Purification of pharmaceuticals and nutraceutical compounds by sub- and supercritical extraction and chromatography

This thesis discusses the use of sub- and supercritical fluids as the medium in extraction and chromatography. Super- and subcritical extraction was used to separate essential oils from herbal plant Angelica archangelica. The effect of extraction parameters was studied and sensory analyses of the extracts were done by an expert panel. The results of the sensory analyses were compared to the analytically determined contents of the extracts. Sub- and supercritical fluid chromatography (SFC) was used to separate and purify high-value pharmaceuticals. Chiral SFC was used to separate the enantiomers of racemic mixtures of pharmaceutical compounds. Very low (cryogenic) temperatures were applied to substantially enhance the separation efficiency of chiral SFC. The thermodynamic aspects affecting the resolving ability of chiral stationary phases are briefly reviewed. The process production rate which is a key factor in industrial chromatography was optimized by empirical multivariate methods. General linear model was used to optimize the separation of omega-3 fatty acid ethyl esters from esterized fish oil by using reversed-phase SFC. Chiral separation of racemic mixtures of guaifenesin and ferulic acid dimer ethyl ester was optimized by using response surface method with three variables per time. It was found that by optimizing four variables (temperature, load, flowate and modifier content) the production rate of the chiral resolution of racemic guaifenesin by cryogenic SFC could be increased severalfold compared to published results of similar application. A novel pressure-compensated design of industrial high pressure chromatographic column was introduced, using the technology developed in building the deep-sea submersibles (Mir 1 and 2). A demonstration SFC plant was built and the immunosuppressant drug cyclosporine A was purified to meet the requirements of US Pharmacopoeia. A smaller semi-pilot size column with similar design was used for cryogenic chiral separation of aromatase inhibitor Finrozole for use in its development phase 2.

Modernity, postmodernity and identity of jazz in Chile : The cases of the generation of 1990 and Ángel Parra

This research is about jazz in Chile in relation to modernity and identity. Final chapters focus and detach latest jazz musician s generation in 1990 decade and composer guitarist Angel Parra. An historic and sociological approach is developed, which will be useful for modernity and identity analysis, and so on post modernity and globalization. Modernity has been studied in texts of Adorno, Baudrillard, Brünner, García Canclini, Habermas and Jameson. Identity has been studied in texts of Aharonián, Cordúa, Garretón, Gissi, Larraín and others. Chapter 3 is about Latin-American musicology and jazz investigations, in relation to approach developed in chapter 2. Chapters 4 and 5 are about history of jazz in Chile until beginning of XXI century. Chapter 6 focuses in Ángel Parra Orrego. Conclusions of this investigation detach the modernist mechanical that has conducted jazz development in Chile, which in Ángel Parra´s case has been overcame by a post modernist behaviour. This behaviour has solved in a creative way, subjects like modernity and identity in jazz practice in a Latin-American country.

Supervisors' emerging role in second-generation knowledge management

This study examines supervisors' emerging new role in a technical customer service and home customers division of a large Finnish telecommunications corporation. Data of the study comes from a second-generation knowledge management project, an intervention research, which was conducted for supervisors of the division. The study exemplifies how supervision work is transforming in high technology organization characterized with high speed of change in technologies, products, and in grass root work practices. The intervention research was conducted in the division during spring 2000. Primary analyzed data consists of six two-hour videorecorded intervention sessions. Unit of analysis has been collective learningactions. Researcher has first written conversation transcripts out of the video-recorded meetings and then analyzed this qualitative data using analytical schema based on collective learning actions. Supervisors' role is conceptualized as an actor of a collective and dynamic activity system, based on the ideas from cultural historical activity theory. On knowledge management researcher has takena second-generation knowledge management viewpoint, following ideas fromcultural historical activity theory and developmental work research. Second-generation knowledge management considers knowledge embedded and constructed in collective practices, such as innovation networks or communities of practice (supervisors' work community), which have the capacity to create new knowledge. Analysis and illustration of supervisors' emerging new role is conceptualized in this framework using methodological ideas derived from activity theory and developmental work research. Major findings of the study show that supervisors' emerging new role in a high technology telecommunication organization characterized with high speed of discontinuous change in technologies, products, and in grass-root practices cannot be defined or characterized using a normative management role/model. Their role is expanding two-dimensionally, (1) socially and (2) in new knowledge, and work practices. The expansion in organization and inter-organizational network (social expansion) causes pressures to manage a network of co-operation partners and subordinates. On the other hand, the faster speed of change in technological solutions, new products, and novel customer wants (expansion in knowledge) causes pressures for supervisors to innovate quickly new work practices to manage this change. Keywords: Activity theory, knowledge management, developmental work research, supervisors, high technology organizations, telecommunication organizations, second-generation knowledge management, competence laboratory, intervention research, learning actions.

