| 1. |
- Culina, Antica, et al.
(författare)
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Connecting the data landscape of long-term ecological studies : The SPI-Birds data hub
- 2021
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Ingår i: Journal of Animal Ecology. - : John Wiley & Sons. - 0021-8790 .- 1365-2656. ; 90:9, s. 2147-2160
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Tidskriftsartikel (refereegranskat)abstract
- The integration and synthesis of the data in different areas of science is drastically slowed and hindered by a lack of standards and networking programmes. Long-term studies of individually marked animals are not an exception. These studies are especially important as instrumental for understanding evolutionary and ecological processes in the wild. Furthermore, their number and global distribution provides a unique opportunity to assess the generality of patterns and to address broad-scale global issues (e.g. climate change). To solve data integration issues and enable a new scale of ecological and evolutionary research based on long-term studies of birds, we have created the SPI-Birds Network and Database ()-a large-scale initiative that connects data from, and researchers working on, studies of wild populations of individually recognizable (usually ringed) birds. Within year and a half since the establishment, SPI-Birds has recruited over 120 members, and currently hosts data on almost 1.5 million individual birds collected in 80 populations over 2,000 cumulative years, and counting. SPI-Birds acts as a data hub and a catalogue of studied populations. It prevents data loss, secures easy data finding, use and integration and thus facilitates collaboration and synthesis. We provide community-derived data and meta-data standards and improve data integrity guided by the principles of Findable, Accessible, Interoperable and Reusable (FAIR), and aligned with the existing metadata languages (e.g. ecological meta-data language). The encouraging community involvement stems from SPI-Bird's decentralized approach: research groups retain full control over data use and their way of data management, while SPI-Birds creates tailored pipelines to convert each unique data format into a standard format. We outline the lessons learned, so that other communities (e.g. those working on other taxa) can adapt our successful model. Creating community-specific hubs (such as ours, COMADRE for animal demography, etc.) will aid much-needed large-scale ecological data integration.
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| 2. |
- Harboe, Morten, et al.
(författare)
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Properdin binding to complement activating surfaces depends on initial C3b deposition
- 2017
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 114:4, s. E534-E539
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Tidskriftsartikel (refereegranskat)abstract
- Two functions have been assigned to properdin; stabilization of the alternative convertase, C3bBb, is well accepted, whereas the role of properdin as pattern recognition molecule is controversial. The presence of nonphysiological aggregates in purified properdin preparations and experimental models that do not allow discrimination between the initial binding of properdin and binding secondary to C3b deposition is a critical factor contributing to this controversy. In previous work, by inhibiting C3, we showed that properdin binding to zymosan and Escherichia coli is not a primary event, but rather is solely dependent on initial C3 deposition. In the present study, we found that properdin in human serum bound dose-dependently to solid-phase myeloperoxidase. This binding was dependent on C3 activation, as demonstrated by the lack of binding in human serum with the C3-inhibitor compstatin Cp40, in C3-depleted human serum, or when purified properdin is applied in buffer. Similarly, binding of properdin to the surface of human umbilical vein endothelial cells or Neisseria meningitidis after incubation with human serum was completely C3-dependent, as detected by flow cytometry. Properdin, which lacks the structural homology shared by other complement pattern recognition molecules and has its major function in stabilizing the C3bBb convertase, was found to bind both exogenous and endogenous molecular patterns in a completely C3-dependent manner. We therefore challenge the view of properdin as a pattern recognition molecule, and argue that the experimental conditions used to test this hypothesis should be carefully considered, with emphasis on controlling initial C3 activation under physiological conditions.
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| 3. |
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| 4. |
- Abrahamsson, Victor, et al.
