| 83541. |
- Tjäder, Jimmy, 1971-
(författare)
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Systemimplementering i praktiken : en studie av logiker i fyra projekt
- 1999
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Att framgångsrikt leda implementeringar av informationssystem är en fråga om att dels skapa goda förutsättningar för lärande och dels genomföra projekt effektivt. Tidigare studier visar att det är vanligt förekommande att något eller båda dessa behov är förbisedda. En orsak till detta är att lärande och effektivitet ställer olika krav på hur projektledare leder projekt. Detta är kopplat till två olika typer av logiker som kan användas av projektledare för att förklara egna och andras handlingar, en som skapar goda förutsättningar för effektivitet (kontrollogik) och en som skapar goda förutsättningar för lärande (lärandelogik). I syfte att belysa denna problematik studeras i denna avhandling projektledares redogörelser av sina och andras ageranden vid systemimplementeringar och de två logikernas konsekvenser för systemimplementeringar belyses. Avhandlingen är baserad på två studier. Den första studien belyser hur projektledares logik förändras under ett projektförlopp. Det empiriska materialet till denna studie är hämtat från tre systemimplementeringar som genomförts av ABB lnfosystems. Dessa projekt syftar till att implementera ett affärssystem, ett CAM-system (Computer Aided Manufacturing) och ett egenutvecklat system. Den andra studien belyser relationen mellan en projektledares logik och ett socialt sammanhang. Det empiriska materialet är hämtat från en omfattande implementering av ett affärssystem, genomförd av ABB lnfosystems med ABB Industrial Systems som beställare. De datainsamlingsmetoder som används i de två studierna är intervjuer, studier av dokumentation och e-post samt deltagande observation.En kontroilogiks framgång är beroende av att det finns tidigare erfarenhet. Logiken har en tendens att skapa en stor informationsbelastning för projektledaren och dåliga förutsättningar för kunskapsutbyte mellan beställare och konsulter. En lärandelogik är svår att upprätthålla i ett projektsammanhang då den är svår att förena med projektledningspraxis. I studierna finns det dock projektförlopp som genomsyras av en lärandelogik Under dessa förlopp skapas arenor där olika aktörers tolkningar kan mötas. Slutligen är en intressant observation att det inte i något av projekten finns exempel på en övergång från en lärandelogik till en kontrollogik. En viktig orsak till detta är avsaknaden av externa aktörer som kan introducera konkurrerande tolkningar, vilka behövs för att skapa förutsättningar för en lärandelogik
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| 83542. |
- Tjäderborn, Micaela, 1983-
(författare)
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Psychoactive prescription drug use disorders, misuse and abuse : Pharmacoepidemiological aspects
- 2016
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: There is a widespread and increasing use of psychoactive prescription drugs, such as opioid analgesics, anxiolytics, hypnotics and anti-epileptics, but their use is associated with a risk of drug use disorder, misuse and abuse. Today, these are globally recognized and emerging public health concerns.Aim: The aim of this thesis is to estimate the prevalence of psychoactive prescription drug (PPD) use disorders, misuse and abuse, and to investigate the association with some potential risk factors.Methods: A study using register data from forensic cause of death investigations investigated and described cases of fatal unintentional intoxication with tramadol (Study I). Based on register data on spontaneously reported adverse drug reactions (ADRs) reported cases of tramadol dependence were investigated and summarised (Study II). In a study in suspected drug-impaired drivers with a toxicology analysis confirming the intake of one out of five pre-specified PPDs, the prevalence of non-prescribed use was assessed and associated factors were investigated (Study III). From a cohort of patients initiating prescribed treatment with pregabalin, using data on prescription fills, a study investigated longitudinal utilisation patterns during five years with regards to use of the drug above the maximum approved daily dose (MAD), and factors associated with the utilisation patterns (Study IV).Results: In the first study, 17 cases of unintentional intoxications were identified, of which more concerned men, the median age was 44 years and the majority used multiple psychoactive substances (alcohol, illicit drugs and prescription drugs). The second study identified 104 spontaneously reported cases of tramadol dependence, in which more concerned women, the median age was 45 years, and a third reported a history of substance abuse and 40% of past psychoactive medication use. In the third study, more than half of the individuals suspected of drug-impaired driving used the drug without a recent prescription. Non prescribed use was most frequent in users of benzodiazepines and tramadol, and was more likely in younger individuals and in multiple-substance users. In the last paper five longitudinal utilisation patterns were found in pregabalin users, with two patterns associated with a particularly high risk of doses above the maximum approved dosing recommendation. This pattern of use was associated with male sex, younger age, non-urban residency and a recent prescribed treatment with an antiepileptic or opioid analgesic drug.Conclusions: This thesis shows that psychoactive prescription drug use disorders, misuse and abuse occur and may have serious and even fatal consequences. The prevalence varies between different drugs and populations. Abuse and misuse seem to be more common in young people. Fatal intoxications and misuse of prescribed drugs may be more common in men, while drug use disorders following prescribed treatment may be more common in women and non-prescribed use equally distributed between women and men. Individuals with a history of mental illness, substance use disorder or abuse, or of past use of psychoactive medications are likely important risk groups. In summary, the findings suggest a potential for improvements in the utilisation of psychoactive prescription drugs. The results may be useful in the planning of clinical and regulatory preventive interventions to promote the rational, individualised and safe use of such drugs.
