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Genetic and Epigenetic Characterisation of Breast Tumours

Breast tumours harbour a large amount of genetic and epigenetic alterations, which are associated with e.g. tumour aggressiveness, prognosis, and response to therapy. The heterogeneity of breast tumours is reflected in the identification of at least five molecular subtypes named basal-like, luminal A, luminal B, HER2-enriched and normal-like, which are believed to originate from different cell typ

Predictive markers for tamoxifen response in primary breast cancer

It is well-known that a majority of breast cancers are hormone-dependent, making endocrine therapy an important adjuvant treatment after surgery. Susceptibility to endocrine treatment is determined by the presence of estrogen receptors (ER) and progesterone receptors (PR) in the tumors. Tamoxifen is the most well-established endocrine treatment available, inhibiting tumor growth and improving surv

Negative Pressure Wound Therapy - Mechanisms of Action and Protecting Exposed Blood Vessels in the Wound Bed

NPWT has recently been associated with severe complications and bleeding when used in wounds with exposed blood vessels. The aims of this work were to investigate the mechanisms of action of NPWT and to explore the possibility of using thin plastic discs to protect exposed blood vessels in the wound bed during NPWT. Three different kinds of wounds were created in pigs: 6 cm and 10 cm diameter circ

Ultrasound features of human carotid plaques

Atherosclerotic plaques in the carotid arteries are common in a middle-aged population. When a carotid plaque ruptures it may result in a cerebrovascular event. However, only a minor part of carotid plaques will eventually rupture. Finding those plaques is essential to decide the most appropriate treatment strategy. With non-invasive ultrasound the carotid plaques can be visualized for assessment

Pointwise and Genomewide Significance Calculations in Gene Mapping through Nonparametric Linkage Analysis: Theory, Algorithms and Applications

In linkage analysis or, in a wider sense, gene mapping one searches for disease loci along a genome. This is done by observing so called marker genotypes (alleles) and phenotypes (affecteds/unaffecteds) of a pedigree set, i.e. a set of multigenerational families, in order to locate the loci corresponding to the underlying disease genes or, at least, to narrow down the interesting genome regions. I

Airway mechanics of mice and men

In this thesis we explore and further develop several techniques used in the animal laboratory as well as in the clinical setting. In particular, we expand the understanding and usefulness of plethysmographic techniques in small rodents. Study I shows that the pressure signal from an un-restrained plethysmograph (UP) depends largely on heating and humidification of the inhaled air. This brings int

Development of a Passive Immunization Strategy Against Atherosclerosis

Atherosclerosis is a chronic inflammatory disease, characterized by the accumulation of lipids and fibrous tissue in the wall of medium and large-sized arteries. The characteristic culprit of the disease is the atheroma, or atherosclerotic plaque, a patchy thickening of the arterial wall which affects the lumen, inducing various degrees of stenosis. The rupture of the atherosclerotic plaques, foll

Nitrogen transformations in wetlands: Effects of water flow patterns

In this thesis, I have studied nitrogen turnover processes in watermeadows. A watermeadow is a wetland where water infiltrates through the soil of a grassland field. It is hypothesized that infiltration of water through the soil matrix promotes nutrient transformations compared to surface flow of water, by increasing the contact between water, nutrients, soil organic matter and bacteria. I have st

Lack of association between genetic variations in the KALRN region and ischemic stroke

Objectives: To investigate whether KALRN gene variation is associated with ischemic stroke (IS). Design and methods: Associations to overall IS and IS subtypes were investigated in SAHLSIS, which comprises 844 patients with IS and 668 controls. Results: Associations between KALRN SNPs and overall IS and cardioembolic stroke were detected. Associations for overall IS were investigated in two additi

Sphenothallus from the Furongian (Cambrian) of Scandinavia

Sphenothallus, a Palaeozoic genus of uncertain affinity, possibly a hydrozoan, is reported from the Furongian (Cambrian) of Scandinavia. This is the only known occurrence of the genus in Cambrian rocks outside of China, western North America and Bohemia, and also the first report of Sphenothallus in the Cambrian-Ordovician of Baltica. The material is from the upper Furongian (upper Protopeltura an

Laser-Driven Plasma Waves for Particle Acceleration and X-ray Production

This thesis presents experimental results related to laser plasma accelerators. These rely on very different principles from conventional particle accelerators. They are able to accelerate particles over a very short distance and produce synchrotron x-rays at the same time, potentially providing a compact particle accelerator and x-ray source for many future applications. The laser pulses used in

Immuno Gene Therapy of Rat Brain Tumors with interferon-gamma transfected glioma cells

Immunotherapy is a new promising approach in cancer treatment. In the future, it will hopefully offer an alternative to existing brain tumors treatments, which are unable to cure. We have established an experimental, low immunogenic, brain tumor model in the rat. We have increased tumor cell immunogenicity with mutagen treatment or transfection of IFN-g. Mutagen treated glioma cells (tum-) could c

Effects of dopamine and excitotoxicity in experimental models of Huntington's disease

Huntington's disease (HD) is a hereditary neurodegenerative disorder caused by an expansion of a CAG repeat in the HD gene, that leads to dysfunction and death of striatal neurons. The pathogenetic mechanisms underlying HD are not known, but excitotoxicity and dopamine (DA) have been suggested to play a role. In this thesis, the effects of excitotoxicity and DA have been studied in striatal in vit

Molecular studies of genetic changes in myxoid and round cell liposarcoma

Chromosomal translocations commonly result in the production of fusion genes and the fusion genes are often tumor-type specific. In myxoid and round cell liposarcomas (MLS/RCLS), almost 95% of the cases carry a t(12;16)(q13;p11). In the remaining 5% of the MLS/RCLS tumors, another translocation and fusion gene can be found, i.e. the t(12;22)(q13;q12). These translocations fuse CHOP on chromosome 1

Mechanisms and time course of cell death in embryonic nigral tissue and intrastriatal transplants.

Parkinson’s disease (PD) is the second most common neurodegenerative disorder and severely affects about one in a hundred persons over the age of fifty years. In PD, there is a reduced striatal concentration of the neurotransmittor dopamine, mainly caused by a degeneration of the dopaminergic neurons in the substantia nigra. Transplantation of embryonic dopamine neurons has been developed as an al

Factors Affecting Rates of Change in Soil Bacterial Communities

The soil bacterial community is under the constant influence of its environment. Changing any of the factors affecting the bacterial community will induce a selection pressure which, with time, will change the community. In this work the effect of changing the temperature or pH on the soil bacterial community was studied. Measurements using the [3H]-thymidine incorporation technique showed that th