The Role of Oxidative Stress in Environmental Responses of Fennoscandian Animals

All aerobic organisms have to deal with the toxicity of oxygen. Oxygen enables more efficient energy production compared to anaerobic respiration or fermentation, but at the same time reactive oxygen species (ROS) are being formed. ROS can also be produced by external factors such as UV-radiation and contamination. ROS can cause damage to biomolecules such as DNA, lipids and proteins and organisms try to keep the damage as small as possible by repairing biomolecules and metabolizing ROS. All ROS are not harmful, because they are used as signaling molecules. To cope against ROS organism have an antioxidant (AOX) system which consists both enzymatic and non-enzymatic AOX defense. Some AOX are produced by the organism itself and some are gained via diet. In this thesis I studied environmentally caused changes in the redox regulation of different wild vertebrate animals to gain knowledge on the temporal, spatial and pollution-derived-effects on the AOX systems. As study species I used barn swallow, ringed seal and the Baltic salmon. For the barn swallow the main interest was the seasonal fluctuation in the redox regulation and its connection to migration and breeding. The more contaminated ringed seals of the Baltic Sea were compared to seals from cleaner Svalbard to investigate whether they suffered from contaminant induced oxidative stress. The regional and temporal variation in redox regulation and regional variation in mRNA and protein expressions of Baltic salmon were studied to gain knowledge if the salmon from different areas are equally stressed. As a comparative aspect the redox responses of these different species were investigated to see which parts of the AOX system are substantial in which species. Certain parts of AOX system were connected to breeding and others to migration in barn swallows, there was also differences in biotransformation between birds caught from Africa and Finland. The Baltic ringed seal did not differ much from the seals from Svalbard, despite the difference in contaminant load. A possible explanation to this could be the enhanced AOX mechanisms against dive-associated oxidative stress in diving air-breathing animals, which also helps to cope with ROS derived from other sourses. The Baltic salmon from Gulf of Finland (GoF) showed higher activities in their AOX defense enzymes and more oxidative damage than fish from other areas. Also on mRNA and proteomic level, stress related metabolic changes were most profound in in the fish from GoF. Mainly my findings on species related differences followed the pattern of mammals showing highest activities and least damage and birds showing lower activities and most damage, fish being intermediate. In general, the glutathione recycling-related enzymes and the ratio of oxidized and reduced glutathione seemed to be the most affected parameters in all of the species.

A modified nominal stress method for fatigue assessment of steel plates with thermally cut edges

Thermal cutting methods, are commonly used in the manufacture of metal parts. Thermal cutting processes separate materials by using heat. The process can be done with or without a stream of cutting oxygen. Common processes are Oxygen, plasma and laser cutting. It depends on the application and material which cutting method is used. Numerically-controlled thermal cutting is a cost-effective way of prefabricating components. One design aim is to minimize the number of work steps in order to increase competitiveness. This has resulted in the holes and openings in plate parts manufactured today being made using thermal cutting methods. This is a problem from the fatigue life perspective because there is local detail in the as-welded state that causes a rise in stress in a local area of the plate. In a case where the static utilization of a net section is full used, the calculated linear local stresses and stress ranges are often over 2 times the material yield strength. The shakedown criteria are exceeded. Fatigue life assessment of flame-cut details is commonly based on the nominal stress method. For welded details, design standards and instructions provide more accurate and flexible methods, e.g. a hot-spot method, but these methods are not universally applied to flame cut edges. Some of the fatigue tests of flame cut edges in the laboratory indicated that fatigue life estimations based on the standard nominal stress method can give quite a conservative fatigue life estimate in cases where a high notch factor was present. This is an undesirable phenomenon and it limits the potential for minimizing structure size and total costs. A new calculation method is introduced to improve the accuracy of the theoretical fatigue life prediction method of a flame cut edge with a high stress concentration factor. Simple equations were derived by using laboratory fatigue test results, which are published in this work. The proposed method is called the modified FAT method (FATmod). The method takes into account the residual stress state, surface quality, material strength class and true stress ratio in the critical place.

Life without Phd? – Phd Oxygen Sensor Proteins in Hypoxic Carcinoma Cell Survival

The microenvironment within the tumor plays a central role in cellular signaling. Rapidly proliferating cancer cells need building blocks for structures as well as nutrients and oxygen for energy production. In normal tissue, the vasculature effectively transports oxygen, nutrient and waste products, and maintains physiological pH. Within a tumor however, the vasculature is rarely sufficient for the needs of tumor cells. This causes the tumor to suffer from lack of oxygen (hypoxia) and nutrients as well as acidification, as the glycolytic end product lactate is accumulated. Cancer cells harbor mutations enabling survival in the rough microenvironment. One of the best characterized mutations is the inactivation of the von Hippel-Lindau protein (pVHL) in clear cell renal cell carcinoma (ccRCC). Inactivation causes constitutive activation of hypoxia-inducible factor HIF which is an important survival factor regulating glycolysis, neovascularization and apoptosis. HIFs are normally regulated by HIF prolyl hydroxylases (PHDs), which in the presence of oxygen target HIF α-subunit to ubiquitination by pVHL and degradation by proteasomes. In my thesis work, I studied the role of PHDs in the survival of carcinoma cells in hypoxia. My work revealed an essential role of PHD1 and PHD3 in cell cycle regulation through two cyclin-dependent kinase inhibitors (CKIs) p21 and p27. Depletion of PHD1 or PHD3 caused a cell cycle arrest and subjected the carcinoma cells to stress and impaired the survival.