221 research outputs found

    Testing hypotheses of the cause of peripheral thinning of the Greenland Ice Sheet: is land-terminating ice thinning at anomalously high rates?

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    Recent observations have shown that the periphery of the Greenland ice sheet (GrIS) is thinning rapidly and that this thinning is greatest around marine-terminating outlet glaciers. Several theories have been proposed which provide a link between climate and ice thinning. We present surface elevation change (<i>dh/dt</i>) data from NASA's Program for Arctic Regional Climate Assessment (PARCA) laser altimetry surveys for fourteen and eleven of the largest outlet glaciers in Southern Greenland from 1993 to 1998 and 1998 to 2006 respectively to test the applicability of these theories to the GrIS. <br><br> Initially, outlet glacier <i>dh/dt</i> data are compared with data from concurrent surveys over inland ice (slow flowing ice that is not obviously draining into an outlet glacier) to confirm the effect of ice flow on surface thinning rates. Land-terminating and marine-terminating outlet glacier <i>dh/dt</i> data are then compared from 1993 to 1998 and from 1998 to 2006. Finally, ablation anomalies (the difference between the "normal" ablation rate from 1970 to 2000 and the ablation rate in the time period of interest) calculated with a positive degree day model are compared to both marine-terminating and land-terminating outlet glacier <i>dh/dt</i> data. <br><br> Our results support earlier conclusions that certain marine-terminating outlet glaciers have thinned much more than land-terminating outlet glaciers during both time periods. Furthermore we show that these differences are not limited to the largest, fastest-flowing outlet glaciers – almost all marine-terminating outlet glaciers are thinning more than land-terminating outlet glaciers. There was a four fold increase in mean marine-terminating outlet glacier thinning rates below 1000 m elevation between the periods 1993 to 1998 and 1998 to 2006, while thinning rates of land-terminating outlet glaciers remained statistically unchanged. This suggests that a change in a controlling mechanism specific to the thinning rates of marine-terminating outlet glaciers occurred in the late 1990s and that this change did not affect thinning rates of land-terminating outlet glaciers. <br><br> Thinning rates of land-terminating outlet glaciers are statistically the same as ablation anomalies, while thinning rates of marine-terminating outlet glaciers are not. Thinning of land-terminating outlet glaciers therefore seems to be a response to changes in local mass balance (principally increases in air temperature) while thinning of marine-terminating outlet glaciers is principally controlled by ice dynamics. The mechanism by which this dynamic thinning occurs is still not clear although its association with marine-terminating outlet glaciers suggests perturbations at marine termini (calving) as the likely cause

    Mixing theory for culture and harvest in bioreactors of human mesenchymal stem cells on microcarriers

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    The use of human mesenchymal stem cells (hMSCs) in regenerative medicine is a potential major advance for the treatment of many medical conditions, especially with the use of allogeneic therapies where the cells from a single donor can be used to treat ailments in many patients. Such cells must be grown attached to surfaces and for large scale production, it is shown that stirred bioreactors containing ~200 μm particles (microcarriers) can provide such a surface. It is also shown that the just suspended condition, agitator speed NJS, provides a satisfactory condition for cell growth by minimizing the specific energy dissipation rate, εT, in the bioreactor whilst still meeting the oxygen demand of the cells. For the cells to be used for therapeutic purposes, they must be detached from the microcarriers before being cryopreserved. A strategy based on a short period (~7 min) of very high εT, based on theories of secondary nucleation, is effective at removing >99% cells. Once removed, the cells are smaller than the Kolmogorov scale of turbulence and hence not damaged. This approach is shown to be successful for culture and detachment in 4 types of stirred bioreactors from 15 mL to 5 L

    Process development of human mesenchymal stem cell microcarrier culture using an automated high-throughput microbioreactor

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    Improvements to process development technology will have a significant impact in reducing the overall costs associated with the manufacture and scale-up of human cell-based therapies. Small-scale models, including microbioreactors, play a critical role in this regard as they reduce reagent requirements and can facilitate high-throughput screening of process parameters and culture conditions. Here we have demonstrated, for the first time, the amenability of the automated ambr15 cell culture microbioreactor system (originally designed for free suspension culture) for adherent hMSC microcarrier culture. We also demonstrated that the ambr15 could be used for bioprocess development of a microcarrier process which was subsequently validated with larger-scale spinner flask studies. The results were achieved by a combination of strategies including adapting the free suspension design of the vessel to improve the suspension and mixing of the microcarriers. A more effective cell attachment method was also developed by using only 50% of the final working volume of medium for the first 24 h combined with an intermittent agitation strategy. These improvements led to a reduction in the initial lag phase which in turn resulted in \u3e 150 % increase in viable cell density after 24 h compared to the original process (no agitation for 24 h and 100 % working volume). Using the same methodology as in the ambr 15, similar improvements were obtained in larger scale spinner flask studies. Finally, this improved bioprocess methodology, which was developed for a serum-based medium process, was applied to a serum-free process in the ambr15; this resulted in \u3e 250% increase in yield compared to the ambr15 serum-based process. The use of the ambr15, with its improved control compared to the spinner flask, reduced the coefficient of variation on viable cell density in the serum containing medium from 7.65% to 4.08%, and the switch to the serum free medium further reduced these to 1.06% and 0.54% respectively. The combination of both serum-free and automated processing improved the consistency more than 10-fold compared to the initial manual, serum-based spinner flask work. The findings of this study demonstrate that the ambr15 microbioreactor is an effective tool for bioprocess development of hMSC microcarrier cultures and that a combination of serum-free medium and automation improves both process yield and consistency. Please click Additional Files below to see the full abstract

