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- Ahlund, Mikael
(författare)
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Landskapets röster : Studier i Elias Martins bildvärld
- 2011
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis is about the Swedish landscape painter Elias Martin (1739-1818). The main interest is in his depictions of nature, landscape images and topographical views. Chronologically, it covers the period 1760 to 1810. The first part puts Martin's artistic achievement in a historiographic perspective and presents an overview of his artistic career - from his birthplace Stockholm to Paris and from there to London, where he successfully established himself on the English art scene in the 1770s. Returning to his native Sweden in 1780, he soon emerged as the country's leading landscapist of the period.In the second part of the thesis, a study is presented of Martin's relationship to the art markets of England and Sweden, and in the third an attempt is made, through the medium of a specific genre of Swedish eighteenth-century literature - travel writings - to gain a deeper insight into the attitudes and values of the period. Here, the focus of interest is on different ways of viewing nature and landscape art in Sweden in the late eighteenth century. On the basis of this discussion, an attempt is made to reconstruct a Swedish 'period eye', specific to the upper-class culture of the Gustavian age.These discussions of the importance of the market and of a Swedish period eye form the basis for an answer to the overarching question of this thesis, concerning the relationship between Martin's images and contemporary perceptions of nature. From the conclusions drawn, it becomes clear that different ways of relating to landscape existed side by side. The attitudes discernible in the artist's pictures, as in the travel writings of the period, are diverse and contradictory, complicating an understanding of the eighteenth century's view of nature as something uniform. Elias Martin's art thus illuminates the many vantage points and variations in the Gustavian era's feeling for nature.
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| 3. |
- Björkegren, Karin
(författare)
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Studies on Vitamin B12 and Folate Deficiency Markers in the Elderly : A Population-based Study
- 2003
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The aims of this study were to document the levels of cobalamin, folate, methylmalonic acid (MMA) and total homocysteine (tHcy) in serum and their relations to symptoms, clinical findings, and other factors in order to improve the possibilities of detecting early deficiency of vitamin B12 or folate, and to study the effects of cobalamin and folic acid treatment over a three-year period. The study population consisted of a 20% random sample of persons 70 years or older living in Älvkarleby in mid-Sweden. They were invited to a survey and 224 (88.4%) persons responded. Data were obtained by questionnaire, laboratory investigations and physical examination for the period 1993 – 1999. In a multivariate analysis performed at baseline, serum MMA and tHcy were significantly and independently correlated to age, serum cobalamin, and creatinine levels, and tHcy also to sex and serum folate. Neither serum cobalamin, folate, MMA nor tHcy had any significant correlation to haemoglobin or mean red cell volume. Almost half of the study population had signs of low tissue levels of vitamin B12 or folate. Among those who took multivitamin preparations, the proportion was much lower, 25%. Among traditional symptoms and clinical findings that have been linked to vitamin B12 or folate tissue deficiency, only changes in the tongue mucosa and mouth angle stomatitis were significantly associated with abnormal serum folate and tHcy levels. Traditional symptoms of vitamin deficiency may appear later in the course. 69 persons who had laboratory indications of early or overt tissue deficiency of vitamin B12 or folate and who had no ongoing vitamin treatment were given cobalamin for six months. Those whose MMA or tHcy levels did not normalise were given folic acid in addition to cobalamin. After further treatment for three months, all persons but one had normal levels. The laboratory effect still remained after three years of treatment. There was a tendency towards improvement of vibration sense, especially in the long nerve paths, and improvement of neurological symptoms and oral mucosa findings. Conclusion: A substantial proportion of elderly persons have laboratory signs of incipient tissue deficiency of vitamin B12 and folate. Treatment normalises lab parameters and some symptoms.
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| 4. |
- Bodén, Roger, 1979-
(författare)
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Microactuators for Powerful Pumps
- 2008
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- When paraffin wax melts it exhibits a large, relatively incompressible volume expansion. This can be used in microactuators for strong and large displacements, a rare combination among actuators. Furthermore, paraffin is inexpensive, inert and environmentally friendly, as well as easily processed and actuated. Together, these properties give paraffin actuators great potential for use in both low-cost and high-performance applications.In microfluidics, the miniaturization of various analysis systems decreases the volumes of samples and reagents needed, as well as the analysis throughput time. Using on-chip micropumps increases the efficiency of the microfluidic system, but a challenge for such pumps is the high back-pressure associated with separation, filtration or narrower channels.The objective of this thesis is to increase the understanding of paraffin in microactuators, as well as to further explore its possibilities and limitations. The main application area has been on-chip micropumps.For low-cost applications, actuators, pumps and dispensers have been fabricated in plastics and then evaluated. The dispenser is intended for on-chip storage and dispensing of liquids in a lab-on-a-chip that could be used in, e.g., point-of-care testing (POCT).For high-performance applications, metallic actuators, pumps and dispensers have been accomplished. The micropump is the world’s strongest mechanical micropump in sub-cubic centimetre size, capable of pressures of above 5 MPa. Possible applications are strong microhydraulics, on-chip chromatography, or medical microdosage systems.A limitation of paraffin is the relatively slow thermal actuation. In this thesis the thermal properties have also been turned into an advantage: Directional solidification is used to accomplish multiple stable states of the actuator displacement, withheld without any power consumption.For the future, the high-pressure capability may be improved by new designs. Optimization of speed and power consumption can be made by further work on modelling as well as on drive and control of the heating.
