459 research outputs found

    The 1969/1970 Stanford spectral data management system - Infrared spectrometry studies

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    Infrared spectrometer data analysis system report with program listing

    “Lift Up a Living Nation”: Community and Nation, Socialism and Religion in The English Hymnal, 1906

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    The lead editors of The English Hymnal (1906), Percy Dearmer and Ralph Vaughan Williams, found Victorian hymnody in need of serious revision, and not just aesthetically. This musical book was intended as an expression of the editors' Christian socialist politics involving in the participation of the congregation. This article examines how they achieved this by the encouragement of active citizenship through communal music-making, using folksong tunes alongside texts which affirmed community. This article argues that the editors wedded religion and high-quality music with a focus on citizenship drawn from British Idealism; using a cultural movement to seek social change

    Developing a process control strategy for the consistent and scalable manufacture of human mesenchymal stem cells

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    Human mesenchymal stem cells (hMSCs) have been identified as a promising cell-based therapy candidate to treat a number of unmet clinical indications, however, in vitro expansion will be required to increase the available number of cells and meet this demand. Scalable manufacturing processes, amenable to closed, single-use and automated technology, must therefore be developed in order to produce safe, effective and affordable hMSC therapies. To address this challenge, a controlled serum-free end-to-end microcarrier process has been developed for hMSCs, which is amenable to large-scale manufacture and therefore increasing economies of scale. Preliminary studies in monolayer culture assessed the level of variability in growth between five hMSC donors, which was found to have a variance of 25.3 % after 30 days in culture. This variance was subsequently reduced to 4.5% by the development of a serum-free monolayer culture process with the maintenance of critical hMSC characteristics and an increased number of population doublings. In order to transfer this into a scalable system, the serum and serum-free expansion processes were transferred into suspension by the addition of plastic microcarriers in 100 mL spinner flasks without control of pH or dissolved oxygen (DO). This achieved a maximum cell density of 0.08 ± 0.01 · 106 cells.mL-1 in FBS-based medium, 0.12 ± 0.01 · 106 cells.mL-1 in HPL-based medium and 0.27 ± 0.03· 106 cells.mL-1 in serum free medium after six days. In order to drive consistency and yield into the manufacturing process, a process control system was developed for the FBS-based microcarrier expansion process in a 100 mL DASbox bioreactor platform to control DO, pH, impeller rate and temperature. Reduced impeller rates and DO concentrations were found to be beneficial, with a final cell density of 0.11 ± 0.02 · 106 cells.mL-1 and improved post-harvest outgrowth and colony-forming unit (CFU) potential compared to uncontrolled microcarrier and monolayer culture. This controlled bioreactor expansion process was then applied to the previously developed serum-free microcarrier process, eventually achieving a final cell density of 1.04 ± 0.07 · 106 cells.mL-1, whilst retaining key post-harvest hMSC characteristics. Following the controlled serum-free expansion and harvest of hMSCs, a downstream and cryopreservation process was developed to assess the impact of prolonged holding times and subsequent unit-operations on hMSC quality characteristics. This showed that hMSCs are able to maintain key characteristics throughout the entire end-to-end process, demonstrating their potential for commercial scale manufacture

    Scalability and process transfer of mesenchymal stromal cell production from monolayer to microcarrier culture using human platelet lysate

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    Background aims: The selection of medium and associated reagents for human mesenchymal stromal cell (hMSC) culture forms an integral part of manufacturing process development and must be suitable for multiple process scales and expansion technologies. Methods: In this work, we have expanded BM-hMSCs in fetal bovine serum (FBS)- and human platelet lysate (HPL)-containing media in both a monolayer and a suspension-based microcarrier process. Results: The introduction of HPL into the monolayer process increased the BM-hMSC growth rate at the first experimental passage by 0.049 day and 0.127/day for the two BM-hMSC donors compared with the FBS-based monolayer process. This increase in growth rate in HPL-containing medium was associated with an increase in the inter-donor consistency, with an inter-donor range of 0.406 cumulative population doublings after 18 days compared with 2.013 in FBS-containing medium. Identity and quality characteristics of the BM-hMSCs are also comparable between conditions in terms of colony-forming potential, osteogenic potential and expression of key genes during monolayer and post-harvest from microcarrier expansion. BM-hMSCs cultured on microcarriers in HPL-containing medium demonstrated a reduction in the initial lag phase for both BM-hMSC donors and an increased BM-hMSC yield after 6 days of culture to 1.20 ± 0.17 × 105 and 1.02 ± 0.005 × 105 cells/mL compared with 0.79 ± 0.05 × 105 and 0.36 ± 0.04 × 105 cells/mL in FBS-containing medium. Conclusions: This study has demonstrated that HPL, compared with FBS-containing medium, delivers increased growth and comparability across two BM-hMSC donors between monolayer and microcarrier culture, which will have key implications for process transfer during scale-up

    Application of data assimilation with the Root Zone Water Quality Model for soil moisture profile estimation in the upper Cedar Creek, Indiana

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    Data assimilation techniques have been proven as an effective tool to improve model forecasts by combining information about observed variables in many areas. This article examines the potential of assimilating surface soil moisture observations into a field-scale hydrological model, the Root Zone Water Quality Model, to improve soil moisture estimation. The Ensemble Kalman Filter (EnKF), a popular data assimilation technique for nonlinear systems, was applied and compared with a simple direct insertion method. In situ soil moisture data at four different depths (5, 20, 40, and 60 cm) from two agricultural fields (AS1 and AS2) in northeastern Indiana were used for assimilation and validation purposes. Through daily update, the EnKF improved soil moisture estimation compared with the direct insertion method and model results without assimilation, having more distinct improvement at the 5 and 20 cm depths than for deeper layers (40 and 60 cm). Local vertical soil property heterogeneity in AS1 deteriorated soil moisture estimates with the EnKF. Removal of systematic bias in the forecast model was found to be critical for more successful soil moisture data assimilation studies. This study also demonstrates that a more frequent update generally contributes in enhancing the open loop simulation; however, large forecasting error can prevent more frequent update from providing better results. In addition, results indicate that various ensemble sizes make little difference in the assimilation results. An ensemble of 100 members produced results that were comparable with results obtained from larger ensembles

    Agitation conditions for the culture and detachment of hMSCs from microcarriers in multiple bioreactor platforms

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    In our recent work in different bioreactors up to 2.5L in scale, we have successfully cultured hMSCs using the minimum agitator speed required for complete microcarrier suspension, N JS. In addition, we also reported a scaleable protocol for the detachment from microcarriers in spinner flasks of hMSCs from two donors. The essence of the protocol is the use of a short period of intense agitation in the presence of enzymes such that the cells are detached; but once detachment is achieved, the cells are smaller than the Kolmogorov scale of turbulence and hence not damaged. Here, the same approach has been effective for culture at N JS and detachment in-situ in 15mL ambr™ bioreactors, 100mL spinner flasks and 250mL Dasgip bioreactors. In these experiments, cells from four different donors were used along with two types of microcarrier with and without surface coatings (two types), four different enzymes and three different growth media (with and without serum), a total of 22 different combinations. In all cases after detachment, the cells were shown to retain their desired quality attributes and were able to proliferate. This agitation strategy with respect to culture and harvest therefore offers a sound basis for a wide range of scales of operation
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