Molecular Alterations in Asbestos-Related Lung Cancer

Background: Asbestos is a well known cancer-causing mineral fibre, which has a synergistic effect on lung cancer risk in combination with tobacco smoking. Several in vitro and in vivo experiments have demonstrated that asbestos can evoke chromosomal damage and cause alterations as well as gene expression changes. Lung tumours, in general, have very complex karyotypes with several recurrently gained and lost chromosomal regions and this has made it difficult to identify specific molecular changes related primarily to asbestos exposure. The main aim of these studies has been to characterize asbestos-related lung cancer at a molecular level. Methods: Samples from asbestos-exposed and non-exposed lung cancer patients were studied using array comparative genomic hybridization (aCGH) and fluorescent in situ hybridization (FISH) to detect copy number alterations (CNA) as well as microsatellite analysis to detect allelic imbalance (AI). In addition, asbestos-exposed cell lines were studied using gene expression microarrays. Results: Eighteen chromosomal regions showing differential copy number in the lung tumours of asbestos-exposed patients compared to those of non-exposed patients were identified. The most significant differences were detected at 2p21-p16.3, 5q35.3, 9q33.3-q34.11, 9q34.13-q34.3, 11p15.5, 14q11.2 and 19p13.1-p13.3 (p<0.005). The alterations at 2p and 9q were validated and characterized in detail using AI and FISH analysis in a larger study population. Furthermore, in vitro studies were performed to examine the early gene expression changes induced by asbestos in three different lung cell lines. The results revealed specific asbestos-associated gene expression profiles and biological processes as well as chromosomal regions enriched with genes believed to contribute to the common asbestos-related responses in the cell lines. Interestingly, the most significant region enriched with asbestos-response genes was identified at 2p22, close to the previously identified region showing asbestos-related CNA in lung tumours. Additionally, in this thesis, the dysregulated biological processes (Gene Ontology terms) detected in the cell line experiment were compared to dysregulated processes identified in patient samples in a later study (Ruosaari et al., 2008a). Commonly affected processes such as those related to protein ubiquitination, ion transport and surprisingly sensory perception of smell were identified. Conclusions: The identification of specific CNA and dysregulated biological processes shed some light on the underlying genes acting as mediators in asbestos-related lung carcinogenesis. It is postulated that the combination of several asbestos-specific molecular alterations could be used to develop a diagnostic method for the identification of asbestos-related lung cancer.

Mutations as molecular tools : The metabolic-rate dependent molecular clock and DNA barcoding of allied species

Mutation and recombination are the fundamental processes leading to genetic variation in natural populations. This variation forms the raw material for evolution through natural selection and drift. Therefore, studying mutation rates may reveal information about evolutionary histories as well as phylogenetic interrelationships of organisms. In this thesis two molecular tools, DNA barcoding and the molecular clock were examined. In the first part, the efficiency of mutations to delineate closely related species was tested and the implications for conservation practices were assessed. The second part investigated the proposition that a constant mutation rate exists within invertebrates, in form of a metabolic-rate dependent molecular clock, which can be applied to accurately date speciation events. DNA barcoding aspires to be an efficient technique to not only distinguish between species but also reveal population-level variation solely relying on mutations found on a short stretch of a single gene. In this thesis barcoding was applied to discriminate between Hylochares populations from Russian Karelia and new Hylochares findings from the greater Helsinki region in Finland. Although barcoding failed to delineate the two reproductively isolated groups, their distinct morphological features and differing life-history traits led to their classification as two closely related, although separate species. The lack of genetic differentiation appears to be due to a recent divergence event not yet reflected in the beetles molecular make-up. Thus, the Russian Hylochares was described as a new species. The Finnish species, previously considered as locally extinct, was recognized as endangered. Even if, due to their identical genetic make-up, the populations had been regarded as conspecific, conservation strategies based on prior knowledge from Russia would not have guaranteed the survival of the Finnish beetle. Therefore, new conservation actions based on detailed studies of the biology and life-history of the Finnish Hylochares were conducted to protect this endemic rarity in Finland. The idea behind the strict molecular clock is that mutation rates are constant over evolutionary time and may thus be used to infer species divergence dates. However, one of the most recent theories argues that a strict clock does not tick per unit of time but that it has a constant substitution rate per unit of mass-specific metabolic energy. Therefore, according to this hypothesis, molecular clocks have to be recalibrated taking body size and temperature into account. This thesis tested the temperature effect on mutation rates in equally sized invertebrates. For the first dataset (family Eucnemidae, Coleoptera) the phylogenetic interrelationships and evolutionary history of the genus Arrhipis had to be inferred before the influence of temperature on substitution rates could be studied. Further, a second, larger invertebrate dataset (family Syrphidae, Diptera) was employed. Several methodological approaches, a number of genes and multiple molecular clock models revealed that there was no consistent relationship between temperature and mutation rate for the taxa under study. Thus, the body size effect, observed in vertebrates but controversial for invertebrates, rather than temperature may be the underlying driving force behind the metabolic-rate dependent molecular clock. Therefore, the metabolic-rate dependent molecular clock does not hold for the here studied invertebrate groups. This thesis emphasizes that molecular techniques relying on mutation rates have to be applied with caution. Whereas they may work satisfactorily under certain conditions for specific taxa, they may fail for others. The molecular clock as well as DNA barcoding should incorporate all the information and data available to obtain comprehensive estimations of the existing biodiversity and its evolutionary history.

