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EMBRYONIC GLIA AND FOREBRAIN NEUROGENESIS; in vitro generation and differentiation of telencephalic neurons

The current thesis is aimed to increase our understanding of the generation and differentiation of telencephalic neurons, with emphasis on the role of glial cells in these processes. Using in vitro methods we have studied the role of glial cells in neurogenesis, inheritance of genetic regional specification, and influence on differentiation of neurons. We demonstrate that expanded cell cultures ex

Improvement of Wastewater Sludge Digestion

The reduction of sludge volumes for disposal is a topic of high interest for wastewater treatment plants (WWTP) all over the world. Steadily increasing volumes for disposal create an economic, environmental, legislative and technological challenge. Researchers and process developers try to minimise the sludge during its genesis or in the downstream treatment. Due to rising costs and scarcity of fo

Studies on streptococcal M proteins. Interactions with IgA and human complement regulators

The human pathogenic bacterium Streptococcus pyogenes (group A Streptococcus) expresses several different virulence factors. Of these, the M protein is regarded as one of the most important, because it confers resistance to phagocytosis, allowing the bacterium to multiply in blood. A remarkable property of M proteins is their ability to bind different human plasma proteins, in partic

On the estimation of ligand binding affinities

A method to accurately estimate the binding affinity of a small molecule to a receptor would be indispensable in numerous fields. For instance, most drugs exert their action by binding to a macromolecule target. Thus, a lot of time and resources could be saved in drug design by predicting affinities by computer programs. In a series of 15 papers, we have tested, compared, and improved the most p

Effects of polyamine pool manipulation on genes expressed during the cell cycle

The polyamines - putrescine, spermidine and spermine - are polycations found within cells. They have been shown to be essential for optimal cell proliferation and cell survival. Cells maintain their polyamine levels in a well-regulated system involving biosynthesis, catabolism and uptake/excretion. The biosynthetic enzymes - ornithine decarboxylase (ODC) and S-adenosylmethionine decarboxylase (Ado

Macrophages, Nitric oxide synthases and Heme oxygenases: possible roles during peripheral nerve regeneration

The purpose of this study was to investigate the suggestions that macrophages, and the systems generating nitric oxide (NO) and carbon monoxide (CO), i.e. nitric oxide synthases (NOS) and heme oxygenases (HO), could be important for peripheral nerve regeneration. Immunocytochemistry was used to visualise invading and resident macrophages, inducible NOS (iNOS), two isoforms of HO (HO-1 and HO-2),

Identification of Arthritis Regulating Genes in Rats

The immune response is designed to protect the body from harmful microbial invasions. However, when the immune system attacks itself instead, an autoimmune reaction starts that damage our own cells, tissues and organs. Despite decades of research concerning the etiology of autoimmune diseases the molecular mechanisms of these disorders are poorly understood as they are complex and influenced by bo

Extraction of PCBs from Sediments: Towards Bioavailability Assessment Based on Supercritical Fluid Extraction

Persistent organic pollutants (POPs) pose serious threats to our global environment. These compounds have high chemical and biological stability and they are also very lipophilic. These characteristics not only render POPs the ability to spread widely and pollute remote areas, they also make them prone to accumulate in adipose tissues of living organisms. Consequently, it is important to monitor P

Burns in Zimbabwe. Epidemiology, Immunosuppression, Infection and Surgical Management

Background: The burden of burn injuries is in developing countries, the majority of deaths (98%) related to fire burns are in developing countries.These injuries are associated with poverty and are mainly related to accidents with fires in the home environment. Aims: The aims of the thesis were to record the risk factors, causes, magnitude and outcome of burn treatment as well as establish circums

Escalation: Explorative studies of high-risk situations from the theoretical perspectives of complexity and joint cognitive systems

The main aim of the research is to explore different aspects of organisational resilience in escalating situations, with an investigation of both theoretical and practical implications. From the platform of an explorative approach, this study makes use of naturalistic research in the domain of health care and experimental simulation studies, in order to establish a broad theoretical framework vis-

Insights into breast cancer: New familial patterns and identification of a potential predictive marker

