| 1. |
- Bergstrand, Martin, et al.
(författare)
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Mechanistic modeling of a magnetic marker monitoring study linking gastrointestinal tablet transit, in vivo drug release, and pharmacokinetics
- 2009
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Ingår i: Clinical Pharmacology and Therapeutics. - : Springer Science and Business Media LLC. - 0009-9236 .- 1532-6535. ; 86:1, s. 77-83
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Tidskriftsartikel (refereegranskat)abstract
- Magnetic marker monitoring (MMM) is a new technique for visualizing transit and disintegration of solid oral dosage forms through the gastrointestinal (GI) tract. The aim of this work was to develop a modeling approach for gaining information from MMM studies using data from a food interaction study with felodipine extended-release (ER) formulation. The interrelationship between tablet location in the GI tract, in vivo drug release, and felodipine disposition was modeled. A Markov model was developed to describe the tablet's movement through the GI tract. Tablet location within the GI tract significantly affected drug release and absorption through the gut wall. Food intake decreased the probability of tablet transition from the stomach, decreased the rate with which released felodipine left the stomach, and increased the fraction absorbed across the gut wall. In conclusion, the combined information of tablet location in the GI tract, in vivo drug release, and plasma concentration can be utilized in a mechanistically informative way with integrated modeling of data from MMM studies.
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| 2. |
- Buchholt, Kristina, 1978-, et al.
(författare)
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Electrochemically Synthesised Pd- and Au-nanoparticles as sensing layers in NOx-sensitive field effect devices
- 2008
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Ingår i: Smart Sensors and Sensing Technology. - Berlin, Heidelberg : Springer. - 9783540795896 - 9783540795902 ; , s. 63-75
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- An environmental pollutant of great concern is NOx (nitrogen monoxide and nitrogen dioxide). Here we report the utilisation of electrochemically synthesised gold and palladium nanoparticles as catalytically active gate material on gas sensitive field effect sensor devices. The synthesised nanoparticles have been characterised by TEM and XPS, and the morphology of the thermally treated nanostructured sensing layers has been investigated using SEM and XPS. Measurements on the gas response of the palladium as well as the gold nanoparticle sensors towards a number of analytes found in automotive gas exhausts were performed and their response patterns were compared. The initial gas response measurements show interesting sensing properties for both the gold and the palladium nanoparticle sensors towards NOx detection.
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| 3. |
- Dueñas, M., et al.
(författare)
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A point mutation in a murine immunoglobulin V-region strongly influences the antibody yield in Escherichia coli
- 1995
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Ingår i: Gene. - 0378-1119. ; 158:1, s. 61-66
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Tidskriftsartikel (refereegranskat)abstract
- Recombinant DNA technology has made it possible to produce specific Fab and scFv antibody (Ab) fragments in prokaryotic host cells. Using vectors designed for periplasmic expression of encoded Ab fragments, we have been studying how the sequence and genetic localization of the light chain (L-chain) variable region gene of a mouse Ab (CB-Nm.1) determined the level of Ab production. The variable region was shown to belong to the VKV family and contained a previously unreported Ile72. Nine different Ab constructions were tested in monocistronic (scFv) or dicistronic (Fab) operons for their ability to affect the synthesis level of the L-chain. When the gene coding for the L-chain was located downstream from the Fd fragment gene, the substitution of codons encoding Ile by a codon encoding Thr was found to be crucial for any expression of the L-chain fragment. This was, however, not accompanied by an increase in L-chain-specific mRNA, neither was there any change in the size of the mRNA. The fact that the unmutated L-chain protein was produced from cells transformed with certain other constructions indicated that the protein as such was not incompatible with the prokaryotic environment. Together, this suggested that the translation process was involved in the restricted production of the L-chain. Thus, surprisingly small substitutions significantly affected the expression level, a fact that will have important implications on the library size expressed in prokaryotic hosts, including phagedisplayed Ab libraries.
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| 4. |
- Hairer, E, et al.
(författare)
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Explicit, time reversible, adaptive step size control
- 2005
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Ingår i: SIAM Journal on Scientific Computing. - : Society for Industrial & Applied Mathematics (SIAM). - 1064-8275 .- 1095-7197. ; 26:6, s. 1838-1851
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Tidskriftsartikel (refereegranskat)abstract
- Adaptive step size control is difficult to combine with geometric numerical integration. As classical step size control is based on "past" information only, time symmetry is destroyed and with it the qualitative properties of the method. In this paper we develop completely explicit, reversible, symmetry-preserving, adaptive step size selection algorithms for geometric numerical integrators such as the Stormer-Verlet method. A new step density controller is proposed and analyzed using backward error analysis and reversible perturbation theory. For integrable reversible systems we show that the resulting adaptive method nearly preserves all action variables and, in particular, the total energy for Hamiltonian systems. It has the same excellent long-term behavior as that obtained when constant steps are used. With variable steps, however, both accuracy and efficiency are greatly improved.
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| 5. |
- Jirholt, P., et al.
