On the charging state of atmospheric aerosols and ion-induced nucleation

Floating in the air that surrounds us is a number of small particles, invisible to the human eye. The mixture of air and particles, liquid or solid, is called an aerosol. Aerosols have significant effects on air quality, visibility and health, and on the Earth's climate. Their effect on the Earth's climate is the least understood of climatically relevant effects. They can scatter the incoming radiation from the Sun, or they can act as seeds onto which cloud droplets are formed. Aerosol particles are created directly, by human activity or natural reasons such as breaking ocean waves or sandstorms. They can also be created indirectly as vapors or very small particles are emitted into the atmosphere and they combine to form small particles that later grow to reach climatically or health relevant sizes. The mechanisms through which those particles are formed is still under scientific discussion, even though this knowledge is crucial to make air quality or climate predictions, or to understand how aerosols will influence and will be influenced by the climate's feedback loops. One of the proposed mechanisms responsible for new particle formation is ion-induced nucleation. This mechanism is based on the idea that newly formed particles were ultimately formed around an electric charge. The amount of available charges in the atmosphere varies depending on radon concentrations in the soil and in the air, as well as incoming ionizing radiation from outer space. In this thesis, ion-induced nucleation is investigated through long-term measurements in two different environments: in the background site of Hyytiälä and in the urban site that is Helsinki. The main conclusion of this thesis is that ion-induced nucleation generally plays a minor role in new particle formation. The fraction of particles formed varies from day to day and from place to place. The relative importance of ion-induced nucleation, i.e. the fraction of particles formed through ion-induced nucleation, is bigger in cleaner areas where the absolute number of particles formed is smaller. Moreover, ion-induced nucleation contributes to a bigger fraction of particles on warmer days, when the sulfuric acid and water vapor saturation ratios are lower. This analysis will help to understand the feedbacks associated with climate change.

Temperature and thiol-induced desensitization of a Ca2+-sensitive cyclic-3',5'-nucleotide phosphodiesterase from sheep lung

Ca2+-sensitivity of sheep lung cyclic-3',5'-nucleotide phosphodiesterase is provided by endogenous tightly bound calmodulin. The calcium sensitivity of a highly purified enzyme was desensitized by increasing the assay temperature. It could also be desensitized to Ca2+-activation by thiols such as dithiothreitol. The thiol-induced desensitization could be partially reversed by dialysis and almost completely reversed by dilution. The results presented in this paper indicate that thiols are possibly involved in the interaction of calmodulin with cyclic-3',5'-nucleotide phosphodiesterase. This is the first report on temperature and thiol-induced desensitization of Ca2+-sensitivity of a cyclic-3',5'-nucleotide phosphodiesterase.

