Polymerization of Ethene and Branched α-olefins with Group IV Metal Complexes Bearing Nitrogen- and Oxygen-Based Ligands

The commodity plastics that are used in our everyday lives are based on polyolefin resins and they find wide variety of applications in several areas. Most of the production is carried out in catalyzed low pressure processes. As a consequence polymerization of ethene and α-olefins has been one of the focus areas for catalyst research both in industry and academia. Enormous amount of effort have been dedicated to fine tune the processes and to obtain better control of the polymerization and to produce tailored polymer structures The literature review of the thesis concentrates on the use of Group IV metal complexes as catalysts for polymerization of ethene and branched α-olefins. More precisely the review is focused on the use of complexes bearing [O,O] and [O,N] type ligands which have gained considerable interest. Effects of the ligand framework as well as mechanical and fluxional behaviour of the complexes are discussed. The experimental part consists mainly of development of new Group IV metal complexes bearing [O,O] and [O,N] ligands and their use as catalysts precursors in ethene polymerization. Part of the experimental work deals with usage of high-throughput techniques in tailoring properties of new polymer materials which are synthesized using Group IV complexes as catalysts. It is known that the by changing the steric and electronic properties of the ligand framework it is possible to fine tune the catalyst and to gain control over the polymerization reaction. This is why in this thesis the complex structures were designed so that the ligand frameworks could be fairly easily modified. All together 14 complexes were synthesised and used as catalysts in ethene polymerizations. It was found that the ligand framework did have an impact within the studied catalyst families. The activities of the catalysts were affected by the changes in complex structure and also effects on the produced polymers were observed: molecular weights and molecular weight distributions were depended on the used catalyst structure. Some catalysts also produced bi- or multi-modal polymers. During last decade high-throughput techniques developed in pharmaceutical industries have been adopted into polyolefin research in order to speed-up and optimize the catalyst candidates. These methods can now be regarded as established method suitable for both academia and industry alike. These high-throughput techniques were used in tailoring poly(4-methyl-1-pentene) polymers which were synthesized using Group IV metal complexes as catalysts. This work done in this thesis represents the first successful example where the high-throughput synthesis techniques are combined with high-throughput mechanical testing techniques to speed-up the discovery process for new polymer materials.

Novel Mass Spectrometric Analysis Methods for Anabolic Androgenic Steroids in Sports Drug Testing

The feasibility of different modern analytical techniques for the mass spectrometric detection of anabolic androgenic steroids (AAS) in human urine was examined in order to enhance the prevalent analytics and to find reasonable strategies for effective sports drug testing. A comparative study of the sensitivity and specificity between gas chromatography (GC) combined with low (LRMS) and high resolution mass spectrometry (HRMS) in screening of AAS was carried out with four metabolites of methandienone. Measurements were done in selected ion monitoring mode with HRMS using a mass resolution of 5000. With HRMS the detection limits were considerably lower than with LRMS, enabling detection of steroids at low 0.2-0.5 ng/ml levels. However, also with HRMS, the biological background hampered the detection of some steroids. The applicability of liquid-phase microextraction (LPME) was studied with metabolites of fluoxymesterone, 4-chlorodehydromethyltestosterone, stanozolol and danazol. Factors affecting the extraction process were studied and a novel LPME method with in-fiber silylation was developed and validated for GC/MS analysis of the danazol metabolite. The method allowed precise, selective and sensitive analysis of the metabolite and enabled simultaneous filtration, extraction, enrichment and derivatization of the analyte from urine without any other steps in sample preparation. Liquid chromatographic/tandem mass spectrometric (LC/MS/MS) methods utilizing electrospray ionization (ESI), atmospheric pressure chemical ionization (APCI) and atmospheric pressure photoionization (APPI) were developed and applied for detection of oxandrolone and metabolites of stanozolol and 4-chlorodehydromethyltestosterone in urine. All methods exhibited high sensitivity and specificity. ESI showed, however, the best applicability, and a LC/ESI-MS/MS method for routine screening of nine 17-alkyl-substituted AAS was thus developed enabling fast and precise measurement of all analytes with detection limits below 2 ng/ml. The potential of chemometrics to resolve complex GC/MS data was demonstrated with samples prepared for AAS screening. Acquired full scan spectral data (m/z 40-700) were processed by the OSCAR algorithm (Optimization by Stepwise Constraints of Alternating Regression). The deconvolution process was able to dig out from a GC/MS run more than the double number of components as compared with the number of visible chromatographic peaks. Severely overlapping components, as well as components hidden in the chromatographic background could be isolated successfully. All studied techniques proved to be useful analytical tools to improve detection of AAS in urine. Superiority of different procedures is, however, compound-dependent and different techniques complement each other.

