scholarly journals Considerations of the Impacts of Cell-Specific Growth and Production Rate on Clone Selection—A Simulation Study

Processes ◽  
2021 ◽  
Vol 9 (6) ◽  
pp. 964
Author(s):  
Tanja Hernández Rodríguez ◽  
Sophie Morerod ◽  
Ralf Pörtner ◽  
Florian M. Wurm ◽  
Björn Frahm
Keyword(s):  
Growth Rates ◽  
Mammalian Cells ◽  
Specific Growth ◽  
Chinese Hamster ◽  
Stability Study ◽  
Ovary Cell ◽  
Cell Populations ◽  
Model Parameters ◽  
Specific Growth Rates ◽  
Process Productivity

For the manufacturing of complex biopharmaceuticals using bioreactors with cultivated mammalian cells, high product concentration is an important objective. The phenotype of the cells in a reactor plays an important role. Are clonal cell populations showing high cell-specific growth rates more favorable than cell lines with higher cell-specific productivities or vice versa? Five clonal Chinese hamster ovary cell populations were analyzed based on the data of a 3-month-stability study. We adapted a mechanistic cell culture model to the experimental data of one such clonally derived cell population. Uncertainties and prior knowledge concerning model parameters were considered using Bayesian parameter estimations. This model was used then to define an inoculum train protocol. Based on this, we subsequently simulated the impacts of differences in growth rates (±10%) and production rates (±10% and ±50%) on the overall cultivation time, including making the inoculum train cultures; the final production phase, the volumetric titer in that bioreactor and the ratio of both, defined as overall process productivity. We showed thus unequivocally that growth rates have a higher impact (up to three times) on overall process productivity and for product output per year, whereas cells with higher productivity can potentially generate higher product concentrations in the production vessel.

scholarly journals Systematic evaluation of parameters for genome-scale metabolic models of cultured mammalian cells

2020 ◽  
Author(s):  
Song-Min Schinn ◽  
Carly Morrison ◽  
Wei Wei ◽  
Lin Zhang ◽  
Nathan E. Lewis
Keyword(s):  
Mammalian Cells ◽  
Performance Metrics ◽  
Chinese Hamster ◽  
Nutrient Utilization ◽  
Ovary Cell ◽  
Systematic Evaluation ◽  
Model Parameters ◽  
Metabolic Models ◽  
Genome Scale ◽  
Parameter Values

AbstractGenome-scale metabolic models describe cellular metabolism with mechanistic detail. Given their high complexity, such models need to be parameterized correctly to yield accurate predictions and avoid overfitting. Effective parameterization has been well-studied for microbial models, but it remains unclear for higher eukaryotes, including mammalian cells. To address this, we enumerated model parameters that describe key features of cultured mammalian cells – including cellular composition, bioprocess performance metrics, mammalian-specific pathways, and biological assumptions behind model formulation approaches. We tested these parameters by building thousands of metabolic models and evaluating their ability to predict the growth rates of a panel of phenotypically diverse Chinese Hamster Ovary cell clones. We found the following considerations to be most critical for accurate parameterization: (1) cells limit metabolic activity to maintain homeostasis, (2) cell morphology and viability change dynamically during a growth curve, and (3) cellular biomass has a particular macromolecular composition. Depending on parameterization, models predicted different metabolic phenotypes, including contrasting mechanisms of nutrient utilization and energy generation, leading to varying accuracies of growth rate predictions. Notably, accurate parameter values broadly agreed with experimental measurements. These insights will guide future investigations of mammalian metabolism.