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| 5. |
- Chatzakos, Vicky, 1977-
(författare)
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Studies of bioactive lipids in cancer
- 2012
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Lipids are a broad class of molecules that, besides being a major form of energy storage and components of cell membranes, act as bioactive signalling molecules. N-acyl taurines are structurally related to endocannabinoids that are known to exert antiproliferative actions in a variety of cancer cells. We have evaluated the cytotoxicity of N-oleoyl taurine and N-arachidonoyl taurine and found N-acyl taurines to reduce proliferation of prostate cancer cells.The sphingolipids ceramide and sphingosine act as tumour suppressors. We found selenite treatment to cause reduced viability, induction of neutral sphingomyelinase activity and accumulation of ceramide in the liver cancer cells. Inhibition of sphingosine kinase 1 (SK1) sensitized the cells to selenite treatment with regards to ceramide accumulation, arrest of cells in the G1/S phases of the cell cycle and formation of reactive oxygen species. Whereas combined selenite treatment and SK1 inhibition synergistically reduced the number of viable cells, the non-tumorigenic hepatocyte cell line, remained unaffected.Furthermore, we studied the involvement of sphingolipid metabolism in bladder cancer cells treated with Bacillus Calmette-Guérin (BCG), and found BCG to induce formation of nitric oxide and upregulation of nitric oxide synthase 2 as well as SK1 protein levels. Additionally, pharmacological inhibition of SK1 enhanced the viability reduction, ceramide accumulation and induction of apoptosis observed following BCG treatment.In conclusion, our findings have shown that N-acyl taurines exert antiproliferative effects on prostate cancer cells. Furthermore, sphingolipids were shown to be involved in cytotoxic treatment with selenite and BCG in liver cancer and bladder cancer cells respectively, and inhibition of SK1 increased the cytotoxicity. Our findings raise the possibility that modulation of ceramide-metabolizing enzymes could be used to enhance the effects of selenite and BCG in these cancer cell types.
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| 6. |
- Dahl, Anna, 1975-
(författare)
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Body mass index, cognitive ability, and dementia : prospective associations and methodological issues in late life
- 2009
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The aims of the present study were to investigate the association between overweight and cognitive ability and dementia, and to evaluate the usefulness of self-reported body mass index (BMI) in late life and various data sources commonly used in epidemiological studies to identify persons with dementia. Data were drawn from three population-based studies: the Swedish Adoption/Twin Study of Aging (SATSA), Aging in Women and Men: A Longitudinal Study of Gender Differences in Health Behaviour and Health among Elderly (the Gender Study), and the Finnish Lieto Study. In Study I, the agreement between self-reported and measured BMI over time was evaluated among 774 men and women, ages 40 to 88 years at baseline (mean age 63.9) participating in both the questionnaire phase and in-person testing of SATSA. Latent growth curve (LGC) modeling showed a small but significant increase between self-reported and measured BMI (0.02 kg/m2/y) over time, which would probably not affect the results if self-reported BMI were used as a continuous variable in longitudinal research. In Study II, the agreement between dementia diagnoses from various sources and dementia diagnoses set at a consensus conference was evaluated. Among the 498 elderly people ages 70 to 81 at baseline (mean age 74.5) enrolled in the Gender Study, 87 were diagnosed with dementia during an eight-year period. Review of medical records and nurse evaluations yielded the highest sensitivity (0.83 and 0.80, respectively) and a high specificity (0.98 and 0.96), indicating that these sources might be good proxies of dementia, while data extraction from the Swedish Inpatient Discharge Registry underestimated the prevalence of dementia (sensitivity 0.26). In Study III, the association between being overweight in midlife and cognitive ability in late life was examined in SATSA. The 781 participants ages 25 to 63 at baseline (mean age 41.6) in 1963 or 1973 self-reported their height and weight. From 1986 until 2002, they were assessed five times using a cognitive test battery. LGC models showed that people with higher midlife BMI scores had significantly lower cognitive ability and a significantly steeper decline than their thinner counterparts, an association that persisted when those who developed dementia during the study period were excluded from the analysis. This finding indicates that being overweight might affect cognitive ability independently of dementia. In Study IV, the association between BMI and dementia risk in older persons was described among 605 persons without dementia and ages 65 to 92 at baseline (mean age 70.8) in the Lieto Study. Among these, 86 persons were diagnosed with dementia during eight years of follow-up. Cox regression analyses indicated that for each unit increase in BMI score, the risk of dementia decreased 8% (hazard ratio = 0.92, 95% confidence interval = 0.87–0.97) and the association remained significant when individuals who developed dementia during the first four years of follow-up were excluded from the analyses. This result suggests that low BMI scores are present almost a decade before clinical dementia onset.