(författare)
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Method development in inverse modeling applied to supercritical fluid extraction of lipids
- 2016
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Ingår i: Journal of Supercritical Fluids. - : Elsevier BV. - 0896-8446. ; 111, s. 14-27
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Tidskriftsartikel (refereegranskat)abstract
- Modeling of the supercritical fluid extraction of solid materials is an important aspect in order to understand and predict the process. A comparison of two empirical models, two semi-empirical models and two mechanistic models is performed using calibration of single experiments. It is concluded that the best fit is obtained using a simple empirical expression. Furthermore, single calibrations did not generate reliable parameters with physical meaning and a methodology is proposed for inverse modeling with complete calibration using several experiments. The experimental dataset contained 29 extractions of lipids from crushed linseeds with varying temperatures, pressures and flow rates. A general rate model and a proposed extension of the hot ball model were evaluated for this purpose. The methodology includes data acquisition, model structure estimation, model calibration and a cross-validation. In general, it was found that the solubility model of Sovová outperformed the other evaluated correlations, and for the general rate model the Toth partition isotherm was also found in the top model structures. However, no generalization could be made regarding the correlations describing the Nernst diffusion layer and diffusivity.
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| 5. |
- Abrahamsson, Victor, et al.
(författare)
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Multicomponent inverse modeling of supercritical fluid extraction of carotenoids, chlorophyll A, ergosterol and lipids from microalgae
- 2018
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Ingår i: Journal of Supercritical Fluids. - : Elsevier BV. - 0896-8446. ; 139, s. 53-61
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Tidskriftsartikel (refereegranskat)abstract
- The fundamentals of analyte extractable fraction, solubility, partitioning and mass transfer resistance in supercritical fluid extraction were studied using inverse modeling. These phenomena are essential for understanding, predicting and optimizing the supercritical fluid extraction process. Carotenoids, chlorophyll A, ergosterol and total lipids were extracted from the microalgae Chlorella sp. The analytes were measured continuously in-line and on-line using UV/Vis absorption spectroscopy measurements and by evaporative light scattering detection. Various pressures, temperatures, flow rates and fractions of ethanol as a co-solvent were evaluated. The extractable fraction of carotenoids, chlorophyll A and total lipids were dependent on the co-solvent fraction in the extraction phase. The additional amount that could be extracted by using more co-solvent followed a normal distribution, indicating that analytes should not simply be categorized into weakly or strongly bound. The characteristics of diminishing extraction rates over time was accounted for by analyte partitioning rather than intra-particle diffusion limitations.
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| 6. |
- Andersson, Jonas, 1977-, et al.
(författare)
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Effect of intensive lifestyle intervention on C-reactive protein in subjects with impaired glucose tolerance and obesity : results from a randomized controlled trial with 5-year follow-up
- 2008
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Ingår i: Biomarkers: biochemical indicators of exposure, response, and susceptibility to chemicals. - : Informa UK Limited. - 1366-5804. ; 13:7, s. 671-679
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Tidskriftsartikel (refereegranskat)abstract
- C-reactive protein (CRP) is a marker of metabolic and cardiovascular disease. To study the effects of lifestyle on CRP in a high-risk population we conducted a randomized controlled trial on 200 obese subjects (BMI > 27 kg m(-2)) with impaired glucose tolerance recruited from primary care settings. They were randomized to either a 1-month stay at a wellness centre focusing on diet, exercise and stress management (intervention group) or 30-60 min of oral and written information on lifestyle intervention (control group). A significant reduction of CRP was observed after 1 month and 1 year in the intervention group. They reduced their CRP levels more than the control group 1 year after intervention (p=0.004). In conclusion lifestyle intervention can decrease CRP in obese individuals with impaired glucose tolerance for up to 1 year. Further research is needed to evaluate whether the CRP level reduction translates into a decreased risk for cardiovascular morbidity.
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| 7. |
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| 8. |
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| 9. |
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| 10. |
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| 11. |
- Andersson, Niklas, et al.
(författare)
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Calibration of a polyethylene plant for grade change optimisations
- 2011
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Ingår i: 21ST European Symposium on Computer Aided Process Engineering. - 1570-7946. - 9780444538956 ; 29, s. 673-677
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Konferensbidrag (refereegranskat)abstract
- A polyethylene plant model coded in Modelica and based on a nonlinear MPC model currently used at Borealis AB is considered for calibration. A case study of model calibration at steady-state for four different operating points are analysed, both when looking at one operating point separately, but also to calibrate several simultaneously. Both model parameters and reactor inputs are calibrated for true plant measurement data. To solve the parameter estimation problem, the JModelica.org platform is used, offering tools to express and solve calibration problems. Calibration was obtained with narrow confidence intervals and shows a potential to improve the model accuracy by changing the parameter values. The results will be used for dynamic optimisations of grade changes.
