| 1. |
- Anguelova, Milena, 1978, et al.
(författare)
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An Efficient Method for Structural Identiability Analysis of Large Dynamic Systems
- 2012
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Ingår i: 16th IFAC Symposium on System Identification. - 1474-6670. - 9783902823069 ; 16:1, s. 941-946
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Konferensbidrag (refereegranskat)abstract
- Ordinary differential equation models often contain a large number of parameters that must be determined from measurements by parameter estimation. For a parameter estimation procedure to be successful, there must be a unique set of parameters that can have produced the measured data. This is not the case if a model is not structurally identifiable with the given set of outputs selected as measurements. We describe the implementation of a recent probabilistic semi-numerical method for testing local structural identifiability based on computing the rank of a numerically instantiated Jacobian matrix (observability/identifiability matrix). To obtain this, matrix parameters and initial conditions are specialized to random integer numbers, inputs are specialized to truncated random integer coefficient power series, and the corresponding output of the state space system is computed in terms of a truncated power series, which then is utilized to calculate the elements of a Jacobian matrix. To reduce the memory requirements and increase the speed of the computations all operations are done modulo a large prime number. The method has been extended to handle parametrized initial conditions and is demonstrated to be capable of handling systems in the order of a hundred state variables and equally many parameters on a standard desktop computer.
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| 2. |
- Anguelova, Milena, 1978, et al.
(författare)
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Minimal output sets for identifiability
- 2012
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Ingår i: Mathematical Biosciences. - : Elsevier BV. - 1879-3134 .- 0025-5564.
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Tidskriftsartikel (refereegranskat)abstract
- Ordinary differential equation models in biology often contain a large number of parameters that must be determined from measurements by parameter estimation. For a parameter estimation procedure to be successful, there must be a unique set of parameters that can have produced the measured data. This is not the case if a model is not uniquely structurally identifiable with the given set of outputs selected as measurements. In designing an experiment for the purpose of parameter estimation, given a set of feasible but resource-consuming measurements, it is useful to know which ones must be included in order to obtain an identifiable system, or whether the system is unidentifiable from the feasible measurement set. We have developed an algorithm that, from a user-provided set of variables and parameters or functions of them assumed to be measurable or known, determines all subsets that when used as outputs give a locally structurally identifiable system and are such that any output set for which the system is structurally identifiable must contain at least one of the calculated subsets. The algorithm has been implemented in Mathematica and shown to be feasible and efficient. We have successfully applied it in the analysis of large signalling pathway models from the literat
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| 3. |
- Buker, P., et al.
(författare)
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DO3SE modelling of soil moisture to determine ozone flux to forest trees
- 2012
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Ingår i: Atmospheric Chemistry and Physics. - : Copernicus GmbH. - 1680-7316 .- 1680-7324. ; 12:12, s. 5537-5562
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Tidskriftsartikel (refereegranskat)abstract
- The DO3SE (Deposition of O-3 for Stomatal Exchange) model is an established tool for estimating ozone (O-3) deposition, stomatal flux and impacts to a variety of vegetation types across Europe. It has been embedded within the EMEP (European Monitoring and Evaluation Programme) photochemical model to provide a policy tool capable of relating the flux-based risk of vegetation damage to O-3 precursor emission scenarios for use in policy formulation. A key limitation of regional flux-based risk assessments has been the assumption that soil water deficits are not limiting O-3 flux due to the unavailability of evaluated methods for modelling soil water deficits and their influence on stomatal conductance (g(sto)), and subsequent O-3 flux. This paper describes the development and evaluation of a method to estimate soil moisture status and its influence on g(sto) for a variety of forest tree species. This DO3SE soil moisture module uses the Penman-Monteith energy balance method to drive water cycling through the soil-plant-atmosphere system and empirical data describing g(sto) relationships with pre-dawn leaf water status to estimate the biological control of transpiration. We trial four different methods to estimate this biological control of the transpiration stream, which vary from simple methods that relate soil water content or potential directly to g(sto), to more complex methods that incorporate hydraulic resistance and plant capacitance that control water flow through the plant system. These methods are evaluated against field data describing a variety of soil water variables, g(sto) and transpiration data for Norway spruce (Picea abies), Scots pine (Pinus sylvestris), birch (Betula pendula), aspen (Populus tremuloides), beech (Fagus sylvatica) and holm oak (Quercus ilex) collected from ten sites across Europe and North America. Modelled estimates of these variables show consistency with observed data when applying the simple empirical methods, with the timing and magnitude of soil drying events being captured well across all sites and reductions in transpiration with the onset of drought being predicted with reasonable accuracy. The more complex methods, which incorporate hydraulic resistance and plant capacitance, perform less well, with predicted drying cycles consistently underestimating the rate and magnitude of water loss from the soil. A sensitivity analysis showed that model performance was strongly dependent upon the local parameterisation of key model drivers such as the maximum g(sto), soil texture, root depth and leaf area index. The results suggest that the simple modelling methods that relate g(sto) directly to soil water content and potential provide adequate estimates of soil moisture and influence on g(sto) such that they are suitable to be used to assess the potential risk posed by O-3 to forest trees across Europe.