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| 83543. |
- Tjällén, Biörn
(författare)
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Church and nation : The discourse on authority in Ericus Olai's Chronica regni Gothorum (c. 1471)
- 2007
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The Chronica regni Gothorum is the first Latin national history of Sweden. Completed after 1471 by a canon of Uppsala, Ericus Olai, it testifies to the articulation at the Swedish arch see of the dominant political issues of the day: the status of the Swedish realm in the union with Denmark-Norway, and the relations between the king, aristocracy and ecclesiastical leadership. This thesis analyses the discourse on authority in the Chronica. It investigates the normative basis of Ericus’s treatment of contemporary political issues as a source for the social-political outlooks of Sweden’s ecclesiastical power elite, a group not previously studied in this respect. In particular, it argues for the importance of two prescriptive assumptions on social order, which lie at the heart of the authority discourse in the Chronica: God divided the world into self-governing peoples and realms, and He instituted the lay and clerical orders as parallel hierarchies of societal authority.The thesis situates the production of the Chronica within the educational concerns of the Uppsala institution. It scrutinizes the commonplaces – derived from various fields of knowledge – through which Ericus articulated his dualist and nationalist assumptions. The realization of these notions in his historical account is examined in sections of the text where matters of importance for the Uppsala church are evident. Special attention is paid to Ericus’s account of the royal martyr, St Erik, the so-called Engelbrekt rebellion, and the contemporary strife between the Uppsala church and the kings. The thesis ends with a study of the reception of the Chronica in the 1520s, a time when the Reformation and the consolidation of a strong national monarchy in Sweden brought the authority issues addressed by Ericus to conclusion.
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| 83544. |
- Tjärnberg, Andreas, 1981-
(författare)
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Exploring the Boundaries of Gene Regulatory Network Inference
- 2015
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- To understand how the components of a complex system like the biological cell interact and regulate each other, we need to collect data for how the components respond to system perturbations. Such data can then be used to solve the inverse problem of inferring a network that describes how the pieces influence each other. The work in this thesis deals with modelling the cell regulatory system, often represented as a network, with tools and concepts derived from systems biology. The first investigation focuses on network sparsity and algorithmic biases introduced by penalised network inference procedures. Many contemporary network inference methods rely on a sparsity parameter such as the L1 penalty term used in the LASSO. However, a poor choice of the sparsity parameter can give highly incorrect network estimates. In order to avoid such poor choices, we devised a method to optimise the sparsity parameter, which maximises the accuracy of the inferred network. We showed that it is effective on in silico data sets with a reasonable level of informativeness and demonstrated that accurate prediction of network sparsity is key to elucidate the correct network parameters. The second investigation focuses on how knowledge from association networks can be transferred to regulatory network inference procedures. It is common that the quality of expression data is inadequate for reliable gene regulatory network inference. Therefore, we constructed an algorithm to incorporate prior knowledge and demonstrated that it increases the accuracy of network inference when the quality of the data is low. The third investigation aimed to understand the influence of system and data properties on network inference accuracy. L1 regularisation methods commonly produce poor network estimates when the data used for inference is ill-conditioned, even when the signal to noise ratio is so high that all links in the network can be proven to exist for the given significance. In this study we elucidated some general principles for under what conditions we expect strongly degraded accuracy. Moreover, it allowed us to estimate expected accuracy from conditions of simulated data, which was used to predict the performance of inference algorithms on biological data. Finally, we built a software package GeneSPIDER for solving problems encountered during previous investigations. The software package supports highly controllable network and data generation as well as data analysis and exploration in the context of network inference.
