| 1. |
- Bozic, Nina
(författare)
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Choreographing innovative practice in everyday work
- 2018
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The thesis argues for a humanistic and democratic approach to innovation management that puts employees and their engagement in the center of organizational efforts for innovation. It proposes that a culture for innovation can be built by enabling all employees to develop their innovative practice as part of their everyday work and not as an extra activity on top of their existing responsibilities. The aim of this approach to innovation is to build more human-centered organizations that help employees improve their own motivation, creativity, well-being, and self-fulfillment at work. This presupposes that they need to be able to connect with their body, feelings, fantasy, intuition, and will, and to be able to innovate more from within, balancing external expectations from management and users with their own personal needs. Since there is a lack of discussing embodied aspects of knowledge and learning in connection to innovative competence in the current innovation management literature, knowledge and methods from contemporary dance and choreography are explored to support a more holistic approach to innovative competence development. Based on integrating research from both innovation management and contemporary dance fields, a model of innovative practice in everyday work is developed. The model suggests what kind of skills and activities can enable employees develop their personal innovative practice that is adjusted to their work context and their specific needs. It is proposed that as employees practice innovating in everyday work, they will slowly move from innovating incrementally towards developing the competence for more radical innovation. Different practical tools and exercises for enabling innovative competence development that were inspired by choreographic practices, and adjusted and tested in organizational context are described. Ideas around how contemporary dance and choreography can be used to design and implement long-term art-based interventions in organizations that can create value on strategic level are proposed. The research approach used in the thesis is participatory action research done by several iterative cycles between practice and theory. Two empirical and two theoretical studies that were part of the research process are presented. The empirical studies were implemented in the Eskilstuna municipality and at the Art of Management and Organization conference. The theoretical studies were performed in the fields of innovative competence and contemporary dance and choreography.
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| 2. |
- Dersjö, Tomas, 1981-
(författare)
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Methods for reliability based design optimization of structural components
- 2012
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Cost and quality are key properties of a product, possibly even the two most important. Onedefinition of quality is fitness for purpose. Load-bearing products, i.e. structural components,loose their fitness for purpose if they fail. Thus, the ability to withstand failure is a fundamentalmeasure of quality for structural components. Reliability based design optimization(RBDO) is an approach for development of structural components which aims to minimizethe cost while constraining the probability of failure. However, the computational effort ofan RBDO applied to large-scale engineering problems has prohibited it from employment inindustrial applications. This thesis presents methods for computationally efficient RBDO.A review of the work presented on RBDO algorithms reveals that three constituentsof an RBDO algorithm has rendered significant attention; i ) the solution strategy for andnumerical treatment of the probabilistic constraints, ii ) the surrogate model, and iii) theexperiment design. A surrogate model is ”a model of a model”, i.e. a computationally cheapapproximation of a physics-based but computationally expensive computer model. It is fittedto responses from the physics-motivated model obtained via a thought-through combinationof experiments called an experiment design.In Paper A, the general algorithm for RBDO employed in this work, including the sequentialapproximation procedure used to treat the probabilistic constraints, is laid out. A singleconstraint approximation point (CAP) is used to save computational effort with acceptablelosses in accuracy. The approach is used to optimize a truck component and incorporatesthe effect that production related design variables like machining and shot peening have onfatigue life.The focus in Paper B is on experiment design. An algorithm employed to construct anovel experiment design for problems with multiple constraints is presented. It is based onan initial screening and uses the specific problem structure to combine one-factor-at-a-timeexperiments to a several-factors-at-a-time experiment design which reduces computationaleffort.In Paper C, a surrogate model tailored for RBDO is introduced. It is motivated by appliedsolid mechanics considerations and the use of the first order reliability method to evaluate theprobabilistic constraint. An optimal CAP is furthermore deduced from the surrogate model.In Paper D, the paradigm to use sets of experiments rather than one experiment at atime is challenged. A new procedure called experiments on demand (EoD) is presented. TheEoD procedure utilizes the core of RBDO to quantify the demand for new experiments andaugments it by a D-optimality criterion for added robustness and numerical stability.
