Information, risk and trust in the food chain : Ex-ante valuation of consumer willingness to pay for beef quality information using the contingent valuation method

The safety of food has become an increasingly interesting issue to consumers and the media. It has also become a source of concern, as the amount of information on the risks related to food safety continues to expand. Today, risk and safety are permanent elements within the concept of food quality. Safety, in particular, is the attribute that consumers find very difficult to assess. The literature in this study consists of three main themes: traceability; consumer behaviour related to both quality and safety issues and perception of risk; and valuation methods. The empirical scope of the study was restricted to beef, because the beef labelling system enables reliable tracing of the origin of beef, as well as attributes related to safety, environmental friendliness and animal welfare. The purpose of this study was to examine what kind of information flows are required to ensure quality and safety in the food chain for beef, and who should produce that information. Studying the willingness to pay of consumers makes it possible to determine whether the consumers consider the quantity of information available on the safety and quality of beef sufficient. One of the main findings of this study was that the majority of Finnish consumers (73%) regard increased quality information as beneficial. These benefits were assessed using the contingent valuation method. The results showed that those who were willing to pay for increased information on the quality and safety of beef would accept an average price increase of 24% per kilogram. The results showed that certain risk factors impact consumer willingness to pay. If the respondents considered genetic modification of food or foodborne zoonotic diseases as harmful or extremely harmful risk factors in food, they were more likely to be willing to pay for quality information. The results produced by the models thus confirmed the premise that certain food-related risks affect willingness to pay for beef quality information. The results also showed that safety-related quality cues are significant to the consumers. In the first place, the consumers would like to receive information on the control of zoonotic diseases that are contagious to humans. Similarly, other process-control related information ranked high among the top responses. Information on any potential genetic modification was also considered important, even though genetic modification was not regarded as a high risk factor.

Ionic Liquids and Microwaves in Promotion of Organic Synthesis : Friedel-Crafts reaction, deuterolabelling and O-Demethylation

The use of ionic liquids in chemical research has gained considerable interest and activity in recent years. Due to their unique and varied physicochemical properties, in comparison to molecular solvents, the potential applications for ionic liquids are enormous. The use of microwave irradiation, as a powerful dielectric heating technique, in synthetic organic chemistry has been known since 1986. Since then, it has gained significant recognition for its research and application in both academia and industry. The use of either ionic liquids or microwave irradiation in synthetic organic chemistry has been known to afford improved, alternative or complimentary selectivities, in comparison to traditional processes. In this study, the use of ionic liquids as solvents, co-solvents and catalytic media was explored in Friedel-Crafts, deuterolabelling and O-demethylation reactions. Alternative methods for the production of a variety of aromatic ketones using the Friedel-Crafts acylation methodology were investigated using ionic liquid catalyst or ionic liquid acidic additive systems. The disclosed methods, i.e. metal bistriflamides and chloroindate ionic liquids systems, possessed good catalytic activity in the synthesis of typical benzophenones. These catalytic systems were also recyclable. Microwave irradiation was found to be useful in the synthesis of various polyhydroxydeoxybenzoins and arylpropanones as synthetic precursors to naturally occurring or potentially bioactive compounds. Under optimized condition, the reaction occurred in only four minutes using systems such as [bmim][NTf2]/HNTf2 and [bmim][BF4]/BF3·OEt2. Naturally occurring polyphenols, such as isoflavones, can possess various types of biological or pharmacological activity. In particular, some are noted for their beneficial effects on human health. Isotopically labelled analogues of polyphenols are valuable as analytical standards in the quantification of these compounds from biological matrices. A new strategy for deuterolabelling of polyphenols was developed using ionic liquids as co-solvents and 35% DCl/D2O, as a cheap deuterium source, under microwave irradiation. Under these conditions, perdeuterated compounds were achieved in short reaction times, in high isotopic purity and in excellent yields. An O-demethylation reaction was developed, using an ionic liquid reaction medium with BBr3 for the deprotection of a variety methyl protected polyphenolic compounds, such as isoflavons and lignans. This deprotection procedure was found to be very practical as the reaction occurred under mild reaction conditions and in short reaction times. The isolation and purification steps were particularly straightforward and high yielding, in comparison to traditional methods.