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| 12. |
- Andersson, Niklas, et al.
(författare)
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Design and control of integrated chromatography column sequences
- 2017
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Ingår i: Biotechnology Progress. - : Wiley. - 1520-6033 .- 8756-7938. ; 00:00
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Tidskriftsartikel (refereegranskat)abstract
- To increase the productivity in biopharmaceutical production, a natural step is to introduce integrated continuous biomanufacturing which leads to fewer buffer and storage tanks, smaller sizes of integrated unit operations, and full automation of the operation. The main contribution of this work is to illustrate a methodology for design and control of a downstream process based on integrated column sequences. For small scale production, for example, pre-clinical studies, integrated column sequences can be implemented on a single chromatography system. This makes for a very efficient drug development platform. The proposed methodology is composed of four steps and is governed by a set of tools, that is presented, that makes the transition from batch separations to a complete integrated separation sequence as easy as possible. This methodology, its associated tools and the physical implementation is presented and illustrated on a case study where the target protein is separated from impurities through an integrated four column sequence. This article shows that the design and control of an integrated column sequence was successfully implemented for a tertiary protein separation problem.
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| 13. |
- Andersson, Niklas, et al.
(författare)
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Methodology for fast development of digital solutions in integrated continuous downstream processing
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Ingår i: Biotechnology and Bioengineering. - 0006-3592.
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Tidskriftsartikel (refereegranskat)abstract
- The methodology for production of biologics is going through a paradigm shift from batch-wise operation to continuous production. Lot of efforts are focused on integration, intensification, and continuous operation for decreased foot-print, material, equipment, and increased productivity and product quality. These integrated continuous processes with on-line analytics become complex processes, which requires automation, monitoring, and control of the operation, even unmanned or remote, which means bioprocesses with high level of automation or even autonomous capabilities. The development of these digital solutions becomes an important part of the process development and needs to be assessed early in the development chain. This work discusses a platform that allows fast development, advanced studies, and validation of digital solutions for integrated continuous downstream processes. It uses an open, flexible, and extendable real-time supervisory controller, called Orbit, developed in Python. Orbit makes it possible to communicate with a set of different physical setups and on the same time perform real-time execution. Integrated continuous processing often implies parallel operation of several setups and network of Orbit controllers makes it possible to synchronize complex process system. Data handling, storage, and analysis are important properties for handling heterogeneous and asynchronous data generated in complex downstream systems. Digital twin applications, such as advanced model-based and plant-wide monitoring and control, are exemplified using computational extensions in Orbit, exploiting data and models. Examples of novel digital solutions in integrated downstream processes are automatic operation parameter optimization, Kalman filter monitoring, and model-based batch-to-batch control.
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| 14. |
- Andersson, Niklas, et al.
(författare)
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Model-Based Comparison of Batch and Continuous Preparative Chromatography in the Separation of Rare Earth Elements
- 2014
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Ingår i: Industrial & Engineering Chemistry Research. - : American Chemical Society (ACS). - 0888-5885 .- 1520-5045. ; 53:42, s. 16485-16493
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Tidskriftsartikel (refereegranskat)abstract
- The demand for rare earth elements (REEs) is growing, while the future supply is uncertain. Their unique electronic characteristics make them irreplaceable, and the commercial value of pure fractions is high. A model-based simulation study is presented that compares batch chromatography with the twin-column MCSGP (multicolumn countercurrent solvent gradient purification) process for ion-exchange chromatography of the four-component system neodymium, samarium, europium, and gadolinium. The last three components are considered products with individual purity requirements of 99%. The twin-column process has been shown to be a good alternative to the batch process regarding modifier consumption and productivity since it enables internal recycling to achieve high purities. A new cut strategy for MCSGP is applied where subfractions are taken from each outlet. Two multiobjective optimizations with yield, solvent productivity, and productivity objectives show that the MCSGP process is a better alternative than batch chromatography.
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| 15. |
- Andersson, Niklas, et al.