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| 4. |
- Calles, Olle, 1974-, et al.
(författare)
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Success of a low-sloping rack for improving downstream passage of silver eels at a hydroelectric plant
- 2013
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Ingår i: Freshwater Biology. - : John Wiley & Sons. - 0046-5070 .- 1365-2427. ; 58, s. 2168-2179
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Tidskriftsartikel (refereegranskat)abstract
- 1. The European eel (Anguilla anguilla) is a critically endangered species, and one major threat is thesurvival of silver eels migrating downstream towards the sea from lake and river rearing areas. Duringthis migration, many eels are impinged and die on intake racks, or are injured or killed whenpassing through turbines.2. Intake racks at a hydroelectric plant were modified to avoid impingement and to collect eels withoutinjury; high mortality on both racks and in turbines was previously documented. Modificationsconsisted of reducing the rack gap width from 20 to 18 mm, decreasing the rack slope from 63 to 35degrees, increasing the rack surface area by 58% and installing six openings in the rack leading totraps.3. Downstream passage conditions for silver eels at the hydroelectric plant were significantlyimproved, reducing mortality from >70% at the old steep 20 mm racks to <10% at the modified18 mm rack collection facility. No tagged eels were impinged and killed on the racks, and 80%entered the collection facility.4. Survival can probably be improved even more, as the individuals that passed the facility mostlikely escaped through holes in the traps. Moreover, injured untagged eels were still encountered atthe modified racks, illustrating the need for rehabilitative measures to be implemented at all obstaclesbetween the main eel rearing areas and the sea.
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| 5. |
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| 6. |
- Friberg-Fernros, Henrik, 1972, et al.
(författare)
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The Consensus Paradox: Does Deliberative Agreement Impede Rational Discourse?
- 2014
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Ingår i: Political Studies. - : SAGE Publications. - 0032-3217 .- 1467-9248. ; 62:S1 (suppl.), s. 99-116
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Tidskriftsartikel (refereegranskat)abstract
- This article explores a tension in deliberative democratic theory. The tension consists in that deliberative opinion formation ideally aims to reach consensus, while a consensus, once established, will likely impede the conditions for further rational public discourse. Hence, over time, deliberative democracy might risk undermining itself. While the tension is demonstrable in theory, we also suggest three cognitive and socio-psychological mechanisms by which consensus might hamper the rationality of public discourse: after an agreement, participants cease to develop new arguments, they tend to forget existing arguments and their fear of deviating from the social norm promotes conformism. Existing research has largely neglected to study how consensus in decision making affects future public deliberation. Our article thus serves three purposes: to elaborate the consensus paradox in deliberative democratic theory; to open up a research agenda for examining the paradox empirically; and to assess the theoretical implications of the paradox.
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| 7. |
- Ingelsten, Madeleine, 1978, et al.
