind pressure on the sign in both axial directions and effects of vortex shedding were examined. Findings include: 1) the walkway had a minimal effect on the system’s mass and natural frequencies, 2) the walkway had a minimal influence on the wind-induced force on the sign, 3) vortex shedding was not exacerbated with removal of a walkway attachment, and 4) walkway removal did not significantly change stress magnitudes at the connection between the cantilever and mast. Based on these findings, the removal of walkways from KDOT’s COSS was not found to problematic.The Kansas Department of Transportatio

    The final verdict by XMM-Newton: the X-ray obscured Seyfert galaxy NGC5506 has a broad Fe K-alpha line

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    We present the first unambiguous evidence of a broad (Gaussian width ~330 eV) component of the iron K-alpha fluorescent emission line in the X-ray obscured Narrow Line Seyfert 1 Galaxy NGC5506. This is the main results of a spectroscopic monitoring campaign on this source performed with the XMM-Newton observatory between February 2001 and January 2009. The broad line lacks extreme redwards skewness. If modelled with a relativistic component, the profile of the line is consistent with a flat emissivity radial dependence (alpha~1.9). The disk inclination (~40 degrees) is nominally larger then typically observed in unobscured AGN, in agreement with most measurements of broadened iron lines in Seyfert 2 galaxies. The quality of the data allows us to decompose the full iron emission line complex, and to study its long-term (timescales of weeks to years) variability pattern. The intensity of the neutral and narrow iron K-alpha core remains constant during the monitoring campaign. This indicates that the optically thick gas responsible for the non-relativistic reprocessing of the primary AGN continuum in NGC5506 is probably located in the torus rather than in the optical Broad Line Region.Comment: 11 pages, 8 figures, accepted for publication in MNRA

    Shining new light on mammalian diving physiology using wearable near-infrared spectroscopy

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    Investigation of marine mammal dive-by-dive blood distribution and oxygenation has been limited by a lack of non-invasive technology for use in freely diving animals. Here, we developed a non-invasive near-infrared spectroscopy (NIRS) device to measure relative changes in blood volume and haemoglobin oxygenation continuously in the blubber and brain of voluntarily diving harbour seals. Our results show that seals routinely exhibit preparatory peripheral vasoconstriction accompanied by increased cerebral blood volume approximately 15 s before submersion. These anticipatory adjustments confirm that blood redistribution in seals is under some degree of cognitive control that precedes the mammalian dive response. Seals also routinely increase cerebral oxygenation at a consistent time during each dive, despite a lack of access to ambient air. We suggest that this frequent and reproducible reoxygenation pattern, without access to ambient air, is underpinned by previously unrecognised changes in cerebral drainage. The ability to track blood volume and oxygenation in different tissues using NIRS will facilitate a more accurate understanding of physiological plasticity in diving animals in an increasingly disturbed and exploited environment
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