| 1. |
- Karlsson, Mattias, 1981-
(författare)
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Modulation of cellular innate immune responses by lactobacilli
- 2012
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Lactobacillus is a genus of lactic acid bacteria frequently used as healthpromoting probiotics. Using probiotics to treat or prevent infections is a novel experimental approach with vast impact on future therapy. Lactobacillus rhamnosus GR-1 is a probiotic investigated for its ability to reduce urogenital disease including urinary tract infections caused by pathogenic Escherichia coli. L. rhamnosus GR-1 has been shown to modulate immunity, thought to influence its probiotic effect. In this thesis, the aim was to study immunomodulation by L. rhamnosus GR-1 and other lactobacilli, with emphasis on elicited immune responses such as nuclear factor-kappaB (NF-κB) activation and cytokine release from human urothelial cells.Viable, heat-killed, and isolated released products from L. rhamnosus GR-1 augmented NF-κB activation in E. coli-challenged urothelial cells. Blocking of lipopolysaccharide binding to toll-like receptor 4 completely quelled this augmentation. Size-fractionation, urothelial cell challenge, and two-dimensional gel electrophoresis of L. rhamnosus GR-1 released products presented several candidate proteins with NF-κB modulatory actions including chaperonin GroEL, elongation factur Tu, and a protein from the NLP/P60 protein family. While tumor necrosis factor was correspondingly augmented by L. rhamnosus GR-1, the release of two other cytokines, interleukin (IL)-6 and CXCL8, was reduced. Similar effects were observed in macrophage-like cells stimulated with L. rhamnosus GR-1.Many immunomodulatory effects of lactobacilli are believed to be species and strain dependent. Therefore, twelve Lactobacillus strains were used to screen for their effects on CXCL8 release from urothelial cells. A majority of these strains were able to influence CXCL8 release from the cells. Phylogenetic analysis revealed close evolutionary linkage between lactobacilli with similar actions on CXCL8. Increased knowledge on probiotic bacterial products and the mechanism(s) of action could lead to improved future treatments for infections.
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| 2. |
- Karlsson, Robert, 1970-
(författare)
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Investigations of binder rejuvenation related to asphalt recycling
- 2002
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Investigations described in this doctoral thesis concernmaterial behaviour related to asphalt recycling. More indetail, the thesis describes development and application ofmethods for characterisation of the rejuvenation process, inwhich old and new binders are mixed. The thesis also includes astate-of-the-art report on asphalt recycling focusing onmaterial-related aspects. As the rejuvenation process involves diffusion of bituminousbinders, a method for measuring rate of diffusion based onFTIR-ATR (Fourier Transform Infrared Spectroscopy by AttenuatedTotal Reflectance) was developed. The method was employed forstudying influence of parameters such as temperature, size andshape of the diffusing molecules as well as the viscosity ofthe medium in which the diffusion takes place. Well-definedsubstances, referred to as markers, were used in some of theseinvestigations. By aid of the FTIR-ATR method, influence ofdegree of binder ageing on the rate of diffusion was analysed.Diffusion in bituminous binders was also characterised byrheological measurements. Finally, knowledge on structuralstability of recycled binders was obtained by solubilitystudies using turbidimetric titrations and three differenttitrants showing widely different solubility parameters(iso-octane, isooctanol and methyl-ethyl-ketone). The literature review shows that there are numerouspublications related to asphalt recycling, but fewinvestigations can be characterised as fundamental, whichillustrates the complexity of the research area. The resultspresented show, among other things, that the influence ofdegree of ageing is in principle negligible. A possibleexplanation for this behaviour could be that diffusion takesplace in the maltene phase, which is relatively unaffected byageing. The change in recorded rheological parameterscorrelated fairly well with the rates of diffusion observedusing FTIR-ATR, which indicates that chemical diffusion isaccompanied by changes in binder stiffness. Nothing in theresults presented regarding structural stability of mixtures ofold and new binder suggests that binder stability should be alimiting factor in asphalt recycling, on condition that the oldand new binder are compatible. The doctoral thesis is based onthe following papers, which will be referred to by their Romannumerals: I. Karlsson R., Isacsson U.“Material-Related Aspectsof Asphalt Recycling–State-of-the-art”Submittedfor publication in ASCE J of Transportation Eng. II. Karlsson R., Isacsson U.“Application of FTIR-ATRto Characterisation of Bitumen Rejuvenator Diffusion”Accepted for publ. in ASCE J of Materials in Civil Eng. III. Karlsson R., Isacsson U.“Bitumen RejuvenatorDiffusion as Influenced by Ageing”Int’l J of RoadMaterials and Pavement Design. 3(2) 2002 IV. Karlsson R., Isacsson U.“Laboratory studies ofdiffusion in bitumen using markers”Submitted forpublication in J of Materials Science. V. Karlsson R., Isacsson U., Ekblad J.“RheologicalCharacterisation of Bitumen Diffusion”Submitted forpublication in J of Rheology. VI. Karlsson R., Isacsson U.“Bitumen StructuralStability Characterisation using Turbidimetric Titration”Submitted for publication in Energy and Fuels.