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| 83545. |
- Tjärnemo, Heléne
(författare)
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Eco-marketing & Eco-management. Exploring the eco-orientation - performance link in food retailing.
- 2001
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The purpose of this thesis was to develop a conceptual framework of food retailers’ ecological orientation that considers the interaction between ecological marketing and ecological management. In this context, the relationship was examined between ecological orientation and sales of ecological food products and the overall store performance of Swedish food retailers. To fulfil this purpose eco-orientation was conceptualised into two dimensions: eco-marketing and eco-management based on indications in the greening literature that companies’ responses to ecological issues have often been skewed to the marketing side rather than integrated into strategic and operative substantive actions. The study contributes to the theoretical fields of green and retail marketing. In the empirical data, (based on a standardised questionnaire administered to a random sample of Swedish storekeepers) I found three distinct groups of stores. The three groups were positioned along the diagonal of the two dimensions of eco-orientation; thus the stores differed in the degree of eco-orientation and not by having skewed eco-orientations. In fact, the data showed consistency in the integration of eco-aspects in marketing and management over a wide area of functions and activities. The findings from the study indicated that there was a positive relationship between ecological orientation and sales of ecological food products as well as overall store performance. However, eco-orientation seems to contribute more to the explanation of the sales of the ecological range rather than to overall sales. This study not only supports the notions of the important role of the store for the sales and market development of ecological food products, but also indicates that the more a store integrates ecological aspects into both marketing and management the better the development of its sales of ecological food products. Moreover, the study indicated that those storekeepers who considered it possible to combine eco-concern with good business were more likely to integrate eco-issues into their store operations than storekeepers who only had a general positive attitude to eco-issues.
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| 83546. |
- Tjärnlund, Anna
(författare)
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Mucosal Immunity in Mycobacterial infections
- 2007
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- More than a century after the identification of the tubercle bacillus and the first attempts at vaccination, tuberculosis (TB) still remains one of the world’s most serious infectious diseases. TB, caused by the bacterium Mycobacterium tuberculosis, is typically a disease of the lung, which serves both as port of entry and as the major site of disease manifestation. The currently used vaccine, BCG, is administered parenterally and induces a systemic immune response. However, it fails to protect against pulmonary TB, thereby raising the question whether vaccination targeting the mucosal immunity in the lungs could be favourable. The respiratory mucosal surfaces represent the first line of defence against a multitude of pathogens. Secretory IgA, in mucosal secretions has an important function by blocking entrance of pathogenic organisms and preventing infections. Additionally, a role for IgA in modulation of immune responses is currently being revealed. In this work, we investigated the relevance of mucosal IgA in protection against mycobacterial infections using mice deficient for IgA and the polymeric Ig receptor, the receptor responsible for mucosal secretions of IgA. Gene-targeted mice were more susceptible to mycobacterial infections in the respiratory tract and displayed reduced production of proinflammatory, and protective, factors such as IFN-γ and TNF-α in the lungs. The mechanisms explaining the defective proinflammatory responses in the lungs of deficient mice might involve impaired signalling through Fcα receptors, or homologous receptors, which could lead to inadequate activation of pulmonary macrophages. This could subsequently result in suboptimal induction and production of cytokines and chemokines important for attraction and migration of immune cells to the site of infection. Induction of optimal adaptive immune responses to combat mycobacterial infections requires prompt innate immune activation. Toll-like receptors (TLRs) are vital components of the innate branch of the immune system, ensuring early recognition of invading pathogens. Using TLR-deficient mice we demonstrated an important role for TLR2, and partly TLR4, in protection against mycobacterial infection in the respiratory tract. TLR2-deficient mice failed to induce proper proinflammatory responses at the site of infection, and macrophages derived from the knockout mice displayed impaired anti-mycobacterial activity. Experimental evidence has concluded that the immune response upon an infection can influence the outcome of succeeding infections with other pathogens. Concurrent infections might additionally interfere with responses to vaccinations and have deleterious effects. We developed an in vitro model to study the effect of a malaria infection on a successive M. tuberculosis infection. Our results demonstrate that a malaria blood-stage infection enhances the innate immune response to a subsequent M. tuberculosis infection with a Th1 prone profile. Reduced infectivity of malaria-exposed dendritic cells implies that a malaria infection could impose relative resistance to ensuing M. tuberculosis infection. However, a prolonged Th1 response may interfere with malaria parasite control. The outcome of this work emphasizes the importance of generating effective immune responses in the local mucosal environment upon respiratory mycobacterial infections. It furthermore puts new light on the immunological interaction between parasites and mycobacteria, which could have implications for future vaccine research.