(författare)
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Parameter Selection in the Parameter Estimation of Grade Transitions in a Polyethylene Plant
- 2015
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Ingår i: Studies in Engineering and Technology. - : Redfame Publishing. - 2330-2038 .- 2330-2046. ; 3:1, s. 1-18
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Tidskriftsartikel (refereegranskat)abstract
- A polyethylene plant at Borealis AB is modelled in the Modelica language and considered for parameter estimations at grade transitions. Parameters have been estimated for both the steady-state and the dynamic case using the JModelica.org platform, which offers tools for steady-state parameter estimation and supports simulation with parameter sensitivies. The model contains 31 candidate parameters, giving a huge amount of possible parameter combinations. The best parameter sets have been chosen using a parameter-selection algorithm that identified parameter sets with poor numerical properties. The parameter-selection algorithm reduces the number of parameter sets that is necessary to explore. The steady-state differs from the dynamic case with respect to parameter selection. Validations of the parameter estimations in the dynamic case show a significant reduction in an objective value used to evaluate the quality of the solution from that of the nominal reference, where the nominal parameter values are used.
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| 16. |
- Andersson, Niklas, et al.
(författare)
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Smart platform for development of small-scale integrated continuous downstream processes
- 2022
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Ingår i: Advances in Chemical Engineering. - : Elsevier. - 0065-2377. ; 59:1, s. 131-158
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Bokkapitel (refereegranskat)abstract
- This chapter presents and discuss a platform for small-scale drug candidate production, process development and performance studies of integrated continuous downstream processes. The main idea of the platform methodology is to use common available equipment and reconfigure them for advanced downstream processing. Five different industrial case studies are discussed. The resulting processes are automated and controlled by the external supervisory controller, called Orbit. Orbit communicate with the local equipment control system, resulting in a minimum of adjustment in the laboratory infrastructure. Orbit is implemented in python, making it an open, flexible, and extendable control system. Orbit give support for integration of multiple chromatography columns, operate downstream processes on multiple parallel setups, integrated online analytics, use of advanced feedback control and batch-to-batch control. This functionality is presented in ten examples. The platform has successful been used in number of industrial case studies, particular in early drug and process development and for efficient small-scale drug candidate production.
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| 17. |
- Arkell, Karolina, et al.
(författare)
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Mechanistic Modeling of Reversed-Phase Chromatography of Insulins with Potassium Chloride and Ethanol as Mobile-Phase Modulators
- 2017
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Ingår i: ACS Omega. - : American Chemical Society (ACS). - 2470-1343. ; 2, s. 136-146
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Tidskriftsartikel (refereegranskat)abstract
- The purpose of this study was to investigate the adsorption mechanism in reversed-phase chromatography (RPC) of proteins and to develop a model for the effect of dual mobile phase modulators—a salt and an organic solvent—on this process. Two different adsorption mechanisms were considered: (1) pure association of a protein molecule and one or more ligands and (2) displacement of the organic modulator, with which the adsorbent is saturated, by the protein upon association with one or more ligands. One model was then derived from each of the two considered mechanisms, combining thermodynamic theories on salting-in, RPC, and the solubility of proteins. The model was then applied to chromatographic data from an earlier report as well as supplementary data for solubility and vapor–liquid equilibria, and case-specific simplifications were made. We found that an adaptation of Kirkwood’s electrostatic theories to hydrophobic interaction chromatography describes the observed effect of KCl well. Combining chromatographic and solubility data for one of the insulins, we concluded that the variation in the activity coefficient of the insulin with respect to the concentration of ethanol alone cannot describe its effect on retention. Consequently, one or more other phenomena must affect the adsorption process. Our second model fits the retention data well, supporting the hypothesis that ethanol is directly involved in the adsorption mechanism in this case. Using additional experiments at a high-protein load, we extended the linear-range equilibrium model into a dynamic model for preparative conditions. This model shows good agreement with the high-load data for one of the insulin variants, without any additional effects of the modulator concentrations on the adsorption capacity.
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| 18. |
- Arkell, Karolina, et al.