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| 3. |
- Karlsson, Robert
(författare)
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Molecular epidemiology of complex heritable disease : applications in genomics and metabolomics
- 2013
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Modern high-throughput molecular technologies (collectively referred to as “omic” platforms) are generating unprecedented amounts of data on human variation. The four papers in this thesis each investigate and characterize associations between common, complex, heritable disease, and genetic or metabolomic markers from omic platforms. In paper I, we searched bipolar affective disorder (BPAD) pedigrees for genomic copy-number variants (CNVs, segmental deletions or duplications) segregating with disease. In one pedigree, a deletion in the gene MAGI1 was observed in six out of six affected members. Upon further inspection, another pedigree was found with two out of three affected members carrying a duplication in the same gene. A pooled association analysis was subsequently carried out using in-house and public data sets on CNVs in control subjects and cases of BPAD, schizophrenia (SZ), or schizoaffective disorder (SA). MAGI1 CNVs greater than 100 kb were found to be rare, non-significantly more common in BPAD cases than in controls, and significantly more common in the pooled case sample of BPAD, SZ, and SA than in controls. In paper II, we studied a rare single nucleotide polymorphism (SNP) in the gene HOXB13, which had been recently reported to be strongly associated with prostate cancer (PC) risk. We genotyped and analyzed the variant G84E (rs138213197) in the two large Swedish PC case-control samples CAPS and Stockholm-1 (in total 4,903 cases and 4,589 controls). G84E was less rare in the Swedish samples than in the United States population previously studied, with a carrier rate over 1% in Swedish population controls. The variant was associated with a more than threefold increased relative risk of PC in both Swedish samples. G84E carriers’ absolute lifetime risk to age 80 of PC was estimated to 33%. For G84E carriers in the uppermost quartile of a genetic risk score based on common risk SNPs, the same lifetime risk was estimated to 48%. In paper III, a replication study of previously reported genetic associations with testicular germ cell tumor (TGCT) risk was performed. SNPs in six genes (ATF7IP, BAK1, DMRT1, KITLG, SPRY4, and TERT) were genotyped and analyzed in a combined case-parent, case-control sample from Sweden and Norway. In total, 831 case-parent triads, 474 dyads, 712 singleton cases, and 3,919 control subjects were analyzed. Our results supported the previously reported association with TGCT risk for SNPs in all six genes. Tests of interaction effects revealed no allelic effect differences for the two major TGCT histological subtypes seminoma and non-seminoma. However, a variant in the gene SPRY4 was found to differ significantly in effect depending on the sex of the parent from which it was inherited. Only maternally inherited alleles were associated with TGCT risk. In paper IV, a large range of small molecules in human serum, collectively called the metabolome, were studied for association with PC risk and aggressiveness. Samples from 188 controls, 188 PC patients with indolent disease, and 99 PC patients with aggressive disease were analyzed by ultra-performance liquid chromatography coupled with mass spectrometry, generating 6,138 quantitative molecular features. All features were tested for association with PC status, adjusted for patient age and sample storage time. Two features were significantly associated after correction for multiple testing, but none of them could be identified as specific molecules. Testing the PC-associated features for association with 1.4 million SNPs genome-wide produced the strongest associations in variants in annotated genes, which may aid future molecular identification efforts. In conclusion, we have used omics platforms and modern computational tools to increase our knowledge about specific genetic risk factors and metabolomic markers for complex heritable disease. Our results may come of use in future etiological research as well as in genetic and molecular risk assessment.
