| 1. |
- Bohlin, Lars
(author)
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Taxation of intermediate goods : a CGE analysis
- 2010
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Doctoral thesis (other academic/artistic)abstract
- This dissertation is concerned with tax rates for the use of commodities in general, and energy in particular. Computable General Equilibrium (CGE) models are used to analyze the normative question of whether the tax rate for intermediate use by firms should be the same as the tax rate for final consumption by households. To answer this question, a distinction needs to be made between fiscal taxes for the purpose of raising revenue for the government, and Pigovian taxes for the purpose of changing behaviour. Concerning fiscal taxes, firms should not pay taxes on their use of inputs if the tax rates in final consumption are at their optimal level. If the tax rate for households is above the optimal level, intermediate use in firms should be taxed in order to increase the price of other commodities and reduce the distortion of relative prices. Essay 1 ascertains what factors determine the optimal relation between the tax rate for final consumption by households and intermediate use by firms. Essay 2 analyses Swedish energy taxes from the perspective of reducing global emission of CO2. It is found that the welfare maximizing tax rates are equal for households and firms not participating in emission trading, while firms that participate in emission trading should have a zero tax rate. Essays 3 and 4 deal with methodological issues. Essay 3 derives a new method for estimation of symmetric input-output tables from supply and use tables. This method solves the problem of negative coefficients, makes it possible to use both the industry and commodity technology assumptions simultaneously and enables the commodity technology assumption to be used even when the number of commodities is larger than the number of industries. Essay 4 describes the model used in the first two essays. The price structure developed here makes it possible to take into account price differences between different purchasers other than differences in tax rates. This essay also makes a comparison between the Swedish implementation of this model and other Swedish CGE-models used to analyse climate policy and energy taxation.
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| 2. |
- Backåker, Lars, 1984-
(author)
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The Influence of Customer Agreements and Planning Principles on Rail Freight Performance
- 2012
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Licentiate thesis (other academic/artistic)abstract
- Rail freight transportation is recognized worldwide as a suitable transportation mode when it comes to long haul transportation of heavy commodities. The industry is also known to be capital intensive, highly dependent on infrastructural developments and requires thorough planning of operations. Despite intensive planning of operations, great challenges remain in how to make best use of existing resources. Especially uncertainties related to up-coming daily freight volumes stand as central causes behind such planning challenges. This thesis focuses on rail freight carload transportation and concerns how customer commitments influence operational performance as well as potentials for improvements of operational planning principles. Problem statements are addressed using three separate studies and all experiments involve quantitative approaches. The first study investigates effects of a potential Volume Variation Allowance (VVA) policy through simulation. The policy dictates how much freight volumes are allowed to vary by day of week. Results indicate that effects of the policy are relatively small, but an overall decrease in transportation times is observed. The study also identifies improvement potentials with respect to the current operational planning principles used within Swedish railways. The second study proposes a new optimization-based approach for trip plan generation. The approach, including a number of extensions, is evaluated against the current industry practice. Results confirm the potentials for reduced transportation times, shunting activities as well as service frequencies. All experiments satisfy existing customer commitments. The third study explores effects of a Fixed Carload Capacity (FCC) concept which partially allows capacity reservation on services. The study adopts an extension of the previously developed optimization approach. Results confirm the hypothetical trade-off between customer groups and the dependency on capacity reservation levels, but indicate that the concept has relatively small effects with respect to regular carload customers. On the other hand, benefits in terms of guarantee of service and reliability in transportation times can be observed for the customer under the agreement.
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| 3. |
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| 4. |
- Bohlin, Lars, et al.
(author)
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Natural products in modern life science
- 2010
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In: Phytochemistry Reviews. - : Springer Science and Business Media LLC. - 1568-7767 .- 1572-980X. ; 9:2, s. 279-301
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Journal article (peer-reviewed)abstract
- With a realistic threat against biodiversity in rain forests and in the sea, a sustainable use of natural products is becoming more and more important. Basic research directed against different organisms in Nature could reveal unexpected insights into fundamental biological mechanisms but also new pharmaceutical or biotechnological possibilities of more immediate use. Many different strategies have been used prospecting the biodiversity of Earth in the search for novel structure-activity relationships, which has resulted in important discoveries in drug development. However, we believe that the development of multidisciplinary incentives will be necessary for a future successful exploration of Nature. With this aim, one way would be a modernization and renewal of a venerable proven interdisciplinary science, Pharmacognosy, which represents an integrated way of studying biological systems. This has been demonstrated based on an explanatory model where the different parts of the model are explained by our ongoing research. Anti-inflammatory natural products have been discovered based on ethnopharmacological observations, marine sponges in cold water have resulted in substances with ecological impact, combinatory strategy of ecology and chemistry has revealed new insights into the biodiversity of fungi, in depth studies of cyclic peptides (cyclotides) has created new possibilities for engineering of bioactive peptides, development of new strategies using phylogeny and chemography has resulted in new possibilities for navigating chemical and biological space, and using bioinformatic tools for understanding of lateral gene transfer could provide potential drug targets. A multidisciplinary subject like Pharmacognosy, one of several scientific disciplines bridging biology and chemistry with medicine, has a strategic position for studies of complex scientific questions based on observations in Nature. Furthermore, natural product research based on intriguing scientific questions in Nature can be of value to increase the attraction for young students in modern life science.
