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Disputationer

Via universitetsbibliotekets databas över doktorsavhandlingar kan du söka publicerade doktorsavhandlingar vid Göteborgs högskola/universitet från 1902 och framåt. Databasen innehåller också information om kommande disputationer.

UB:s databas över doktorsavhandlingar

Kommande disputationer

Exploring the heterogeneity of the hematopoietic stem and progenitor cell pool in cord blood

[2017-10-17] Title: Exploring the heterogeneity of the hematopoietic stem and progenitor cell pool in cord blood Authors: Frändberg, Sofia Abstract: Hematopoietic stem cell transplantation (HSCT) is a curative treatment for a wide range of malignant and hereditary disorders. It is yet the only clinically established stem cell treatment. Hematopoietic stem and progenitor cells (HSPC) can be harvest-ed from bone marrow (BM), stimulated peripheral blood (PBSC) or umbilical cord blood (CB) collected from the placenta after clamping of the cord. A critical factor for the success of HSCT is the dose of functioning HSPC the recipient receives. The Na-tional Swedish Cord Blood Bank (NSCBB) was founded in 2005. We compiled the achievements of the NSCBB and investigated the impact of a change of practices from early to delayed clamping on CB collection volume and nucleated cell number. We developed novel methods using flow cytometry for measurement of functional HSPC in CB, firstly for the simultaneous definition of the Hoechst Side Population (SP), Aldehyde Dehydrogenase activity (ALDH) and the expression of the surface protein CD34 and secondly for the definition of viable and apoptotic cells in the ALDH and CD34 positive populations respectively. Finally, we screened for bi-omarkers in CB plasma that may predict the HSPC content in the corresponding CB collection using a multiplex immunoassay. The NSCBB stands up well in international comparison and the implementation of delayed clamping had no major effect on collection efficiency. There was no overlap between the SP and the ALDH popula-tions, suggesting that they define HSPC pools with different properties. Few apoptotic cells were identified in the ALDH population compared to the viable CD34 positive population, indicating that the ALDH assay intrinsically excludes apoptotic cells. We identified the CDCP-1 protein as a possible biomarker for HSPC content in CB.

Modulation of Receptor Signaling and Functional Selectivity in Neutrophils

[2017-10-17] Title: Modulation of Receptor Signaling and Functional Selectivity in Neutrophils Authors: Gabl, Michael Abstract: Neutrophils are important effector cells of the innate immune system and in the regulation of inflammation. Many of their functions, such as chemotactic migration, secretion of granule constituents and activation of the oxygen radical-producing NADPH-oxidase, are regulated by cell surface receptors. The formyl peptide receptors (FPRs), the ATP receptor (P2Y2R) and the receptor for platelet activating factor (PAFR) belong to the large family of G-protein coupled receptors (GPCRs) and, amongst other receptors, enable neutrophils to sense and respond to host- and pathogen-derived danger signals. Therefore, any regulatory imbalance in GPCR signaling can potentially contribute to the development of severe infections or autoimmune/inflammatory diseases. The work presented in this thesis is focused on basic GPCR-signaling mechanisms in human neutrophils with the aim to generate new knowledge that could be of value for future GPCR-based drug development. To answer the scientific questions raised, numerous cell-biology-based experimental methods were applied, including measurements of neutrophil intracellular calcium release, superoxide production, degranulation, cell migration and cytoskeleton-mediated receptor regulation. The functional responses triggered by GPCRs expressed by neutrophils can be modulated in various ways at the level of receptors/ligand interaction, in dependence of other GPCRs, as well as at the signaling level. Both FPR2 and P2Y2R have been shown to be able to exert functional selective signaling through distinct regulatory mechanisms. An FPR2-specific synthetic lipopeptide allosteric modulator was identified as a biased agonist that does not induce recruitment of β-arrestin or chemotactic migration and exhibits oppositional efficacies for direct FPR2 activation and receptor cross-talk-mediated signaling. Functional selectivity liked to the P2Y2R is not related to biased agonism but instead emerges from an endogenous actin cytoskeleton-dependent regulatory mechanism which selectively inhibits the signals that lead to the generation of oxygen radicals, while leaving other signaling pathways unaffected. In conclusion, this thesis adds new knowledge to the field of neutrophil receptor biology and provides novel insights into the modulation of basic GPCR signaling mechanisms with intend to contribute to strategies for future drug design and treatment of inflammatory disorders and disease.