(författare)
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Mechanistic Modeling of Reversed-Phase Chromatography of Insulins within the Temperature Range 10–40 °C
- 2018
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Ingår i: ACS Omega. - : American Chemical Society (ACS). - 2470-1343. ; 3:2, s. 1946-1954
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Tidskriftsartikel (refereegranskat)abstract
- In the many published theories on the retention in reversed-phase chromatography (RPC), the focus is generally on the effect of the concentration of the mobile phase modulator(s), although temperature is known to have a significant influence both on the retention and on the selectivity between the adsorbates. The aim of this study was to investigate and model the combined effects of the temperature and the modulator concentrations on RPC of three insulin variants. KCl and ethanol were used as mobile phase modulators, and the experiments were performed on two different adsorbents, with C18 and C4 ligands. The temperature dependence was investigated for the interval 10–40 °C and at two different concentrations of each modulator. The model is derived from the expression for the adsorption equilibrium, which assumes that ethanol is adsorbed to the ligands and displaced by the insulin molecules, similar to the displacement of counterions in the steric mass-action model for ion-exchange chromatography. A good model fit to the new linear-range retention data was achieved by only adding and calibrating three parameters for the temperature dependence of the equilibrium. We found that a lower temperature results in a longer retention time for all adsorbates, adsorbents, and modulator concentrations used in this study, indicating that the adsorption process is enthalpy-driven. A comparison of the different contributions to the temperature dependence revealed that the large contribution from the equilibrium constant is dampened by the significant contributions of the opposite sign from the changes in activity coefficients of insulins and ethanol. Neglect of these effects when comparing different adsorbents and modulators might yield incorrect conclusions because the equilibrium constant varies with both, whereas the activity coefficients should be independent of the adsorbent. As expected, the conditions that promote higher retention also give a higher selectivity between the adsorbates. Nonetheless, in relation to its effect on the retention, the influence of the KCl concentration on the selectivity was significantly stronger than that of the temperature or that of the ethanol concentration.
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| 19. |
- Arkell, Karolina, et al.
(författare)
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Pareto-optimal reversed-phase chromatography separation of three insulin variants with a solubility constraint
- 2018
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Ingår i: Journal of Chromatography A. - : Elsevier BV. - 0021-9673. ; 1532, s. 98-104
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Tidskriftsartikel (refereegranskat)abstract
- With the shift of focus of the regulatory bodies, from fixed process conditions towards flexible ones based on process understanding, model-based optimization is becoming an important tool for process development within the biopharmaceutical industry. In this paper, a multi-objective optimization study of separation of three insulin variants by reversed-phase chromatography (RPC) is presented. The decision variables were the load factor, the concentrations of ethanol and KCl in the eluent, and the cut points for the product pooling. In addition to the purity constraints, a solubility constraint on the total insulin concentration was applied. The insulin solubility is a function of the ethanol concentration in the mobile phase, and the main aim was to investigate the effect of this constraint on the maximal productivity.Multi-objective optimization was performed with and without the solubility constraint, and visualized as Pareto fronts, showing the optimal combinations of the two objectives productivity and yield for each case. Comparison of the constrained and unconstrained Pareto fronts showed that the former diverges when the constraint becomes active, because the increase in productivity with decreasing yield is almost halted. Consequently, we suggest the operating point at which the total outlet concentration of insulin reaches the solubility limit as the most suitable one.According to the results from the constrained optimizations, the maximal productivity on the C4 adsorbent (0.41 kg/(m3 column h)) is less than half of that on the C18 adsorbent (0.87 kg/(m3 column h)). This is partly caused by the higher selectivity between the insulin variants on the C18 adsorbent, but the main reason is the difference in how the solubility constraint affects the processes. Since the optimal ethanol concentration for elution on the C18 adsorbent is higher than for the C4 one, the insulin solubility is also higher, allowing a higher pool concentration. An alternative method of finding the suggested operating point was also evaluated, and it was shown to give very satisfactory results for well-mapped Pareto fronts.
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| 20. |
- Bergman, Ingrid-Maria, et al.