Magnetically induced currents and magnetic response properties of molecules

The magnetically induced currents in organic monoring and multiring molecules, in Möbius shaped molecules and in inorganic all-metal molecules have been investigated by means of the Gauge-including magnetically induced currents (GIMIC) method. With the GIMIC method, the ring-current strengths and the ring-current density distributions can be calculated. For open-shell molecules, also the spin current can be obtained. The ring-current pathways and ring-current strengths can be used to understand the magnetic resonance properties of the molecules, to indirectly identify the effect of non-bonded interactions on NMR chemical shifts, to design new molecules with tailored properties and to discuss molecular aromaticity. In the thesis, the magnetic criterion for aromaticity has been adopted. According to this, a molecule which has a net diatropic ring current might be aromatic. Similarly, a molecule which has a net paratropic current might be antiaromatic. If the net current is zero, the molecule is nonaromatic. The electronic structure of the investigated molecules has been resolved by quantum chemical methods. The magnetically induced currents have been calculated with the GIMIC method at the density-functional theory (DFT) level, as well as at the self-consistent field Hartree-Fock (SCF-HF), at the Møller-Plesset perturbation theory of the second order (MP2) and at the coupled-cluster singles and doubles (CCSD) levels of theory. For closed-shell molecules, accurate ring-current strengths can be obtained with a reasonable computational cost at the DFT level and with rather small basis sets. For open-shell molecules, it is shown that correlated methods such as MP2 and CCSD might be needed to obtain reliable charge and spin currents. The basis set convergence has to be checked for open-shell molecules by performing calculations with large enough basis sets. The results discussed in the thesis have been published in eight papers. In addition, some previously unpublished results on the ring currents in the endohedral fullerene Sc3C2@C80 and in coronene are presented. It is shown that dynamical effects should be taken into account when modelling magnetic resonance parameters of endohedral metallofullerenes such as Sc3C2@C80. The ring-current strengths in a series of nano-sized hydrocarbon rings are related to static polarizabilities and to H-1 nuclear magnetic resonance (NMR) shieldings. In a case study on the possible aromaticity of a Möbius-shaped [16]annulene we found that, according to the magnetic criterion, the molecule is nonaromatic. The applicability of the GIMIC method to assign the aromatic character of molecules was confirmed in a study on the ring currents in simple monocylic aromatic, homoaromatic, antiaromatic, and nonaromatic hydrocarbons. Case studies on nanorings, hexaphyrins and [n]cycloparaphenylenes show that explicit calculations are needed to unravel the ring-current delocalization pathways in complex multiring molecules. The open-shell implementation of GIMIC was applied in studies on the charge currents and the spin currents in single-ring and bi-ring molecules with open shells. The aromaticity predictions that are made based on the GIMIC results are compared to other aromaticity criteria such as H-1 NMR shieldings and shifts, electric polarizabilities, bond-length alternation, as well as to predictions provided by the traditional Hückel (4n+2) rule and its more recent extensions that account for Möbius twisted molecules and for molecules with open shells.

Vinyl radical induced Michael additions: Total synthesis of (±)-seychellene

A new strategy for the total synthesis of (±)-seychellene which involves (i) a regiospecific construction of a bicyclo(2.2.2)octene moiety having a methyl group at the bridgehead and (ii) a vinyl radical induced intramolecular Michael addition is described.

Introduction of high-content screening method for studying drug-induced mitochondrial dysfunction in hepatocytes

Drug induced liver injury is one of the frequent reasons for the drug removal from the market. During the recent years there has been a pressure to develop more cost efficient, faster and easier ways to investigate drug-induced toxicity in order to recognize hepatotoxic drugs in the earlier phases of drug development. High Content Screening (HCS) instrument is an automated microscope equipped with image analysis software. It makes the image analysis faster and decreases the risk for an error caused by a person by analyzing the images always in the same way. Because the amount of drug and time needed in the analysis are smaller and multiple parameters can be analyzed from the same cells, the method should be more sensitive, effective and cheaper than the conventional assays in cytotoxicity testing. Liver cells are rich in mitochondria and many drugs target their toxicity to hepatocyte mitochondria. Mitochondria produce the majority of the ATP in the cell through oxidative phosphorylation. They maintain biochemical homeostasis in the cell and participate in cell death. Mitochondria is divided into two compartments by inner and outer mitochondrial membranes. The oxidative phosphorylation happens in the inner mitochondrial membrane. A part of the respiratory chain, a protein called cytochrome c, activates caspase cascades when released. This leads to apoptosis. The aim of this study was to implement, optimize and compare mitochondrial toxicity HCS assays in live cells and fixed cells in two cellular models: human HepG2 hepatoma cell line and rat primary hepatocytes. Three different hepato- and mitochondriatoxic drugs (staurosporine, rotenone and tolcapone) were used. Cells were treated with the drugs, incubated with the fluorescent probes and then the images were analyzed using Cellomics ArrayScan VTI reader. Finally the results obtained after optimizing methods were compared to each other and to the results of the conventional cytotoxicity assays, ATP and LDH measurements. After optimization the live cell method and rat primary hepatocytes were selected to be used in the experiments. Staurosporine was the most toxic of the three drugs and caused most damage to the cells most quickly. Rotenone was not that toxic, but the results were more reproducible and thus it would serve as a good positive control in the screening. Tolcapone was the least toxic. So far the conventional analysis of cytotoxicity worked better than the HCS methods. More optimization needs to be done to get the HCS method more sensitive. This was not possible in this study due to time limit.

