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- Nilsson Jannesson, Erik B, 1979-
(författare)
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Strategi, styrning och konkurrenskraft : En longitudinell studie av Saab AB
- 2010
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Att skapa sammanhängande koncern-, affärs- och funktionsstrategier (strategisk kongruens), samt ett styrsystem med ett samstämmigt informationsflöde i och mellan de centrala styrverktygen (integrerad styrning), har sedan länge hävdats vara centralt för koncerners konkurrenskraft. I den mängd empiriska studier som legat till grund för detta har främst en eller två organisatoriska nivåer fokuserats när relationerna mellan strategier, styrning och konkurrenskraft diskuterats. Studier som tar ett helhetsgrepp om dessa samband efterfrågas därför för att öka kunskapen om och förståelsen av sambanden. Föreliggande avhandling svarar mot den efterfrågan.En longitudinell fallstudie för perioden 1995–2007 har genomförts. Strategier, ekonomistyrning och produktionsstyrning på koncern-, affärs- och funktionsnivå har studerats inom försvars- och säkerhetskoncernen Saab AB. Tre affärsenheter har studerats i detalj: Saab Aerosystems, Saab Bofors Dynamics och Saab Systems. Det empiriska materialet har samlats in genom 74 intervjuer med totalt 54 respondenter samt via både internt och publikt skriftligt material.Avhandlingen visar att strategisk kongruens och integrerad styrning skapas genom ömsesidig anpassning av strategier och styrning på koncern-, affärs- och funktionsnivå. Genom en sådan ömsesidighet anpassas styrningen till koncernens kritiska framgångsfaktorer och ett integrerat informationsflöde skapas. Inom Saab har detta i sin tur påverkat beteendet på alla nivåer och bidragit till att det förändrats i enlighet med strategierna. De senare har därmed implementerats. Samtidigt som dessa beteendeförändringar skett har Saabs konkurrenskraft varit god. Då implementerade strategier, anpassade utifrån omgivningen, kan antas vara en viktig del i ett företags framgång har Saabs strategiska kongruens och integrerade styrning rimligen haft en väsentlig betydelse för koncernens konkurrenskraft.
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| 2. |
- Boekel, Carolina, 1977-
(författare)
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Integration and topology of membrane proteins
- 2009
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Membrane proteins comprise around 20-30% of most proteomes. They play important roles in most biochemical pathways. All receptors and ion channels are membrane proteins, which make them attractive targets for drug design. Membrane proteins insert and fold co-translationally into the endoplasmic reticular membrane of eukaryotic cells. The protein-conducting channel that inserts the protein into the membrane is called Sec61 translocon, which is a hetero-oligomeric channel that allows transmembrane segments to insert laterally into the lipid bilayer. The focus of this thesis is how the translocon recognizes the transmembrane helices and integrates them into the membrane.We have investigated the sequence requirements for the translocon-mediated integration of a transmembrane α-helix into the ER by challenging the Sec61 translocon with designed polypeptide segments in an in vitro expression system that allows a quantitative assessment of membrane insertion efficiency. Our studies suggest that helices might interact with each other already during the membrane-insertion step, possibly forming helical hairpins that partition into the membrane as a single unit. Further, the insertion efficiency for Nin-Cout vs. Nout-Cin transmembrane helices and the integration efficiency of Alzheimer’s Aβ-peptide fragments has been investigated.Finally, detailed topology mapping was performed on two biologically interesting proteins with unknown topology, the human seipin protein and Drosophila melanogaster odorant receptor OR83b.
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| 3. |
- Johansson, Leif B.G.