    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

    Fluctuations of a Greenlandic tidewater glacier driven by changes in atmospheric forcing : observations and modelling of Kangiata Nunaata Sermia, 1859–present

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    Acknowledgements. The authors wish to thank Stephen Price, Mauri Pelto, and the anonymous reviewer for their reviews and comments that helped to improve the manuscript. RACMO2.1 data were provided by Jan van Angelen and Michiel van den Broeke, IMAU, Utrecht University. MAR v3.2 data used for runoff calculations were provided by Xavier Fettweis, Department of Geography, University of Liège. The photogrammetric DEM used in Figs. 1 and 3 was provided by Kurt H. Kjær, Centre for GeoGenetics, University of Copenhagen. This research was financially supported by J. M. Lea’s PhD funding, NERC grant number NE/I528742/1. Support for F. M. Nick was provided through the Conoco-Phillips/Lundin Northern Area Program CRIOS project (Calving Rates and Impact on Sea Level).Peer reviewedPublisher PD

    A potentially scalable method for the harvesting of hMSCs from microcarriers

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    The use of hMSCs for allogeneic therapies requiring lot sizes of billions of cells will necessitate large-scale culture techniques such as the expansion of cells on microcarriers in bioreactors. Whilst much research investigating hMSC culture on microcarriers has focused on growth, much less involves their harvesting for passaging or as a step towards cryopreservation and storage. A successful new harvesting method has recently been outlined for cells grown on SoloHill microcarriers in a 5L bioreactor [1]. Here, this new method is set out in detail, harvesting being defined as a two-step process involving cell 'detachment' from the microcarriers' surface followed by the 'separation' of the two entities. The new detachment method is based on theoretical concepts originally developed for secondary nucleation due to agitation. Based on this theory, it is suggested that a short period (here 7min) of intense agitation in the presence of a suitable enzyme should detach the cells from the relatively large microcarriers. In addition, once detached, the cells should not be damaged because they are smaller than the Kolmogorov microscale. Detachment was then successfully achieved for hMSCs from two different donors using microcarrier/cell suspensions up to 100mL in a spinner flask. In both cases, harvesting was completed by separating cells from microcarriers using a Steriflip® vacuum filter. The overall harvesting efficiency was >95% and after harvesting, the cells maintained all the attributes expected of hMSC cells. The underlying theoretical concepts suggest that the method is scalable and this aspect is discussed too

    Estimating spring terminus submarine melt rates at a greenlandic tidewater glacier using satellite imagery

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    Oceanic forcing of the Greenland Ice Sheet is believed to promote widespread thinning at tidewater glaciers, with submarine melting proposed as a potential trigger of increased glacier calving, retreat, and subsequent acceleration. The precise mechanism(s) driving glacier instability, however, remain poorly understood, and while increasing evidence points to the importance of submarine melting, estimates of melt rates are uncertain. Here we estimate submarine melt rate by examining freeboard changes in the seasonal ice tongue of Kangiata Nunaata Sermia (KNS) at the head of Kangersuneq Fjord (KF), southwest Greenland. We calculate melt rates for March and May 2013 by differencing along-fjord surface elevation, derived from high-resolution TanDEM-X digital elevation models (DEMs), in combination with ice velocities derived from offset tracking applied to TerraSAR-X imagery. Estimated steady state melt rates reach up to 1.4 ± 0.5m d-1 near the glacier grounding line, with mean values of up to 0.8 ± 0.3 and 0.7 ± 0.3m d-1 for the eastern and western parts of the ice tongue, respectively. Melt rates decrease with distance from the ice front and vary across the fjord. This methodology reveals spatio-temporal variations in submarine melt rates (SMRs) at tidewater glaciers which develop floating termini, and can be used to improve our understanding of ice-ocean interactions and submarine melting in glacial fjords.Publisher PDFPeer reviewe