Precipitation-induced runoff and leaching from milled peat mining mires by peat types : a comparative method for estimating the loading of water bodies during peat pruduction

Precipitation-induced runoff and leaching from milled peat mining mires by peat types: a comparative method for estimating the loading of water bodies during peat production. This research project in environmental geology has arisen out of an observed need to be able to predict more accurately the loading of watercourses with detrimental organic substances and nutrients from already existing and planned peat production areas, since the authorities capacity for insisting on such predictions covering the whole duration of peat production in connection with evaluations of environmental impact is at present highly limited. National and international decisions regarding monitoring of the condition of watercourses and their improvement and restoration require more sophisticated evaluation methods in order to be able to forecast watercourse loading and its environmental impacts at the stage of land-use planning and preparations for peat production.The present project thus set out from the premise that it would be possible on the basis of existing mire and peat data properties to construct estimates for the typical loading from production mires over the whole duration of their exploitation. Finland has some 10 million hectares of peatland, accounting for almost a third of its total area. Macroclimatic conditions have varied in the course of the Holocene growth and development of this peatland, and with them the habitats of the peat-forming plants. Temperatures and moisture conditions have played a significant role in determining the dominant species of mire plants growing there at any particular time, the resulting mire types and the accumulation and deposition of plant remains to form the peat. The above climatic, environmental and mire development factors, together with ditching, have contributed, and continue to contribute, to the existence of peat horizons that differ in their physical and chemical properties, leading to differences in material transport between peatlands in a natural state and mires that have been ditched or prepared for forestry and peat production. Watercourse loading from the ditching of mires or their use for peat production can have detrimental effects on river and lake environments and their recreational use, especially where oxygen-consuming organic solids and soluble organic substances and nutrients are concerned. It has not previously been possible, however, to estimate in advance the watercourse loading likely to arise from ditching and peat production on the basis of the characteristics of the peat in a mire, although earlier observations have indicated that watercourse loading from peat production can vary greatly and it has been suggested that differences in peat properties may be of significance in this. Sprinkling is used here in combination with simulations of conditions in a milled peat production area to determine the influence of the physical and chemical properties of milled peats in production mires on surface runoff into the drainage ditches and the concentrations of material in the runoff water. Sprinkling and extraction experiments were carried out on 25 samples of milled Carex (C) and Sphagnum (S) peat of humification grades H 2.5 8.5 with moisture content in the range 23.4 89% on commencement of the first sprinkling, which was followed by a second sprinkling 24 hours later. The water retention capacity of the peat was best, and surface runoff lowest, with Sphagnum and Carex peat samples of humification grades H 2.5 6 in the moisture content class 56 75%. On account of the hydrophobicity of dry peat, runoff increased in a fairly regular manner with drying of the sample from 55% to 24 30%. Runoff from the samples with an original moisture content over 55% increased by 63% in the second round of sprinkling relative to the first, as they had practically reached saturation point on the first occasion, while those with an original moisture content below 55% retained their high runoff in the second round, due to continued hydrophobicity. The well-humified samples (H 6.5 8.5) with a moisture content over 80% showed a low water retention capacity and high runoff in both rounds of sprinkling. Loading of the runoff water with suspended solids, total phosphorus and total nitrogen, and also the chemical oxygen demand (CODMn O2), varied greatly in the sprinkling experiment, depending on the peat type and degree of humification, but concentrations of the same substances in the two sprinklings were closely or moderately closely correlated and these correlations were significant. The concentrations of suspended solids in the runoff water observed in the simulations of a peat production area and the direct surface runoff from it into the drainage ditch system in response to rain (sprinkling intensity 1.27 mm/min) varied c. 60-fold between the degrees of humification in the case of the Carex peats and c. 150-fold for the Sphagnum peats, while chemical oxygen demand varied c. 30-fold and c. 50-fold, respectively, total phosphorus c. 60-fold and c. 66-fold, total nitrogen c. 65-fold and c. 195-fold and ammonium nitrogen c. 90-fold and c. 30-fold. The increases in concentrations in the runoff water were very closely correlated with increases in humification of the peat. The correlations of the concentrations measured in extraction experiments (48 h) with peat type and degree of humification corresponded to those observed in the sprinkler experiments. The resulting figures for the surface runoff from a peat production area into the drainage ditches simulated by means of sprinkling and material concentrations in the runoff water were combined with statistics on the mean extent of daily rainfall (0 67 mm) during the frost-free period of the year (May October) over an observation period of 30 years to yield typical annual loading figures (kg/ha) for suspended solids (SS), chemical oxygen demand of organic matter (CODmn O2), total phosphorus (tot. P) and total nitrogen (tot. N) entering the ditches with respect to milled Carex (C) and Sphagnum (S) peats of humification grades H 2.5 8.5. In order to calculate the loading of drainage ditches from a milled peat production mire with the aid of these annual comparative values (in kg/ha), information is required on the properties of the intended production mire and its peat. Once data are available on the area of the mire, its peat depth, peat types and their degrees of humification, dry matter content, calorific value and corresponding energy content, it is possible to produce mutually comparable estimates for individual mires with respect to the annual loading of the drainage ditch system and the surrounding watercourse for the whole service life of the production area, the duration of this service life, determinations of energy content and the amount of loading per unit of energy generated (kg/MWh). In the 8 mires in the Köyhäjoki basin, Central Ostrobothnia, taken as an example, the loading of suspended solids (SS) in the drainage ditch networks calculated on the basis of the typical values obtained here and existing mire and peat data and expressed per unit of energy generated varied between the mires and horizons in the range 0.9 16.5 kg/MWh. One of the aims of this work was to develop means of making better use of existing mire and peat data and the results of corings and other field investigations. In this respect combination of the typical loading values (kg/ha) obtained here for S, SC, CS and C peats and the various degrees of humification (H 2.5 8.5) with the above mire and peat data by means of a computer program for the acquisition and handling of such data would enable all the information currently available and that deposited in the system in the future to be used for defining watercourse loading estimates for mires and comparing them with the corresponding estimates of energy content. The intention behind this work has been to respond to the challenge facing the energy generation industry to find larger peat production areas that exert less loading on the environment and to that facing the environmental authorities to improve the means available for estimating watercourse loading from peat production and its environmental impacts in advance. The results conform well to the initial hypothesis and to the goals laid down for the research and should enable watercourse loading from existing and planned peat production to be evaluated better in the future and the resulting impacts to be taken into account when planning land use and energy generation. The advance loading information available in this way would be of value in the selection of individual peat production areas, the planning of their exploitation, the introduction of water protection measures and the planning of loading inspections, in order to achieve controlled peat production that pays due attention to environmental considerations.