(författare)
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MBL1 genotypes in wild boar populations from Sweden, Austria, the Czech Republic and Japan
- 2013
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Ingår i: International Journal of Immunogenetics. - : Blackwell Publishing. - 1744-3121 .- 1744-313X. ; 40:2, s. 131-139
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Tidskriftsartikel (refereegranskat)abstract
- The single nucleotide polymorphism (SNP) G949T in the mannose-binding lectin (MBL) 1 gene has been associated with low MBL-A concentration in serum and detected at different frequencies in various European pig populations. However, the origin of this SNP is not known. Part of the MBL1 gene was sequenced in 12 wild boar/Large White crossbred pigs from the second backcross (BC 2) generation in a family material originating from two wild boar x Large White intercrosses. Also, MBL-A serum concentration was measured in the entire BC 2 generation (n = 45). Furthermore, the genotypes of 68 wild boars from Sweden, Austria, the Czech Republic, and Japan were determined in regard to five previously described SNPs in MBL1. The T allele of G949T was present among the BC 2 animals. MBL-A serum concentration in the BC 2 animals showed a bimodal distribution, with one-third of the animals at levels between 0.7 and 1.6 μg mL−1 and the remaining pigs at levels around 13 μg mL−1. There was a co-variation between the presence of the T allele and low MBL-A concentration in serum. The genotyping of the wild boars revealed differences between populations. The T allele of G949T was not detected in the Austrian and Japanese samples and is thus unlikely to be an original feature of wild boars. In contrast, it was present at high frequency (0.35) among the Swedish wild boars, probably representing a founder effect. Five MBL1 haplotypes were resolved. Only two of these were present among the Japanese wild boars compared to four in each of the European populations. This difference may reflect differences in selection pressure and population history.
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| 21. |
- Bodén, Stina, et al.
(författare)
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Dietary inflammatory index and risk of first myocardial infarction : a prospective population-based study
- 2017
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Ingår i: Nutrition Journal. - : BioMed Central. - 1475-2891. ; 16
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Chronic, low-grade inflammation is an established risk factor for cardiovascular disease. The inflammatory impact of diet can be reflected by concentrations of inflammatory markers in the bloodstream and the inflammatory potential of diet can be estimated by the dietary inflammatory index (DII(TM)), which has been associated with cardiovascular disease risk in some previous studies. We aimed to examine the association between the DII and the risk of first myocardial infarction (MI) in a population-based study with long follow-up.METHOD: We conducted a prospective case-control study of 1389 verified cases of first MI and 5555 matched controls nested within the population-based cohorts of the Northern Sweden Health and Disease Study (NSHDS), of which the largest is the ongoing Västerbotten Intervention Programme (VIP) with nearly 100 000 participants during the study period. Median follow-up from recruitment to MI diagnosis was 6.4 years (6.2 for men and 7.2 for women). DII scores were derived from a validated food frequency questionnaire (FFQ) administered in 1986-2006. Multivariable conditional logistic regression models were used to estimate odds ratios (OR) and 95% confidence intervals (CI), using quartile 1 (most anti-inflammatory diet) as the reference category. For validation, general linear models were used to estimate the association between the DII scores and two inflammatory markers, high-sensitivity C-reactive protein (hsCRP) and interleukin 6 (IL-6) in a subset (n = 605) of the study population.RESULTS: Male participants with the most pro-inflammatory DII scores had an increased risk of MI [ORQ4vsQ1 = 1.57 (95% CI 1.21-2.02) P trend = 0.02], which was essentially unchanged after adjustment for potential confounders, including cardiovascular risk factors [ORQ4vsQ1 = 1.50 (95% CI 1.14-1.99), P trend = 0.10]. No association was found between DII and MI in women. An increase of one DII score unit was associated with 9% higher hsCRP (95% CI 0.03-0.14) and 6% higher IL-6 (95% CI 0.02-0.11) in 605 controls with biomarker data available.CONCLUSION: A pro-inflammatory diet was associated with an elevated risk of first myocardial infarction in men; whereas for women the relationship was null. Consideration of the inflammatory impact of diet could improve prevention of cardiovascular disease.
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| 22. |
- Borg, Niklas, et al.
(författare)
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Effects of uncertainties in experimental conditions on the estimation of adsorption model parameters in preparative chromatography
- 2013
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Ingår i: Computers & Chemical Engineering. - : Elsevier BV. - 1873-4375 .- 0098-1354. ; 55, s. 148-157
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Tidskriftsartikel (refereegranskat)abstract
- Model-based process design is increasingly popular when designing pharmaceutical purification processes. The effect of uncertainties in concentration measurements on the estimation of model parameters is analyzed for two cases of non-isocratic adsorption chromatography. A model, calibrated to experiments, is used to generate data by adding a Monte Carlo sampled error in the inlet concentrations. New model parameters are estimated by minimizing the deviation between the synthetic data and the model. The first case is a separation of rare earth elements by ion-exchange chromatography and the second case is a purification of insulin from a product-related impurity by reversed-phase chromatography. It is shown that normally distributed errors in the concentrations result in deviations in the UV-signal that are not normally distributed. With the applied method, known concentration distributions can be translated into probability distributions of the model parameters, which can be taken into account in the model-based process design. (C) 2013 Elsevier Ltd. All rights reserved.