Electron field emission from sp (2)-induced insulating to metallic behaviour of amorphous carbon (a-C) films

The influence of concentration and size of sp (2) cluster on the transport properties and electron field emissions of amorphous carbon films have been investigated. The observed insulating to metallic behaviour from reduced activation energy derived from transport measurement and threshold field for electron emission of a-C films can be explained in terms of improvements in the connectivity between sp (2) clusters. The connectivity is resulted by the cluster concentration and size. The concentration and size of sp (2) content cluster is regulated by the coalescence of carbon globules into clusters, which evolves with deposition conditions.

Polymorphism in a TADDOL analogue induced by the presence of a chiral impurity

Crystallization of a TADDOL analogue results in an orthorhombic P2(1)2(1)2(1) form while the presence of a minute amount of a chiral impurity in the crystallization is found to be responsible for crystallization in a monoclinic P2(1) form.

Biochemical, histopathological and ultrastructural changes in rat liver induced by r-( + )-pulegone, a monoterpene ketone

Biochemical, histopathological and ultrastructural changes occurring at different time points after intraperitoneal administration of a single dose of pulegone (300 mg/kg) were studied. Significant decreases in the level of liver microsomal cytochrome P-450 (67%), heme (37%), aminopyrine N-demethylase (60%) and glucose-6-phosphatase (58%), were noticed 24 hr after pulegone treatment. Alanine amino transferase (ALT) levels increased in a time dependent manner, following exposure of rats to pulegone. Light microscopic studies of liver tissues showed dilation of central veins and distention of sinusoidal spaces 6 hr after pulegone treatment. Initial centrilobular necrosis was noticed at 12 hr. Centrilobular necrosis became severe at 18 hr and nuclear changes included karyorrhexis and karyolysis. Midzonal and periportal degenerative changes in addition to centrilobular necrosis was observed 24 hr after pulegone administration. Electron microscopic changes showed severe degeneration of endoplasmic reticulum, swelling of mitochondria and nuclear changes, 24 hr after administration of pulegone. The time course profile of the hepatocytes after treatment with pulegone indicates that endoplasmic reticulum is the organelle most affected, following which other degenerative changes occur ultimately leading to cell death.

News Media, Crime and Fear of Violence

Finland witnessed a surge in crime news reporting during the 1990s. At the same time, there was a significant rise in the levels of fear of crime reported by surveys. This research examines whether and how the two phenomena: news media and fear of violence were associated with each other. The dissertation consists of five sub-studies and a summary article. The first sub-study is a review of crime reporting trends in Finland, in which I have reviewed prior research and used existing Finnish datasets on media contents and crime news media exposure. The second study examines the association between crime media consumption and fear of crime when personal and vicarious victimization experiences have been held constant. Apart from analyzing the impact of crime news consumption on fear, media effects on general social trust are analyzed in the third sub-study. In the fourth sub-study I have analyzed the contents of the Finnish Poliisi-TV programme and compared the consistency of the picture of violent crime between official data sources and the programme. In the fifth and final sub-study, the victim narratives of Poliisi-TV s violence news contents have been analyzed. The research provides a series of results which are unprecedented in Finland. First, it observes that as in many other countries, the quantity of crime news supply has increased quite markedly in Finland. Second, it verifies that exposure to crime news is related to being worried about violent victimization and avoidance behaviour. Third, it documents that exposure to TV crime reality-programming is associated with reduced social trust among Finnish adolescents. Fourth, the analysis of Poliisi-TV shows that it transmits a distorted view of crime when contrasted with primary data sources on crime, but that this distortion is not as big as could be expected from international research findings and epochal theories of sociology. Fifth, the portrayals of violence victims in Poliisi-TV do not fit the traditional ideal types of victims that are usually seen to dominate crime media. The fact that the victims of violence in Poliisi-TV are ordinary people represents a wider development of the changing significance of the crime victim in Finland. The research concludes that although the media most likely did have an effect on the rising public fears in the 1990s, the mechanism was not as straight forward as has often been claimed. It is likely that there are other factors in the fear-media equation that are affecting both fear levels and crime reporting and that these factors are interactive in nature. Finally, the research calls for a re-orientation of media criminology and suggests more emphasis on the positive implications of crime in the media. Keywords: crime, media, fear of crime, violence, victimization, news