On linear order and computation : The expressiveness of interactive computations on linear orders and computations indexed by ordinals

We solve the Dynamic Ehrenfeucht-Fra\"iss\'e Game on linear orders for both players, yielding a normal form for quantifier-rank equivalence classes of linear orders in first-order logic, infinitary logic, and generalized-infinitary logics with linearly ordered clocks. We show that Scott Sentences can be manipulated quickly, classified into local information, and consistency can be decided effectively in the length of the Scott Sentence. We describe a finite set of linked automata moving continuously on a linear order. Running them on ordinals, we compute the ordinal truth predicate and compute truth in the constructible universe of set-theory. Among the corollaries are a study of semi-models as efficient database of both model-theoretic and formulaic information, and a new proof of the atomicity of the Boolean algebra of sentences consistent with the theory of linear order -- i.e., that the finitely axiomatized theories of linear order are dense.

Variation in the Understanding of Lutheranism and Its Implications for Religious Education : Meaning Discernment of Students and Teachers in Finnish Upper Secondary Schools

The study investigated variation in the ways in which a group of students and teachers of Evangelical Lutheran religious education in Finnish upper secondary schools understand Lutheranism and searched for educational implications for learning in religious education. The aim of understanding the qualitative variation in understanding Lutheranism was explored through the relationship between the following questions, which correspond to the results reported in the following original refereed publications: 1) How do Finnish students understand Lutheranism? 2) How do Finnish teachers of religious education constitute the meaning of Lutheranism? 3) How could phenomenography and the Variation Theory of Learning contribute to learning about and from religion in the context of Finnish Lutheran Religious Education as compared to religious education in the UK? Two empirical studies (Hella, 2007; Hella, 2008) were undertaken from a phenomenographic research perspective (e.g., Marton, 1981) and the Variation Theory of Learning (e.g., Marton & Tsui et al. 2004) that developed from it. Data was collected from 63 upper secondary students and 40 teachers of religious education through written tasks with open questions and complementary interviews with 11 students and 20 teachers for clarification of meanings. The two studies focused on the content and structure of meaning discernment in students and teachers expressed understandings of Lutheranism. Differences in understandings are due to differences in the meanings that are discerned and focused on. The key differences between the ways students understand varied from understanding Lutheranism as a religion to personal faith with its core in mercy. The logical relationships between the categories that describe variation in understanding express a hierarchy of ascending complexity, according to which more developed understandings are inclusive of less developed ones. The ways the teachers understand relate to student s understandings in a sequential manner. Phenomenography and Variation Theory were discussed in the context of religious education in Finland and the UK in relation to the theoretical notion of learning about and from religion (Hella & Wright, 2008). The thesis suggests that variation theory enables religious educators to recognise the unity of learning about and from religion, as learning is always learning about something and involves simultaneous engagement with the object of learning and development as a person. The study also suggests that phenomenography and variation theory offer a means by which it is possible for academics, policy makers, curriculum designers, teachers and students to learn to discern different ways of understanding the contested nature of religions. Keywords: Lutheranism, understanding, variation, teaching, learning, phenomenography, religious education