(författare)
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A central core structure in an antibody variable domain determines antigen specificity
- 2001
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Ingår i: Protein Engineering. - : Oxford University Press (OUP). - 1460-213X. ; 14:1, s. 67-74
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Tidskriftsartikel (refereegranskat)abstract
- Antibody binding sites provide an adaptable surface capable of interacting with essentially any molecular target. Using CDR shuffling, residues important for the assembly of mucin-1 specific paratopes were defined by random recombination of the complementarity determining regions derived from a set of mucin-1 specific clones, previously selected from an antibody fragment library. It was found that positions 33 and 50 in the heavy chain and 32, 34, 90, 91 and 96 in the light chain were conserved in many of the clones. These particular residues seem to be located centrally in the binding site as indicated by a structure model analysis. The importance of several of these conserved residues was supported by their presence in a mouse monoclonal antibody with a known structure and the same epitope specificity. Several of these corresponding residues in the mouse monoclonal antibody are known to interact with the antigen. In conclusion, critical residues important for maintaining a human antigen-specific binding site during the process of in vitro antibody evolution were defined. Furthermore, an explanation for the observed restricted germline gene usage in certain antibody responses against protein epitopes is provided.
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| 6. |
- Jirholt, P., et al.
(författare)
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Exploiting sequence space : Shuffling in vivo formed complementarity determining regions into a master framework
- 1998
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Ingår i: Gene. - 0378-1119. ; 215:2, s. 471-476
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Tidskriftsartikel (refereegranskat)abstract
- A novel approach in molecular design is presented, where in vivo formed complementarity determining regions (CDR) from antibody genes were shuffled into a specific framework region. A synthetic gene library of soluble VH-fragments was created and the complexity of the library was determined by sequencing. The synthetic genes were diverse and contained random combinations of CDR from different germlines. All CDR were randomised in one step and by using in vivo formed CDR, the length, sequence and combination were varied simultaneously.
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| 7. |
- Landa, A., et al.
(författare)
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Ab initio study of advanced metallic nuclear fuels for fast breeder reactors
- 2012
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Ingår i: Actinides And Nuclear Energy Materials. - : Materials Research Society. - 9781605114217 ; , s. 67-78
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Konferensbidrag (refereegranskat)abstract
- Density-functional formalism is applied to study the ground state properties of γ-U-Zr and γ-U-Mo solid solutions. Calculated heats of formation are compared with CALPHAD assessments. We discuss how the heat of formation in both alloys correlates with the charge transfer between the alloy components. The decomposition curves for γ-based U-Zr and U-Mo solid solutions are derived from Ising-type Monte Carlo simulations. We explore the idea of stabilization of the γ-UZr2 compound against the α-Zr (hcp) structure due to increase of Zr d-band occupancy by the addition of U to Zr. We discuss how the specific behavior of the electronic density of states in the vicinity of the Fermi level promotes the stabilization of the U2Mo compound. The mechanism of possible Am redistribution in the U-Zr and U-Mo fuels is also discussed.
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| 8. |
- Lindberg, Hans, et al.
(författare)
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Devaluation Expectations : The Swedish Krona 1982-1991
- 1991
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Devaluation expectations for the Swedish krona are estimated for the period 1982-1991 with several methods. First the "simplest test" is applied under either only the minimal assumption of "no positive minimum profit" or the additional assumption of uncovered interest parity. Then a more precise method suggested by Bertola and Svensson is used, in which expected rates of depreciation within the exchange rate band, estimated in several ways, are subtracted from interest rate differentials. Finally, estimated devaluations expectations are to some extent explained by a few macrovariables and parliament elections.
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| 9. |
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| 10. |
- Pulverer, G, et al.
(författare)
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Automatic Grid Control in Adaptive BVP Solvers
- 2011
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Ingår i: Numerical Algorithms. - : Springer Science and Business Media LLC. - 1572-9265 .- 1017-1398. ; 56:1, s. 61-92
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Tidskriftsartikel (refereegranskat)abstract
- Grid adaptation in two-point boundary value problems is usually based on mapping a uniform auxiliary grid to the desired nonuniform grid. Here we combine this approach with a new control system for constructing a grid density function I center dot(x). The local mesh width Delta x (j + 1/2) = x (j + 1) -aEuro parts per thousand x (j) with 0 = x (0) < x (1) < ... < x (N) = 1 is computed as Delta x (j + 1/2) = epsilon (N) / phi (j + 1/2), where {phi j+1/2}(0) (N-1) is a discrete approximation to the continuous density function I center dot(x), representing mesh width variation. The parameter epsilon (N) = 1/N controls accuracy via the choice of N. For any given grid, a solver provides an error estimate. Taking this as its input, the feedback control law then adjusts the grid, and the interaction continues until the error has been equidistributed. Digital filters may be employed to process the error estimate as well as the density to ensure the regularity of the grid. Once I center dot(x) is determined, another control law determines N based on the prescribed tolerance TOL. The paper focuses on the interaction between control system and solver, and the controller's ability to produce a near-optimal grid in a stable manner as well as correctly predict how many grid points are needed. Numerical tests demonstrate the advantages of the new control system within the bvpsuite solver, ceteris paribus, for a selection of problems and over a wide range of tolerances. The control system is modular and can be adapted to other solvers and error criteria.
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