Ion channel gene variants predisposing to severe human ventricular arrhythmias

Congenital long QT syndrome (LQTS) with an estimated prevalence of 1:2000-1:10 000 manifests with prolonged QT interval on electrocardiogram and risk for ventricular arrhythmias and sudden death. Several ion channel genes and hundreds of mutations in these genes have been identified to underlie the disorder. In Finland, four LQTS founder mutations of potassium channel genes account for up to 40-70% of genetic spectrum of LQTS. Acquired LQTS has similar clinical manifestations, but often arises from usage of QT-prolonging medication or electrolyte disturbances. A prolonged QT interval is associated with increased morbidity and mortality not only in clinical LQTS but also in patients with ischemic heart disease and in the general population. The principal aim of this study was to estimate the actual prevalence of LQTS founder mutations in Finland and to calculate their effect on QT interval in the Finnish background population. Using a large population-based sample of over 6000 Finnish individuals from the Health 2000 Survey, we identified LQTS founder mutations KCNQ1 G589D (n=8), KCNQ1 IVS7-2A>G (n=1), KCNH2 L552S (n=2), and KCNH2 R176W (n=16) in 27 study participants. This resulted in a weighted prevalence estimate of 0.4% for LQTS in Finland. Using a linear regression model, the founder mutations resulted in a 22- to 50-ms prolongation of the age-, sex-, and heart rate-adjusted QT interval. Collectively, these data suggest that one of 250 individuals in Finland may be genetically predisposed to ventricular arrhythmias arising from the four LQTS founder mutations. A KCNE1 D85N minor allele with a frequency of 1.4% was associated with a 10-ms prolongation in adjusted QT interval and could thus identify individuals at increased risk of ventricular arrhythmias at the population level. In addition, the previously reported associations of KCNH2 K897T, KCNH2 rs3807375, and NOS1AP rs2880058 with QT interval duration were confirmed in the present study. In a separate study, LQTS founder mutations were identified in a subgroup of acquired LQTS, providing further evidence that congenital LQTS gene mutations may underlie acquired LQTS. Catecholaminergic polymorphic ventricular tachycardia (CPVT) is characterized by exercise-induced ventricular arrhythmias in a structurally normal heart and results from defects in the cardiac Ca2+ signaling proteins, mainly ryanodine receptor type 2 (RyR2). In a patient population of typical CPVT, RyR2 mutations were identifiable in 25% (4/16) of patients, implying that noncoding variants or other genes are involved in CPVT pathogenesis. A 1.1 kb RyR2 exon 3 deletion was identified in two patients independently, suggesting that this region may provide a new target for RyR2-related molecular genetic studies. Two novel RyR2 mutations showing a gain-of-function defect in vitro were identified in three victims of sudden cardiac death. Extended pedigree analyses revealed some surviving mutation carriers with mild structural abnormalities of the heart and resting ventricular arrhythmias suggesting that not all RyR2 mutations lead to a typical CPVT phenotype, underscoring the relevance of tailored risk stratification of a RyR2 mutation carrier.