Normalization and Charter 77 : Violence, Commitment and Resistance in Czechoslovakia

In Czechoslovakia, the occupation of 1968 denoted the beginning of normalization , a political and societal stagnation that lasted two decades. Dissident initiative Charter 77 emerged in 1977, demanding that the leaders of the country respect human rights. The Helsinki process provided a macro-level framework that influenced opposition and dissident activities throughout Eastern Europe. The study contributes a focused empirical analysis of the period of normalization and the dissident movement Charter 77. Dissent in general is seen as an existential attitude; it can be encapsulated as a morally rationalized critical stance as derived from shared experience or interpretation of injustice, which serves as a basis for a shared collective identity comprising oppositional consciousness as one unifying factor. The study suggests that normalization can be understood as a fundamentally violent process and discusses the structural and cultural manifestations of violence with relation to Charter 77. In general, the aim of the system was to passivize the society to such an extent that it would not constitute a potential threat to the hegemonic rule of the regime. Normalization caused societal stagnation and apoliticization, but it also benefited those who accepted the new political reality. The study, however, questions the image of Czechoslovakia s allegedly highly repressive rule by showing that there was also quite considerable tolerance of Charter 77 and consideration before severe repression was brought to bear against dissidents. Furthermore, the study provides understanding of the motives and impetuses behind dissent, the strategic shifts in Charter 77 activities, and the changes in the regime s policies toward Charter 77. The study also adds new perspective on the common image of Charter 77 as a non political initiative and suggests that Charter 77 was, in fact, a political entity, an actively political one in the latter half of the 1980s. Charter 77 was a de facto hybrid of a traditional dissident initiative and an oppositional actor. Charter 77 adopted a two-dimension approach: firstly, it still emphasized its role as a citizens initiative supporting human rights, but, secondly, at the same time, it was a directly political actor supporting and furthering the development of political opposition against the ruling power.

Democratic Legitimacy and the Politics of Rights : A comparative analysis of the conceptual relationship between democracy and rights in contemporary political theories

Democratic Legitimacy and the Politics of Rights is a research in normative political theory, based on comparative analysis of contemporary democratic theories, classified roughly as conventional liberal, deliberative democratic and radical democratic. Its focus is on the conceptual relationship between alternative sources of democratic legitimacy: democratic inclusion and liberal rights. The relationship between rights and democracy is studied through the following questions: are rights to be seen as external constraints to democracy or as objects of democratic decision making processes? Are individual rights threatened by public participation in politics; do constitutionally protected rights limit the inclusiveness of democratic processes? Are liberal values such as individuality, autonomy and liberty; and democratic values such as equality, inclusion and popular sovereignty mutually conflictual or supportive? Analyzing feminist critique of liberal discourse, the dissertation also raises the question about Enlightenment ideals in current political debates: are the universal norms of liberal democracy inherently dependent on the rationalist grand narratives of modernity and incompatible with the ideal of diversity? Part I of the thesis introduces the sources of democratic legitimacy as presented in the alternative democratic models. Part II analyses how the relationship between rights and democracy is theorized in them. Part III contains arguments by feminists and radical democrats against the tenets of universalist liberal democratic models and responds to that critique by partly endorsing, partly rejecting it. The central argument promoted in the thesis is that while the deconstruction of modern rationalism indicates that rights are political constructions as opposed to externally given moral constraints to politics, this insight does not delegitimize the politics of universal rights as an inherent part of democratic institutions. The research indicates that democracy and universal individual rights are mutually interdependent rather than oppositional; and that democracy is more dependent on an unconditional protection of universal individual rights when it is conceived as inclusive, participatory and plural; as opposed to robust majoritarian rule. The central concepts are: liberalism, democracy, legitimacy, deliberation, inclusion, equality, diversity, conflict, public sphere, rights, individualism, universalism and contextuality. The authors discussed are e.g. John Rawls, Jürgen Habermas, Seyla Benhabib, Iris Young, Chantal Mouffe and Stephen Holmes. The research focuses on contemporary political theory, but the more classical work of John S. Mill, Benjamin Constant, Isaiah Berlin and Hannah Arendt is also included.