From Polymorph Screening to Dissolution Testing - Solid Phase Analysis during Pharmaceutical Development and Manufacturing

Solid materials can exist in different physical structures without a change in chemical composition. This phenomenon, known as polymorphism, has several implications on pharmaceutical development and manufacturing. Various solid forms of a drug can possess different physical and chemical properties, which may affect processing characteristics and stability, as well as the performance of a drug in the human body. Therefore, knowledge and control of the solid forms is fundamental to maintain safety and high quality of pharmaceuticals. During manufacture, harsh conditions can give rise to unexpected solid phase transformations and therefore change the behavior of the drug. Traditionally, pharmaceutical production has relied on time-consuming off-line analysis of production batches and finished products. This has led to poor understanding of processes and drug products. Therefore, new powerful methods that enable real time monitoring of pharmaceuticals during manufacturing processes are greatly needed. The aim of this thesis was to apply spectroscopic techniques to solid phase analysis within different stages of drug development and manufacturing, and thus, provide a molecular level insight into the behavior of active pharmaceutical ingredients (APIs) during processing. Applications to polymorph screening and different unit operations were developed and studied. A new approach to dissolution testing, which involves simultaneous measurement of drug concentration in the dissolution medium and in-situ solid phase analysis of the dissolving sample, was introduced and studied. Solid phase analysis was successfully performed during different stages, enabling a molecular level insight into the occurring phenomena. Near-infrared (NIR) spectroscopy was utilized in screening of polymorphs and processing-induced transformations (PITs). Polymorph screening was also studied with NIR and Raman spectroscopy in tandem. Quantitative solid phase analysis during fluidized bed drying was performed with in-line NIR and Raman spectroscopy and partial least squares (PLS) regression, and different dehydration mechanisms were studied using in-situ spectroscopy and partial least squares discriminant analysis (PLS-DA). In-situ solid phase analysis with Raman spectroscopy during dissolution testing enabled analysis of dissolution as a whole, and provided a scientific explanation for changes in the dissolution rate. It was concluded that the methods applied and studied provide better process understanding and knowledge of the drug products, and therefore, a way to achieve better quality.

Käsityksistä ajatuksen poluille : Ammattikorkeakoulun tutkimus- ja kehitystoiminnan kehittäminen