    Modelling the transfer of supraglacial meltwater to the bed of Leverett Glacier, Southwest Greenland

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    This is the final version of the article. Available from EGU via the DOI in this record.Meltwater delivered to the bed of the Greenland Ice Sheet is a driver of variable ice-motion through changes in effective pressure and enhanced basal lubrication. Ice surface velocities have been shown to respond rapidly both to meltwater production at the surface and to drainage of supraglacial lakes, suggesting efficient transfer of meltwater from the supraglacial to subglacial hydrological systems. Although considerable effort is currently being directed towards improved modelling of the controlling surface and basal processes, modelling the temporal and spatial evolution of the transfer of melt to the bed has received less attention. Here we present the results of spatially distributed modelling for prediction of moulins and lake drainages on the Leverett Glacier in Southwest Greenland. The model is run for the 2009 and 2010 ablation seasons, and for future increased melt scenarios. The temporal pattern of modelled lake drainages are qualitatively comparable with those documented from analyses of repeat satellite imagery. The modelled timings and locations of delivery of meltwater to the bed also match well with observed temporal and spatial patterns of ice surface speed-ups. This is particularly true for the lower catchment ( < 1000 m a.s.l.) where both the model and observations indicate that the development of moulins is the main mechanism for the transfer of surface meltwater to the bed. At higher elevations (e.g. 1250-1500 m a.s.l.) the development and drainage of supraglacial lakes becomes increasingly important. At these higher elevations, the delay between modelled melt generation and subsequent delivery of melt to the bed matches the observ ed delay between the peak air temperatures and subsequent velocity speed-ups, while the instantaneous transfer of melt to the bed in a control simulation does not. Although both moulins and lake drainages are predicted to increase in number for future warmer climate scenarios, the lake drainages play an increasingly important role in both expanding the area over which melt accesses the bed and in enabling a greater proportion of surface melt to reach the bed.We acknowledge the College of Physical Sciences, University of Aberdeen, the Leverhulme Trust through a Study Abroad Studentship and the Swedish Radiation Safety Authority, for funding awarded to C. Clason. Data collection was supported by the UK Natural Environment Research Council (through a studentship to I. Bartholomew and grants to P. Nienow and D. Mair) and the Edinburgh University Moss Centenary Scholarship (I. Bartholomew)

    Development of a process control strategy for the serum-free microcarrier expansion of human mesenchymal stem cells towards cost-effective and commercially viable manufacturing

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    Human Mesenchymal Stem Cells (hMSCs) are advancing through clinical development with the first allogeneic adult hMSC therapy receiving approval in Europe. To enable successful large-scale manufacture of hMSC therapies, increased product consistency and yield, and a reduced batch-to-batch variation must be achieved. This paper addresses ways to reduce variation by controlling the processing conditions, in particular the dissolved oxygen concentration (dO2), and the culture medium. Bone marrow derived hMSCs were cultured in DASGIP DASbox bioreactors on Plastic P-102 L microcarriers in FBS-containing and serum free (SFM) media at various dO2 values from 100% to 10%, experiencing the same dO2 value throughout the culture process. The superior control of pH and dO2 in the bioreactor led to improved performances compared to poorly controlled spinner flasks, particularly at reduced dO2 concentrations. At 25% dO2, there was a 300 % increase in the BM-hMSC yield in the bioreactor across the two donor BM-hMSCs in SFM compared to FBS-containing medium. Overall, the process yield increased by an average of around 500% for both donors under controlled conditions in SFM at 25% dO2 in the bioreactor compared to the poorly controlled expansion at atmospheric conditions in FBS-containing medium in spinner flasks. Process control significantly reduced the BM-hMSC variation in yield from 79.1% in FBS-containing medium in spinner flasks to < 15% in controlled SFM bioreactor culture

    Stretching and mixing of non-Newtonian fluids in time-periodic flows

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    The stretching of fluid elements and the dynamics of mixing are studied for a variety of polymer solutions in nearly two-dimensional magnetically driven flows, in order to distinguish between the effects of viscoelasticity and shear thinning. Viscoelasticity alone is found to suppress stretching and mixing mildly, in agreement with some previous experiments on time-periodic flows. On the other hand, the presence of shear thinning viscosity (especially when coupled with elasticity) produces a dramatic enhancement in stretching and mixing compared to a Newtonian solution at the same Reynolds number. In order to understand this observation, we study the velocity field separately in the sheared and elongational regions of the flow for various polymer solutions. We demonstrate that the enhancement is accompanied by a breaking of time-reversal symmetry of the particle trajectories, on the average. Finally, we discuss possible causes for the time lags leading to this temporal symmetry breaking, and the resulting enhanced mixing
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