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| 8. |
- Granquist, Sandra M., 1979-
(författare)
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Ecology, tourism and management of harbour seals (Phoca vitulina)
- 2016
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- In cases where human and wildlife are co-using the same geographical areas and resources, management issues often get complex and stakeholder conflicts are common. The Icelandic harbour seal (Phoca vitulina) population is rapidly decreasing, but direct culling of seals still occurs. At the same time seals are becoming an important resource due to increased interest in wildlife watching. Despite the complicated management situation, the Icelandic harbour seal population is one of the least studied pinniped populations in the world. Mapping the typical haul-out pattern is an important foundation for further studies. In paper I haul-out behaviour of harbour seals was investigated and a seasonal haul-out pattern was detected with the maximum number of seals hauling out during summer. A bimodal distribution curve was found during the summer time, suggesting that pupping period occurs in late May to early June, while moulting occurs in late July to early August. Tidal state, air-temperature and wind-speed affected the haul-out boots. Today, the main reason for culling harbour seals in Iceland is to reduce harbour seal predation on salmonids, despite limited knowledge on the effect of seal predation on salmonid populations and salmon angling. The diet of harbour seals that haul out in the estuary area of Bjargós and Ósar in NW-Iceland was therefore investigated using hard-part (paper II) and DNA metabarcoding analysis (paper III). Both methods showed that the main prey species were sand eels, flatfishes, gadoids, herring and capelin, while salmonids were not an important prey in this area. Based on these results, culling of harbour seals in the area is not likely to have a positive effect on salmonid angling. These results have crucial management implications, especially in the light of the severe decline in the Icelandic harbour seal population. Potential effects of seal watching tourism on the harbour seal population must also be considered in management plans. In paper IV, we investigated the effects of land based seal watching on seal behaviour and found that spatial distribution and vigilance was affected by tourists. Calm tourists behaviour had less effect, meaning that disturbance could be reduced if tourist behaviour is modified. In paper V, this line of investigation was followed by analysing knowledge transfer from academia to the tourist industry and a model was presented where a synergy effect of working interdisciplinary is hypothesised. Finally, in paper VI, the effect of signage on tourist behaviour was studied. Empirical testing showed that teleological information is more effective than ontological in terms of modifying general tourist behaviour. In this thesis, I present new knowledge on behaviour and diet of harbour seals, as well as new empirical findings on tourist behaviour in wildlife tourism settings. Further I explore interdisciplinary management approaches for seal watching tourism. The findings presented in this thesis have an important value within academic research in environmental-, life- and social sciences and the knowledge can be applied in several areas of harbour seal management in Iceland and elsewhere.