This study deals with the formation of the idea of research and development (r&d) activity at one particular university of applied sciences in Finland. In this study I proceed from examining the conceptions of management regarding r&d-activities to exploring the development of the complex concept that guides these r&d-activities. The aim of this study is, first, to describe conceptions of r&d-activities, and then, second, to describe the formation of a new concept for r&d-activities in one field of study at the university of applied sciences. I used phenomenographic analysis to elucidate the conceptions and collected the data in interviews of personnel (22) who belong to the management of the university of applied sciences. The data for analysing the obstacles faced and the ways of overcoming them during the formation process of the new concept consist of the video-recorded material from ten change laboratory sessions held for the specific field of study at the university of applied sciences. In researching the formation of the concept of the activity, such research and analysis methods are used in which the concept is understood as a material construction, and with the help of which one can work out the formation of the concept during the development process. When the systematic development of the r&d-work was underway, the management of the university of applied sciences held differing views regarding the content, target, factors and organisation of the r&d-activities, as well as regarding the position of dissertations as a part of r&d-activity. Obstacles for developing rd concerned the unclear object and outcomes of the new activity, not having the tools (such as adequate know-how) for the new activity and not having found the necessary solutions for the distribution of work. In addition the rules that quide the activities of the university of applied sciences did not support working according to the new way. To improve r&d-activity, the school’s management defined three development strategies to encourage adequate rd-activity to support working life, regional development and learning. The strategies were based on the expansion of existing methods, such as service activities, dissertation work and the research activities of the teachers. Of the three possible routes, the concept of dissertation in this study was expanded to integrate the services of organisation development and the occupational growth of the students. A group of teachers in the field of social and health studies participated in the development work. The change laboratory method was used as a tool for this work. Analysis of the cognitive trails indicated that, in addition to the cycle of expansive learning activities, microcycles with different purposes can exist. According to Cussins (1992), something already in existence in each microcycle is destabilised, and something else is stabilised to replace it. In this study three microcycles were identified, during which the teachers first destabilised the existing concepts of dissertation work that guided their thinking, and then began to use new concepts to structure their thinking. Secondly, they undermined the existing concepts with material structure that defined their practical work, and developed new practical models to replace them. Thirdly, the problems accumulating in researching and testing the new activities caused the developers to destabilise the r&d-strategies of the university of applied sciences and to define a new conceptual model for r&d-work in the field. During this third cycle, the teachers developed a research arena model, which was a significant expansive innovation. In the cognitive trails developing the new concept for the r&d-activity, the teachers indeed faced the obstacles the management had described as their conceptions. These obstacles manifested themselves as contradictions. During the development process, the nature of the obstacles (i.e. contradictions) changed as the development proceeded. Solving the first and second degree contradictions highlighted the third and fourth degree contradictions. To overcome the obstacles, the teachers had to to articulate the value and motive of the development work throughout the development process. Developing the new concept for r&d-activity required many reconfigurations of practical solutions to overcome the obstacles. Developing the new concept for r&d-activity, both at the level of representations and of new practices, requires universities of applied sciences to adopt new methods in which the actors are partake in construction of new concepts of activity through adequate discussion, analysis and debate. R&d -activity can progress, if instead of implementing partial solutions, the totality of the activities (i.e. the group of partial solutions acting together) will be constructed. The development of the activity system requires many simultaneous changes as well as wide-ranging know-how and discussion related to these changes. What is perhaps most important, however, is that the group of developers mature into a determined collective actor which can engage in many agentive actions. The development of the agency is fundamental to progress.

Methodological and Empirical Advances in the Quantitative Analysis of Spontaneous Responses in Psychophysiological Time Series

The aim of the present study was to advance the methodology and use of time series analysis to quantify dynamic structures in psychophysiological processes and thereby to produce information on spontaneously coupled physiological responses and their behavioral and experiential correlates. Series of analyses using both simulated and empirical cardiac (IBI), electrodermal (EDA), and facial electromyographic (EMG) data indicated that, despite potential autocorrelated structures, smoothing increased the reliability of detecting response coupling from an interindividual distribution of intraindividual measures and that especially the measures of covariance produced accurate information on the extent of coupled responses. This methodology was applied to analyze spontaneously coupled IBI, EDA, and facial EMG responses and vagal activity in their relation to emotional experience and personality characteristics in a group of middle-aged men (n = 37) during the administration of the Rorschach testing protocol. The results revealed new characteristics in the relationship between phasic end-organ synchronization and vagal activity, on the one hand, and individual differences in emotional adjustment to novel situations on the other. Specifically, it appeared that the vagal system is intimately related to emotional and social responsivity. It was also found that the lack of spontaneously synchronized responses is related to decreased energetic arousal (e.g., depression, mood). These findings indicate that the present process analysis approach has many advantages for use in both experimental and applied research, and that it is a useful new paradigm in psychophysiological research. Keywords: Autonomic Nervous System; Emotion; Facial Electromyography; Individual Differences; Spontaneous Responses; Time Series Analysis; Vagal System

Prevention of type 2 diabetes with lifestyle intervention - emphasis on dietary composition and identification of high-risk individuals