A study on boundary-layer transition induced by free-stream turbulence

Boundary-layer transition at different free-stream turbulence levels has been investigated using the particle-image velocimetry technique. The measurements show organized positive and negative fluctuations of the streamwise fluctuating velocity component, which resemble the forward and backward jet-like structures reported in the direct numerical simulation of bypass transition. These fluctuations are associated with unsteady streaky structures. Large inclined high shear-layer regions are also observed and the organized negative fluctuations are found to appear consistently with these inclined shear layers, along with highly inflectional instantaneous streamwise velocity profiles. These inflectional velocity profiles are similar to those in the ribbon-induced boundary-layer transition. An oscillating-inclined shear layer appears to be the turbulent spot-precursor. The measurements also enabled to compare the actual turbulent spot in bypass transition with the simulated one. A proper orthogonal decomposition analysis of the fluctuating velocity field is carried out. The dominant flow structures of the organized positive and negative fluctuations are captured by the first few eigenfunction modes carrying most of the fluctuating energy. The similarity in the dominant eigenfunctions at different Reynolds numbers suggests that the flow prevails its structural identity even in intermittent flows. This analysis also indicates the possibility of the existence of a spatio-temporal symmetry associated with a travelling wave in the flow.

Mother-Infant Antibodies to Pneumococcal Polysaccharides and Proteins : Transfer and Persistence of Maternal Antibodies and Development of Vaccine-Induced and Naturally Acquired Antibodies in Infants

Symptomless nasopharyngeal carriage of Streptococcus pneumoniae (pneumococcus) is very common in young children. Occasionally the carriage proceeds into mild mucosal diseases, such as sinusitis or acute otitis media, or into serious life-threatening diseases, such as pneumonia, sepsis or meningitis. Each year, up to one million children less than five years of age worldwide die of invasive pneumococcal diseases (IPD). Especially in the low-income countries IPD is a leading health problem in infants; 75% of all IPD cases occur before one year of age. This stresses the need of increased protection against pneumococcus in infancy. Anti-pneumococcal antibodies form an important component in the defence against pneumococcal infection. Maternal immunisation and early infant immunisation are two possible ways by which potentially protective antibody concentrations against pneumococci could be achieved in early infancy. The aim of this thesis is to increase the knowledge of antibody mediated protection against pneumococcal disease in infants and young children. We investigated the transfer of maternal anti-pneumococcal antibodies from Filipino mothers to their infants, the persistence of the transferred antibodies in the infants, the immunogenicity of the 23-valent pneumococcal polysaccharide vaccine (PPV) in infants and the response of the children to a second dose of PPV at three years of age. We also investigated the development of antibodies to pneumococcal protein antigens in relation to culture-confirmed pneumococcal carriage in infants. Serum samples were collected from the mothers, the umbilical cords and from the infants at young age as well as at three years of age. The samples were used to determine the antibody concentrations to pneumococcal serotypes 1, 5, 6B, 14, 18C and 19F, as well as to the pneumococcal proteins PspA, PsaA, Ply, PspC, PhtD, PhtDC and LytC by the enzyme immunoassay. The findings of the present study confirm previously obtained results and add to the global knowledge of responses to PPV in young children. Immunising pregnant women with PPV provides the infants with increased concentrations of pneumococcal polysaccharide antibodies. Of the six serotypes examined, serotypes 1 and 5 were immunogenic already in infants. At three years of age, the children responded well to the second dose of PPV suggesting that maternal and early infant immunisations might not induce hyporesponsiveness to polysaccharide antigens after subsequent immunisations. The anti-protein antibody findings provide useful information for the development of pneumococcal protein vaccines. All six proteins studied were immunogenic in infancy and the development of anti-protein antibodies started early in life in relation to pneumococcal carriage.