The last proportion of heredity in breast cancer has proven to be somewhat elusive despite massive attempts to identify the associated factors. Approximately 50 percent of breast cancer caused by familial factors is currently explained. The five-year survival for breast cancer patients is excellent; however, breast cancer is considered a chronic disease, and given enough time, new tumors can devel

A systematic approach to improving pharmacotherapy in the elderly

The aim of this thesis was to investigate whether a structured and systematic approach on improving pharmacotherapy in the elderly (the LIMM-model) would lead to a more appropriate and accurate drug use in the elderly. The elderly use many drugs and are more prone to suffer from adverse drug reaction. It is therefore important to address the quality of their drug therapy. The first study presente

Radioimmunotherapy of Metastatic Disease - Studies of Alpha- and Beta-particle-Emitting Radionuclides in a Preclinical Model

In radioimmunotherapy, monoclonal antibodies (mAbs) are used as a targeting agent carrying a toxic payload consisting of radionuclides. This treatment allows the irradiation of small lesions, even on the microscopic level. In the present work, two radionuclides with different properties were used. Lutetium-177 (177Lu) is a beta-particle-emitting radionuclide (t½=6.7 days) and astatine-211 (211At)

Targeting the hematopoietic stem cell to correct osteopetrosis

This thesis focuses on developing stem cell targeted gene therapy for the severe hereditary disorder Infantile Malignant Osteopetrosis (IMO) as well as increasing the understanding of how the genetic defect present in IMO affects the hematopoietic stem cells and hematopoiesis in general. IMO is a rare congenital disorder associated with an increased number of non-functional osteoclasts and the a

Neurogenesis from Neural Stem Cells, Ependymal Cells and Fibroblasts

Stroke is a major cause of death and disability around the world. Stroke leads to loss of neurons and also other cells in the brain due to lack of blood supply. Currently no therapies are available to treat stroke-related disability. It has been shown that stroke leads to increased neurogenesis, birth of new neurons, within the brain. This increased neurogenesis is not sufficient to restore lost f

PET in the evaluation of head and neck cancer treatment - management of the neck

The treatment for head and neck squamous cell carcinoma (HNSCC) is surgery or (chemo)radiotherapy +/- surgery. Side effects related to therapy are long lasting and adversely affects quality of life. The incidence of oropharyngeal cancer is increasing and patients commonly present an advanced tumour stage with neck metastases at the time of diagnosis. The treatment protocol previously comprised rad

Gene-environment interactions for arsenic metabolism and metal-related oxidatively generated DNA damage

Over 100 million people around the world are exposed to high concentrations of arsenic (As) in drinking water, associated with a number of adverse health effects such as skin, lung and bladder cancer, vascular diseases and diabetes. In humans, As is metabolized via alternating reduction and methylation reactions, from inorganic As (iAs) into monomethylated (MMA) and dimethylated As (DMA). The most

Preterm intraventricular haemorrhage - Effects of extracellular haemoglobin

Intraventricular haemorrhage (IVH) is the most common brain lesion in preterm infants and is most commonly seen in the sickest children, with 15-20% of very preterm infants developing IVH. The mortality of infants with severe IVH is 20-50 % in the neonatal period and over 50 % of surviving infants develop post-haemorrhagic ventricular dilatation (PHVD) and 40-80 % develop severe neurological impai

Redistribution of moisture and ions in cement based materials

There were two principal objectives for this thesis. The first was to develop a methodology and evaluation model of moisture redistribution in order to make the future relative humidity in a screeded concrete slab predictable. The second objective was to develop a method to determine the critical humidity for ion transport in concrete. Residual moisture in screeded concrete slabs may be redistrib

Integrating fluvial processes into the global Si cycle

Silicon (Si) is ubiqutious in natural waters as dissolved silica (DSi) and is used as a nutrient by many plant and animal species. DSi ultimately derives from the weathering of silicate minerals, a process which also consumes atmospheric CO2 and couples the silicon and carbon cycles. These processes, among others, impart observable fractionations to the stable isotopes of silicon, which makes the