Women, environmental changes and forestry-related development : Gender-affected roles of rural people in land degradation and environmental rehabilitation in a dry region of Sudan

The purpose of the present study was to increase understanding of the interaction of rural people and, specifically, women with the environment in a dry area in Sudan. The study that included both nomadic pastoralists and farmers aimed at answering two main research questions, namely: What kinds of roles have the local people, and the women in particular, had in land degradation in the study area and what kinds of issues would a gender-sensitive, forestry-related environmental rehabilitation intervention need to consider there? The study adopted the definition of land degradation as proposed by the United Nations Convention to Combat Desertification (UNCCD), which describes land degradation as reduction or loss the biological or economic productivity and complexity of land in arid, semi-arid and dry sub-humid areas. The Convention perceives desertification as land degradation. The dry study area in Sudan, South of the Sahara, has been the subject of land degradation or desertification discussions since the 1970s, and other studies have been also conducted to assess the degradation in the area. Nevertheless, the exact occurrence, scale and local significance of land degradation in the area is still unclear. This study explored how the rural population whose livelihood depended on the area, perceived environmental changes occurring there and compared their conceptions with other sources of information of the area such as research reports. The main fieldwork methods included interviews with open-ended questions and observation of people and the environment. The theoretical framework conceptualised the rural population as land users whose choices of environmental activities are affected by multiple factors in the social and biophysical contexts in which they live. It was emphasised that these factors have their own specific characteristics in different contexts, simultaneously recognising that there are also factors that generally affect environmental practices in various areas such as the land users' environmental literacy (conceptions of the environment), gender and livelihood needs. The people studied described that environmental changes, such as reduced vegetation cover and cropland production, had complicated the maintenance of their livelihoods in the study area. Some degraded sites were also identified through observations during the fieldwork. Whether a large-scale reduction of cropland productivity had occurred in the farmers' croplands remained, however, unclear. The study found that the environmental impact of the rural women's activities varied and was normally limited. The women's most significant environmental impact resulted from their cutting of trees, which was likely to contribute, at least in some places, to land degradation, affecting the environment together with climate and livestock. However, when a wider perspective is taken, it becomes questionable whether the women have really played roles in land degradation, since gender, poverty and the need to maintain livelihood had caused them to conduct environmentally harmful activities. The women have had, however, no power to change the causes of their activities. The findings further suggested that an inadequate availability of food was the most critical problem in the study area. Therefore, an environmental programme in the area was suggested to include technical measures to increase the productivity of croplands, opportunities for income generation and readiness to co-operate with other programmes to improve the local people's abilities to maintain their livelihoods. In order to protect the environment and alleviate the women's work burden, the introduction of fuel-saving stoves was also suggested. Furthermore, it was suggested that increased planting of trees on homesteads would be supported by an easy availability of tree seedlings. Planting trees on common property land was, however, perceived as extremely demanding in the study area, due to scarcity of such land. In addition, it became apparent that the local land users, and women in particular, needed to allocate their labour to maintain the immediate livelihood of their families and were not motivated to allocate their labour solely for environmental rehabilitation. Nonetheless, from the point of view of the existing social structures, women's active participation in a community-based environmental programme would be rather natural, particularly among the farmer women who had already formed a women's group and participated in communal decision making. Forming of a women group or groups was suggested to further support both the farmer women's and pastoral women's active participation within an environmental programme and their general empowerment. An Environmental programme would need to acknowledge that improving rural people's well-being and maintaining their livelihood in the study area requires development and co-operation with various sectors in Sudan.

Rural Income Generation and Diversification : A Case Study in Eastern Zambia

Rural income diversification has been found to be rather the norm than the exception in developing countries. Smallholder households tend to diversify their income sources because of the need to manage risks, secure a smooth flow of income, allocate surplus labour, respond to various kinds of market failures, and apply coping strategies. The Agricultural Household Model provides a theoretical rationale for income diversification in that rural households aim at maximising their utility. There are several elements involved, such as agricultural production for their own consumption and markets, leisure activities and income from non-farm sources. The aim of the present study is to enhance understanding of the processes of rural income generation and diversification in eastern Zambia. Specifically, it explores the relationship between household characteristics, asset endowments and income-generation patterns. According to the sustainable- rural-livelihoods framework, the assets a household possesses shape its capacity to seize new economic opportunities. The study is based on two surveys conducted among rural smallholder households in four districts of Eastern Province in Zambia in 1985/86 and 2003. Sixty-seven of the interviewed households were present in both surveys and this panel allows comparison between the two points of time. The initial descriptive analysis is complemented with an econometric analysis of the relationships between household assets and income sources. The results show that, on average, 30 per cent of the households income originated from sources outside their own agriculture. There was a slight increase in the proportion of non-farm income from 1985/86 to 2003, but total income clearly declined mainly on account of diminishing crop income. The land area the household was able to cultivate, which is often dependent on the available labour, was the most significant factor affecting both the household-income level and the diversification patterns. Diversification was, in most cases, a coping strategy rather than a voluntary choice. Measured as income/capita/day, all households were below the poverty line in 2003. The agricultural reforms in Zambia, combined with other trends such as changes in rainfall pattern, the worsening livestock situation and the incidence of human disease, had a negative impact on agricultural productivity and income between 1985/86 and 2003. Sources of non-farm income were closely linked to agriculture either upstream or downstream and the income they generated was not enough to compensate for the decline of agricultural income. Household assets and characteristics had a smaller impact on diversification patterns than expected, which could reflect the lack of opportunities in the remote rural environment.

