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Regulation of cellular growth and identification of stromal gene signatures in breast cancer

Normal tissue is tightly controlled to keep a balance between reproduction and elimination of cells. In cancer, these regulated processes are disrupted, resulting in uncontrolled cell growth. Regulation of RNA stability and turnover is important to maintain cellular homeostasis and can be controlled by various mechanisms. During stress, the cell can form cytoplasmic complexes of proteins and RNAs,

Gas exchange with a reflecting system for inhalational anaesthesia

In order to reduce comsumption of inhalational anaesthetsics during high flow anaesthesia a system open in regard to oxygen, nitogen and nitrous oxide, but closed to inhalational anaesthetics, was developed. This was achieved by a reflecting filter for inhalational anaesthetics made of active carbon. The principle has been developed into the commersially available Anesthetic Conserving Device (ACD

Midkine - a host defence protein

Every day we encounter many potentially harmful microbes in our environment. The epithelial linings constitute an anatomical barrier protecting us and they also produce antimicrobial polypeptides (AMPs) that act as a chemical barrier. These AMPs are small and positively charged, killing a broad range of microbes rapidly. They can either be constitutively produced or rapidly induced when epithelial

Pancreatic Cancer - Early Detection, Prognostic Factors, and Treatment

Background: Pancreatic cancer is the fourth leading cause of cancer-related death. Only about 6% of patients are alive 5 years after diagnosis. One reason for this low survival rate is that most patients are diagnosed at a late stage, when the tumor has spread to surrounding tissues or distant organs. Less than 20% of cases are diagnosed at an early stage that allows them to undergo potentially cu

Molecular Epidemiology of Breast Cancer

Hereditary breast cancer constitutes a considerable fraction of the total number of breast cancer cases occurring each year. Up until recently very few breast cancer predisposing genes were known, but many new common polymorphisms contributing to increased cancer susceptibility are continuously being identified. This thesis has focused on familial breast cancer and identifying as well as investi

Cryptanalysis of Selected Stream Ciphers

The aim of this dissertation is to show some cryptanalytical results on a selection of stream ciphers. We have grouped theory and results into three main parts. The first part focuses on the FCSR-based constructions X-FCSR and F-FCSR-H v3. For the X-FCSR family of stream ciphers we perform a severe state recovery attack. This attack works for both X-FCSR-128 and X-FCSR-256. We then develop a gen

Mechanistic studies on the role of extracellular vesicles in the tumor microenvironment

The transition from normal into malignant cells with acquired uncontrolled growth is a process where cancer cells viciously develop adaptive strategies to overcome microenvironmental and metabolic stress. Hypoxia, or deficient oxygen supply, is a common feature of the expanding tumor which alters cell metabolism and consecutively causes lowered intracellular pH. To alleviate hypoxic and acidotic s

Changes in gene expression during delayed neuronal death after cerebral ischemia in the rat

After transient global cerebral ischemia, selected populations of neurons in the brain will die after a period of 2-3 days, a phenomenon termed delayed neuronal death. This is of clinical importance as delayed neuronal death has been found to occur in humans as well. The mechanism that kills a neuron 2-3 days after the initial insult is unclear, but transcriptional steps have been implicated. The

Histamine receptors and neuropeptides in the cranial circulation

The sensory neuropeptides substance P (SP) and calcitonin gene-related peptide (CGRP) are present in human cerebral, meningeal and temporal arteries, as are peptides associated with the sympathetic (neuropeptide Y, NPY) and parasympathetic (vasoactive intestinal peptide, VIP) nervous system. NPY is a vasoconstrictor in cerebral and meningeal arteries and potentiates noradrenaline (NA) as a vasocon

Experimental and Clinical Studies of SLPI, with Special Reference to IgE-Mediated Allergic Reactions

In this study we demonstrated the production of SLPI (Secretory Leukocyte Protease Inhibitor) in serous glands in the nasal mucosa. We have shown that the pattern of the expression of mRNA corresponds to the encoded protein. The encoded protein was detected by immunohistochemical methods and mRNA was discovered by in situ hybridisation. Nasal mucosa from 11 test subjects without atopic disposition