(författare)
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Postischemic Inflammatory Response in an Auxiliary Liver Graft Predicts Renal Graft Outcome in Sensitized Patients
- 2011
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Ingår i: Transplantation. - 0041-1337 .- 1534-6080. ; 91:8, s. 888-894
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Tidskriftsartikel (refereegranskat)abstract
- Background. The liver is considered a tolerogenic organ that favors the induction of peripheral tolerance and protects other organs from the same donor from rejection. This has been exploited in combined auxiliary liver-kidney transplantation, where a renal graft is transplanted against a positive crossmatch under the protection of a liver transplanted from the same donor. Methods. To elucidate mechanisms behind the liver protective effect, we studied early transcriptional changes of inflammatory mediators in the grafts during combined auxiliary liver-kidney transplantation using microarrays and real-time polymerase chain reaction. The results were correlated to clinical data. Results. Liver and kidney grafts both exhibited an upregulation of the leukocyte-recruiting chemokines CCL2, CCL3, and CCL4. Notably, liver grafts strongly upregulated CCL20, a dendritic cell, and T-cell recruiting chemokine. By comparing the gene expression in liver grafts with the clinical outcome, we found that 14 of 45 investigated inflammatory genes were expressed significantly higher in patients without early rejection when compared with those with early rejections. This included the above-mentioned chemokines and the T-cell-recruiting CX3CL1, NFKB1, and the tolerance-inducing gene indoleamine 2,3-dioxygenase. Conclusions. In this study, the protective role of the liver was associated with a proinflammatory reaction within this organ after ischemia-reperfusion. In particular, we found an increased expression of leukocyte-recruiting chemokines in patients without rejection, indicating a protective role of host inflammatory cells infiltrating the auxiliary liver graft in presensitized patients. Second, gene expression profiling of transplant biopsies shortly after reperfusion predicted the risk of early rejection in these patients.
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| 8. |
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| 9. |
- Klingberg, Jenny, 1978, et al.
(författare)
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Ozone risk for vegetation in the future climate of Europe based on stomatal ozone uptake calculations
- 2011
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Ingår i: Tellus A. - : Stockholm University Press. ; 63, s. 174-187
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Tidskriftsartikel (refereegranskat)abstract
- The negative impacts of surface ozone (O3) on vegetation are determined by external exposure, leaf gas exchange and plant antioxidant defence capacity, all dependent on climate and CO2 concentrations. In this study the influence of climate change on simulated stomatal O3 uptake of a generic crop and a generic deciduous tree at ten European sites was investigated, using the LRTAP Mapping Manual stomatal flux model. O3 concentrations are calculated by a chemistry transport model (MATCH) for three 30-year time-windows (1961-1990, 2021-2050, 2071-2100), with constant precursor emissions and meteorology from a regional climate model (RCA3). Despite substantially increased modelled future O3 concentrations in central and southern Europe, the flux-based risk for O3 damage to vegetation is predicted to remain unchanged or decrease at most sites, mainly as a result of projected reductions in stomatal conductance under rising CO2 concentrations. Drier conditions in southern Europe are also important for this result. At northern latitudes, the current parameterisation of the stomatal conductance model suggest O3 uptake to be mainly limited by temperature. This study demonstrates the importance of accounting for the influences by climate and CO2 on stomatal O3 uptake, and of developing their representation in models, for risk assessment involving climate change.
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| 10. |
- Meyer, René, et al.
(författare)
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Heterogeneous kinetics of AKT signaling in individual cells are accounted for by variable protein concentration
- 2012
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Ingår i: Frontiers in Physiology. - : Frontiers Media SA. - 1664-042X. ; 3:451
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Tidskriftsartikel (refereegranskat)abstract
- In most solid cancers, cells harboring oncogenic mutations represent only a sub-fraction of the entire population. Within this sub-fraction the expression level of mutated proteins can vary significantly due to cellular variability limiting the efficiency of targeted therapy. To address the causes of the heterogeneity, we performed a systematic analysis of one of the most frequently mutated pathways in cancer cells, the phosphatidylinositol 3 kinase (PI3K) signaling pathway. Among others PI3K signaling is activated by the hepatocyte growth factor (HGF) that regulates proliferation of hepatocytes during liver regeneration but also fosters tumor cell proliferation. HGF mediated responses of PI3K signaling were monitored both at the single cell and cell population level in primary mouse hepatocytes and in the hepatoma cell line Hepa1_6. Interestingly, we observed that the HGF mediated AKT responses at the level of individual cells is rather heterogeneous. However, the overall average behavior of the single cells strongly resembled the dynamics of AKT activation determined at the cell population level. To gain insights into the molecular cause for the observed heterogeneous behavior of individual cells, we employed dynamic mathematical modeling in a stochastic framework. Our analysis demonstrated that intrinsic noise was not sufficient to explain the observed kinetic behavior, but rather the importance of extrinsic noise has to be considered. Thus, distinct from gene expression in the examined signaling pathway fluctuations of the reaction rates has only a minor impact whereas variability in the concentration of the various signaling components even in a clonal cell population is a key determinant for the kinetic behavior.
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