Symptomatic Carotid Stenosis - optimal timing of surgical treatment

[2017-10-17] Title: Symptomatic Carotid Stenosis - optimal timing of surgical treatment Authors: Strömberg, Sofia Abstract: Abstract In patients with symptomatic carotid artery stenosis is convincing evidence that carotid endarterectomy (CEA) confers maximum benefit if performed within 14 days from index event. Patients with TIA or minor stroke have an increased risk of early recurrent stroke in the first weeks after the index event, then declining over months. This is the rationale to perform CEA as soon as possible after an index event. However, the procedural risk within the urgent time period is unknown. Aim The overall aim of this thesis was to investigate the optimal timing of surgical treatment in patients with symptomatic carotid stenosis. Methods In study I, registry data, obtained from Swedvasc, was analyzed regarding procedural risk of CEA, stratified for delay from index event. Mortality and stroke rate was studied at four time points, 0-2 days, 3-7 days, 8-14 days and 15-180 days. A multivariable analysis was performed to find other risk factors for CEA than time from referring event. In study II, 397 patients from WINGA, a region based registry for ultrasound investigations, were analyzed. All included patient had a significant symptomatic carotid stenosis. The risk of recurrent stroke at day 2, 7 and 30 after the index event was analyzed. Study III, was a prospective population based study with 418 consecutive patients comparing CEA within 48 hours with CEA after 48 hours to 14 days from most recent event. Primary endpoint was 30 days stroke and/or mortality rate after CEA. Study IV, included all CEA for symptomatic carotid stenosis registered in Swedvasc from May, 2008 to October, 2014. All medical records for CEA performed within 2 days were collected, and also a control group with CEA 3 to 7 days from index event. Analysis of validated and crude data regarding procedural risk stratified for delay was made. Optimal Timing of Surgical Treatment 6…,,,. Results The overall results from the four studies in the thesis shows an early risk of recurrent stroke at 1.7-2.0% day 2, 4% at one week and 7.5% at day 30. The procedural risk was 7.3-11.5% when CEA was performed within 2 days, 2.9-3.6% in patients with CEA 3 to 7 days, and 3.0-5.0% if surgery was performed 3 to 14 days after index event. Conclusions In summary, the procedural risk exceeds the risk of recurrent stroke day 0 to 2 in the studies in this thesis. The procedural risk, when 48 hours have elapsed after index event are not associated with an increased risk compared to even later surgery. This advocate a more expedited intervention than today’s guidelines recommend. The exception should be day 0 and 1, where only a minority of patients benefit from surgery. Keywords Carotid artery stenosis, carotid endarterectomy, stroke, transient ischemic attack, ocular transient ischemic attack

Sweet Taste Perception in Relation to Oral and General Health

[2017-10-17] Title: Sweet Taste Perception in Relation to Oral and General Health Authors: Ashi, Heba Abstract: The aims of this thesis were to study the difference in sweet taste perception, dental caries and BMI between three different geographical areas (Italy, Mexico and Saudi Arabia) and to elucidate the relationship of sweet taste perception with caries and BMI. Dietary habits were also assessed in relation to sweet taste perception in Saudi Arabia. In addition, the differences in sweet taste perception and plaque acidogenicity between pregnant and non-pregnant Saudi Arabian women were assessed. Materials and methods: For papers I, II and III, 669 schoolchildren, 13-15 years-old (220 Italian, 224 Mexican and 225 Saudi Arabian) were included, while in Paper IV the study subjects were a total of 121 Saudi Arabian women (41 non-pregnant, 40 early pregnant and 40 late pregnant). Sweet taste perception was determined by evaluating the sweet taste threshold (TT) and sweet taste preference (TP). For caries registration, DMFS, DMFT and ICDAS indices were used. The BMI-for-age scale was used for anthropometric assessments of the schoolchildren in paper II. In paper III, Saudi schoolchildren were assessed on their dietary habits via an estimated three-day dietary record and questionnaire. Plaque acidogenicity was determined for Saudi Arabian women in paper IV using the strip method. Comparisons between sweet taste perception and the different variables were conducted using different parametric and non-parametric tests. Results: Differences were found when comparing the three countries in terms of sweet taste perception (TT and TP). When assessing differences between the countries regarding the dental caries variables, a significant difference was found for DMFS and initial caries, with the highest mean value found among the Saudi Arabian schoolchildren. Sweet taste perception (TT and TP) was found to be related to DMFS and manifest caries in the three countries (Italy, Mexico and Saudi Arabia). A statistically significant difference was found between the three countries in terms of BMI value. No correlation was found for sweet taste perception (TT and TP) and BMI. In Saudi Arabia, sweet taste perception was found to be related to different dietary habits. Sweet taste perception differed significantly between non-pregnant, early pregnant and late pregnant women. In addition, significant differences were reported for plaque acidogenicity, with a lower pH value in the pregnant group. In conclusion, the existing differences observed in schoolchildren between the countries in terms of sweet taste perception, dental caries and BMI are believed to be due to cultural and environmental factors. The sweet taste perception level was found to have an effect on dental health while no such relationship was found with BMI. In addition, findings also suggest a higher risk of developing dental caries among pregnant women. Thus, they should be addressed as high risk group.