Dirichlet problem at infinity for p-harmonic functions on negatively curved spaces

The object of this dissertation is to study globally defined bounded p-harmonic functions on Cartan-Hadamard manifolds and Gromov hyperbolic metric measure spaces. Such functions are constructed by solving the so called Dirichlet problem at infinity. This problem is to find a p-harmonic function on the space that extends continuously to the boundary at inifinity and obtains given boundary values there. The dissertation consists of an overview and three published research articles. In the first article the Dirichlet problem at infinity is considered for more general A-harmonic functions on Cartan-Hadamard manifolds. In the special case of two dimensions the Dirichlet problem at infinity is solved by only assuming that the sectional curvature has a certain upper bound. A sharpness result is proved for this upper bound. In the second article the Dirichlet problem at infinity is solved for p-harmonic functions on Cartan-Hadamard manifolds under the assumption that the sectional curvature is bounded outside a compact set from above and from below by functions that depend on the distance to a fixed point. The curvature bounds allow examples of quadratic decay and examples of exponential growth. In the final article a generalization of the Dirichlet problem at infinity for p-harmonic functions is considered on Gromov hyperbolic metric measure spaces. Existence and uniqueness results are proved and Cartan-Hadamard manifolds are considered as an application.

Generation and Characterization of the Cation-Chloride Cotransporter KCC2 Hypomorphic Mouse

The cation-Cl- cotransporter (CCC) family comprises of Na+-Cl- cotransporter (NCC), Na+-K+-2Cl- cotransporters (NKCC1-2), and four K+-Cl- cotransporters (KCC1-4). These proteins are involved in several physiological activities, such as cell volume regulation. In neuronal tissues, NKCC1 and KCC2 are important in determining the intracellular Cl- levels and hence the neuronal responses to inhibitory neurotransmitters GABA and glycine. One aim of the work was to elucidate the roles for CCC isoforms in the control of nervous system development. KCC2 mRNA was shown to be developmentally up-regulated and follow neuronal maturation, whereas NKCC1 and KCC4 transcripts were highly expressed in the proliferative zones of subcortical regions. KCC1 and KCC3 mRNA displayed low expression throughout the embryogenesis. These expression profiles suggest a role for CCC isoforms in maturation of synaptic responses and in the regulation of neuronal proliferation during embryogenesis. The major aim of this work was to study the biological consequences of KCC2-deficiency in the adult CNS, by generating transgenic mice retaining 15-20% of normal KCC2 levels. In addition, by using these mice as a tool for in vivo pharmacological analysis, we investigated the requirements for KCC2 in tonic versus phasic GABAA receptor-mediated inhibition. KCC2-deficient mice displayed normal reproduction and life span, but showed several behavioral abnormalities, including increased anxiety-like behavior, impaired performance in water maze, alterations in nociceptive processing, and increased seizure susceptibility. In contrast, the mice displayed apparently normal spontaneous locomotor activity and motor coordination. Pharmacological analysis of KCC2-deficient mice revealed reduced sensititivity to diazepam, but normal gaboxadol-induced sedation, neurosteroid hypnosis and alcohol-induced motor impairment. Electrophysiological recordings from CA1-CA3 subregions of the hippocampus showed that KCC2 deficiency affected the reversal potentials of both the phasic and tonic GABA currents, and that the tonic conductance was not affected. The results suggest that requirement for KCC2 in GABAergic neurotransmission may differ among several functional systems in the CNS, which is possibly due to the more critical role of KCC2 activity in phasic compared to tonic GABAergic inhibition.

