| 1. |
- Karlsson, A., et al.
(författare)
-
Nanofluidic networks based on surfactant membrane technology
- 2003
-
Ingår i: Analytical Chemistry. - 0003-2700 .- 1520-6882. ; 75:11, s. 2529-37
-
Tidskriftsartikel (refereegranskat)abstract
- We explore possibilities to construct nanoscale analytical devices based on lipid membrane technology. As a step toward this goal, we present nanotube-vesicle networks with fluidic control, where the nanotube segments reside at, or very close (<2 microm) to optically transparent surfaces. These nanofluidic systems allow controlled transport as well as LIF detection of single nanoparticles. In the weak-adhesion regime, immobilized vesicles can be approximated as perfect spheres with nanotubes attached at half the height of the vesicle in the axial (z) dimension. In the strong-adhesion regime (relative contact area, Sr* approximately 0.3), nanotubes can be adsorbed to the surface with a distance to the interior of the nanotubes defined by the membrane thickness of approximately 5 nm. Strong surface adsorption restricts nanotube self-organization, enabling networks of nanotubes with arbitrary geometries. We demonstrate LIF detection of single nanoparticles (30-nm-diameter fluorescent beads) inside single nanotubes. Transport of nanoparticles was induced by a surface tension differential applied across nanotubes using a hydrodynamic injection protocol. Controlled transport in nanotubes together with LIF detection enables construction of nanoscale fluidic devices with potential to operate with single molecules. This opens up possibilities to construct analytical platforms with characteristic length scales and volume orders of magnitudes smaller than employed in traditional microfluidic devices.
|
|
| 2. |
- Karlsson, A., et al.
(författare)
-
Nanofluidic networks based on surfactant membrane technology
- 2003
-
Ingår i: Analytical Chemistry. - 0003-2700 .- 1520-6882. ; 75:11, s. 2529-37
-
Tidskriftsartikel (refereegranskat)abstract
- We explore possibilities to construct nanoscale analytical devices based on lipid membrane technology. As a step toward this goal, we present nanotube-vesicle networks with fluidic control, where the nanotube segments reside at, or very close (
|
|
| 3. |
- Karlsson, Mattias, 1980, et al.
(författare)
-
Micropipet-assisted formation of microscopic networks of unilamellar lipid bilayer nanotubes and containers
- 2001
-
Ingår i: Langmuir. - : American Chemical Society (ACS). - 0743-7463 .- 1520-5827. ; 17:22, s. 6754-6758
-
Tidskriftsartikel (refereegranskat)abstract
- We describe a novel micropipet-assisted technique for the construction of complex, surface-immobilized two-dimensional microscopic networks of unilamellar phospholipid bilayer vesicles (1-50 pm in diameter, 10(-15)-10(-12) L) interconnected by lipid nanotubes (100-300 nm in diameter). As starting material for the construction of networks, we used twinned vesicle pairs, one of which is multilamellar and functions as a membrane donor and the other unilamellar and functions as a membrane acceptor upon manipulation. By electromechanical insertion of a pipet tip into the unilamellar vesicle followed by lateral pulling of the micropipet away from the vesicle, a nanotube was formed. Buffer solution contained in the pipet was then injected into the nanotube orifice, forming a vesicle of controlled size that was immobilized on the surface. The networks have controlled connectivity and are well-defined with regard to the container size, angle between nanotube extensions, and nanotube length. The internal fluid composition of individual vesicles is defined during the formation of a network by selection of the solution contained in the micropipet.
|
|
| 4. |
- Baverel, Paul G, et al.
(författare)
-
Predictive performance of internal and external validation procedures
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Purpose: To compare estimates of predictive performance between internal (IV) and external data-splitting (EV) validation procedures. Methods: Datasets of different study size (n=6, 12, 24, 48, 96, 192, or 384 individuals) were simulated from a one compartment, first-order absorption, pharmacokinetic model and both parametric (FOCE), and nonparametric (NONP) parameter estimates were obtained in NONMEM. From these, three different validation procedures (IV, EV, and a population validation (PV)) were undertaken by means of numerical predictive checks (NPCs) to provide estimates of predictive performance, the PV procedure serving as a reference to assess performance of IV and EV. The predictive performance of NONP versus FOCE estimates was further assessed. Results: Estimates of predictive performance for predicting the median of the population distribution had in general significantly lower imprecision for IV than EV, with little bias for both procedures. For small study sizes, n=6-12 (FOCE) or n=6-24 (NONP), the tails of the population distribution were significantly more biased with IV than EV, but similar imprecision was obtained. The predictive performance for FOCE was similar or superior to that of NONP. Conclusions: Data-splitting is inferior to IV when evaluating predictive models to retain sufficient precision both in predictions and in estimates of predictive performance.
|
|
| 5. |
- Bergström, Ann-Kristin, et al.