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| 3. |
- Fransson, Moa, 1981-
(författare)
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CNS-Targeted Cell Therapy for Multiple Sclerosis
- 2010
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Multiple sclerosis (MS) is an autoimmune disorder of the central nervous system (CNS). In the current thesis, we have preformed an immunological investigation of patients with MS and developed an immunosuppressive cell therapy that could be beneficial for these patients. MS has been considered to be driven by T helper type1 (Th1) lymphocytes but new data indicate the involvement of Th17 responses. T cells from patients with MS that were evaluated for immunological status secreted both interferon-γ and interleukin-17 upon stimulation. However, T cells from patients with MS in remission, in contrast to relapse, had poor proliferative capacity suggesting that they are controlled and kept in anergy. T regulatory cells (Tregs) are important to maintain self-tolerance and the role of CD4+CD25+FoxP3+ Tregs in autoimmunity has been extensively investigated. We analyzed Tregs from patients with MS in relapse and remission by multicolor flow cytometry for the expression of CD3, CD4, IL2R (CD25), FoxP3 and the IL7R (CD127). Patients in relapse exhibited higher levels of FoxP3-positive Tregs lacking CD25 compared to healthy controls, indicating that Tregs might attempt to restrain immune activity during relapse. In the murine experimental autoimmune encephalomyelitis (EAE) model of MS, therapy with suppressive cells such as Tregs or mesenchymal stromal cells (MSCs) has proven beneficial. However, systemic administration of such cells may immunologically compromise the recipient and promote infections due to general immunosuppression. We hypothesized that suppressive cells can be equipped with a CNS-targeting receptor and be delivered intra-nasally to avoid systemic exposure. CD4+ T cells were modified with a lentiviral vector system to express a myelin oligodendrocyte (MOG)-targeting receptor in trans with the FoxP3 gene that drives Treg differentiation. Genetically engineered Tregs demonstrated suppressive capacity in vitro and localized to the brain and suppressed ongoing encephalomyelitis in vivo. Cured mice were rechallenged with an EAE-inducing inoculum but remained healthy. MSCs are a heterogeneous population of stromal cells residing in most connective tissues and have the capacity to suppress effector cells of the immune system. MSCs were engineered to express MOG-targeting receptors using lentiviral vectors. Genetically engineered MSCs retained their suppressive capacity in vitro and successfully targeted the brain upon intranasal delivery. Engineered MSCs cured mice from disease symptoms and these mice were resistant to further EAE challenge. Encephalitic T cells isolated from cured mice displayed an anergic profile while peripheral T cells were still responsive to stimuli. In conclusion, MS patients have peripheral CNS-reactive T cells of both Th1 and Th17 type that, while in remission, are kept in anergy. Also, MS patients in relapse exhibit increased levels of CD25 negative Tregs indicating an attempt to restrain immune activity. Finally, immunosuppressive cells can be genetically engineered to target CNS and efficiently suppress encephalomyelitis in an active EAE model upon intranasal delivery.