Pathways to health : Determinants of health, health behaviour and health inequalities in early adulthood

There is increasing evidence that the origins of poor adult health and health inequalities can be traced back to circumstances preceding current socioeconomic position and living conditions. The life-course approach to examining the determinants of health has emphasised that exposure to adverse social and economic circumstances in earlier life or concurrent adverse circumstances due to unfavourable living conditions in earlier life may lead to poor health, health-damaging behaviour, disease or even premature death in adulthood. There is, however, still a lack of knowledge about the contribution of social and economic circumstances in childhood and youth to adult health and health inequalities, and even less is known about how environmental and behavioural factors in adulthood mediate the effects of earlier adverse experiences. The main purpose of this study was to deepen our understanding of the development of poor health, health-damaging behaviours and health inequalities during the life-course. Its aim was to find out which factors in earlier and current circumstances determine health, the most detrimental indicators of health behaviour (smoking, heavy drinking and obesity as a proxy for the balance between nutrition and exercise), and educational health differences in young adults in Finland. Following the ideas of the social pathway theory, it was assumed that childhood environment affects adult health and its proximal determinants via different pathways, including educational, work and family careers. Early adulthood was studied as a significant phase of life when many behavioural patterns and living conditions relevant to health are established. In addition, socioeconomic health inequalities seem to emerge rapidly when moving into adulthood; they are very small or non-existent in childhood and adolescence, but very marked by early middle age. The data of this study were collected in 2000 2001 as part of the Health 2000 Survey (N = 9,922), a cross-sectional and nationally representative health interview and examination survey. The main subset of data used in this thesis was the one comprising the age group 18 29 years (N = 1,894), which included information collected by standardised structured computer-aided interviews and self-administered questionnaires. The survey had a very high participation rate at almost 90% for the core questions. According to the results of this study, childhood circumstances predict the health of young adults. Almost all the childhood adversities studied were found to be associated with poor self-rated health and psychological distress in early adulthood, although fewer associations were found with the somatic morbidity typical of young adults. These effects seemed to be more or less independent of the young adult s own education. Childhood circumstances also had a strong effect on smoking and heavy drinking, although current circumstances and education in particular, played a role in mediating this effect. Parental smoking and alcohol abuse had an influence on the corresponding behaviours of offspring. Childhood circumstances had a role in the development of obesity and, to a lesser extent, overweight, particularly in women. The findings support the notion that parental education has a strong effect on early adult obesity, even independently of the young adult s own educational level. There were marked educational differences in self-rated health in early adulthood: those in the lowest educational category were most likely to have average or poorer health. Childhood social circumstances seemed to explain a substantial part of these educational differences. In addition, daily smoking and heavy drinking contributed substantially to educational health differences. However, the contribution of childhood circumstances was largely shared with health behaviours adopted by early adulthood. Employment also shared the effects of childhood circumstances on educational health differences. The results indicate that childhood circumstances are important in determining health, health behaviour and health inequalities in early adulthood. Early recognition of childhood adversities followed by relevant support measures may play an important role in preventing the unfortunate pathways leading to the development of poor health, health-damaging behaviour and health inequalities. It is crucially important to recognise the needs of children living in adverse circumstances as well as children of substance abusing parents. In addition, single-parent families would benefit from support. Differences in health and health behaviours between different sub-groups of the population mean that we can expect to see ever greater health differences when today s generation of young adults grows older. This presents a formidable challenge to national health and social policy as well as health promotion. Young adults with no more than primary level education are at greatest risk of poor health. Preventive policies should emphasise the role of low educational level as a key determinant of health-damaging behaviours and poor health. Keywords: health, health behaviour, health inequalities, life-course, socioeconomic position, education, childhood circumstances, self-rated health, psychological distress, somatic morbidity, smoking, heavy drinking, BMI, early adulthood

Combined Tevatron upper limit on gg->H->W+W- and constraints on the Higgs boson mass in fourth-generation fermion models

We combine results from searches by the CDF and D0 collaborations for a standard model Higgs boson (H) in the process gg->H->W+W- in p=pbar collisions at the Fermilab Tevatron Collider at sqrt{s}=1.96 TeV. With 4.8 fb-1 of integrated luminosity analyzed at CDF and 5.4 fb-1 at D0, the 95% Confidence Level upper limit on \sigma(gg->H) x B(H->W+W-) is 1.75 pb at m_H=120 GeV, 0.38 pb at m_H=165 GeV, and 0.83 pb at m_H=200 GeV. Assuming the presence of a fourth sequential generation of fermions with large masses, we exclude at the 95% Confidence Level a standard-model-like Higgs boson with a mass between 131 and 204 GeV.

Rigorous scaling law for the heat current in disordered harmonic chain

We study the energy current in a model of heat conduction, first considered in detail by Casher and Lebowitz. The model consists of a one-dimensional disordered harmonic chain of n i.i.d. random masses, connected to their nearest neighbors via identical springs, and coupled at the boundaries to Langevin heat baths, with respective temperatures T_1 and T_n. Let EJ_n be the steady-state energy current across the chain, averaged over the masses. We prove that EJ_n \sim (T_1 - T_n)n^{-3/2} in the limit n \to \infty, as has been conjectured by various authors over the time. The proof relies on a new explicit representation for the elements of the product of associated transfer matrices.