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| 4. |
- Karlsson, Robert S.
(författare)
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Radio Resource Sharing in Hierarchical Cellular Systems
- 2001
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Hierarchical Cell Structures (HCSs) is generally believed tobe a solution to capacity problems of future mobilecommunication systems. In such systems we have a mix of cellsizes that handle different types of traffic. We can have largecells providing wide area coverage and small cells providinghigh capacity. Large macro cells serve fast moving users tominimize the number of handoffs (changing base station) in thesystem, small micro cells provide very high capacities per areaunit. The key question in these scenarios is how to share thescarce frequency spectrum between layers. Splitting thespectrum between layers results in lower trunking efficiency(lower number of users per frequency resource) but sharing thesame spectrum in several layers results in severe inter-layerinterference.We investigate different strategies for sharing the radiospectrum between layers in an HCS. These strategies are spreadspectrum sharing, i.e., DS-CDMA among macro users and TDMAamong micro users (System I) and vice versa (System II),DS-CDMA in both layers (System III). The commonly usedfrequency splitting (i.e., dedicated bands for each layer,System IV). We also investigate reuse of macro frequencies inunderlying systems (System V) and Slow Frequency Hopping inboth layers (System VI). For frequency splitting we make ananalysis of the effects of Adjacent Channel Interference on thecapacity. We compare all systems in terms of the capacity,i.e., the supported number of users per cell. We develop a newanalytical method for the capacity analysis of mobilecommunication systems, including the effects of soft handoffs,log-normal fading, thermal noise and constant received powercontrol.The analysis show that quality based power control canhandle the varying layer external interference in HCSs. Becauseof the severe inter-layer interference is the capacity tradeoff bad for all systems sharing the same spectrum in bothlayers (System I, II, III and VI) except when reusing macrofrequency channels in underlying layers (System V). System Vperforms better than the frequency splitting (System IV) in theup-link, for the down-link is the performance of these twoschemes close. The results indicates that the severeinter-layer interference can not be balanced by the trunkinggain from not splitting the spectrum.
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| 5. |
- Lundh, Robert, 1978-
(författare)
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Robots that help each other : self-configuration of eistributed robot systems
- 2009
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Imagine the following situation. You give your favorite robot, named Pippi, the task to fetch a heavy parcel that just arrived at your front door. While pushing the parcel back to you, she must travel through a door. Unfortunately, the parcel she is pushing is blocking her camera, giving her a hard time to see the door. If she cannot see the door, she cannot safely push the parcel through it. What would you as a human do in a similar situation? Most probably you would ask someone for help, someone to guide you through the door, as we ask for help when we need to park our car in a tight parking spot. Why not let the robots do the same? Why not let robots help each other? Luckily for Pippi, there is another robot, named Emil, vacuum cleaning the floor in the same room. Since Emil has a video camera and can view both Pippi and the door at the same time, he can estimate Pippi's position relative to the door and use this information to guide Pippi through the door by wireless communication. In that way he can enable Pippi to deliver the parcel to you. The goal of this thesis is to endow robots with the ability to help each other in a similar way. More specifically, we consider distributed robot systems in which: (1) each robot includes modular functionalities for sensing, acting and/or processing; and (2) robots can help each other by offering those functionalities. A functional configuration of such a system is any way to allocate and connect functionalities configuration among the robots. An interesting feature of a system of this type is the possibility to use different functional configurations to make the same set of robots perform different tasks, or to perform the same task under different conditions. In the above example, Emil is offering a perceptual functionality to Pippi. In a different situation, Emil could offer his motion functionality to help Pippi push a heavier parcel. In this thesis, we propose an approach to automatically generate, at run time, a functional configuration of a distributed robot system to perform a given task in a given environment, and to dynamically change this configuration in response to failures. Our approach is based on artificial intelligence planning techniques, and it is provably sound, complete and optimal. In order to handle tasks that require more than one step (i.e., one configuration) to be accomplished, we also show how methods for automatic configuration can be integrated with methods for task planning to produce a complete plan were each step is a configuration. For the scenario above, generating a complete plan before the execution starts enables Pippi to know before hand if she will be able to get the parcel or not. We also propose an approach to merge configurations, which enables concurrent execution of configurations, thus reducing execution time. We demonstrate the applicability of our approach on a specific type of distributed robot system, called Peis-Ecology, and show experiments in which configurations and sequences of configurations are automatically generated and executed on real robots. Further, we give an experiment where merged configurations are created and executed on simulated robots.