Pentitol phosphate dehydrogenases: Discovery, characterization and use in D-arabitol and xylitol production by metabolically engineered Bacillus subtilis

The ultimate goal of this study has been to construct metabolically engineered microbial strains capable of fermenting glucose into pentitols D-arabitol and, especially, xylitol. The path that was chosen to achieve this goal required discovery, isolation and sequencing of at least two pentitol phosphate dehydrogenases of different specificity, followed by cloning and expression of their genes and characterization of recombinant arabitol and xylitol phosphate dehydrogenases. An enzyme of a previously unknown specificity, D-arabitol phosphate dehydrogenase (APDH), was discovered in Enterococcus avium. The enzyme was purified to homogenity from E. avium strain ATCC 33665. SDS/PAGE revealed that the enzyme has a molecular mass of 41 ± 2 kDa, whereas a molecular mass of 160 ± 5 kDa was observed under non-denaturing conditions implying that the APDH may exist as a tetramer with identical subunits. Purified APDH was found to have narrow substrate specificity, converting only D-arabitol 1-phosphate and D-arabitol 5-phosphate into D-xylulose 5-phosphate and D-ribulose 5-phosphate, respectively, in the oxidative reaction. Both NAD+ and NADP+ were accepted as co-factors. Based on the partial protein sequences, the gene encoding APDH was cloned. Homology comparisons place APDH within the medium chain dehydrogenase family. Unlike most members of this family, APDH requires Mn2+ but no Zn2+ for enzymatic activity. The DNA sequence surrounding the gene suggests that it belongs to an operon that also contains several components of phosphotransferase system (PTS). The apparent role of the enzyme is to participate in arabitol catabolism via the arabitol phosphate route similar to the ribitol and xylitol catabolic routes described previously. Xylitol phosphate dehydrogenase (XPDH) was isolated from Lactobacillus rhamnosus strain ATCC 15820. The enzyme was partially sequenced. Amino acid sequences were used to isolate the gene encoding the enzyme. The homology comparisons of the deduced amino acid sequence of L. rhamnosus XPDH revealed several similar enzymes in genomes of various species of Gram-positive bacteria. Two enzymes of Clostridium difficile and an enzyme of Bacillus halodurans were cloned and their substrate specificities together with the substrate specificity of L. rhamnosus XPDH were compared. It was found that one of the XPDH enzymes of C. difficile and the XPDH of L. rhamnosus had the highest selectivity towards D-xylulose 5-phosphate. A known transketolase-deficient and D-ribose-producing mutant of Bacillus subtilis (ATCC 31094) was further modified by disrupting its rpi (D-ribose phosphate isomerase) gene to create D-ribulose- and D-xylulose-producing strain. Expression of APDH of E. avium and XPDH of L. rhamnosus and C. difficile in D-ribulose- and D-xylulose-producing strain of B. subtilis resulted in strains capable of converting D-glucose into D-arabitol and xylitol, respectively. The D-arabitol yield on D-glucose was 38 % (w/w). Xylitol production was accompanied by co-production of ribitol limiting xylitol yield to 23 %.

The Emerging Phenotype: Ecological Genetics of Color, Form and Sex in the Common Frog

One of the main aims of evolutionary biology is to explain why organisms vary phenotypically as they do. Proximately, this variation arises from genetic differences and from environmental influences, the latter of which is referred to as phenotypic plasticity. Phenotypic plasticity is thus a central concept in evolutionary biology, and understanding its relative importance in causing the phenotypic variation and differentiation is important, for instance in anticipating the consequences of human induced environmental changes. The aim of this thesis was to study geographic variation and local adaptation, as well as sex ratios and environmental sex reversal, in the common frog (Rana temporaria). These themes cover three different aspects of phenotypic plasticity, which emerges as the central concept for the thesis. The first two chapters address geographic variation and local adaptation in two potentially thermally adaptive traits, namely the degree of melanism and the relative leg length. The results show that although there is an increasing latitudinal trend in the degree of melanism in wild populations across Scandinavian Peninsula, this cline has no direct genetic basis and is thus environmentally induced. The second chapter demonstrates that although there is no linear, latitudinally ordered phenotypic trend in relative leg length that would be expected under Allen s rule an ecogeographical rule linking extremity length to climatic conditions there seems to be such a trend at the genetic level, hidden under environmental effects. The first two chapters thus view phenotypic plasticity through its ecological role and evolution, and demonstrate that it can both give rise to phenotypic variation and hide evolutionary patterns in studies that focus solely on phenotypes. The last three chapters relate to phenotypic plasticity through its ecological and evolutionary role in sex determination, and consequent effects on population sex ratio, genetic recombination and the evolution of sex chromosomes. The results show that while sex ratios are strongly female biased and there is evidence of environmental sex reversals, these reversals are unlikely to have caused the sex ratio skew, at least directly. The results demonstrate that environmental sex reversal can have an effect on the evolution of sex chromosomes, as the recombination patterns between them seem to be controlled by phenotypic, rather than genetic, sex. This potentially allows Y chromosomes to recombine, lending support for the recent hypothesis suggesting that sex-reversal may play an important role on the rejuvenation of Y chromosomes.