Proactive Software Complexity Assessment

[2017-10-16] Title: Proactive Software Complexity Assessment Authors: Antinyan, Vard Abstract: Large software development companies primarily deliver value to their customers by continuously enhancing the functionality of their products. Continuously developing software for customers insures the enduring success of a company. In continuous development, however, software complexity tends to increase gradually, the consequence of which is deteriorating maintainability over time. During short periods of time, the gradual complexity increase is insignificant, but over longer periods of time, complexity can develop to an unconceivable extent, such that maintenance is no longer profitable. Thus, proactive complexity assessment methods are required to prevent the gradual growth of complexity and instead build quality into developed software. Many studies have been conducted to delineate methods for complexity assess-ment. These focus on three main areas: 1) the landscape of complexity, i.e., the source of the complexity; 2) the possibilities for complexity assessment, i.e., how complexity can be measured and whether the results of assessment reflects reality; and 3) the practicality of using complexity assessment methods, i.e., the successful integration and use of assessment methods in continuous software development. Partial successes were achieved in all three areas. Firstly, it is clear that com-plexity is understood in terms of its consequences, such as spent time or re-sources, rather than in terms of its structure per se, such as software character-istics. Consequently, current complexity measures only assess isolated aspects of complexity and fail to capture its entirety. Finally, it is also clear that existing complexity assessment methods are used for isolated activities (e.g., defect and maintainability predictions) and not for integrated decision support (e.g., con-tinuous maintainability enhancement and defect prevention). This thesis presents 14 new findings across these three areas. The key findings are that: 1) Complexity increases maintenance time multifold when software size is constant. This consequential effect is mostly due to a few software characteristics, and whilst other software characteristics are essential for software development, they have an insignificant effect on complexity growth; 2) Two methods are proposed for complexity assessment. The first is for source code, which represents a combination of existing complexity measures to indicate deteriorating areas of code. The second is for textual requirements, which represents new complexity measures that can detect the inflow of poorly specified requirements; 3) Both methods were developed based on two critical factors: (i) the accuracy of assessment, and (ii) the simplicity of interpretation. The methods were integrated into practitioners’ working environments to allow proactive complexity assessment, and prevent defects and deteriorating maintainability. In addition, several additional key observations were made: Primarily the focus should be in creating more sophisticated software complexity measures based on empirical data indicative of the code characteristics that most influence com-plexity. It is desirable to integrate such complexity assessment measures into the practitioners’ working environments to ensure that complexity is assessed and managed proactively. This would allow quality to be built into the product rather than having to conduct separate, post-release refactoring activities.

The Dynamic Development of Cognitive and Socioemotional Traits and Their Effects on School Grades and Risk of Unemployment

[2017-10-13] Title: The Dynamic Development of Cognitive and Socioemotional Traits and Their Effects on School Grades and Risk of Unemployment Authors: Johannesson, Elias Abstract: The purpose of this thesis is to examine the dynamic development of cognitive and socioemotional traits and how these traits influence academic achievement and predict risk of unemployment. Data was retrieved from the Evaluation Through Following-up (ETF) database. The data consists of 9,080 students born in 1972, who answered a questionnaire and completed cognitive ability tests in 3rd and 6th grade. In addition, register-based data was used for students’ grades and for various background variables. All analyses were conducted using structural equation modelling (SEM). The dynamic development of the relationships between cognitive and socioemotional traits between 3rd and 6th grade is driven by cognitive ability factors. Support was found for Cattell’s investment hypothesis, which states that fluid cognitive ability (Gf) influences development of crystallized cognitive ability (Gc). No influence of socioemotional traits on either cognitive traits or socioemotional traits was found. The evidence of a Gc reading achievement trait complex was weak. Furthermore, both cognitive and socioemotional traits are related to academic achievement. In the prediction of unemployment risk, effects of almost all cognitive and socioemotional traits are captured by grades. Gc has both a direct effect on unemployment risk and an indirect effect via grades on unemployment risk. All other effects of socioemotional traits and Gf are related to the risk of unemployment via academic achievement. The strongest determinant of unemployment risk is academic achievement, which has a protective effect on the risk of unemployment.