Features of the geomagnetic field during the Holocene and Proterozoic

The geomagnetic field is one of the most fundamental geophysical properties of the Earth and has significantly contributed to our understanding of the internal structure of the Earth and its evolution. Paleomagnetic and paleointensity data have been crucial in shaping concepts like continental drift, magnetic reversals, as well as estimating the time when the Earth's core and associated geodynamo processes begun. The work of this dissertation is based on reliable Proterozoic and Holocene geomagnetic field intensity data obtained from rocks and archeological artifacts. New archeomagnetic field intensity results are presented for Finland, Estonia, Bulgaria, Italy and Switzerland. The data were obtained using sophisticated laboratory setups as well as various reliability checks and corrections. Inter-laboratory comparisons between three laboratories (Helsinki, Sofia and Liverpool) were performed in order to check the reliability of different paleointensity methods. The new intensity results fill up considerable gaps in the master curves for each region investigated. In order to interpret the paleointensity data of the Holocene period, a novel and user-friendly database (GEOMAGIA50) was constructed. This provided a new tool to independently test the reliability of various techniques and materials used in paleointensity determinations. The results show that archeological artifacts, if well fired, are the most suitable materials. Also lavas yield reliable paleointensity results, although they appear more scattered. This study also shows that reliable estimates are obtained using the Thellier methodology (and its modifications) with reliability checks. Global paleointensity curves during Paleozoic and Proterozoic have several time gaps with few or no intensity data. To define the global intensity behavior of the Earth's magnetic field during these times new rock types (meteorite impact rocks) were investigated. Two case histories are presented. The Ilyinets (Ukraine) impact melt rocks yielded a reliable paleointensity value at 440 Ma (Silurian), whereas the results from Jänisjärvi impact melts (Russian Karelia, ca. 700 Ma) might be biased towards high intensity values because of non-ideal magnetic mineralogy. The features of the geomagnetic field at 1.1 Ga are not well defined due to problems related to reversal asymmetries observed in Keweenawan data of the Lake Superior region. In this work new paleomagnetic, paleosecular variation and paleointensity results are reported from coeval diabases from Central Arizona and help understanding the asymmetry. The results confirm the earlier preliminary observations that the asymmetry is larger in Arizona than in Lake Superior area. Two of the mechanisms proposed to explain the asymmetry remain plausible: the plate motion and the non-dipole influence.

Understanding the chemistry of atmospheric aerosol particle formation via observations of physical properties

It is widely accepted that the global climate is heating up due to human activities, such as burning of fossil fuels. Therefore we find ourselves forced to make decisions on what measures, if any, need to be taken to decrease our warming effect on the planet before any irrevocable damage occurs. Research is being conducted in a variety of fields to better understand all relevant processes governing Earth s climate, and to assess the relative roles of anthropogenic and biogenic emissions into the atmosphere. One of the least well quantified problems is the impact of small aerosol particles (both of anthropogenic and biogenic origin) on climate, through reflecting solar radiation and their ability to act as condensation nuclei for cloud droplets. In this thesis, the compounds driving the biogenic formation of new particles in the atmosphere have been examined through detailed measurements. As directly measuring the composition of these newly formed particles is extremely difficult, the approach was to indirectly study their different characteristics by measuring the hygroscopicity (water uptake) and volatility (evaporation) of particles between 10 and 50 nm. To study the first steps of the formation process in the sub-3 nm range, the nucleation of gaseous precursors to small clusters, the chemical composition of ambient naturally charged ions were measured. The ion measurements were performed with a newly developed mass spectrometer, which was first characterized in the laboratory before being deployed at a boreal forest measurement site. It was also successfully compared to similar, low-resolution instruments. The ambient measurements showed that sulfuric acid clusters dominate the negative ion spectrum during new particle formation events. Sulfuric acid/ammonia clusters were detected in ambient air for the first time in this work. Even though sulfuric acid is believed to be the most important gas phase precursor driving the initial cluster formation, measurements of the hygroscopicity and volatility of growing 10-50 nm particles in Hyytiälä showed an increasing role of organic vapors of a variety of oxidation levels. This work has provided additional insights into the compounds participating both in the initial formation and subsequent growth of atmospheric new aerosol particles. It will hopefully prove an important step in understanding atmospheric gas-to-particle conversion, which, by influencing cloud properties, can have important climate impacts. All available knowledge needs to be constantly updated, summarized, and brought to the attention of our decision-makers. Only by increasing our understanding of all the relevant processes can we build reliable models to predict the long-term effects of decisions made today.