Type 2 diabetes is an increasing, serious, and costly public health problem. The increase in the prevalence of the disease can mainly be attributed to changing lifestyles leading to physical inactivity, overweight, and obesity. These lifestyle-related risk factors offer also a possibility for preventive interventions. Until recently, proper evidence regarding the prevention of type 2 diabetes has been virtually missing. To be cost-effective, intensive interventions to prevent type 2 diabetes should be directed to people at an increased risk of the disease. The aim of this series of studies was to investigate whether type 2 diabetes can be prevented by lifestyle intervention in high-risk individuals, and to develop a practical method to identify individuals who are at high risk of type 2 diabetes and would benefit from such an intervention. To study the effect of lifestyle intervention on diabetes risk, we recruited 522 volunteer, middle-aged (aged 40 - 64 at baseline), overweight (body mass index > 25 kg/m2) men (n = 172) and women (n = 350) with impaired glucose tolerance to the Diabetes Prevention Study (DPS). The participants were randomly allocated either to the intensive lifestyle intervention group or the control group. The control group received general dietary and exercise advice at baseline, and had annual physician's examination. The participants in the intervention group received, in addition, individualised dietary counselling by a nutritionist. They were also offered circuit-type resistance training sessions and were advised to increase overall physical activity. The intervention goals were to reduce body weight (5% or more reduction from baseline weight), limit dietary fat (< 30% of total energy consumed) and saturated fat (< 10% of total energy consumed), and to increase dietary fibre intake (15 g / 1000 kcal or more) and physical activity (≥ 30 minutes/day). Diabetes status was assessed annually by a repeated 75 g oral glucose tolerance testing. First analysis on end-points was completed after a mean follow-up of 3.2 years, and the intervention phase was terminated after a mean duration of 3.9 years. After that, the study participants continued to visit the study clinics for the annual examinations, for a mean of 3 years. The intervention group showed significantly greater improvement in each intervention goal. After 1 and 3 years, mean weight reductions were 4.5 and 3.5 kg in the intervention group and 1.0 kg and 0.9 kg in the control group. Cardiovascular risk factors improved more in the intervention group. After a mean follow-up of 3.2 years, the risk of diabetes was reduced by 58% in the intervention group compared with the control group. The reduction in the incidence of diabetes was directly associated with achieved lifestyle goals. Furthermore, those who consumed moderate-fat, high-fibre diet achieved the largest weight reduction and, even after adjustment for weight reduction, the lowest diabetes risk during the intervention period. After discontinuation of the counselling, the differences in lifestyle variables between the groups still remained favourable for the intervention group. During the post-intervention follow-up period of 3 years, the risk of diabetes was still 36% lower among the former intervention group participants, compared with the former control group participants. To develop a simple screening tool to identify individuals who are at high risk of type 2 diabetes, follow-up data of two population-based cohorts of 35-64 year old men and women was used. The National FINRISK Study 1987 cohort (model development data) included 4435 subjects, with 182 new drug-treated cases of diabetes identified during ten years, and the FINRISK Study 1992 cohort (model validation data) included 4615 subjects, with 67 new cases of drug-treated diabetes during five years, ascertained using the Social Insurance Institution's Drug register. Baseline age, body mass index, waist circumference, history of antihypertensive drug treatment and high blood glucose, physical activity and daily consumption of fruits, berries or vegetables were selected into the risk score as categorical variables. In the 1987 cohort the optimal cut-off point of the risk score identified 78% of those who got diabetes during the follow-up (= sensitivity of the test) and 77% of those who remained free of diabetes (= specificity of the test). In the 1992 cohort the risk score performed equally well. The final Finnish Diabetes Risk Score (FINDRISC) form includes, in addition to the predictors of the model, a question about family history of diabetes and the age category of over 64 years. When applied to the DPS population, the baseline FINDRISC value was associated with diabetes risk among the control group participants only, indicating that the intensive lifestyle intervention given to the intervention group participants abolished the diabetes risk associated with baseline risk factors. In conclusion, the intensive lifestyle intervention produced long-term beneficial changes in diet, physical activity, body weight, and cardiovascular risk factors, and reduced diabetes risk. Furthermore, the effects of the intervention were sustained after the intervention was discontinued. The FINDRISC proved to be a simple, fast, inexpensive, non-invasive, and reliable tool to identify individuals at high risk of type 2 diabetes. The use of FINDRISC to identify high-risk subjects, followed by lifestyle intervention, provides a feasible scheme in preventing type 2 diabetes, which could be implemented in the primary health care system.