Effects of turbidity on prey consumption and growth in brook trout and implications for bioenergetics modeling

2001 ◽  
Vol 58 (2) ◽  
pp. 386-393 ◽  
Author(s):  
John A Sweka ◽  
Kyle J Hartman
Keyword(s):  
Growth Rates ◽  
Brook Trout ◽  
Specific Growth ◽  
Abiotic Factors ◽  
Foraging Strategies ◽  
Turbid Water ◽  
Daily Consumption ◽  
Consumption Rates ◽  
The Difference ◽  
Specific Growth Rates

Brook trout (Salvelinus fontinalis) were held in an artificial stream to observe the influence of turbidity on mean daily consumption and specific growth rates. Treatment turbidity levels ranged from clear (<3.0 nephelometric turbidity units (NTU)) to very turbid water (> 40 NTU). Observed mean daily specific consumption rates were standardized to the mean weight of all brook trout tested. Turbidity had no significant effect on mean daily consumption, but specific growth rates decreased significantly as turbidity increased. Brook trout in turbid water became more active and switched foraging strategies from drift feeding to active searching. This switch was energetically costly and resulted in lower specific growth rates in turbid water as compared with clear water. Bioenergetics simulations were run to compare observed growth with that predicted by the model. Observed growth values fell below those predicted by the model and the difference increased as turbidity increased. Abiotic factors, such as turbidity, which bring about changes in the activity rates of fish, can have implications for the accuracy of predicted growth by bioenergetics models.

Sex Ratio and Sex-Specific Growth Rates of Immature Green Turtles, Chelonia mydas, in the Southern Bahamas

Copeia ◽  
1992 ◽  
Vol 1992 (4) ◽  
pp. 1098 ◽  
Author(s):  
Alan B. Bolten ◽  
Karen A. Bjorndal ◽  
Janice S. Grumbles ◽  
David W. Owens
Keyword(s):  
Sex Ratio ◽  
Growth Rates ◽  
Specific Growth ◽  
Chelonia Mydas ◽  
Green Turtles ◽  
Specific Growth Rates

Physiological and cell morphology adaptation ofBacillus subtilisat near-zero specific growth rates: a transcriptome analysis

2014 ◽  
Vol 17 (2) ◽  
pp. 346-363 ◽  
Author(s):  
Wout Overkamp ◽  
Onur Ercan ◽  
Martijn Herber ◽  
Antonius J. A. van Maris ◽  
Michiel Kleerebezem ◽  
...  
Keyword(s):  
Cell Morphology ◽  
Transcriptome Analysis ◽  
Growth Rates ◽  
Specific Growth ◽  
Specific Growth Rates

scholarly journals Investigation of the Biological Treatability of Pistachio Processing Industry Wastewaters in a Batch-operated Aerobic Bioreactor

2021 ◽  
Author(s):  
Sevtap Tırınk ◽  
Alper Nuhoğlu ◽  
Sinan Kul
Keyword(s):  
Kinetic Parameters ◽  
Growth Rates ◽  
Specific Growth ◽  
Batch Reactor ◽  
The Other ◽  
Batch Experiments ◽  
Processing Industry ◽  
Specific Growth Rates ◽  
Biological Treatability ◽  
Best Fit

Abstract This study encompasses investigation of treatment of pistachio processing industry wastewaters in a batch reactor under aerobic conditions, calculation of kinetic parameters and comparison of different inhibition models. The mixed microorganism culture used in the study was adapted to pistachio processing industry wastewaters for nearly one month and then concentrations from 50-1000 mg L− 1 of pistachio processing industry wastewaters were added to the medium and treatment was investigated in batch experiments. The Andrews, Han-Levenspiel, Luong and Aiba biokinetic equations were chosen for the correlations between the concentration of pistachio processing industry wastewaters and specific growth rates, and the kinetic parameters in these biokinetic equations were calculated. The µmax, Ks and Ki parameters, included in the Aiba biokinetic equation providing best fit among the other equations, had values calculated as 0.25 h− 1, 19 mg L− 1, and 516 mg L− 1, respectively.

scholarly journals Isolated Microbial Single Cells and Resulting Micropopulations Grow Faster in Controlled Environments

