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Development of Computational Methods for Cancer Research: Strategies for closing the feedback loop in omics workflows

As the ultimate workhorses of the living things, proteins undergo significant regulatory activity throughout the lifetime of a cell or an organism. Many complex diseases effect the protein composition, expression or modification in the cells or tissues they arise in. It is then no surprise that proteomics is a field full of promise, one which is expected to generate significant insights towards fu

Chromosomal Instability and Genomic Amplification in Bone and Soft Tissue Tumours

Acquired genetic abnormalities are found in all types of malignant tumours and may contribute to neoplastic processes by altering protein structure or dosage. Many bone and soft tissue tumours (BSTT) are characterised by complex patterns of chromosome changes, including extensive intratumour heterogeneity and amplification of DNA sequences. The results presented in this thesis demonstrate that the

Hormone-Sensitive Lipase and the Pancreatic Beta-Cell

Hormone-sensitive lipase (HSL) is a key enzyme in fatty acid mobilization. It is acutely regulated by extracellular signals via reversible phosphorylation. In the recent past, the focus of type 2 diabetes research has moved towards the lipid component. Lipids interfere with glucose homeostasis in a multitude of ways; they can decrease insulin sensitivity of tissues and cause β-cell dysfunction. Co

Causes and consequences of blood parasite infections in birds

Parasites are ubiquitous and can cause significant fitness reductions to their hosts. Therefore, selection for the evolution of host resistance should be strong. However, resistance may be costly and should be traded-off against other fitness related traits. Parasites could therefore have a significant impact on the evolution of fitness related characters of their hosts. It has been suggested that

Probiotics and berry-associated polyphenols: catabolism and antioxidative effects

Oxidative stress can cause damage to DNA, proteins and lipids and is associated with inflammation and various human diseases as cancer, atherosclerosis, and autoimmune diseases. Polyphenol-rich diet, such as fruits and berries, may act as antioxidants and prevent oxidative stress and, thereby, associated diseases. Administration of lactic acid bacteria (LAB) can affect the microflora in the gastro

Suicide in Severe Depression: A Longitudinal Case-Control Study

Suicide in Severe Depression. A Longitudinal Case-Control Study. The present thesis is based on a case-control study of suicide victims with a severe depression/ melancholia. All patients admitted to the Department of Psychiatry 1956-1969 who received this diagnosis on a multiaxial schedule (1206 patients) were followed up in two sessions to 1984 and to 1998 concerning suicide and general mortali

Neurohormonal Modulators in the Parathyroid Gland. Localization and regulation.

The occurrence and distribution of neurohormonal peptides, neuroendocrine markers and receptors in parathyroid nerve fibers and endocrine cells are described, using immunocytochemistry, in situ hybridization, image analysis and reverse transcriptase polymerase chain reaction. Immunocytochemical studies revealed that parathyroid glands of chicken, rat, guinea-pig, cat, dog and sheep contained adren

Attenuation correction in pulmonary and myocardial single photon emission computed tomography.

The objective was to develop and validate methods for single photon emission computed tomography, SPECT, allowing quantitative physiological and diagnostic studies of lung and heart. A method for correction of variable attenuation in SPECT, based on transmission measurements before administration of an isotope to the subject, was developed and evaluated. A protocol based upon geometrically well de

On the Challenges for Time-of-Flight Electron Spectroscopy at Storage Rings

Time-of-flight (TOF) techniques for energy analysis have been common in electron spectroscopy for many decades. TOF-based electron spectrometers benefit from higher transmission and information rate compared to their main competitor: the hemispherical analyser; the drawback being their lower energy resolution. However, the advent of angle-resolved TOF spectrometers for electron energy analysis cha

Advances and Applications of Antibody Arrays - Proteomic Profiling of Pancreatic Disease

Recombinant antibody microarrays have advanced into indispensable tools for large-scale, high-throughput multiplexed serum proteomics. This thesis, based upon five original papers, deals with the development of an in-house designed antibody microarray platform, and its applications for serum profiling of pancreatic disease. Pancreatic cancer is the 4th deadliest cancer, with a 5-year survival rat

Echocardiography/Doppler for the evaluation of coronary artery function, left ventricular function and the relationship between early diastolic and systolic function

Two specific areas of development in echocardiography are assessment of left ventricular (LV) diastolic function and myocardial ischemia. This thesis describes echocardiographic methodology in these two areas. In the first study, two new echocardiographic methods, the early diastolic flow propagation velocity (Vp) and the early diastolic atrioventricular plane downward slope (EDS), were tested as

Radiography and bone scintigraphy in osteoarthritis of the knee: comparison with MR imaging

The aim was to compare radiography of the tibiofemoral joint (TFJ) and the patellofemoral joint (PFJ), as well as bone scinigraphy with MR imaging in middle-aged individuals with chronic knee pain in the format of a prospective study of knee osteoarthritis. Individuals aged 35-54 years with chronic knee pain were identified. The prevalence of chronic knee pain was 15% (279/2000). Within this grou

Protein kinase C epsilon and neurite outgrowth

Protein kinase C (PKC) is a serine/threonine kinase family with 10 identified isoforms. The contribution of PKC isoforms to cell growth and differentiation, with focus on neurite outgrowth, was investigated, using neuroblastoma and immortalised neural cells as model systems. In neuroblastoma cells one or several of the classical PKC isoforms are of importance for driving proliferation, protecting

FOXC2 and CAPN10 as candidate genes for obesity, insulin resistance and type 2 diabetes

The worldwide prevalence of obesity and type 2 diabetes is increasing rapidly. Both disorders depend on genetic and environmental factors. The studies included in this thesis investigated the possible association of the FOXC2 and CAPN10 genes with obesity, insulin resistance, type 2 diabetes, and related phenotypes. FOXC2 encodes a forkhead transcription factor, which was identified as a key regul

Basic Body Awareness Therapy , assessment, treatment and interaction

The purpose of the present thesis was to investigate Basic Body Awareness Therapy (Basic BAT) in psychiatric outpatient care and the BAS-H, an assessment method for analysing movements and movement behaviour. Important factors in the interaction, therapeutic relationship and working alliance between patient and physiotherapist (PT) were also explored. The results revealed the construct validity of

Contact activation on bacterial surfaces - a virulence mechanism

Life-threatening conditions from bacterial infections are a major clinical problem. During a severe infection, the host responds by a massive release of pro-inflammatory mediators together with a systemic activation of systems such as the coagulation, fibrinolytic, and complement systems. These events could result in the development of complications such as disseminated intravascular coagulation a