Complement factor C4 and immunoglobulins in recurrent or chronic mucosal infections

The study assessed whether plasma concentrations of complement factors C3, C4, or immunoglobulins, serum classical pathway hemolytyic activity, or polymorphisms in the class I and II HLA genes, isotypes and gene numbers of C4, or allotypes of IgG1 and IgG3 heavy chain genes were associated with severe frequently recurring or chronic mucosal infections. According to strict clinical criteria, 188 consecutive voluntary patients without a known immunodeficiency and 198 control subjects were recruited. Frequencies of low levels in IgG1, IgG2, IgG3 and IgG4 were for the first time tested from adult general population and patients with acute rhinosinusitis. Frequently recurring intraoral herpes simplex type 1 infections, a rare form of the disease, was associated with homozygosity in HLA -A*, -B*, -C*, and -DR* genes. Frequently recurrent genital HSV-2 infections were associated with low levels of IgG1 and IgG3, present in 54% of the recruited patients. This association was partly allotype-dependent. The G3mg,G1ma/ax haplotype, together with low IgG3, was more common in patients than in control subjects who lacked antibodies against herpes simplex viruses. This is the first found immunogenetic deficiency in otherwise healthy adults that predisposes to highly frequent mucosal herpes recurrences. According to previous studies, HSV effectively evades the allotype G1ma/ax of IgG1, whereas G3mg is associated with low IgG3. Certain HLA genes were more common in patients than in control subjects. Having more than one C4A or C4B gene was associated with neuralgias caused by the virus. Low levels of IgA, IgG1, IgG2, IgG3, and IgG4 were common in the general adult population, but even more frequent in patients with chronic sinusitis. Only low IgG1 was more common chronic than in acute rhinosinusitis. Clinically, nasal polyposis and bronchial asthma were associated with complicated disease forms. The best differentiating immunologic parameters were C4A deficiency and the combination of low plasma IgG4 together with low IgG1 or IgG2, performing almost equally. The lack of C4A, IgA, and IgG4, all known to possess anti-inflammatory activity, together with a concurrently impaired immunity caused by low subclass levels, may predispose to chronic disease forms. In severe chronic adult periodontitis, any C4A or C4B deficiency combined was associated with the disease. The new quantitative analysis of C4 genes and the conventional C4 allotyping method complemented each other. Lowered levels of plasma C3 or C4 or both, and serum CH50 were found in herpes and periodontitis patients. In rhinosinusitis, there was a linear trend with the highest levels found in the order: acute > chronic rhinosinusitis > general population > blood donors with no self-reported history of rhinosinusitis. Complement is involved in the defense against the tested mucosal infections. Seemingly immunocompetent patients with chronic or recurrent mucosal infections frequently have subtle weaknesses in different arms of immunity. Their susceptibility to chronic disease forms may be caused by these. Host s subtly impaired immunity often coincides with effective immune evasion from the same arms of immunity by the disease-causing pathogens. The interpretation of low subclass levels, if no additional predisposing immunologic factors are tested, is difficult and of limited value in early diagnosis and treatment.

Numerical approaches to new particle formation and growth in the atmosphere

Aerosols impact the planet and our daily lives through various effects, perhaps most notably those related to their climatic and health-related consequences. While there are several primary particle sources, secondary new particle formation from precursor vapors is also known to be a frequent, global phenomenon. Nevertheless, the formation mechanism of new particles, as well as the vapors participating in the process, remain a mystery. This thesis consists of studies on new particle formation specifically from the point of view of numerical modeling. A dependence of formation rate of 3 nm particles on the sulphuric acid concentration to the power of 1-2 has been observed. This suggests nucleation mechanism to be of first or second order with respect to the sulphuric acid concentration, in other words the mechanisms based on activation or kinetic collision of clusters. However, model studies have had difficulties in replicating the small exponents observed in nature. The work done in this thesis indicates that the exponents may be lowered by the participation of a co-condensing (and potentially nucleating) low-volatility organic vapor, or by increasing the assumed size of the critical clusters. On the other hand, the presented new and more accurate method for determining the exponent indicates high diurnal variability. Additionally, these studies included several semi-empirical nucleation rate parameterizations as well as a detailed investigation of the analysis used to determine the apparent particle formation rate. Due to their high proportion of the earth's surface area, oceans could potentially prove to be climatically significant sources of secondary particles. In the lack of marine observation data, new particle formation events in a coastal region were parameterized and studied. Since the formation mechanism is believed to be similar, the new parameterization was applied in a marine scenario. The work showed that marine CCN production is feasible in the presence of additional vapors contributing to particle growth. Finally, a new method to estimate concentrations of condensing organics was developed. The algorithm utilizes a Markov chain Monte Carlo method to determine the required combination of vapor concentrations by comparing a measured particle size distribution with one from an aerosol dynamics process model. The evaluation indicated excellent agreement against model data, and initial results with field data appear sound as well.