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| 4. |
- Hellberg, Sandra, 1986-
(författare)
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Effects of Pregnancy and Hormones on T cell Immune Regulation in Multiple Sclerosis
- 2019
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Multiple sclerosis (MS) is characterized by a dysregulated immune system leading to chronic inflammation in the central nervous system. Despite increasing number of treatments, many patients continue to deteriorate. A better understanding of the underlying disease mechanisms involved in driving disease is a pre-requisite for finding new biomarkers and new treatment targets. The improvement of MS during pregnancy, comparable to the beneficial effects of the most effective treatment, suggests that the transient and physiological immune tolerance established during pregnancy could serve as a model for successful immune regulation. Most likely the immune-endocrine alterations that take place during pregnancy to accommodate the presence of the semi-allogenic fetus contribute to the observed disease improvement.The aim of this thesis was to characterize the dysregulated immune system in MS and define potential factors and mechanisms established during pregnancy that could be involved in the pregnancy-induced effects in MS, focusing on CD4+ T cells as one of the main drivers in immunity and in the MS pathogenesis. Using a network-based modular approach based on gene expression profiling, we could show that CD4+ T cells from patients with MS displayed an altered dynamic gene response to activation, in line with a dysregulated immune system in MS. The resulting gene module disclosed cell activation and chemotaxis as central components in the deviating response, results that form a basis for further studies on its modulation during pregnancy. Moreover, a combination of secreted proteins (OPN+CXCL1-3+CXCL10-CCL2), identified from the module, could be used to separate patients and controls, predict disease activity after 2 years and discriminate between high and low responders to treatment, highlighting their potential use as biomarkers for predicting disease activity and response to treatment.The pregnancy hormone progesterone (P4), a potential factor involved in the pregnancy-induced amelioration of MS, was found to significantly dampen CD4+ T cell activation. Further detailed transcriptomic profiling revealed that P4 almost exclusively down-regulated immune-related pathways in activated T cells, several related to or downstream of T cell activation such as JAKSTAT signaling, T cell receptor signaling and cytokine-cytokine receptor interaction. In particular, P4 significantly affected genes of relevance to diseases known to be modulated during pregnancy, where genes associated to MS were most significantly affected, supporting a role for P4 in the pregnancy-induced immunomodulation. By using another approach, the role of thymus in T cell regulation during pregnancy was assessed. Two established measures of thymic output, CD31 expression and TREC content, were used and showed that thymic output of T cells is maintained during human pregnancy, or even possibly increased in terms of regulatory T cells.This thesis further supports a pivotal role for CD4+ T cells and T cell activation in the MS pathogenesis and adds to the knowledge of how they could be involved in driving disease. We identified a novel strategy for capturing central aspects of the deviating response to T cell activation that could be translated into potentially clinically relevant biomarkers. Further, P4 is emerging as a promising candidate for the pregnancy-induced immunomodulation that could be of importance as a future treatment option. Lastly, maintained thymic output of T cells during human pregnancy challenges the rodent-based dogma of an inactive thymus during pregnancy. Thymic dysfunction has been reported not only in MS but also in rheumatoid arthritis, another inflammatory disease that improves during pregnancy, which highlights a potential role for thymus in immune regulation that could be involved in the pregnancy-induced amelioration.
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| 5. |
- Jonsson, Linda, 1963-
(författare)
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Mellan tradition och förnyelse : Utmaningar i religionsläraruppdraget
- 2016
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The current assignment of religious studies teachers is grounded on a confession-free foundation, expressed through the values of Swedish society. However, the subject still carries traces of a confessional tradition. Up until recently, Christianity played a major role in both teaching and teacher assignments. This study focuses on the complexity that emerges when it comes to the assignment of religious studies teachers in Swedish schools. In order to shed light on two traditions of importance – a confessional Christian tradition and an objective religious tradition, an analytical contextualisation is constructed within the time span 1842–1994. Such a long-term perspective is seen as a necessary historical contextualisation for the empirical study, which contains an analysis of the contemporary religious studies teacher assignment, here called the uncertain period (1994-2011). The study is to be regarded as an analysis of a school subject related challenge from a general didactical approach. In order to study the religious studies teacher assignment, religion as a school subject will be a key component in this study. The use of the subject – in the sense of its status, role and function – is clarified, and has implications for the teacher assignment as such. The historical context has its starting point in a literature study of policy documents and texts, and shall be regarded as the study’s secondary literature. The empirical material of the study comes from a journal entitled Religion & Livsfrågor (Religion and Life Issues) from the time span of 1994–2011. The material is analysed and attention drawn to different voices on the religious studies teacher assignment. The challenges that the teacher assignment is facing are summarised in three concluding challenges: Between tradition and renewal, Limitless assignment in limited time, and Pupil-related questions or “when-it-pops-up”-pedagogy. An account is given of the contributions made by two educational philosophers, John Dewey and Wolfgang Klafki, in the latter part of the study. These contributions serve as basis for analyses of the challenges in the uncertain period of contemporary religious studies teacher assignment. Their writings on theory and practice, tradition and renewal, as well as teacher engagement, add a valuable perspective to the analyses in order to understand the challenges the teacher assignment faces. In conclusion, the analyses of the voices on the religious studies teacher assignment and its challenges are summarised and related to their historical context characterised both by a confessional and an objective tradition. The thesis provides a more detailed image on the complexity of the religious studies teacher assignment, through a contextualization of the contemporary assignment in curriculum historical perspective.
