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Malaria is a serious disease that causes around 800 000 deaths per year. Current malaria control efforts are hampered by the widespread resistance to common antimalarial drugs, such as the 4-aminoquinoline derivative called chloroquine. Previous research has shown that specific modifications of chloroquine, including inclusion of organometallic fragments into the organic framework, can result in c
Ferrochelatase catalyses the terminal step in heme biosynthesis by inserting a ferrous ion into protoporphyrin IX. The reaction mechanism has in this thesis been studied by mainly crystallographic methods. The structure of ferrochelatase from Bacillus subtilis co-crystallized with N-methyl mesoporphyrin allowed for the first time a characterization of the active site of the enzyme. The structure
Endocrine cells as well as neurons release their hormones and transmitters by regulated exocytosis. In the pancreatic B-cell, stimuli like glucose initiate biochemical and electrical processes that culminate in influx of Ca2+, which then triggers exocytosis of insulin-containing granules. Fusion of the secretory vesicles occurs rapidly upon Ca2+-influx but requires a granule to be ?primed? by an A
This thesis is based on work trying to understand the normal and pathological interactions taking place between the immune system and cartilage, specifically involving the cartilage-specific protein typ II collagen (CII). The work has been carried out in an experimental model of rheumatoid arthritis namely collagen type II induced arthritis (CIA) in mice. CIA can be triggered in mice of certain MH
Transplantation antigens encoded in the major histocompatibility complex (MHC) bind peptides and present them to T cells. We showed that mouse T cells expressing transgenic human CD8 can recognise human MHC class I. Expression on mature T cells is sufficient for activation in a mixed lymphocyte culture but expression both on thymocytes and mature T cells is necessary for peptide specific MHC restr
The work presented in this thesis covers how laser-induced fluorescence (LIF) and photofragmentation laser-induced fluorescence (PF-LIF) can be used to determine quantitative species concentrations in different combustion environments. To attain species concentrations with LIF it is of vital importance to investigate the influence of collisional quenching on the fluorescence signal strength, which
Total hip replacement (THR) is a common procedure, generally performed in elderly persons. Previous studies indicated that the use of isoxazolyl penicillins could induce a transient post-operative renal dysfunction in these patients. By measuring urinary levels of markers for glomerular (albumin, IgG) and tubular (protein HC) function we studied the influence of systemic cloxacillin, the gentamic
Large areas of grazed, species rich semi-natural grassland were lost in Europe during the last two centuries and as a consequence led to decreases in grassland specialist species. Therefore, today the “restoration” of grassland on previously arable fields is recommended for the protection of grassland specialists. Even “substitute habitats” for lost grasslands are discussed as temporary alternativ
The brain-derived protein S100B is a 21 Kda dimerand have been used as a serum marker for brain damage of different etiology. The feasability of protein S100B as serum marker for brain damage after cardiac surgery was studied in this thesis. One unexpected finding was made, which changed the basis for interpration of S100B levels. Shed blood collected during surgery with cardiotomy suction contain
The aim of the this thesis was surface modification of a biomedical polyurethane (PUR), Pellethane 2363-80AE*, to improve the biocompatibility. Surfaces modified by poly(ethylene oxide) (PEO) were prepared either by grafting PEO covalently at the PUR surface by a two-step reaction, or by using amphiphilic polymers containing PEO as the hydrophilic part. The amphiphilic polymers consisted of one co
In the first part of the PhD work, small chemical entities (fragments) found to inhibit human dihydroorotate dehydrogenase (DHODH), were chemically optimized. As part of an ample program at Active Biotech to find new drugs against autoimmune diseases, expanded fragments were repeatedly designed, synthesized and evaluated in a human DHODH assay. Potent inhibitors were identified within three classe
The purpose of this study was to investigate how total body protein and its fraction of body weight (body protein fraction) change in cancer patients during different anti-tumor treatments, and to see if these changes have any clinical significance in the form of prognostic value or correlation with disease course and tumor response. In 84 patients, 28 with lung cancer, 24 with gastrointestinal t
Beginning with the notion that spatial and material qualities of architecture set limits and create conditions for how we make use of it, the overall aim and ambition of this thesis is to develop this notion and to contribute to a deeper understanding of the relationships that are produced between the materiality of architecture and a bodily appropriation of it. To investigate this the thesis esta
Chromoendoscopy, endoscopic tissue staining, is an adjunctive method using chemical agents applied to the mucosal surface in order to aid gastrointestinal endoscopic diagnosis and therapy. Acid producing mucosa in the GI tract may be visualized endoscopically by Congo red staining in combination with stimulation of gastric acid production. Congo red is a reactive indicator dye that changes color f
Interest in sustainable development has increased throughout society during the past decades, and the chemical industry is no exception. The appeal for renewable raw materials has consequently increased and has paved the way for the implementation of industrial biotechnology. Since enzymes are used to convert biomass in nature, they may also be a good choice in the chemical industry. However, to i
Neuroblastoma is a tumor of sympathetic nervous system derivation, mostly afflicting young children. This thesis is focused on a group of receptor proteins for neurotrophic factors, the Trk family, and on N-Myc, a transcription factor, all important in the formation of the sympathetic nervous system as well as in determining neuroblastoma patient outcome. Expression of trkA and trkC is linked to f
Antibody-based microarrays are among the novel class of rapidly evolving proteomic technologies. In recent years, antibody microarrays have emerged as a unique tool for high-throughput protein expression profiling with great promise within biomedicine and a wide range of potential applications, including disease diagnostics and biomarker discovery. In order to evolve the technology from small dedi
Aquaporins constitute a class of membrane proteins that create pores through the lipid bilayer of biological membranes, facilitating the passage of water and other small solutes. Nearly all living organisms possess a more or less intricate set up of aquaporin proteins and the importance of these channels has been implicated in many aspects of health and disease. The aim of the projects summarized
Wilms’ tumor gene 1 (WT1) is a zinc-finger transcription factor that is involved in the development of urogenital organs and mesothelial tissues. It was initially identified as a tumor suppressor gene, based on the observation that somatic inactivation of the gene predispose for development of the pediatric kidney cancer Wilms’ tumor. A role for WT1 in hematopoiesis was suggested based on the fact
This thesis dealswith the field of high-energy particle physics. It ismainly concernedwith two issues: the “renormalization of effective field theories” and the “detection of hidden sectors”. The first two papers are dedicated to the renormalization issue while the second two deal with the hidden sectors. Renormalization is crucial when one calculates physical observables to a high degree of preci