Ionosphere-atmosphere interaction during solar proton events

Among the most striking natural phenomena affecting ozone are solar proton events (SPE), during which high-energy protons precipitate into the middle atmosphere in the polar regions. Ionisation caused by the protons results in changes in the lower ionosphere, and in production of neutral odd nitrogen and odd hydrogen species which then destroy ozone in well-known catalytic chemical reaction chains. Large SPEs are able to decrease the ozone concentration of upper stratosphere and mesosphere, but are not expected to significantly affect the ozone layer at 15--30~km altitude. In this work we have used the Sodankylä Ion and Neutral Chemistry Model (SIC) in studies of the short-term effects caused by SPEs. The model results were found to be in a good agreement with ionospheric observations from incoherent scatter radars, riometers, and VLF radio receivers as well as with measurements from the GOMOS/Envisat satellite instrument. For the first time, GOMOS was able to observe the SPE effects on odd nitrogen and ozone in the winter polar region. Ozone observations from GOMOS were validated against those from MIPAS/Envisat instrument, and a good agreement was found throughout the middle atmosphere. For the case of the SPE of October/November 2003, long-term ozone depletion was observed in the upper stratosphere. The depletion was further enhanced by the descent of odd nitrogen from the mesosphere inside the polar vortex, until the recovery occurred in late December. During the event, substantial diurnal variation of ozone depletion was seen in the mesosphere, caused mainly by the the strong diurnal cycle of the odd hydrogen species. In the lower ionosphere, SPEs increase the electron density which is very low in normal conditions. Therefore, SPEs make radar observations easier. In the case of the SPE of October, 1989, we studied the sunset transition of negative charge from electrons to ions, a long-standing problem. The observed phenomenon, which is controlled by the amount of solar radiation, was successfully explained by considering twilight changes in both the rate of photodetachment of negative ions and concentrations of minor neutral species. Changes in the magnetic field of the Earth control the extent of SPE-affected area. For the SPE of November 2001, the results indicated that for low and middle levels of geomagnetic disturbance the estimated cosmic radio noise absorption levels based on a magnetic field model are in a good agreement with ionospheric observations. For high levels of disturbance, the model overestimates the stretching of the geomagnetic field and the geographical extent of SPE-affected area. This work shows the importance of ionosphere-atmosphere interaction for SPE studies. By using both ionospheric and atmospheric observations, we have been able to cover for the most part the whole chain of SPE-triggered processes, from proton-induced ionisation to depletion of ozone.

Sticking and erosion at carbon-containing plasma-facing materials in fusion reactors

Controlled nuclear fusion is one of the most promising sources of energy for the future. Before this goal can be achieved, one must be able to control the enormous energy densities which are present in the core plasma in a fusion reactor. In order to be able to predict the evolution and thereby the lifetime of different plasma facing materials under reactor-relevant conditions, the interaction of atoms and molecules with plasma first wall surfaces have to be studied in detail. In this thesis, the fundamental sticking and erosion processes of carbon-based materials, the nature of hydrocarbon species released from plasma-facing surfaces, and the evolution of the components under cumulative bombardment by atoms and molecules have been investigated by means of molecular dynamics simulations using both analytic potentials and a semi-empirical tight-binding method. The sticking cross-section of CH3 radicals at unsaturated carbon sites at diamond (111) surfaces is observed to decrease with increasing angle of incidence, a dependence which can be described by a simple geometrical model. The simulations furthermore show the sticking cross-section of CH3 radicals to be strongly dependent on the local neighborhood of the unsaturated carbon site. The erosion of amorphous hydrogenated carbon surfaces by helium, neon, and argon ions in combination with hydrogen at energies ranging from 2 to 10 eV is studied using both non-cumulative and cumulative bombardment simulations. The results show no significant differences between sputtering yields obtained from bombardment simulations with different noble gas ions. The final simulation cells from the 5 and 10 eV ion bombardment simulations, however, show marked differences in surface morphology. In further simulations the behavior of amorphous hydrogenated carbon surfaces under bombardment with D^+, D^+2, and D^+3 ions in the energy range from 2 to 30 eV has been investigated. The total chemical sputtering yields indicate that molecular projectiles lead to larger sputtering yields than atomic projectiles. Finally, the effect of hydrogen ion bombardment of both crystalline and amorphous tungsten carbide surfaces is studied. Prolonged bombardment is found to lead to the formation of an amorphous tungsten carbide layer, regardless of the initial structure of the sample. In agreement with experiment, preferential sputtering of carbon is observed in both the cumulative and non-cumulative simulations

Aerosol Particle Formation: Meteorological and Synoptic Processes behind the Event