Mass spectrometry and n-in-one analytics in early drug discovery: Combinatorial chemistry libraries, lipophilicity and absorption screening

This thesis describes current and past n-in-one methods and presents three early experimental studies using mass spectrometry and the triple quadrupole instrument on the application of n-in-one in drug discovery. N-in-one strategy pools and mix samples in drug discovery prior to measurement or analysis. This allows the most promising compounds to be rapidly identified and then analysed. Nowadays properties of drugs are characterised earlier and in parallel with pharmacological efficacy. Studies presented here use in vitro methods as caco-2 cells and immobilized artificial membrane chromatography for drug absorption and lipophilicity measurements. The high sensitivity and selectivity of liquid chromatography mass spectrometry are especially important for new analytical methods using n-in-one. In the first study, the fragmentation patterns of ten nitrophenoxy benzoate compounds, serial homology, were characterised and the presence of the compounds was determined in a combinatorial library. The influence of one or two nitro substituents and the alkyl chain length of methyl to pentyl on collision-induced fragmentation was studied, and interesting structurefragmentation relationships were detected. Two nitro group compounds increased fragmentation compared to one nitro group, whereas less fragmentation was noted in molecules with a longer alkyl chain. The most abundant product ions were nitrophenoxy ions, which were also tested in the precursor ion screening of the combinatorial library. In the second study, the immobilized artificial membrane chromatographic method was transferred from ultraviolet detection to mass spectrometric analysis and a new method was developed. Mass spectra were scanned and the chromatographic retention of compounds was analysed using extract ion chromatograms. When changing detectors and buffers and including n-in-one in the method, the results showed good correlation. Finally, the results demonstrated that mass spectrometric detection with gradient elution can provide a rapid and convenient n-in-one method for ranking the lipophilic properties of several structurally diverse compounds simultaneously. In the final study, a new method was developed for caco-2 samples. Compounds were separated by liquid chromatography and quantified by selected reaction monitoring using mass spectrometry. This method was used for caco-2 samples, where absorption of ten chemically and physiologically different compounds was screened using both single and nin- one approaches. These three studies used mass spectrometry for compound identification, method transfer and quantitation in the area of mixture analysis. Different mass spectrometric scanning modes for the triple quadrupole instrument were used in each method. Early drug discovery with n-in-one is area where mass spectrometric analysis, its possibilities and proper use, is especially important.

Understanding Human Drug Conjugating Enzymes; Regio- and Stereoselectivity in Sulfotransferase 1A3 and the UDP-Glucuronosyltransferases

Sulfotransferases (SULTs) and UDP-glucuronosyltransferases (UGTs) are important detoxification enzymes and they contribute to bioavailability and elimination of many drugs. SULT1A3 is an extrahepatic enzyme responsible for the sulfonation of dopamine, which is often used as its probe substrate. A new method for analyzing dopamine-3-O-sulfate and dopamine-4-O-sulfate by high-performance liquid chromatography was developed and the enzyme kinetic parameters for their formation were determined using purified recombinant human SULT1A3. The results show that SULT1A3 strongly favors the 3-hydroxy group of dopamine, which indicates that it may be the major enzyme responsible for the difference between the circulating levels of dopamine sulfates in human blood. All 19 known human UGTs were expressed as recombinant enzymes in baculovirus infected insect cells and their activities toward dopamine and estradiol were studied. UGT1A10 was identified as the only UGT capable of dopamine glucuronidation at a substantial level. The results were supported by studies with human intestinal and liver microsomes. The affinity was low indicating that UGT1A10 is not an important enzyme in dopamine metabolism in vivo. Despite the low affinity, dopamine is a potential new probe substrate for UGT1A10 due to its selectivity. Dopamine was used to study the importance of phenylalanines 90 and 93 in UGT1A10. The results revealed distinct effects that are dependent on differences in the size of the side chain and on the differences in their position within the protein. Examination of twelve mutants revealed lower activity in all of them. However, the enzyme kinetic studies of four mutants showed that their affinities were similar to that of UGT1A10 suggesting that F90 and F93 are not directly involved in dopamine binding in the active site. The glucuronidation of β-estradiol and epiestradiol (α-estradiol) was studied to elucidate how the orientation of the 17-OH group affects conjugation at the 3-OH or the 17-OH of either diastereomer. The results show that there are clear differences in the regio- and stereoselectivities of UGTs. The most active isoforms were UGT1A10 and UGT2B7 demonstrating opposite regioselectivity. The stereoselectivities of UGT2Bs were more complex than those of UGT1As. The amino acid sequences of the human UGTs 1A9 and 1A10 are 93% identical, yet there are large differences in their activity and substrate selectivity. Several mutants were constructed to identify the residues responsible for the activity differences. The results revealed that the residues between Leu86 and Tyr176 of UGT1A9 determine the differences between UGT1A9 and UGT1A10. Phe117 of UGT1A9 participated in 1-naphthol binding and the residues at positions 152 and 169 contributed to the higher glucuronidation rates of UGT1A10. In summary, the results emphasize that the substrate selectivities, including regio- and stereoselectivities, of UGTs are complex and they are controlled by many amino acids rather than one critical residue.