Regulating Vessel-Source Air Pollution - Standard-Setting in the Regulation of SOx Emissions

[2017-10-11] Title: Regulating Vessel-Source Air Pollution - Standard-Setting in the Regulation of SOx Emissions Authors: Almestrand Linné, Philip Abstract: Emissions of sulphur oxides (SOx) cause considerable global environmental and human health impacts including acidification, climate change, and increased premature deaths in human populations due to serious heart and lung diseases. Although recently revised regulations in MARPOL 73/78 Annex VI are expected to decrease SOx emissions from ships, it is clear that these regulations will need further development. Even forthcoming requirements for SOx emissions from marine sources will still be considerably less strict in 2020 than the requirements for SOx emissions from terrestrial emission sources in force today. Without further regulatory developments, emissions of harmful SOx emissions from ships will persist, and will also indirectly hinder the efficient operation of available exhaust aftertreatment devices for other air emissions from ships. This thesis examines the regulation of SOx emissions from ships with a focus on the dominant type of regulation: ‘command and control’ (CAC) regulation. The purpose is to identify and examine historical and current differences between standard-setting in the regulation of SOx emissions from terrestrial sources, and the regulation of SOx emissions from marine sources. Standard-setting differences are considered across three regulatory scales (international, regional, national), with a theoretical and methodological foundation mainly in international environmental law and regulatory studies, and with the further aims of identifying the underlying rationales for the key differences in standard-setting, the regulatory effects of these differences, and the possibilities of improvement of SOx emissions regulation in the marine setting. Five categories of environmental standard-setting are examined: (a) product standards; (b) process standards; (c) emission standards; (d) environmental quality standards; and (e) other standards. In conclusion, this thesis argues that standard-setting in the regulation of terrestrial and marine SOx emission sources differs on all regulatory scales, both historically and presently. A key difference in standard-setting is that the control of SOx emissions from terrestrial sources has relied on combinations of standard-setting approaches, whereas marine emission sources have primarily been controlled with product standards. Arguably, the emission to be controlled has been a crucial decisive factor for the choice of standard-setting type. Other decisive factors were inter alia technical, economic, and institutional. The regulatory effects of the key differences are that experiences were gained in the terrestrial regulatory setting from using various forms of regulatory standards compared to the marine setting. The possibilities of improvement of SOx emissions regulation in the marine setting depend on perspectives and priorities. If the ambition is to refine the precision of standard-setting in SOx emissions regulation, there are improvement possibilities. Three broader implications of this study’s results are highlighted: regulatory studies can provide deeper understandings of the design of regulation; the analysis of standard-setting against a surrounding explanatory context can demonstrate the influence on standard choice of factors such as emission type, technology, and science; and regulatory studies can be used to analyse large quantities of multiscale regulatory material, which can yield better overviews of a regulatory landscape.

Contracts and Computation — Formal modelling and analysis for normative natural language

[2017-10-11] Title: Contracts and Computation — Formal modelling and analysis for normative natural language Authors: Camilleri, John J. Abstract: Whether we are aware of it or not, our digital lives are governed by contracts of various kinds, such as privacy policies, software licenses, service agreements, and regulations. At their essence, normative documents like these dictate the permissions, obligations, and prohibitions of two or more parties entering into an agreement, including the penalties which must be paid when someone breaks the rules. Such documents are often lengthy and hard to understand, and most people tend to agree to these legally binding contracts without ever reading them. Our goal is to create tools which can take a natural language document as input and allow an end user to easily ask questions about its implications, getting back meaningful answers in natural language within a reasonable amount of time. We do this by bringing formal methods to the analysis of normative texts, investigating how they can be effectively modelled and the kinds of automatic processing that these models enable. This thesis includes six research papers by the author which cover the various aspects of this approach: entity recognition and modality extraction from natural language, controlled natural languages and visual diagrams as interfaces for modelling, logical formalisms which can be used for contract representation, and analysis via syntactic filtering, trace evaluation, random testing, and model checking. These components are then combined into a prototype tool for end users, allowing for end-to-end analysis of normative texts in natural language.