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| 6. |
- Lundin, Erik, 1982-
(författare)
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The role of inland waters in the carbon cycle at high latitudes
- 2014
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Understanding the drivers of climate change requires knowledge about the global carbon (C) cycle. Although inland waters play an important role in the C cycle by emitting and burying C, streams and lakes are in general overlooked in bottom-up approached C budgets. In this thesis I estimated emissions of carbon dioxide (CO2) and methane (CH4) from all lakes and streams in a 15 km2 subarctic catchment in northern Sweden, and put it in relation to the total catchment C exchange. I show that high-latitude aquatic systems in general and streams in particular are hotspots for C emission to the atmosphere. Annually, the aquatic systems surveyed in this study emitted about 10.8 ± 4.9 g C m-2 yr-1 (ca. 98 % as CO2) which is more than double the amount of the C laterally exported from the catchment. Although the streams only covered about 4% of the total aquatic area they emitted ca. 95% of the total aquatic C emission. For lake emissions, the ice break-ups were the most important annual events, counting for ca. 45% of the emissions. Overall, streams dominated the aquatic CO2 emission in the catchment while lakes dominated CH4 emission, 96 % and 62 % of the totals, respectively. When summing terrestrial and aquatic C fluxes together it showed that the aquatic emissions alone account for approximately two thirds of the total annual catchment C loss. The consequence of not including inland waters in bottom-up derived C budgets is therefore a risk of overestimating the sink capacity of the subarctic landscape. However, aquatic systems can also act as C sinks, by accumulating C in sediment and thereby storing C over geological time frames. Sediment C burial rates were estimated in six lakes from a chronology based on 210Pb dating of multiple sediment cores. The burial rate ranged between 5 - 25 g C m-2 yr-1, which is of the same magnitude as lake C emissions. I show that the emission:burial ratio is about ten times higher in boreal compared to in subarctic-arctic lakes. These results indicate that the balance between lakes C emission and burial is both directly and indirectly dependent on climate. This process will likely result in a future increase of C emissions from high-latitude lakes, while the C burial capacity of these same lakes sediments weaken.