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| 5. |
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| 6. |
- Bohlin, Maria, et al.
(author)
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Affinity studies of beta-2-glycoprotein I using capillary electrophoresis
- 2010
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Conference paper (peer-reviewed)abstract
- Beta2-glycoprotein I (b2gpI), also known as apolipoprotein H, is a plasma protein which is involved in the blood coagulation cascade. It binds negatively charged substances such as heparin, DNA, and anionic phospholipids. A number of functions of b2gpI have been proposed, however, the precise function is still not entirely known. Circulating autoantibodies against b2gpI are associated with increased risk of thrombotic events, such as thrombosis and reoccurring fetal loss. It is therefore of interest to functionally characterize b2gpI including the influence of anti-b2gpI autoantibodies on the ligand binding behavior of the protein. The characterization of interactions between biological molecules may be accomplished by capillary electrophoresis under non-denaturing conditions, without the need for immobilization. To avoid charge dependent analyte adsorption to the negative charges of the capillary wall we found the pH hysteresis effect of silica very useful. An acidic pretreatment of the capillary made it possible to perform a subsequent analysis at neutral pH. We were able to perform binding studies between b2gpI and heparin and monosaccharides at different ionic strengths and temperatures in a simple way. We could also study the effect of mildly denaturing conditions on the binding to the different ligands simply by adding sodium dodecyl sulfate (SDS), urea and ACN to the background electrolyte. The approach is simple, fast and automatic. The ionic strength, temperature and other parameters such as denaturing agents could easily be changed to characterize the binding between b2gpI and different ligands.
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| 7. |
- Bohlin, Maria E, 1979-, et al.
(author)
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Effects of ionic strength, temperature and conformation on affinity interactions of β2-glycoprotein I monitored by capillary electrophoresis
- 2011
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In: Electrophoresis. - : Wiley. - 0173-0835 .- 1522-2683. ; 32, s. 728-737
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Journal article (peer-reviewed)abstract
- We have used CE to evaluate the interaction between β2-glycoprotein I (β2gpI) and heparin. β2gpI is a human plasma protein involved in the blood coagulation cascade. It is of interest to functionally characterize the interactions of β2gpI because the exact function is not entirely known and because circulating autoantibodies against β2gpI are associated with an increased risk of thrombotic events. The effect of the ionic strength, temperature, and conformation of the protein on the interaction between β2gpI and heparin has been studied. The CE procedure for this study is simple, fast and automatic. β2gpI and heparin were allowed to interact during electrophoresis at different ionic strength buffers and at different capillary temperatures. To mimic perturbation of the conformation of β2gpI, different denaturing agents (SDS, ACN and urea) were added to the background electrolyte. While simple 1:1 binding isotherms were obtained at 22 °C the data strongly suggests that at physiological temperature the binding stoichiometry is not 1:1 and/or that cooperative interactions begin to play a role. We found that (i) the KD values differed by a factor of 60 at the ionic strengths studied (ii) β2gpI was resistant to denaturation with SDS and ACN, but was partially denatured by urea and (iii) the KD for the β2gpI-heparin interaction in the presence of urea was 10 times higher than the KD determined at the same conditions without urea added. Therefore, we conclude that the interaction between β2gpI and heparin is dependent on electrostatic interactions and on the conformation of β2gpI.