(författare)
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Asymmetric Oligothiophenes : Chemical Evolution of Multimodal Amyloid Ligands
- 2015
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Luminescent conjugated polymers (LCPs) and luminescent conjugated oligothiophenes (LCOs) can be used as molecular probes to study diseases associated with protein aggregation. The conventionally used dyes to study and detect protein aggregates, denoted amyloid, have been Congo red (CR) and Thioflavin T (ThT). In contrast to these amyloid ligands, LCOs offer the possibility to detect aggregated proteinaceous species occurring at earlier stages of amyloid formation as well as to distinguish different morphotypes of protein aggregates. The interaction between the LCOs and the protein deposits can be studied by fluorescence spectroscopy and microscopy both in vitro and ex vivo. In this thesis we report the development of multimodal asymmetric LCOs that can be utilized with two novel techniques, Surface Plasmon Resonance (SPR) and Positron Emission Tomography (PET), to study the interaction between LCO and amyloid fibrils in real time. With SPR, we have been able to determine binding affinities between LCO and amyloid, and with PET we have shown that radiolabelled LCOs can be used as a non-invasive method to study amyloid deposits in vivo. In addition, by alteration of the backbone (change of thiophene units), and of adding different side chains functionalities, we have shown that the properties of the amyloid ligands have a huge impact of the binding to different stages or forms of protein aggregates. By making asymmetrical LCOs, which can be attached to a surface, we also foresee a methodology that will offer the possibility to create a sensitive and selective detection method, and maybe lead to a lab-on-a-chip-application.
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| 8. |
- Nilsson, Robert, 1981-
(författare)
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Competitive performance prediction of elite alpine skiers
- 2019
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Introduction: The overall aim of this doctoral thesis was to identify physiological and anthropometric variables valid for prediction of competitive performance in alpine skiing (indicated by FIS points).Method: Paper I-III in this doctoral thesis followed an experimental, hypothesis-generating design which included both junior and senior elite alpine skiers. In all papers, physiological and anthropometric test results (X-variables) were correlated with FIS points (Y-variables) in order to investigate the predictive power of physiological and anthropometric variables for competitive performance in alpine skiing. The significance of the included test results was examined using bivariate and multivariate data analysis.Results: The results of Paper I show that included aerobic test results, neither alone nor in combination with anthropometric variables, could predict competitive performance of junior elite alpine skiers. Principal component analysis shows that male and female junior alpine skiers could be separated based on test results but that none of the included tests were important for sport-specific performance. The best multivariate models reached R2 = 0.51 to 0.86 and Q2 = -0.73 to 0.18. While several significant regression models could be observed, none of these met the criteria for valid models. The lack of predictive power of observed prediction models was confirmed by cross-validation. The results of Paper II show that included physiological test results from the test battery Fysprofilen could not predict competitive performance of senior elite female alpine skiers. Principal component analysis shows that there is a high correlation between individual physiological test results and their corresponding Fysprofilen score points, indicating that they can be used interchangeably. The Mann-Whitney U test was not significant neither for SL nor for GS. This suggests that Fysprofilen score points (summarized as Fysprofilen Index) and competitive performance (indicated by FIS points) are independent. The best multivariate models for SL and GS reached R2 = 0.27 to 0.43 and Q2 = - 0.8 to - 0.17, indicating low predictive power for competitive performance (as confirmed by cross-validation). The results of Paper III show that included physiological test results from a novel test battery could not predict competitive performance of senior elite female alpine skiers on a group level. When data were analyzed on a group level, the best models for SL and GS reached R2 = 0.39 to 0.40, Q2 = 0.15 to 0.21, indicating low predictive power. In contrast, when data were analyzed on an individual level, valid models with high predictive power (R2 = 0.88 to 0.99 and Q2 = 0.64 to 0.96) were generated. A comparative analysis between individual multivariate models shows that the relative importance of different physiological qualities for athletic performance varies between skiers.Conclusion: When applying tests on alpine skiers, a holistic approach should be considered. This because competitive performance in alpine skiing is the result of a number of interacting dimensions. Before applying physiological tests, the validity and reliability of the test protocols must also be determined. Administering tests that do not meet these criteria will probably waste not only important resources for clubs and ski federations but also risk misleading coaches and athletes when planning and implementing preparatory training.
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| 9. |
- Sakari, Thorbjörn B.