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| 7. |
- Ma, Qing
(författare)
-
Structural and Functional Studies of Gelsolin Family Proteins
- 2009
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The actin cytoskeleton is a complex structure that performs a wide range of cellular functions including: cell locomotion, cytokinesis, chemotaxis, signal transduction and apoptosis. The coordinated assembly and disassembly of actin filaments is controlled by a multitude of proteins (ABPs) in the cell. There are over 160 actin-binding proteins known, which with actin, account for approximately 25% of cellular protein. ABPs are classified to several major groups based on their sequence identity and functions. In this work, we have elucidated the crystal structure of ATP bound gelsolin. We have shown that ATP binding involves the two halves of gelsolin through forming numerous polar and hydrophobic contacts. Amino acid residues that form the ATP-binding sites in inactive gelsolin are widely dispersed in the activated molecule, and hence, ATP binding is disrupted on gelsolin activation. This suggests that binding of ATP may modulate the sensitivity of gelsolin to calcium ions. The structure of human gelsolin domains 1-3 bound to actin revealed a calcium ion bound to domain 2. Here, we demonstrated that only two calcium ions are needed to activate geloslin. We speculate that this domain 2 calcium ion and the one in domain 6 participate in the initial activation of gelsolin. The crystal structure of the activated adseverin C-terminus is highly similar to that of the C-terminus of gelsolin. Comparative analysis suggests that, like the gelsolin C-terminus, adseverin will also contact actin through domain 4 and domain 6. Biochemical experiments, presented here, show that a minimum of one calcium is required for adseverin to depolymerizing actin filaments compared to two calcium for gelsolin. We speculate that this is due to the lack of the C-terminal extension in adseverin. We undertook a comparative analysis of four members of the gelsolin family proteins, gelsolin, adseverin, villin and capG, in the aspects of their calcium binding, pH activation and ATP binding. The results show that only gelsolin and adseverin are able to depolymerize actin filaments at pH < 6 in the absence of calcium ions and only gelsolin bind to ATP.
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| 8. |
- Petersson, Klas, 1982-
(författare)
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Population Pharmacodynamic Modeling and Methods for D2-receptor Antagonists
- 2012
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Early predictions of a potential drug candidate’s time-course of effect and side-effects, based on models describing drug concentrations, drug effects and disease progression, would be valuable to make drug development more efficient. Pharmacodynamic modeling can incorporate and propagate prior knowledge and be used for simulations of different scenarios.In this thesis three population pharmacodynamic models were developed to describe the antipsychotic effects and the side-effects prolactin elevation and Extra Pyramidal Symptoms (EPS) following administration of D2-receptor antagonists, commonly used in the treatment of schizophrenia.Model parameter estimates of prolactin elevating potencies of six compounds correlated with in vitro values of receptor affinities, and parameters related to diurnal prolactin variation and tolerance were similar for the different compounds. The developed prolactin model can thereby be used to predict the time-course of prolactin elevation in patients for a drug candidate using information on in vitro affinity to the D2-receptor. Furthermore, the clinical antipsychotic effect and the prolactin elevation was found to correlate on the individual level for the three antipsychotic compounds investigated and a quantitative relation between D2-receptor occupancy in the brain and prolactin elevation was established. These results support the use of prolactin concentrations as a biomarker in drug development or for individual dose adjustments in clinical care.The developed model for spontaneously reported EPS adverse events, following treatment with one of five antipsychotics drugs, characterized both the duration and severity of EPS. The model successfully described both the proportions and number of transitions between severity grades and was shown to adequately simulate longitudinal categorical EPS data.Complex pharmacodynamic models are often associated with long estimation times and non-normal distributions of individual parameters. A method for shortening computation times by substituting differential equations for difference equations was evaluated and shown to be valuable for some models. In addition, transformation of distributions allowed for non-normal distributions of between-subject variability to be better characterized and thereby simulation properties were improved.In conclusion, population pharmacodynamic models for a range of D2-receptor antagonists were developed and together with the investigated methods the models can facilitate prediction of effects and side-effects in drug development.