(författare)
-
Contrasting plankton stoichiometry and nutrient regeneration in northern arctic and boreal lakes
- 2018
-
Ingår i: Aquatic Sciences. - : Springer. - 1015-1621 .- 1420-9055. ; 80:2
-
Tidskriftsartikel (refereegranskat)abstract
- Contrasting carbon: nitrogen: phosphorus (C: N: P) stoichiometry between phytoplankton and zooplankton affect consumer growth and phytoplankton nutrient limitation via nutrient recycling by zooplankton. However, no study has assessed how regional differences in terrestrial loadings of organic matter affect plankton N: P stoichiometry and recycling in systems with low N deposition and N-limited phytoplankton. We address this question by using data from 14 unproductive headwater arctic and boreal lakes. We found that boreal lakes had higher lake water-and seston C, N and P concentrations than arctic lakes, whereas seston C: N, C: P and N: P ratios did not differ among regions. Boreal zooplankton were also richer in N and P relative to C, with lower somatic N: P ratios, compared to arctic lakes. Consequently, the estimated N: P imbalances between seston and zooplankton were negative in arctic lakes, indicating zooplankton feeding on phytoplankton of suboptimal N content, resulting in low consumer driven N: P recycling (medians arctic sub-mid and high altitude lakes: 11 and 13). In boreal lakes, estimated N: P imbalance did not differ from zero, with a seston N: P stoichiometry matching the N: P requirements of zooplankton, which resulted in higher consumer driven N: P recycling (median 18). Our results imply that regional climate induced catchment differences, through enhanced terrestrial nutrient inputs, affect plankton stoichiometry by raising consumer N: P recycling ratio and changing zooplankton from being mainly N-(arctic) to NP co-limited (boreal). Browning of lakes, in regions with low N deposition, may therefore promote large-scale regional changes in plankton nutrient limitation with potential feedbacks on pelagic food webs.
|
|
| 6. |
- Bergström, Ann-Kristin, et al.
(författare)
-
N-limited consumer growth and low nutrient regeneration N:P ratios in lakes with low N deposition
- 2015
-
Ingår i: Ecosphere. - 2150-8925 .- 2150-8925. ; 6:1
-
Tidskriftsartikel (refereegranskat)abstract
- Nutrient limitation of primary producers and their consumers can have a large influence on ecosystem productivity. The nature and strength of nutrient limitation is driven both by external factors (e.g., nutrient loading) and internal processes (e.g., consumer-driven nutrient regeneration). Here we present results from a field study in 10 low productive headwater lakes in northern subarctic Sweden, where nitrogen (N) deposition is low and phytoplankton is primarily N-limited. We assessed the carbon:nitrogen:phosphorus (C:N:P) stoichiometry of seston and zooplankton and estimated the N:P ratio of consumer-driven nutrient regeneration. Based on stoichiometric models, the estimated elemental imbalances between seston and zooplankton suggest that zooplankton were mainly N-limited and regenerated nutrients with low N:P ratios (median 11.9, atomic ratio). The predicted N:P regeneration ratios were consistent with results from phytoplankton nutrient limitation bioassays in mid-summer, i.e., the N:P regeneration was predicted to be low when phytoplankton were N-limited, and high when phytoplankton were P-limited. During other seasons, when water discharge was high, nutrient loading from the surrounding catchments apparently had the strongest effect on phytoplankton nutrient limitation. We propose that lakes with higher N:P ratios than the open ocean is an effect of N deposition, that N-limitation of consumers and phytoplankton is further enhanced by low nutrient regeneration N:P ratios, and that in the absence of N deposition, lake and ocean N:P stoichiometry are similar.
|
|
| 7. |
- Bergström, Ann-Kristin, et al.