(författare)
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Adhesive small bowel obstruction: aspects on epidemiology, treatment, costs and prevention
- 2023
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Small bowel obstruction (SBO) is a common and sometimes life-threatening clinical condition, usually caused by post-operative adhesions. The aims of this thesis were to investigate the outcome after SBO surgery (Paper I), cost of SBO surgery including follow-up (Paper II), incidence of SBO after colorectal cancer (CRC) surgery (Paper III), and to assess the safety of using the adhesion preventing substance icodextrin in CRC surgery (Paper IV).Paper I, a population-based retrospective study on all patients operated for adhesive SBO (n=402) in the Uppsala and Gävleborg counties between 2007 and 2012. The SBO mechanism was a fibrous band in 56%. Complications and reoperations were recorded in 48% and 10% of patients, respectively. Complications, ICU care and early mortality were associated with age and ASA class. Seventy two patients had a recurrence of SBO, 26 of whom were re-operated. Previous laparotomies, diffuse adhesions, and complicated surgery (bowel injury, longer operation times and bleeding) were predictors of recurrent SBO. Paper II used the same cohort as in Paper I with an extended follow-up (8 years in median). Mean total cost estimates per patients were €40,467 during the study period. Diffuse adhesions and complications were associated with increased costs for SBO in a multivariable analysis (p<0.001).Paper III is a population-based register study based on all CRC cancer patients in Sweden 2007–2017. Among 33,632 CRC patients operated for stage I–III disease, the 5-year cumulative incidence was 7.6% for SBO and 2.2% for SBO surgery. In 198,649 matched CRC-free comparators the corresponding incidences were 0.6% and 0.2%, respectively. Open surgery and radiotherapy were associated with an increased incidence of SBO and SBO surgery. Paper IV is an interim analysis regarding morbidity and mortality, of a randomized controlled multicenter study assessing whether the adhesion preventing substance icodextrin can reduce the risk of postoperative SBO in stage I–III CRC patients. Randomization, to standard treatment with or without icodextrin, was blinded to the authors. Demographic data and overall complications were similar in the groups. Mortality, ICU care, anastomotic leaks and reoperations did not differ.
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| 10. |
- Sisask, Gregor, 1951-
(författare)
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Bone Development and the Nervous System
- 2009
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Innervation of bone influence bone modeling, growth and remodeling. Pro-inflammatory cytokines released after tissue trauma are recognized as neurotrophic factors as well as factors influencing bone formation. The Wnt signaling pathway, essential for cell migration during embryogenesis is found to influence bone formation during fracture healing. Alterations in growth and bone formation are seen in denervating disorders and in manipulated Wnt signaling. The aim of the present thesis was to study; sensory and autonomic innervation in the developing skeleton in rats and mice, a possible influence on bone formation in IL-4 and IL-13 depleted mice, and fracture healing in altered Wnt signaling by glycogen synthase-3β inhibition in rats.Bone innervation with sensory and autonomic nerves in modeling and growth follows a predictable and reproducible pattern both in the rat and in the mouse with sensory nerves occurring prior to autonomic nerves in areas with high chondrogenic and osteogenic activity. The time lag in occurrence between sensory and autonomic nerves indicates the importance of developmental timing between different nerve qualities in skeletal ontogeny. These findings give substantial morphologic support for important regulatory effects by the nervous system on bone development.Depletion of the anti-inflammatory cytokines IL-4 and IL-13 production in mice resulted in an inhibited autonomic innervation and lack of implant capillary ingrowth, studied by DXBM implants. In fracture healing no differences between IL-4/13 knockout mice and wild type mice were found concerning fracture callus parameters, biomechanical properties or histology except that sensory and autonomic nerves were found in the bone marrow in knockout mice but not in wild type mice.An altered canonical Wnt signaling was achieved by the GSK-3β inhibitor AR28. The increase in cytoplasmic β-catenin, due to inhibited degradation, resulted in a remarkable anabolic effect both on the fractured bone and on fracture healing. The histological analysis showed that the fractures healed without the usual formation of fibro-cartilage callus. This finding suggests that inhibition of GSK-3β inhibits the differentiation of chondrocytes and instead promotes the differentiation of mesenchymal progenitor cells into osteogenic cells.
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