Dental acrylates and methacrylates - Interactions with the immune system

[2017-10-10] Title: Dental acrylates and methacrylates - Interactions with the immune system Authors: Alizadehgharib, Sara Abstract: Professionals working in dentistry have reported adverse effects, such as allergic contact dermatitis due to exposure to different methacrylates/acrylates. Leakage of such monomers from dental fillings due to incomplete curing is also common. Monomers are released into the oral cavity and some may also diffuse through the dentin and reach the dental pulp. In the tissue, monomers will come in contact with different cells of the immune system. At present, there is a lack of knowledge of the effects these monomers might have on cells. The main objective of this thesis was to investigate possible effects of four different methacrylate/acrylate monomers on the immune system in vivo and in vitro. The studied methacrylates and acrylate were ethyl methacrylate (EMA), diethylene glycol diacrylate (DEGDA), 2-hydroxyethyl methacrylate (HEMA) and triethylene glycol dimethacrylate (TEGDMA). In summary, our in vivo and in vitro results showed that: • HEMA affects the immune system by inducing formation of the NLRP3 inflammasome (Study I). • TEGDMA has adjuvant properties and the ability to modulate cytokine production from peripheral blood mononuclear cells, which may lead to interference with the normal immune response to various agents, self or non-self, present in the pulp and the oral mucosa (Study II). • HEMA acts as a mucosal adjuvant when applied sublingually together with ovalbumin (OVA) or Streptococcus mutans in mice (Study III). • The different monomers affect the production, increase as well as decrease, of various cytokines in vitro by peripheral blood mononuclear cells. Antibody production and T cell activity to OVA was increased in mice immunized with OVA in combination with methacrylates (Study IV). Bacteria and bacterial products such as hydrogen sulfide (H2S) challenge the oral mucosa. We wanted to investigate whether H2S also affects the immune system in similar way as HEMA, i.e., induce formation of the NLRP3 inflammasome. • Human mononuclear leukocytes exposed to H2S had an enhanced production of NLRP3 inflammasome- dependent secretion of IL-1β and IL-18. (Study V). Thus, this may be a mode for H2S to contribute to the inflammatory host response and pathogenesis of periodontal disease In summary, the different methacrylate/acrylate monomers frequently used in dental restoration materials may interfere with the immune system in many different ways. The increase as well as the decrease in cytokine production from human mononuclear cells is affected by all these methacryleate/acrylate monomers. The T and B cell activity is also affected by all tested methacrylates . Thus, this may be a model that provide some insight into the nature of the immune responses to methacrylates and acrylates, and may advance the development of more biocompatible restorative materials in the future for clinical use.

Sexualitet i klassrummet. Språkundervisning, elevsubjektivitet och heteronormativitet

[2017-10-09] Title: Sexualitet i klassrummet. Språkundervisning, elevsubjektivitet och heteronormativitet Authors: Simonsson, Angelica Abstract: In this thesis, the production of sexuality in secondary language education is examined. More specifically, the aim is to explore how sexuality, pupil subjectivity and heteronormativity are produced within, and as constituent parts of, teaching practices of Swedish and English in secondary school. 31 classroom observations were conducted in two different groups of 8th graders in two different schools during a selection of their classes in Swedish and English. Field notes and teaching material from these observations are analysed in the articles. The theoretical starting-point is taken in queer theoretical perspectives on sexuality and language. I specifically draw on Butler’s (1993/2011, 2004) notions of performativity and normativity in exploring how different sexualities are produced as present or absent within language classroom practices. The compilation thesis consists of four articles. Article I, Default sexualitet i arbetet med noveller i språkundervisning på högstadiet, explores the unmarked repetition of heterosexuality within the teaching of short stories during lessons in Swedish. Article II, Smooth conversations: Sexuality as linguistic resource in a secondary language classroom, examines the function of unmarked repetition of heterosexuality within English language classroom conversations. Article III, Girls’ sexual subjectivity in a secondary language classroom, elaborates on how practices of intimacy in the classroom produce social or sexual subjectivity differently for girls and boys. Article IV, Gay as classroom practice: a study on sexuality in a secondary language classroom, investigates the function of pointed out male homosexuality as represented by a couple of pupils in a classroom rehearsed skit during an English class. The analyses show how heterosexuality is made normative; heterosexuality is employed and produced as an assumed common denominator in the execution of various classroom assignments and is simultaneously being reproduced as normalizing. Moreover, the analyses demonstrate how male homosexuality, as produced in the classroom within the realms of humor and drama, is kept under control and simultaneously made deviant and repudiated. The analyses show how heterosexuality is taken for granted, how male homosexuality is pointed out as well as rejected, and how female homosexuality is made invisible. This reproduces heteronormativity and serves as a pedagogical resource in the classroom. Producing pupil subjectivity through materializing the norm is thus facilitated by heteronormativity.

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