The role of AIP and CDKN1B/p27Kip1 in endocrine neoplasia

Identification of genes predisposing to tumor syndromes has raised general awareness of tumorigenesis. Genetic testing of tumor susceptibility genes aids the recognition of individuals at increased risk of tumors. Identification of novel predisposing genes enables further studies concerning the classification of potential associated tumors and the definition of target patient group. Pituitary adenomas are common, benign neoplasms accounting for approximately 15% of all intracranial tumors. Accurate incidence estimation is challenging since a great portion of these adenomas are small and asymptomatic. Clinically relevant adenomas, that cause symptoms due to the expansion of the cell mass or the over-secretion of normally produced hormones, occur in approximately one of 1 000 individuals. Although the majority of pituitary adenomas are sporadic, a minority occur as components of familial syndromes, such as Multiple Endocrine Neoplasia type 1 (MEN1) and Carney complex (CNC). MEN1 syndrome is caused by germ-line mutations in the MEN1 gene, whereas most of the CNC patients carry the mutated protein kinase A (PKA) regulatory subunit-1-α (PRKAR1A) gene. Recently, other conditions predisposing to endocrine tumors have been identified: Pituitary Adenoma Predisposition (PAP) and MEN type 4 (MEN4). PAP was originally identified in a genetically homogeneous Finnish population. In a population based cohort from Northern Finland, aryl hydrocarbon receptor-interacting protein (AIP) gene mutations were found in 16% of all patients diagnosed with growth hormone (GH) producing pituitary adenoma, and in 40% of the subset of patients who were diagnosed under the age of 35 years. Since AIP mutations were originally described in a defined, homogeneous population from Northern Finland, it was relevant to study whether mutations also occur in more heterogeneous populations. In patient cohorts with different ethnic origins and variable clinical phenotypes, germ-line AIP mutations were detectable at low frequencies (range 0.8-7.4%). AIP mutation-positive patients were often diagnosed with a GH-producing adenoma at a young age, and usually had no family history of endocrine tumors. The low frequency of AIP mutations in randomly selected patients, and the lack of any family history of pituitary adenomas create a challenge for the identification of PAP patients. Our preliminary study suggests that AIP immunohistochemistry may serve as a pre-screening tool to distinguish between the AIP mutation-negative and the mutation-positive tumors. Tumors of various endocrine glands are components of MEN1 and CNC syndromes. Somatic MEN1 and PRKAR1A mutations in sporadic pituitary adenomas are rare, but occur in some of the other tumors related to these syndromes. The role of AIP mutations in endocrine neoplasia was studied and our results indicated that somatic AIP mutations are rare or non-existent in sporadic tumors of endocrine glands (0 of 111). Furthermore, germ-line AIP mutations in prolactin producing adenomas (2 of 9) confirmed the role of this pituitary tumor type in the PAP phenotype. Thyroid disorders are common in the general population, and the majority of them are sporadic. Interestingly, it has been suggested that thyroid disorders might be more common in PAP families. For this reason we studied germ-line AIP mutations in 93 index cases from familial non-medullary thyroid cancer (NMTC) families. The underlying gene or genes for familial NMTC have not been identified yet. None of the patients had any potentially pathogenic AIP mutation. This suggests that AIP is unlikely to play a role in familial NMTCs. A novel multiple endocrine syndrome was originally described in rats with phenotypic features of human MEN type 1 and 2. Germ-line mutations of cyclin-dependent kinase inhibitor 1B (CDKN1B also known as p27Kip1) gene were reported later in these rats and a germ-line mutation was also identified in one human family with MEN1-like phenotype (later named MEN4). To confirm the importance of this gene’s mutations in humans, we performed a mutation screening in MEN-like patients and in patients with pituitary adenoma. Our results indicate that CDKN1B/p27Kip1 mutations appear in a small portion of MEN1-like patients (one of 36), and that such mutations are rare or non-existent in both familial (0 of 19) and sporadic pituitary adenoma patients (0 of 50). In conclusion, this work strengthens the tumor susceptibility role of AIP and CDKN1B/p27Kip1 in endocrine neoplasia. Clarifying the PAP phenotype facilitates the identification of potential AIP mutation carriers. Genetic counseling can be offered to the relatives and follow-up of the mutation carriers can be organized, hence an earlier diagnosis is feasible.