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| 9. |
- Thygesen, Richard, 1977-
(författare)
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Low energy buildings equipped with heat pumps for high self-consumption of photovoltaic electricity
- 2016
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The building sector is a prioritized area in the European Unions (EU) ambition to reduce the total final energy use by 20 %; lower the emission of greenhouse gases by 20 % and using energy 20 % more efficient by 2020. The residential sector in the European Union accounts for 27% of the un-ion’s final energy use and the EU views decentralized energy generation and heat pumps as important measures in reducing the energy demand in the building sector.In recent years a rapid decrease in photovoltaic system prices has led to a growing popularity in Sweden. This fact in combination with a large in-crease of heat pump systems in residential buildings the last decade makes a combination of heat pumps and solar energy systems an interesting sys-tem configuration to analyze. In addition, the electricity price structure in Sweden and the uncertainty of the sustainability of the Swedish solar energy support schemes makes the topic of self-consumption an important research area.Different solar energy systems for residential buildings and two different storage technologies, batteries and hot water storage tanks, have been analyzed with regards to profitability, solar energy fraction and self-consumption levels.The results suggest that the system with a heat pump in combination with a photovoltaic system can be profitable and have high solar energy fractions and high levels of self-consumption and that the systems with storage are not profitable but give high levels of self-consumption and relatively high solar energy fractions. The hot water storage gives almost as high level of self-consumption as batteries but have half of the batteries levelized cost of electricity.A system with a ground source heat pump and a solar thermal system are ineffective, unprofitable and give low solar energy fractions.A system with a weather forecast controller gives a small increase in self-consumption and is unprofitable.The proposed near energy zero building definition proposed by the Swedish National Board of Housing, Building and Planning in 2015 is unclear in terms of what electrical load the PV electricity reduces in the building. This has a fairly large impact on the building specific energy demand.
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| 10. |
- Ulenius, Jakob, 1983-
(författare)
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Maskulinitetens mening : En fenomenologisk undersökning av den psykoterapeutiska situationen
- 2022
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Masculinity is an elusive and ambiguous phenomenon that can manifest itself in many different ways in different contexts. This study focuses on the emergence of masculinity within the psychodynamic psychotherapeutic situation, with a focus on how masculinity is experienced. Both patient and therapist carry notions and experiences of masculinity into the therapy room. In addition, the psychotherapeutic situation, in itself, can evoke notions of gender. Sometimes masculinity can be the focus of the therapy, which previous research to some extent has drawn theoretical attention to, with a focus on certain aspects. However, there is a need for an empirical holistic approach to how masculinity is manifested in psychotherapy.The purpose of the dissertation is to clarify the meaning of masculinity, as it appears in the psychotherapeutic situation. This purpose is answered by empirically describing how masculinity is experienced in psychotherapy from two perspectives – the patient's and the psychotherapist's. The study is based on 27 in-depth interviews which were analyzed using a phenomenological method. The result is presented in the form of two meaning structures; one for the patient's experience of masculinity and another for the psychotherapist's experience. Finally, these two meaning structures are compared, in order to highlight common features and differences.The study shows that the patient's experience of masculinity is primarily rooted in the patient’s lived, first-person perspective, while the therapist's experience to a greater extent is constituted by a second- and third-person perspective. Both patient and therapist symbolize and conceptualize masculinity through different levels, where they share a bodily and a ”taken-for-granted” dimension. Their conceptualizations differ in that the therapist also has access to a theoretically informed perspective. Both patient and therapist constitute masculinity in a normative way; for the patient, the normative dimension is perceived in terms of ego-syntonic and ego-dystonic masculinity ideals and norms, while the therapist defines masculinity as either a positive or a negative phenomenon.A distinctive aspect of the result is, that masculinity can appear in terms of suffering for the patient or in terms of masculinity issues for the therapist. The masculinity suffering/masculinity issues can be associated with a polarized or immature form of masculinity, which – in the context of therapy – can undergo changes until appearing in a non-polarized, mature way. Another type of masculinity suffering, is when the patient does not feel in contact with masculinity. The result describes a changed masculinity experience in terms of a changed masculinity narrative, which can undergo three different elements; the prefigurative ground, the configurative processing, and the refigurative gestalt of masculinity. The study also sheds light on how the patient and therapist relate to one another in the light of a changed masculinity narrative.The comparative analysis shows that masculinity can be attributed with divergent meanings within the psychotherapeutic situation, and also includes a developmental, therapeutic and normative dimension. One conclusion is that masculinity has two sources of meaning; one lived and one theoretical origin. The lived perspective is linked to the life world, while the theoretical perspective has the potential to elaborate and broaden the life world experience of masculinity.
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