(författare)
-
Nitrogen deposition and warming – effects on phytoplankton nutrient limitation in subarctic lakes
- 2013
-
Ingår i: Global Change Biology. - Hoboken, NJ : Wiley-Blackwell. - 1354-1013 .- 1365-2486. ; 19:8, s. 2557-2568
-
Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to predict the combined effects of enhanced nitrogen (N) deposition and warming on phytoplankton development in high latitude and mountain lakes. Consequently, we assessed, in a series of enclosureexperiments, how lake water nutrient stoichiometry and phytoplankton nutrient limitation varied over the growingseason in 11 lakes situated along an altitudinal/climate gradient with low N-deposition (<1 kg N ha1yr1) in northern subarctic Sweden. Short-term bioassay experiments with N- and P-additions revealed that phytoplankton inhigh-alpine lakes were more prone to P-limitation, and with decreasing altitude became increasingly N- andNP-colimited. Nutrient limitation was additionally most obvious in midsummer. There was also a strong positivecorrelation between phytoplankton growth and water temperature in the bioassays. Although excess nutrients wereavailable in spring and autumn, on these occasions growth was likely constrained by low water temperatures. Theseresults imply that enhanced N-deposition over the Swedish mountain areas will, with the exception of high-alpinelakes, enhance biomass and drive phytoplankton from N- to P-limitation. However, if not accompanied by warming,N-input from deposition will stimulate limited phytoplankton growth due to low water temperatures during largeparts of the growing season. Direct effects of warming, allowing increased metabolic rates and an extension of thegrowing season, seem equally crucial to synergistically enhance phytoplankton development in these lakes.
|
|
| 8. |
|
|
| 9. |
- Karlsson, Kristin C., et al.
(författare)
-
A population pharmacokinetic model of gabapentin developed in nonparametric adaptive grid and nonlinear mixed effects modeling
- 2009
-
Ingår i: Therapeutic Drug Monitoring. - 0163-4356 .- 1536-3694. ; 31:1, s. 86-94
-
Tidskriftsartikel (refereegranskat)abstract
- Gabapentin is used in analgesic treatment of neuropathic pain, and large interindividual variation has been observed in the pharmacokinetics (PK) of the drug. The aim of this study was to develop a population PK model for gabapentin appropriate for monitoring patients with neuropathic pain and for individualizing their dose regimens. Steady-state serum concentrations of gabapentin, distributed over a dosage interval, were obtained from 16 adult patients. Data were analyzed with an iterative 2-stage Bayesian and a nonparametric adaptive grid algorithm (NPAG) (USC*PACK) and with nonlinear mixed effects modeling (NONMEM). Compartmental population models for gabapentin PK were developed in NPAG and NONMEM using creatinine clearance and body weight as covariates. Bioavailability was included in the models as a function of dose by using a hyperbolic function derived from data previously reported in the literature. The mean population parameter estimates from the final NPAG model predicted individual serum concentrations reasonably well. The models developed in NONMEM provided additional information about the relevance of the various possible covariates and also allowed for further evaluation by simulation from the model. The population PK model may be utilized in the MM-USCPACK monitoring software (MM: multiple model dosage design) for predicting and achieving individually optimized steady-state serum concentrations of gabapentin.
|
|
| 10. |
- Karlsson, Kristin C., et al.
(författare)
-
Modeling subpopulations with the $MIXTURE subroutine in NONMEM : finding the individual probability of belonging to a subpopulation for the use in model analysis and improved decision making
- 2009
-
Ingår i: AAPS Journal. - : Springer. - 1550-7416. ; 11:1, s. 148-154
-
Tidskriftsartikel (refereegranskat)abstract
- In nonlinear mixed effects modeling using NONMEM, mixture models can be used for multimodal distributions of parameters. The fraction of individuals belonging to each of the subpopulations can be estimated, and the most probable subpopulation for each patient is output (MIXEST(k)). The objective function value (OFV) that is minimized is the sum of the OFVs for each patient (OFV(i)), which in turn is the sum across the k subpopulations (OFV(i,k)). The OFV(i,k) values can be used together with the total probability in the population of belonging to subpopulation k to calculate the individual probability of belonging to the subpopulation (IP(k)). Our objective was to explore the information gained by using IP(k) instead of or in addition to MIXEST(k) in the analysis of mixture models. Two real data sets described previously by mixture models as well as simulations were used to explore the use of IP(k) and the precision of individual parameter values based on IP(k) and MIXEST(k). For both real data-based mixture models, a substantial fraction (11% and 26%) of the patients had IP(k) values not close to 0 or 1 (IP(k) between 0.25 and 0.75). Simulations of eight different scenarios showed that individual parameter estimates based on MIXEST were less precise than those based on IP(k), as the root mean squared error was reduced for IP(k) in all scenarios. A probability estimate such as IP(k) provides more detailed information about each individual than the discrete MIXEST(k). Individual parameter estimates based on IP(k) should be preferable whenever individual parameter estimates are to be used as study output or for simulations.
|
|