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| 6. |
- Liljeholm, Lina, 1979-
(författare)
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Reactive Sputter Deposition of Functional Thin Films
- 2012
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Thin film technology is of great significance for a variety of products, such as electronics, anti-reflective or hard coatings, sensors, solar cells, etc. This thesis concerns the synthesis of thin functional films, reactive magnetron sputter deposition process as such and the physical and functional characterization of the thin films synthesized. Characteristic for reactive sputtering processes is the hysteresis due to the target poisoning. One particular finding in this work is the elimination of the hysteresis by means of a mixed nitrogen/oxygen processing environment for dual sputtering of Alumina-Zirconia thin films. For a constant moderate flow of nitrogen, the hysteresis could be eliminated without significant incorporation of nitrogen in the films. It is concluded that optimum processing conditions for films of a desired composition can readily be estimated by modeling. The work on reactively sputtered SiO2–TiO2 thin films provides guidelines as to the choice of process parameters in view of the application in mind, by demonstrating that it is possible to tune the refractive index by using single composite Six/TiO2 targets with the right composition and operating in a suitable oxygen flow range. The influence of the target composition on the sputter yield is studied for reactively sputtered titanium oxide films. It is shown that by using sub-stoichiometric targets with the right composition and operating in the proper oxygen flow range, it is possible to increase the sputter rate and still obtain stoichiometric coatings. Wurtzite aluminum nitride (w-AlN) thin films are of great interest for electro-acoustic applications and their properties have in recent years been extensively studied. One way to tailor material properties is to vary the composition by adding other elements. Within this thesis (Al,B)N films of the wurtzite structure and a strong c-axis texture have been grown by reactive sputter deposition. Nanoindentation experiments show that the films have nanoindentation hardness in excess of 30 GPa, which is as hard as commercially available hard coatings such as TiN. Electrical properties of w-(Al,B)N thin films were investigated. W-(Al,B)N thin films are found to have a dielectric strength of ~3×106 V/cm, a relatively high k-value around 12 and conduction mechanisms similar to those of AlN. These results serve as basis for further research and applications of w-(Al,B)N thin films. An AlN thin film bulk acoustic resonator (FBAR) and a solidly mounted resonator (SMR) together with a microfluidic transport system have been fabricated. The fabrication process is IC compatible and uses reactive sputtering to deposit piezoelectric AlN thin films with a non-zero mean inclination of the c-axis, which allows in-liquid operation through the excitation of the shear mode. The results on IC-compatibility, Q-values, operation frequency and resolution illustrate the potential of this technology for highly sensitive low-cost micro-biosensor systems for applications in, e.g. point-of-care testing.