2012 ◽  
Vol 78 (19) ◽  
pp. 7132-7136 ◽  
Author(s):  
Christian Dusny ◽  
Frederik Sven Ole Fritzsch ◽  
Oliver Frick ◽  
Andreas Schmid
Keyword(s):  
Pichia Pastoris ◽  
Corynebacterium Glutamicum ◽  
Growth Rates ◽  
Specific Growth ◽  
Single Cells ◽  
Hansenula Polymorpha ◽  
Content Type ◽  
Controlled Environments ◽  
Specific Growth Rates ◽  
Extracellular Environment

ABSTRACTSingularized cells ofPichia pastoris,Hansenula polymorpha, andCorynebacterium glutamicumdisplayed specific growth rates under chemically and physically constant conditions that were consistently higher than those obtained in populations. This highlights the importance of single-cell analyses by uncoupling physiology and the extracellular environment, which is now possible using the Envirostat 2.0 concept.

scholarly journals Scaling of growth rate and mortality with size and its consequence on size spectra of natural microphytoplankton assemblages in the East China Sea

2013 ◽  
Vol 10 (8) ◽  
pp. 5267-5280 ◽  
Author(s):  
F. H. Chang ◽  
E. C. Marquis ◽  
C. W. Chang ◽  
G. C. Gong ◽  
C. H. Hsieh
Keyword(s):  
Growth Rate ◽  
Body Size ◽  
Growth Rates ◽  
Specific Growth ◽  
Size Structure ◽  
Scaling Exponent ◽  
The East China Sea ◽  
Size Category ◽  
Grazing Mortality ◽  
Specific Growth Rates

Abstract. Allometric scaling of body size versus growth rate and mortality has been suggested to be a universal macroecological pattern, as described by the metabolic theory of ecology (MTE). However, whether such scaling generally holds in natural assemblages remains debated. Here, we test the hypothesis that the size-specific growth rate and grazing mortality scale with the body size with an exponent of −1/4 after temperature correction, as MTE predicts. To do so, we couple a dilution experiment with the FlowCAM imaging system to obtain size-specific growth rates and grazing mortality of natural microphytoplankton assemblages in the East China Sea. This novel approach allows us to achieve highly resolved size-specific measurements that would be very difficult to obtain in traditional size-fractionated measurements using filters. Our results do not support the MTE prediction. On average, the size-specific growth rates and grazing mortality scale almost isometrically with body size (with scaling exponent ∼0.1). However, this finding contains high uncertainty, as the size-scaling exponent varies substantially among assemblages. The fact that size-scaling exponent varies among assemblages prompts us to further investigate how the variation of size-specific growth rate and grazing mortality can interact to determine the microphytoplankton size structure, described by normalized biomass size spectrum (NBSS), among assemblages. We test whether the variation of microphytoplankton NBSS slopes is determined by (1) differential grazing mortality of small versus large individuals, (2) differential growth rate of small versus large individuals, or (3) combinations of these scenarios. Our results indicate that the ratio of the grazing mortality of the large size category to that of the small size category best explains the variation of NBSS slopes across environments, suggesting that higher grazing mortality of large microphytoplankton may release the small phytoplankton from grazing, which in turn leads to a steeper NBSS slope. This study contributes to understanding the relative importance of bottom-up versus top-down control in shaping microphytoplankton size structure.

scholarly journals Effect of Specific Growth Rate on Fermentative Capacity of Baker’s Yeast

1998 ◽  
Vol 64 (11) ◽  
pp. 4226-4233 ◽  
Author(s):  
Pim Van Hoek ◽  
Johannes P. Van Dijken ◽  
Jack T. Pronk
Keyword(s):  
Growth Rate ◽  
Specific Growth Rate ◽  
Ethanol Production ◽  
Growth Rates ◽  
Specific Growth ◽  
Pyruvate Decarboxylase ◽  
Baker's Yeast ◽  
Fermentative Capacity ◽  
Yeast Biomass ◽  
Specific Growth Rates