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| 9. |
- Haglund, Sofie
(författare)
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Interindividual differences in thiopurine metabolism : studies with focus on inflammatory bowel disease
- 2011
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The thiopurines, 6-mercaptopurine and its prodrug azathioprine, are used in the treatment of inflammatory bowel disease, ulcerative colitis and Crohn´s disease. The main active metabolites are the phosphorylated thioguanine nucleotides (6-TGNs) and methylated thioinosine monophosphate (meTIMP). Both groups contribute to the immunomodulatory effects. About 30-40% of patients fail to benefit from thiopurine treatment. A well-known cause of adverse reactions is decreased or absent thiopurine S-methyltransferase (TPMT) activity. Low TPMT activity is inherited as an autosomal codominant recessive trait and is present in approximately 10% of the population. Although several clinical issues can be solved from determination of TPMT activity, there are cases where it is not possible. In Sweden approximately 25% of IBD-patients display suboptimal 6-TGN concentrations and unexpectedly high concentrations of meTIMP despite a normal TPMT activity. A high meTIMP/6-TGN concentration ratio has been associated with both unresponsiveness to therapy and emergence of adverse reactions. Inosine 5’-monophosphate dehydrogenase (IMPDH) may constitute a candidate gene to explain this metabolite profile, as it is strategically positioned in the metabolic pathway of thiopurines where it competes with TPMT for their common substrate 6-TIMP.In paper I a pyrosequencing method was developed for genotyping of at that time all known genetic variants of TPMT. The concordance between genotype and phenotype in 30 individuals was 93%. The allele frequencies of TPMT*3A, *3B, *3C and *2 in a Swedish background population (n=800) were in agreement with those in other Caucasian or European populations. In Paper II-IV we explored the molecular basis of different metabolite profiles, i.e. low, normal and high meTIMP/6-TGN concentration ratios. The activity of IMPDH was measured in mononuclear cells (MNC). Patients with high metabolite ratios had lower IMPDH activity than patients with normal or low ratios, explained by an inverse correlation to red blood cells concentration of meTIMP. No correlation to 6-TGN was observed. Downregulation of IMPDH activity in HEK293 cells with genetically engineered TPMT activity was associated with an increase in meTIMP, but unexpectedly also of 6-TGN, irrespective of the TPMT status. These results suggest effects of pharmacogenes other than TPMT and IMPDH. A whole genome expression analysis was performed, (1) to identify new candidate genes that could explain differences in metabolite profiles, and (2) to study genes with known associations to the metabolic pathway of (thio)purines. The whole genome expression analysis did not identify any significant group differences. In analysis of the thiopurine related genes, three clusters of co-regulated genes were defined. A co-operation between expression levels of SLC29A1 and NT5E in explaining the meTIMP/6-TGN concentration ratio was observed, and individually SLC29A1 and NT5E correlated to 6-TGN and meTIMP, respectively.Pysosequencing is a convenient and flexible method which is now run in parallel to phenotyping in our laboratory. Our results also illustrate the complexity of the thiopurine metabolism and suggest that differences between metabolite profiles are explained either by interactions between several genes, each with a small contribution, or at the post-transcriptional level. Search for more precise tools to explain differences in metabolite profiles is needed. Furthermore, in order to investigate small effects it is necessary to analyse metabolite concentrations and gene expression levels, as well as enzyme activities in the target cells of therapy (MNC).
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| 10. |
- Hoffman, Tove
(författare)
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Dispersal of ticks and their microorganisms by African-Western Palaearctic migratory birds
- 2021
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- In Europe, tick-borne diseases are the most widespread and common vector-borne diseases and their geographical distribution is increasing. The dispersal of ticks depends on the movements of their vertebrate hosts. Avian hosts are more likely to be involved in long-distance range expansion of ticks due to their migration pattern. Billions of birds in the African-Palaearctic migration system migrate biannually between breeding grounds in the Palaearctic and wintering grounds in Africa and thereby create natural links between Africa, Europe, and Asia. In this thesis the dispersal of ticks and their microorganisms by northbound migratory birds utilizing flyways in the African-Western Palaearctic region has been investigated and the association between bird ecology and tick taxon addressed. The results suggest that long-distance migratory birds with wintering regions in Africa are involved in northward dispersal of the tick species Hyalomma rufipes, a known vector or Crimean-Congo hemorrhagic fever virus, and that birds with an open or wetland habitat have more H. rufipes in comparison to birds with a winter habitat comprising forest and shrubs. The results also suggest a role for birds in the ecology of Alkhurma hemorrhagic fever virus, a hemorrhagic flavivirus, and a potential mechanism for dispersal of the virus to new regions, including Europe and Asia Minor. The results did not provide evidence for immature ticks of the Hyalomma marginatum complex and birds having a major role in the ecology and northward dispersal of tick-borne Anaplasma phagocytophilum, a zoonotic bacterium causing febrile illness in humans and domestic animals. However, the results give support to the idea of a divergent enzootic cycle of A. phagocytophilum involving birds as hosts. Finally, the results of this thesis suggest that H. rufipes do not serve as vectors or contribute to the transmission of the tularemia-causing bacterium Francisella tularensis and that migratory birds do not contribute to northward dispersal of F. tularensis-infected ticks. However, the results suggest that migratory birds contribute to northward dispersal of H. rufipes carrying both Francisella and spotted fever group Rickettsia species, including Francisella-like endosymbionts and Rickettsia aeschlimannii. In conclusion, this thesis helps to clarify the knowledge about the dispersal of ticks and the microorganisms they carry by northbound migrating birds in the African-Western Palaearctic region. Furthermore, it highlights the need of establishing surveillance programs for monitoring the risk of introduction and establishment of important exotic tick species, such as H. rufipes, and tick-borne pathogens in the Western Palaearctic.
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