Aerosol particles in the atmosphere are known to significantly influence ecosystems, to change air quality and to exert negative health effects. Atmospheric aerosols influence climate through cooling of the atmosphere and the underlying surface by scattering of sunlight, through warming of the atmosphere by absorbing sun light and thermal radiation emitted by the Earth surface and through their acting as cloud condensation nuclei. Aerosols are emitted from both natural and anthropogenic sources. Depending on their size, they can be transported over significant distances, while undergoing considerable changes in their composition and physical properties. Their lifetime in the atmosphere varies from a few hours to a week. New particle formation is a result of gas-to-particle conversion. Once formed, atmospheric aerosol particles may grow due to condensation or coagulation, or be removed by deposition processes. In this thesis we describe analyses of air masses, meteorological parameters and synoptic situations to reveal conditions favourable for new particle formation in the atmosphere. We studied the concentration of ultrafine particles in different types of air masses, and the role of atmospheric fronts and cloudiness in the formation of atmospheric aerosol particles. The dominant role of Arctic and Polar air masses causing new particle formation was clearly observed at Hyytiälä, Southern Finland, during all seasons, as well as at other measurement stations in Scandinavia. In all seasons and on multi-year average, Arctic and North Atlantic areas were the sources of nucleation mode particles. In contrast, concentrations of accumulation mode particles and condensation sink values in Hyytiälä were highest in continental air masses, arriving at Hyytiälä from Eastern Europe and Central Russia. The most favourable situation for new particle formation during all seasons was cold air advection after cold-front passages. Such a period could last a few days until the next front reached Hyytiälä. The frequency of aerosol particle formation relates to the frequency of low-cloud-amount days in Hyytiälä. Cloudiness of less than 5 octas is one of the factors favouring new particle formation. Cloudiness above 4 octas appears to be an important factor that prevents particle growth, due to the decrease of solar radiation, which is one of the important meteorological parameters in atmospheric particle formation and growth. Keywords: Atmospheric aerosols, particle formation, air mass, atmospheric front, cloudiness

Irradiation-mediated tailoring of carbon nanotubes

The ever-increasing demand for faster computers in various areas, ranging from entertaining electronics to computational science, is pushing the semiconductor industry towards its limits on decreasing the sizes of electronic devices based on conventional materials. According to the famous law by Gordon E. Moore, a co-founder of the world s largest semiconductor company Intel, the transistor sizes should decrease to the atomic level during the next few decades to maintain the present rate of increase in the computational power. As leakage currents become a problem for traditional silicon-based devices already at sizes in the nanometer scale, an approach other than further miniaturization is needed to accomplish the needs of the future electronics. A relatively recently proposed possibility for further progress in electronics is to replace silicon with carbon, another element from the same group in the periodic table. Carbon is an especially interesting material for nanometer-sized devices because it forms naturally different nanostructures. Furthermore, some of these structures have unique properties. The most widely suggested allotrope of carbon to be used for electronics is a tubular molecule having an atomic structure resembling that of graphite. These carbon nanotubes are popular both among scientists and in industry because of a wide list of exciting properties. For example, carbon nanotubes are electronically unique and have uncommonly high strength versus mass ratio, which have resulted in a multitude of proposed applications in several fields. In fact, due to some remaining difficulties regarding large-scale production of nanotube-based electronic devices, fields other than electronics have been faster to develop profitable nanotube applications. In this thesis, the possibility of using low-energy ion irradiation to ease the route towards nanotube applications is studied through atomistic simulations on different levels of theory. Specifically, molecular dynamic simulations with analytical interaction models are used to follow the irradiation process of nanotubes to introduce different impurity atoms into these structures, in order to gain control on their electronic character. Ion irradiation is shown to be a very efficient method to replace carbon atoms with boron or nitrogen impurities in single-walled nanotubes. Furthermore, potassium irradiation of multi-walled and fullerene-filled nanotubes is demonstrated to result in small potassium clusters in the hollow parts of these structures. Molecular dynamic simulations are further used to give an example on using irradiation to improve contacts between a nanotube and a silicon substrate. Methods based on the density-functional theory are used to gain insight on the defect structures inevitably created during the irradiation. Finally, a new simulation code utilizing the kinetic Monte Carlo method is introduced to follow the time evolution of irradiation-induced defects on carbon nanotubes on macroscopic time scales. Overall, the molecular dynamic simulations presented in this thesis show that ion irradiation is a promisingmethod for tailoring the nanotube properties in a controlled manner. The calculations made with density-functional-theory based methods indicate that it is energetically favorable for even relatively large defects to transform to keep the atomic configuration as close to the pristine nanotube as possible. The kinetic Monte Carlo studies reveal that elevated temperatures during the processing enhance the self-healing of nanotubes significantly, ensuring low defect concentrations after the treatment with energetic ions. Thereby, nanotubes can retain their desired properties also after the irradiation. Throughout the thesis, atomistic simulations combining different levels of theory are demonstrated to be an important tool for determining the optimal conditions for irradiation experiments, because the atomic-scale processes at short time scales are extremely difficult to study by any other means.