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| 23. |
- Borg, Niklas, et al.
(författare)
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Modeling and robust pooling design of a preparative cation-exchange chromatography step for purification of monoclonal antibody monomer from aggregates.
- 2014
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Ingår i: Journal of Chromatography A. - : Elsevier BV. - 0021-9673. ; 1359, s. 170-181
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Tidskriftsartikel (refereegranskat)abstract
- This study has implemented and calibrated a model that describes the separation of the monomer of monoclonal antibodies from the dimer and larger oligomers on preparative-scale using cation-exchange chromatography. A general rate model with temperature dependent diffusion was coupled to a pH- and temperature-dependent steric mass action model. The model was shown to predict the retention of the monomer, dimer, and oligomer at low loadings for different pH levels and temperatures. Additionally, the model was shown to adequately predict the elution behavior of the monomer and soluble aggregates at high loadings within the same ranges with some limitations. The model was not able to accurately describe the shape of the product break-through curves or the slight levels of co-elution of the dimer and oligomer with the monomer at higher pH. The model was used to predict how 12 process variations impact the separation. The model is used to establish an elution end collection criterion such that the step can robustly provide the target purity of monomers.
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| 24. |
- Borgquist, Per, et al.
(författare)
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Simulation and parametric study of a film-coated controlled-release pharmaceutical.
- 2002
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Ingår i: Journal of Controlled Release. - 1873-4995. ; 80:1-3, s. 229-245
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Tidskriftsartikel (refereegranskat)abstract
- Pharmaceutical formulations can be designed as Multiple Unit Systems, such as Roxiam CR, studied in this work. The dose is administrated as a capsule, which contains about 100 individual pellets, which in turn contain the active drug remoxipride. Experimental data for a large number of single pellets can be obtained by studying the release using microtitre plates. This makes it possible to study the release of the individual subunits making up the total dose. A mathematical model for simulating the release of remoxipride from single film-coated pellets is presented including internal and external mass transfer hindrance apart from the most important film resistance. The model can successfully simulate the release of remoxipride from single film-coated pellets if the lag phase of the experimental data is ignored. This was shown to have a minor influence on the release rate. The use of the present model is demonstrated by a parametric study showing that the release process is film-controlled, i.e. is limited by the mass transport through the polymer coating. The model was used to fit the film thickness and the drug loading to the experimental release data. The variation in the fitted values was similar to that obtained in the experiments.
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| 25. |
- Borgquist, Per, et al.
(författare)
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Simulation of the release from a multiparticulate system validated by single pellet and dose release experiments
- 2004
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Ingår i: Journal of Controlled Release. - 1873-4995. ; 97:3, s. 453-465
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Tidskriftsartikel (refereegranskat)abstract
- A previously described single-pellet release model has been simplified and modified to give predictions of the release from multiple-pellet systems, besides describing the release from single pellets. The simplified single-pellet model has been verified using single-pellet data and has been used to estimate three release-controlling parameters, namely the pellet core radius, the overall mass transfer coefficient, and the lag time. Single-pellet release experiments showed that the release from the individual film-coated drug cores resulted in a wide distribution of release profiles, a phenomenon not observed on the dose level. Therefore, the parameter estimations resulted in distributions of these parameter values. The core radius and the lag times compared well with the experimental data. The distributions were used as input data for the multiple pellet model, in order to predict the release profiles on the dose level, showing results consistent with the measured dose release. The dose-predictive ability of the model was demonstrated in simulations by studying the effect of a change in the size of the single subunits (of constant total dose), showing that smaller pellets give an increased release rate with less variation. The model for predicting dose-release profiles could be of great value in optimising the performance of an existing formulation, as well as in the development of a new control led-release pharmaceutical. (C) 2004 Elsevier B.V. All rights reserved.
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