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| 8. |
- Bohlin, Maria E., 1979-
(author)
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Method development for affinity capillary electrophoresis of ß2-glycoprotein I and biological ligands
- 2011
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Doctoral thesis (other academic/artistic)abstract
- The final goal of this study is to establish a microscale analysis method that allows solution phase characterization of interactions between β2-glycoprotein I (β2gpI) and some of its ligands. Human β2gpI is a phospholipid- and heparin-binding plasma glycoprotein. The physiological role of the protein in normal blood coagulation is not entirely known, nor is its role in autoimmune diseases characterized by blood clotting disturbances (thrombosis). Quantitative binding data of β2gpI interactions with some of its ligands may help elucidating the mechanisms behind these diseases and in the development of new approaches for diagnostics, prevention, and therapy.In this thesis, capillary electrophoresis (CE) was used as methodological platform for the interaction studies. The analysis of peptides and proteins by CE is desirable due to low sample consumption, possibilities for non-denaturing and highly effective separations. The first objective of this thesis was to find an approach to prevent charge dependent adsorption of β2gpI to the inner surface of the capillaries. Analyte adsorption at the negatively charged inner surface of fused silica capillaries is detrimental to interaction analyses. This phenomenon is especially pronounced in the analysis of basic proteins and proteins containing exposed positively charged domains, such as β2gpI. A new strategy to suppress these solute-wall interactions was devised, investigated and optimized. This strategy exploits the pH hysteresis behavior of fused silica surfaces, by simply performing an acidic pretreatment of the capillary. The results in this thesis show that the acidic pretreatment efficiently prevents protein adsorption.
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| 9. |
- Bohlin, Maria, et al.
(author)
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Estimation of the amount of β2-glycoprotein I adsorbed at the inner surface of fused silica capillaries after acidic, neutral and alkaline pretreatment
- 2012
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In: Electrophoresis. - Weinheim, Germany : John Wiley & Sons. - 0173-0835 .- 1522-2683. ; 33:12, s. 1695-1702
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Journal article (peer-reviewed)abstract
- Sample adsorption to the inner surface of fused silica capillaries is a common problem inCE when analyzingmacromolecules and is harmful to the analysis. We previously utilizedthe pH hysteresis effect of fused silica to facilitate electrophoresis of the strongly adsorbingprotein β2gpI in plain-fused silica capillaries at neutral pH. In the present paper, theeffect of different pretreatments of the capillary on the adsorption of the β2-glycoproteinI has been investigated using electroosmosis markers, SDS mobilization, and imagingbased on indirect immunofluorescence microscopy for direct visualization. The amountof β2gpI adsorbed on the surface was probed using all these independent techniques afterelectrophoresis at neutral pH on capillaries pretreated with HCl, background electrolyte(BGE), and NaOH. BGE pretreatment was included as a positive control. We found that80% or more of the starting material was adsorbed to the inner surface of the silicacapillaries during electrophoresis after pretreatment with only BGE or with NaOH, butafter acidic pretreatment the loss was consistently less than 20%. NaOH most efficientlyremoves adsorbed protein between runs. A theoretical calculation of the pH change ofthe BGE showed that electrolysis affects the pH more than the deprotonation of silanolsduring electrophoresis. We conclude that acidic pretreatment of fused silica capillariesdiminishes adsorption of β2gpI by decreasing charge-dependent wall adsorption.
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| 10. |
- Bohlin, Maria, et al.
(author)
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Structure-activity studies of human beta2-glycoprotein I using capillary electrophoresis
- 2011
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Conference paper (peer-reviewed)abstract
- We have investigated various modes of CE to evaluate the interaction between beta2-glycoprotein I (b2gpI) and a number of anionic ligands to contribute to the elucidation of the structure-function relationship of b2gpI. b2gpI is a plasma protein which is involved in the blood coagulation cascade under normal, physiological conditions, however, its precise function is undefined. It is also involved in pathological conditions such as the so-called anti-phospholipid syndrome, where anti-b2gpI autoantibodies induce a prothrombotic state. Therefore, functional characterization of b2gpI under near physiological conditions is of interest. To avoid charge-dependent analyte adsorption to the inner surface of the capillary wall, we have utilized the pH hysteresis effect, where an acidic pretreatment of the capillary made it possible to perform subsequent CE analyses of b2gpI at neutral pH. The interaction between b2gpI and the anionic ligand heparin was studied with migration shift ACE, where the ionic strength, temperature and conformation of b2gpI were easily varied. The interaction between b2gpI and phosphatidylcholine/phosphatidylserine liposomes are subject to an ongoing investigation by means of migration shift ACE, frontal analysis CE, partial filling CE and pre-equilibration partial filling ACE. We conclude that differential, but relatively low binding affinities that are highly dependent on electrostatic interactions and on a preserved conformation of the protein, characterize its interactions with ligands that in vivo will be present in multiple copies on e.g. cell surfaces. The CE procedure for this study is simple, fast and automatic and quantitative binding affinity parameters are conveniently obtained using small amounts of biological materials.
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