Applications of Gauge/Gravity Duality to QCD and Heavy Ion Collisions

The description of quarks and gluons, using the theory of quantum chromodynamics (QCD), has been known for a long time. Nevertheless, many fundamental questions in QCD remain unanswered. This is mainly due to problems in solving the theory at low energies, where the theory is strongly interacting. AdS/CFT is a duality between a specific string theory and a conformal field theory. Duality provides new tools to solve the conformal field theory in the strong coupling regime. There is also some evidence that using the duality, one can get at least qualitative understanding of how QCD behaves at strong coupling. In this thesis, we try to address some issues related to QCD and heavy ion collisions, applying the duality in various ways.

Interatomic potentials for fusion reactor material simulations

Fusion energy is a clean and safe solution for the intricate question of how to produce non-polluting and sustainable energy for the constantly growing population. The fusion process does not result in any harmful waste or green-house gases, since small amounts of helium is the only bi-product that is produced when using the hydrogen isotopes deuterium and tritium as fuel. Moreover, deuterium is abundant in seawater and tritium can be bred from lithium, a common metal in the Earth's crust, rendering the fuel reservoirs practically bottomless. Due to its enormous mass, the Sun has been able to utilize fusion as its main energy source ever since it was born. But here on Earth, we must find other means to achieve the same. Inertial fusion involving powerful lasers and thermonuclear fusion employing extreme temperatures are examples of successful methods. However, these have yet to produce more energy than they consume. In thermonuclear fusion, the fuel is held inside a tokamak, which is a doughnut-shaped chamber with strong magnets wrapped around it. Once the fuel is heated up, it is controlled with the help of these magnets, since the required temperatures (over 100 million degrees C) will separate the electrons from the nuclei, forming a plasma. Once the fusion reactions occur, excess binding energy is released as energetic neutrons, which are absorbed in water in order to produce steam that runs turbines. Keeping the power losses from the plasma low, thus allowing for a high number of reactions, is a challenge. Another challenge is related to the reactor materials, since the confinement of the plasma particles is not perfect, resulting in particle bombardment of the reactor walls and structures. Material erosion and activation as well as plasma contamination are expected. Adding to this, the high energy neutrons will cause radiation damage in the materials, causing, for instance, swelling and embrittlement. In this thesis, the behaviour of a material situated in a fusion reactor was studied using molecular dynamics simulations. Simulations of processes in the next generation fusion reactor ITER include the reactor materials beryllium, carbon and tungsten as well as the plasma hydrogen isotopes. This means that interaction models, {\it i.e. interatomic potentials}, for this complicated quaternary system are needed. The task of finding such potentials is nonetheless nearly at its end, since models for the beryllium-carbon-hydrogen interactions were constructed in this thesis and as a continuation of that work, a beryllium-tungsten model is under development. These potentials are combinable with the earlier tungsten-carbon-hydrogen ones. The potentials were used to explain the chemical sputtering of beryllium due to deuterium plasma exposure. During experiments, a large fraction of the sputtered beryllium atoms were observed to be released as BeD molecules, and the simulations identified the swift chemical sputtering mechanism, previously not believed to be important in metals, as the underlying mechanism. Radiation damage in the reactor structural materials vanadium, iron and iron chromium, as well as in the wall material tungsten and the mixed alloy tungsten carbide, was also studied in this thesis. Interatomic potentials for vanadium, tungsten and iron were modified to be better suited for simulating collision cascades that are formed during particle irradiation, and the potential features affecting the resulting primary damage were identified. Including the often neglected electronic effects in the simulations was also shown to have an impact on the damage. With proper tuning of the electron-phonon interaction strength, experimentally measured quantities related to ion-beam mixing in iron could be reproduced. The damage in tungsten carbide alloys showed elemental asymmetry, as the major part of the damage consisted of carbon defects. On the other hand, modelling the damage in the iron chromium alloy, essentially representing steel, showed that small additions of chromium do not noticeably affect the primary damage in iron. Since a complete assessment of the response of a material in a future full-scale fusion reactor is not achievable using only experimental techniques, molecular dynamics simulations are of vital help. This thesis has not only provided insight into complicated reactor processes and improved current methods, but also offered tools for further simulations. It is therefore an important step towards making fusion energy more than a future goal.