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| 83547. |
- Tjärnlund-Wolf, Anna, 1974
(författare)
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On the Tissue-type Plasminogen Activator (t-PA) -7,351C>T Enhancer Polymorphism. Importance for endothelial t-PA gene expression and arterial thrombotic disease
- 2004
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Local endothelial release of tissue-type plasminogen activator (t-PA) is an important thromboprotective mechanism. Earlier work by our group has identified a common single nucleotide polymorphism (SNP) at the t-PA locus (-7,351C>T), located within a GC-box in the retinoic acid (RA) and steroid hormone responsive t-PA enhancer. This SNP was associated with local t-PA release in vivo, as subjects homozygous for the wild-type -7,351C allele had twice the t-PA release rates compared to carriers of the mutant T allele. The aim of the present thesis was to elucidate the physiological and pathophysiological relevance of this t-PA variant. TaqMan genotyping assays were designed for a set of SNPs in hemostatic genes to facilitate association studies on these SNPs and thrombotic disease. Specificity and reproducibility was confirmed by DNA sequencing and repeated genotyping. The pathophysiologial relevance of the t-PA -7,351C>T SNP was initially addressed in a prospective study on myocardial infarction (MI) in northern Sweden. An independent association for the t-PA -7,351C>T SNP was found, with a greater risk of MI in T allele carriers. In a large case-control study on ischemic stroke from western Sweden we did, however, not detect a similar association. This study also included a genetic variant of the main inhibitor of t-PA, the plasminogen activator inhibitor type-1 (PAI-1) -675 4G>5G SNP. A reduced risk of ischemic stroke was observed for the combined t-PA CC and PAI-1 4G4G genotype.In vitro studies were performed to functionally characterize the t-PA -7,351C>T SNP. Gel shift analysis using nuclear extracts derived form various cell types, including endothelial cells (ECs) and neuronal-like cells, revealed a strongly reduced binding affinity of transcription factors Sp1 and Sp3 to the T allele, which is interesting in view of the role for Sp1 in gene regulation and enhancer action. Transient transfections demonstrated a lower transcriptional activity in the T enhancer variant after stimulation with RA. An interaction between Sp1 and the RA receptor was also observed. ECs carrying the T allele showed a reduced t-PA induction, both at the mRNA and protein level, in response to RA and protein kinase C (PKC) activation. The combination of RA and PKC activation produced a synergistic t-PA response, resulting in a 2-fold difference in t-PA expression between genotypes.In conclusion, the t-PA -7,351C>T SNP affects endothelial t-PA gene expression at the level of transcription. The reduced expression seen with the mutant T allele may explain our finding of an increased risk for MI in individuals carrying this allele. The t-PA -7,351C>T SNP did not show a significant association to ischemic stroke, but a reduced risk was observed in subjects with the combined t-PA CC and PAI-1 4G4G genotype, supporting a differentiated and more complex role for t-PA and PAI-1 in the brain as compared to the heart.
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| 83548. |
- Tjärnström, Fredrik
(författare)
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Variance Expressions and Model Reduction in System Identification
- 2002
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Although system identification is now a mature research field, some problems remain unsolved. Examples of unsolved or partly unsolved problems are; accuracy of subspace identification algorithms, identification via model reduction, identification for control, and identification of non-linear systems. Some problems that fall into these categories are studied in this thesis.This thesis discusses variance expressions in system identification. In particular, variance expressions for reduced models are analyzed.The topic of model reduction via system identification has received little attention during the years. To understand how the variance of a high order model affects the reduced model, a general expression for the variance of the low order model as a function of the reduction method used is derived. This allows the analysis of all model reduction methods that can be written as a minimization criterion, where the function to be minimized is twice continuously differentiable. Many methods can be studied using this approach. However, the popular method of model reduction by balanced truncation of states does not immediately fit into this framework.Many unsolved problems in system identification may be studied with the use of bootstrap methods. This statistical tool, used to assess accuracy in estimation problems, may be adopted to a series of problems in system identification and signal processing. The thesis presents how bootstrap can be adopted in the prediction error framework. In addition, we demonstrate how bootstrap can be applied to problems of constructing condence regions with a simultaneous confidence degree and calculating the variance of undermodeled models.The thesis briefly discusses how set membership identification and prediction error identification can be combined into a more robust estimate. Finally, insights into how model validation can be performed in a more user informative way are also given.