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| 7. |
- Olsson, Anki
(författare)
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Hemostatic function and inflammatory activation after weaning from cardio pulmonary bypass
- 2018
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Cardiopulmonary bypass (CPB) contributes to perioperative platelet dysfunction, increased fibrinolysis and impaired coagulation, which can have an impact on postoperative bleeding. During CPB the blood is exposed to foreign surfaces leading to activation of the coagulation system and a systemic inflammatory response with complement and leukocyte activation. Anticoagulation with heparin is used to prevent immediate blood clotting within the circuit. The heparin effect is reversed with protamine sulfate after weaning from CPB. Protamine has been suggested to impair platelet function in high doses although the mechanism is incompletely understood. Platelet dysfunction can promote bleeding which can necessitate transfusion and sometimes surgical re-exploration.After weaning from CPB the residual blood in the heart lung machine is usually retransfused to the patient in order to reduce the need for blood transfusion. The most common technique to transfuse residual blood is to collect the blood from the CPB circuit in an infusion bag (IB). An alternative way to re-transfuse the residual blood is by chasing it through the heart lung machine with Ringers solution, the Ringer chase technique (RC).The aim of this thesis was to examine a possible inhibitory effect of protamine on platelet aggregation. A second aim was to evaluate different techniques for retransfusion after weaning from CPB.Study I and II in this thesis are focused on the protamine effect on platelet aggregation and study III and IV on the quality of the blood in relation to the two different retransfusion techniques.In Study I we found that platelet aggregation evaluated by impedance aggregometry was reduced by approximately 50% after in vivo protamine administration. Protamine added in vitro also reduced platelet aggregation, by itself or in combination with heparin. Study II showed that protamine induces a marked but transient decrease in platelet aggregation already at a protamine-heparin ratio of 0.7:1, which also was sufficient to reverse the heparin anticoagulation as measured by activated clotting time (ACT). No further decrease was observed when additional protamine was given within three minutes. Platelet aggregation had begun to recover 20 minutes after protamine administration.In study III and IV we evaluated possible differences in quality of the retransfused residual blood from the heart-lung machine depending on if it is returned to the patient by the RC-technique or by an IB. Study III focused on biochemical markers of hemostasis, coagulation and fibrinolysis. Study IV concerns biochemical markers of inflammatory activity characterizing the inflammatory response during cardiac surgery with CPB including heparin binding protein (HBP) a new marker of neutrophil activation. CPB is associated with a marked systemic inflammatory response and levels of HBP indicates a pronounced neutrophil activation as part of a systemic inflammatory process. HBP levels during CPB was much higher than previously found during severe inflammatory conditions. We also concluded that the handling of the blood after weaning from CPB reduces platelet function, activates coagulation and fibrinolysis, increases hemolysis and the inflammatory response. Retransfusion of pump blood with the RC-technique was associated with better preserved platelet function, less hemolysis, less signs of activation of coagulation and fibrinolysis and less pronounced inflammatory activity than the commonly used IB technique. In the event of cell salvage technique not being feasible, we suggest that the RC technique is preferable to the IB technique but acknowledge that the clinical importance of this finding in terms of outcomes warrants further investigation
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| 8. |
- Olsson, Tomas
(författare)
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A Data-Driven Approach to Remote Fault Diagnosis of Heavy-duty Machines
- 2015
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Heavy-duty machines are equipment constructed for working under rough conditions and their design is meant to withstand heavy workloads. However, the last decades technical development in cheap electronically components have lead to an increase of electrical systems in traditionally mainly mechanical systems of heavy-duty machines. As the complexity of these machines increases, so does the complexity of detecting and diagnosing machine faults. However, the addition of new electrical systems, such as on-board computational power and telematics, makes it possible to add new sensors that measure signals relevant for fault detection and diagnosis, and to process signals on-board or off-board the machines.In this thesis, we address the diagnostic problem by investigating data-driven methods for remote diagnosis of heavy-duty machines, where a part of the analysis is performed on-board the machine (fault detection), while another part is performed off-board the machine (fault classification). We propose a diagnostic framework where we use a novel combination of methods for each step in the diagnosis. On-board the machine, we have used logistic regression as an anomaly detector to detect faults that will lead to a stream of individual cases classified as anomalous or not. Then, either on-board or off-board, we can use a probabilistic anomaly detector to identify whether the stream of cases is truly anomalous when we look at the stream of cases as a group. The anomalous group of cases is called a composite case. Thereafter, off-board the machine, each anomalous individual case is classified into a fault type using a case-based reasoning approach to fault diagnosis. In the final step, we fuse the individual classifications into a single aggregated classification for the composite case. In order to be able to assess the reliability of a diagnosis, we also propose a novel case-based approach to estimating the reliability of probabilistic predictions. It can, for instance, be used for assessing the confidence of the classification of a composite case given historical data of the predictive reliability.