III–V Nanowire Surfaces

This dissertation deals with the geometric and electronic structure of surfaces on III–V semiconductor nanowires (NWs). NWs made of InAs, GaAs, and InP have been studied using scanning tunneling microscopy/spectroscopy (STM/S), low energy electron microscopy (LEEM), photoemission electron microscopy (PEEM), and x-ray photoelectron spectroscopy (XPS). All of the mentioned techniques have been devel

The Psychology of Worldviews : Toward a Non-Reductive Science of Personality

Persons are not just mechanical systems of instinctual animalistic proclivities, but also language-producing, existentially aware creatures, whose experiences and actions are drenched in subjective meaning. To understand a human being as a person is to understand him or her as a rational system that wants, fears, hopes, believes, and in other ways imbues the world with meaning, rather than just a

Studies on myeloid differentiation: cytokine influence and identification of a novel marker gene

Hematopoiesis is a highly complex process by which a range of specialized blood cells are generated from a small pool of multipotent stem cells in the bone marrow. The survival, proliferation, and differentiation of hematopoietic stem cells are tightly regulated by both soluble and membrane-bound cytokines produced within the bone marrow microenvironment. Kit Ligand (KL) and Flt3 Ligand (FL) are t

Distribution and Effects of NO and CO in the Human Upper Respiratory Tract

Mucosal inflammation and airway hyperreactivity are regulated by hundreds of different mediators. The recent discovery of gaseous mediators, produced and active within the airways, opens new possibilities for identification of therapeutic targets and ways to monitor airway inflammation. This thesis is focused on two such mediators, nitric oxide (NO) and carbon monoxide (CO) along with their role i

Quality Control for high-throughput Quantitative Proteomics - Harnessing the potential of label-free LC-MS

Multiplex protein quantification, proteomics, is essential for uncovering new biomarkers and understanding biology. Liquid chromatography coupled to mass spectrometry (LC-MS) is the predominant technique for these measurements. In this thesis, optimization and quality control strategies for different phases of the LC-MS pipeline have been developed. Due to the inherent complexity and dynamic rang

A Theory of Architectural Objects to support Design Configuration

The thesis presents the results from a research project targeting architectural design and house-building in a setting of industrialized design process and product platforms. During the early stages of a traditional design process, architects manage a degree of problem complexity, besides technical aspects, also includes user function, material, environment, aesthetics etc. As a result of the des

Glacial geology and palaeo-ice dynamics of two ice-sheet margins, Taymyr Peninsula, Siberia and Jameson Land, East Greenland

The North Taymyr ice-marginal zone (NTZ) on the Taymyr Peninsula, Arctic Siberia and the Ugleelv Valley on Jameson Land, East Greenland, have been investigated with the aim of reconstructing the glacial history, including depositional processes and environments. Geomorphological, sedimentological, stratigraphical and remote sensing methods have been combined to give a comprehensive view of develop

Microvascular inflammatory response in the skin

This thesis examines the microvascular inflammatory response in the skin. The microvascular response includes vasodilatation and plasma exudation. In the first three studies, the combined response was measured in guinea pig skin with a technique based on detection of radiolabelled protein. Transferrin was labelled in vivo by injection of 113mIn and the conversion electrons detected over the skin u

Role of cyclin D1 as an estrogen receptor cofactor and the influence of hypoxia on estrogen receptor regulation, with focus on prognositic and treatment predictive features in breast cancer

Estrogen receptor (ER) status can define breast cancer patients who would benefit from adjuvant tamoxifen therapy. However, resistance to tamoxifen is often observed and possible mechanisms may be loss or reduction of ER, dysfunctional ER- signaling and ligand independent activation of the receptor. Hypoxia and hypoxia inducible factor-1? (HIF-1) expression has been correlated to loss of ER in bre

Genomic analysis of primary and metastatic malignant melanoma

“Cutaneous melanoma is a most unpredictable lesion” wrote Alexander Breslow in 1970. He was one of the first to predict outcome in melanoma patients, based on the thickness of the primary tumor, and today this parameter bears his name and remains the main prognostic factor in melanoma. The aim of this thesis has been to contribute to the understanding of melanoma biology in order to make this canc