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| 83549. |
- Tjärnström, Johan, 1957
(författare)
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Hyperbaric oxygen. Effects on ischemia-reperfusion
- 2002
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Treatment with hyperbaric oxygen (HBO2) is controversial when treating other disorders than decompression sickness. However, HBO2 is a treatment modality that has gained recognition in certain ischemia-reperfusion situations. The aim of the present investigation was to test the hypothesis that, following trauma and ischemia-reperfusion HBO2 inhibits the activation of leukocytes and affects endothelial fibrinolysis.The effects of HBO2 on leukosequestration, measured by a ?-counter calculating leukocyte transit factor and on extracellular superoxide production, measured by nitroblue tetrazolium reduction test (NBT), were studied in two animal models; in the first instance using rats subjected to intestinal ischemia followed by reperfusion and in the second using rats with activation of the leukocytes through activation of the complement system. The effect of hyperbaric oxygen on human leukocytes in vitro, activated with phorbol myristate acetate (PMA) and f-Met-Leu-Phe (f-MLP), was studied, measuring extracellular superoxide production with NBT-test, cytochrome C reduction test and chemiluminescence.The effect of HBO2 on endothelial fibrinolysis analysis of the expression of tissue-type plasminogen activator (t-PA), plasminogen activator inhibitor type 1 (PAI-1) and urokinase plasminogen activator (uPA) with ELISA and PCR technique was studied in two in vitro models.Hyperbaric oxygen reduced the pulmonary leukosequestration following ischemia-reperfusion and inhibited the extracellular production of superoxide in activated neutrophils compared to controls. This effect is on a cellular level. Hyperbaric oxygen affected the fibrinolysis by an elevated secretion of t-PA, PAI-1 and uPA.In conclusion: Neutrophil activation following ischemia-reperfusion and complement activation was inhibited by HBO2 in vivo. Pulmonary leukosequestration following ischemia-reperfusion was inhibited by HBO2 in vivo. Normobaric and hyperbaric oxygen treatment in vitro inhibit neutrophil respiratory burst, following activation by PMA and f-MLP. Hyperbaric oxygen stimulated the endothelial fibrinolytic system.Thus, hyperbaric oxygen treatment could be beneficial in clinical states of trauma and ischemia-reperfusion.
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| 83550. |
- Tjärnström, Robert, 1959-
(författare)
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Simulation and timing verification of CMOS VLSI systems
- 1990
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis is based on new algorithms and methods for computer aided verification of digital CMOS VLSI systems. IC designs need to be verified before fabrication due the big costs associated with each iteration of detecting errors in the chip, re-design and refabrication. Because of the ever increasing complexity of IC designs there is an increasing need for better verification methods and tools.A new algorithm for switch-level simulation (LOS) has been developed. It is based on a local decision approach in contrast to previous approaches which makes global solutions for transistor groups. This object oriented design makes it suitable for uniform integration in a multi-level simulator.It is shown why switch-level simulators, in general, have problems with the pass transistor EXOR gate, and how it can be correctly simulated with the LDS simulator.It is also shown how LDS can be equipped with a mechanism to yield an estimate of averge power dissipation of the design, based on the simulated activity.It is not uncommon for IC designs to have low yield because the design itself is sensitive for variations of process parameters. A method to consider such parameter deviations for switch-level simulation and timing verification is presented. Warnings are then given for circuitry which are not sufficiently robust.The hierarchical timing verifier (HTV) has been developed. It can be used on the transistor level and higher levels, since it is not tailored to a specific abstraction level. The hierarchical approach implies a reduced verification cost since only unique cell types need to be analysed. HTV is independent of clocking strategy and do include skew effects. In addition, it considers deviations of process parameters, and includes a mechanism to detect fundamental design errors.Algorithms have been developed to recognize the circuit classes of combinational gate and C2MOS-gates at the transistor level. The result is timing specifications, including both delay values and timing constraints.A method has been developed to handle level-sensitive latches in timing verification, which long has been considered a serious problem.
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