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| 9. |
- Olsson, Tomas
(författare)
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Development and Characterization of a Global Brain Ischemia Model in the Mouse -A Genetic and Pharmacological Approach
- 2004
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Brain ischemia is a major cause of death and morbidity in the industrialized countries. It is mainly caused by stroke, but may also be the consequence of successful cardiopulmonary resuscitation in victims of cardiac arrest, known as transient global ischemia. Although extensive effort in the field of brain research using experimental rodent models, no neuroprotective treatments are at present available. Advances in gene technology, to manipulate the mouse genome by deleting or overexpressing genes has opened new possibilities to reveal novel pathways in the pathophysiology of ischemic brain damage. The elucidation of the selective neuronal damage following global ischemia, using this genetic approach, has been hampered due to the lack of reproducible models in the mouse. The first aim of this thesis was to develop a global brain ischemia model in the mouse. Twelve minutes of ischemia was induced by bilateral common carotid artery occlusion under halothane anesthesia and artificial ventilation controlled by online measurement of exhaled CO2. Body and head temperature was rigorously controlled. Bilateral monitoring of cerebral blood flow by laser Doppler during the experiment was crucial to only include hemispheres with a sufficient dense ischemia. Extensive damage was found in the striatum and marked cell damage was observed in hippocampal CA1 and CA2 and thalamus, whereas the CA3 region, dentate gyrus and cortex suffered less damage. Also, hippocampal CA1 injury developed in a delayed manner. The second aim was to test the applicability of this model in earlier established views on the mechanisms of ischemic cell death. The robust protective effect of intraischemic hypothermia of 33?C was confirmed, and NMDA receptor blockade could if applied directly following ischemia provide protection. Also the endogenous protective effect of adenosine through the adenosine A1 receptor was enlightened by the aggravated effect of blockade of the A1 receptor. However, and possibly even more interesting was the result that did not support and in fact contradicted general views and also some findings in other animals species. Deletion of the gene coding for the adenosine A1 receptor did not aggravate ischemia-induced damage, contrary to pharmacological inhibition of the receptor, indicating that other compensatory neuroprotective mechanism has been activated due to the gene deletion. The notion of a neuroprotective effect of the stress protein heat shock protein 70 (Hsp70) could not be verified in our murine model of global ischemia were Hsp70 was genetically overexpressed. Using a mouse strain deficient in the protease inhibitor cystatin C, we found that the cell death following global and focal ischemia appears to develop differently, or perhaps more correctly stated, different mechanisms are more or less important. The absence of cystatin C aggravated focal ischemic damage while diminishing to the selective neuronal damage induced by global ischemia. In conclusion, this thesis describes a reliable model of global brain ischemia in the mouse and its applicability to different genetically modified mouse strains show that compensatory mechanisms can be induced in knockout animals and that different mechanisms are involved in focal compared with global ischemic brain damage.
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| 10. |
- Olsson, Tomas
(författare)
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High-Speed Vision and Force Feedback for Motion-Controlled Industrial Manipulators
- 2007
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Over the last decades, both force sensors and cameras have emerged as useful sensors for different applications in robotics. This thesis considers a number of dynamic visual tracking and control problems, as well as the integration of these techniques with contact force control. Different topics ranging from basic theory to system implementation and applications are treated. A new interface developed for external sensor control is presented, designed by making non-intrusive extensions to a standard industrial robot control system. The structure of these extensions are presented, the system properties are modeled and experimentally verified, and results from force-controlled stub grinding and deburring experiments are presented. A novel system for force-controlled drilling using a standard industrial robot is also demonstrated. The solution is based on the use of force feedback to control the contact forces and the sliding motions of the pressure foot, which would otherwise occur during the drilling phase. Basic methods for feature-based tracking and servoing are presented, together with an extension for constrained motion estimation based on a dual quaternion pose parametrization. A method for multi-camera real-time rigid body tracking with time constraints is also presented, based on an optimal selection of the measured features. The developed tracking methods are used as the basis for two different approaches to vision/force control, which are illustrated in experiments. Intensity-based techniques for tracking and vision-based control are also developed. A dynamic visual tracking technique based directly on the image intensity measurements is presented, together with new stability-based methods suitable for dynamic tracking and feedback problems. The stability-based methods outperform the previous methods in many situations, as shown in simulations and experiments.
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