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NMR STUDIES ON STRUCTURE AND DYNAMICS OF TWO-DOMAIN PROTEINS

The general objective of the present thesis work was to examine 3-dimensional structure as well as the motional properties of two different types of two-domain proteins by solution-state NMR. One of the major tasks of this thesis work was to investigate the domain orientation of these molecules by employing residual dipolar couplings (RDC) which can be used as orientational restraints for increasi

Regulatory mechanisms controlling T cell activity

This thesis is based on work studying the immunoregulatory mechanisms that govern the balance between activation and inactivation of T lymphocytes. Most of the work has been carried out in an experimental system using a T cell receptor (TCR-Vb3) transgenic mouse strain to obtain a homogenous T-cell population and utilizing the properties of bacterial superantigens to induce T cell responses and un

HIV-2 infection in Guinea-Bissau, West Africa, with special reference to clinical, immunological and epidemiological aspects

We have followed a cohort of police officers in Guinea-Bissau between 1990 and 1997 for the study of clinical, immunological and epidemiological aspects of HIV-2 infection. Initially the prevalence of HIV-2 was high (11.6 %) and HIV-1 infection was rare (0.4 %), but over the study period the prevalence of HIV-1 increased significantly whereas the incidence of HIV-1 was relatively stable. For HIV-2

The significance of urokinase-type plasminogen activator (u-PA) in tumour growth and Linomide-induced upregulation of u-PA's endogenous inhibitor PAI-2

The progressive process of tumour invasion and generation of metastases is the primary cause of death for most patients with cancer. Some of the regulatory components of this progressive process are adhesion, migration, and proteolysis. Urokinase -type plasminogen activator (u-PA) is a serine protease associated with tissue remodelling, cellular invasiveness, matrix degradation, angiogenesis, and

Estimation in Binary Choice Models with Measurement Errors

In this paper we develop a simple maximum likelihood estimator for probit models where the regressors have measurement error. We first assume precise information about the reliability ratios (or, equivalently, the proxy correlations) of the regressors. We then show how reasonable bounds for the parameter estimates can be obtained when only imprecise information is available. The analysis is also e

Towards a minimal argument structure

In this paper I give a short presentation of a syntactic approach to argument structure, taking a particular implementation of the minimalist framework (Chomsky (1995, 2001 and later)) as my point of departure. The proposed account allows for only 16 different argument structures, thereby reducing the syntactic variation at this level of syntax considerably. The theory also offers an explanation w

Molecular and clinical studies of cartilage and bone macromolecules in arthritis

The pathogenesis of inflammatory arthritides include synovial inflammation and joint tissue destruction. Tissue destruction has traditionally been regarded a consequence of inflammation, but recent observations indicate that the processes are not always closely linked and may proceed uncoupled. The ultimate target organs for the destructive process are articular cartilage and bone. This thesis f

The regulation of factor Va activity by activated protein C -Importance of the individual activated protein C cleavage sites in factor Va

The subject of this thesis is the activated protein C (APC)-mediated inactivation of factor Va. The activated form of factor V (FVa) is a procoagulant cofactor for Factor Xa (FXa) in the conversion of prothrombin to thrombin. The procoagulant function of FVa is down regulated by APC through proteolytic cleavage at three sites, Arg306, Arg506 and Arg679. The cleavage at Arg506 is kinetically favore

Biodiversity in Agricultural Landscapes: Landscape and Scale-Dependent Effects of Organic Farming

Declines in the distribution and abundance of many farmland species during recent decades have been attributed to agricultural intensification. Agri-environment schemes are commonly used in Europe to reduce this loss of farmland biodiversity, but their effectiveness may depend on several external factors. In this thesis, I have used one such scheme, organic faming, as a landscape scale experiment

Alpha-1-microglobulin, heme-binding protein, reductase and antioxidant

This thesis describes structural and functional studies of alpha-1-microglobulin (a1m), a 26 kDa plasma and tissue protein that is evolutionarily well-conserved and belongs to the lipocalin superfamily. The lipocalins are polypeptides of 160-190-amino acids that are folded into an 8-stranded beta-barrel forming a pocket with a hydrophobic interior. a1m carries heterogeneous yellow-brown chromophor

FROM SERUM TO TISSUE: GALECTIN-BINDING GLYCOFORMS OF SERUM GLYCOPROTEINS AS FUNCTIONAL BIOMARKERS

Galectins are small soluble proteins defined by a conserved sequence motif that forms a defining β-galactoside binding site shared among galectins; adjacent binding sites give each galectin a unique fine specificity for a specific subset of galactose containing glycans. A wealth of data now suggests important roles of galectins in both cancer and inflammation. The aim of this project is to get a c

CELL REPLACEMENT THERAPY FOR PARKINSON’S DISEASE: The importance of neuronal subtype, cell source and connectivity for functional recovery

Parkinson’s disease (PD) is a neurodegenerative disorder characterised by motor deficits such as slowness in movement, difficulty in initiating movement and tremor at rest. The cause of these motor symptoms is the selective loss of mesencephalic dopaminergic (mesDA) neurons, located in the substantia nigra (SN). These neurons project axons to the striatum where they release dopamine, a neurotransm

Metal-on-metal joint bearings and hematopoetic malignancy A review

This is a review of the hip arthroplasty era. We concentrate on new metal bearings, surface replacements, and the lessons not learned, and we highlight recent reports on malignancies and joint implants. A low incidence of blood malignancies has been found in bone marrow taken at prosthetic surgery. The incidence is increased after replacement with knee implants that release very low systemic level

Molecular Characterization of Male Breast Cancer

Cancer is today a major healthcare problem worldwide. There are many forms of cancer, which is a genetic disease, believed to result from a multistep process with genetic and epigenetic changes accumulating over time. Breast cancer is one of the most common forms of cancer in women, while it is much more rare in men. Male breast cancer (MBC) exhibits both similarities and differences with female b

Belling the cat: Eli F. Heckscher on the gold standard as a discipline device

Unlike Knut Wicksell, Eli Heckscher did not believe the time had arrived for “managed money” to replace the gold standard after World War I. The war had shown that only a gold standard could bind the central bank to a time-consistent policy with reasonable price stability. Heckscher likened the problem of reinstating the gold standard to “Belling the cat” in Aesop’s fable. When the international g