ABSTRACT The specific growth rate is a key control parameter in the industrial production of baker’s yeast. Nevertheless, quantitative data describing its effect on fermentative capacity are not available from the literature. In this study, the effect of the specific growth rate on the physiology and fermentative capacity of an industrialSaccharomyces cerevisiae strain in aerobic, glucose-limited chemostat cultures was investigated. At specific growth rates (dilution rates, D) below 0.28 h−1, glucose metabolism was fully respiratory. Above this dilution rate, respirofermentative metabolism set in, with ethanol production rates of up to 14 mmol of ethanol · g of biomass−1 · h−1at D = 0.40 h−1. A substantial fermentative capacity (assayed offline as ethanol production rate under anaerobic conditions) was found in cultures in which no ethanol was detectable (D < 0.28 h−1). This fermentative capacity increased with increasing dilution rates, from 10.0 mmol of ethanol · g of dry yeast biomass−1 · h−1 at D= 0.025 h−1 to 20.5 mmol of ethanol · g of dry yeast biomass−1 · h−1 atD = 0.28 h−1. At even higher dilution rates, the fermentative capacity showed only a small further increase, up to 22.0 mmol of ethanol · g of dry yeast biomass−1 · h−1 at D= 0.40 h−1. The activities of all glycolytic enzymes, pyruvate decarboxylase, and alcohol dehydrogenase were determined in cell extracts. Only the in vitro activities of pyruvate decarboxylase and phosphofructokinase showed a clear positive correlation with fermentative capacity. These enzymes are interesting targets for overexpression in attempts to improve the fermentative capacity of aerobic cultures grown at low specific growth rates.

scholarly journals Specific growth rates calculated from CTs in patients with head and neck squamous cell carcinoma: a retrospective study performed in Austria

BMJ Open ◽  
2019 ◽  
Vol 9 (2) ◽  
pp. e025359 ◽  
Author(s):  
Daniel Dejaco ◽  
Teresa Steinbichler ◽  
Volker Hans Schartinger ◽  
Natalie Fischer ◽  
Maria Anegg ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Lymph Node ◽  
Retrospective Study ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Growth Rates ◽  
Specific Growth ◽  
Cd44 Expression ◽  
Specific Growth Rates

ObjectiveTo provide data on specific growth rates (SGRs) of primary tumours (PT-SGR) and largest pathological cervical lymph nodes (LN-SGR) for head and neck squamous cell carcinoma (HNSCC). To explore PT-SGR’s and LN-SGR’s correlation with selected biomarkers epidermal growth factor receptor (EGFR), Ki67 and CD44.Design and settingRetrospective study performed at a tertiary oncological referral centre in Innsbruck, Austria.ParticipantsAdult patients with incident HNSCC treated with primary radiotherapy (RT) or radiochemotherapy (RCT).Outcome measuresVolumes of the primary tumour (PT-volume) and largest pathological cervical lymph node (LN-volume) were measured in CT scans obtained at time of diagnosis and subsequent planning CTs immediately prior to RT or RCT. SGRs were calculated assuming an exponential growth function. PT-SGR’s and LN-SGR’s correlation with EGFR, Ki67 and CD44 were explored.ResultsIn 123 patients, mean interval between diagnostic and planning CT was 29±21 days. PT-SGR was 1.8±1.8% (mean±SD) per day and was positively correlated with EGFR, Ki67 and CD44 expression (p=0.02; p=0.02; p=0.03). LN-SGR was 1.7±2.0% per day and increased with larger initial LN-volume, was lower in laryngeal cancer (p=0.003) and slowed down with time. LN-SGR was not correlated with EGFR, Ki67 or CD44 expression in primary tumours (p>0.12). New cartilage or bone infiltration occurred in 10 patients and new central lymph node necrosis in 8 patients.ConclusionsHNSCCs are fast-growing tumours for which treatment must not be delayed. Clinical tumour growth rates are influences by EGFR, KI67 and CD44 expression.

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