Key Factors Influencing Economic Relationships and Communication in Finnish Food Chains

The aim of this report is to discuss the role of the relationship type and communication in two Finnish food chains, namely the pig meat-to-sausage (pig meat chain) and the cereal-to-rye bread (rye chain) chains. Furthermore, the objective is to examine those factors influencing the choice of a relationship type and the sustainability of a business relationship. Altogether 1808 questionnaires were sent to producers, processors and retailers operating in these two chains of which 224 usable questionnaires were returned (the response rate being 12.4%). The great majority of the respondents (98.7%) were small businesses employing less than 50 people. Almost 70 per cent of the respondents were farmers. In both chains, formal contracts were stated to be the most important relationship type used with business partners. Although for many businesses written contracts are a common business practice, the essential role of the contracts was the security they provide regarding the demand/supply and quality issues. Relative to the choice of the relationship types, the main difference between the two chains emerged especially with the prevalence of spot markets and financial participation arrangements. The usage of spot markets was significantly more common in the rye chain when compared to the pig meat chain, while, on the other hand, financial participation arrangements were much more common among the businesses in the pig meat chain than in the rye chain. Furthermore, the analysis showed that most of the businesses in the pig meat chain claimed not to be free to choose the relationship type they use. Especially membership in a co-operative and practices of a business partner were mentioned as the reasons limiting this freedom of choice. The main business relations in both chains were described as having a long-term orientation and being based on formal written contracts. Typical for the main business relationships was also that they are not based on the existence of the key persons only; the relationship would remain even if the key people left the business. The quality of these relationships was satisfactory in both chains and across all the stakeholder groups, though the downstream processors and the retailers had a slightly more positive view on their main business partners than the farmers and the upstream processors. The businesses operating in the pig meat chain seemed also to be more dependent on their main business relations when compared to the businesses in the rye chain. Although the communication means were rather similar in both chains (the phone being the most important), there was some variation between the chains concerning the communication frequency necessary to maintain the relationship with the main business partner. In short, the businesses in the pig meat chain seemed to appreciate more frequent communication with their main business partners when compared to the businesses in the rye chain. Personal meetings with the main business partners were quite rare in both chains. All the respondent groups were, however, fairly satisfied with the communication frequency and information quality between them and the main business partner. The business cultures could be argued to be rather hegemonic among the businesses both in the pig meat and rye chains. Avoidance of uncertainty, appreciation of long-term orientation and independence were considered important factors in the business cultures. Furthermore, trust, commitment and satisfaction in business partners were thought to be essential elements of business operations in all the respondent groups. In order to investigate which factors have an effect on the choice of a relationship type, several hypotheses were tested by using binary and multinomial logit analyses. According to these analyses it could be argued that avoidance of uncertainty and risk has a certain effect on the relationship type chosen, i.e. the willingness to avoid uncertainty increases the probability to choose stable relationships, like repeated market transactions and formal written contracts, but not necessary those, which require high financial commitment (like financial participation arrangements). The probability of engaging in financial participation arrangements seemed to increase with long-term orientation. The hypotheses concerning the sustainability of the economic relations were tested by using structural equation model (SEM). In the model, five variables were found to have a positive and statistically significant impact on the sustainable economic relationship construct. Ordered relative to their importance, those factors are: (i) communication quality, (ii) personal bonds, (iii) equal power distribution, (iv) local embeddedness and (v) competition.