Design and testing of stand-specific bucking instructions for use on modern cut-to-length harvesters

This study addresses three important issues in tree bucking optimization in the context of cut-to-length harvesting. (1) Would the fit between the log demand and log output distributions be better if the price and/or demand matrices controlling the bucking decisions on modern cut-to-length harvesters were adjusted to the unique conditions of each individual stand? (2) In what ways can we generate stand and product specific price and demand matrices? (3) What alternatives do we have to measure the fit between the log demand and log output distributions, and what would be an ideal goodness-of-fit measure? Three iterative search systems were developed for seeking stand-specific price and demand matrix sets: (1) A fuzzy logic control system for calibrating the price matrix of one log product for one stand at a time (the stand-level one-product approach); (2) a genetic algorithm system for adjusting the price matrices of one log product in parallel for several stands (the forest-level one-product approach); and (3) a genetic algorithm system for dividing the overall demand matrix of each of the several log products into stand-specific sub-demands simultaneously for several stands and products (the forest-level multi-product approach). The stem material used for testing the performance of the stand-specific price and demand matrices against that of the reference matrices was comprised of 9 155 Norway spruce (Picea abies (L.) Karst.) sawlog stems gathered by harvesters from 15 mature spruce-dominated stands in southern Finland. The reference price and demand matrices were either direct copies or slightly modified versions of those used by two Finnish sawmilling companies. Two types of stand-specific bucking matrices were compiled for each log product. One was from the harvester-collected stem profiles and the other was from the pre-harvest inventory data. Four goodness-of-fit measures were analyzed for their appropriateness in determining the similarity between the log demand and log output distributions: (1) the apportionment degree (index), (2) the chi-square statistic, (3) Laspeyres quantity index, and (4) the price-weighted apportionment degree. The study confirmed that any improvement in the fit between the log demand and log output distributions can only be realized at the expense of log volumes produced. Stand-level pre-control of price matrices was found to be advantageous, provided the control is done with perfect stem data. Forest-level pre-control of price matrices resulted in no improvement in the cumulative apportionment degree. Cutting stands under the control of stand-specific demand matrices yielded a better total fit between the demand and output matrices at the forest level than was obtained by cutting each stand with non-stand-specific reference matrices. The theoretical and experimental analyses suggest that none of the three alternative goodness-of-fit measures clearly outperforms the traditional apportionment degree measure. Keywords: harvesting, tree bucking optimization, simulation, fuzzy control, genetic algorithms, goodness-of-fit

Poverty and the Environment : Investment Poverty and the Role of Assets in Generating Welfare for Farmer Households in the Province of Herrera, Panama

Köyhiä maanviljelijöitä on usein syytetty kehitysmaiden ympäristöongelmista. On väitetty, että eloonjäämistaistelu pakottaa heidät käyttämään maata ja muita luonnonvaroja lyhytnäköisesti. Harva asiaa koskeva tutkimus on kuitenkaan tukenut tätä väitettä; perheiden köyhyyden astetta ja heidän aiheuttamaansa ympäristövaikutusta ei ole kyetty kytkemään toisiinsa. Selkeyttääkseen köyhyys-ympäristö –keskustelua, Thomas Reardon ja Steven Vosti kehittivät investointiköyhyyden käsitteen. Se tunnistaa sen kenties suuren joukon maanviljelijäperheitä, jotka eivät ole köyhiä perinteisten köyhyysmittareiden mukaan, mutta joiden hyvinvointi ei ole riittävästi köyhyysrajojen yläpuolella salliakseen perheen investoida kestävämpään maankäyttöön. Reardon ja Vosti korostivat myös omaisuuden vaikutusta perheiden hyvinvointiin, ja uskoivat sen vaikuttavan tuotanto- ja investointipäätöksiin. Tässä tutkimuksessa pyritään vastaamaan kahteen kysymykseen: Miten investointiköyhyyttä voidaan ymmärtää ja mitata? Ja, mikä on viljelijäperheiden omaisuuden hyvinvointia lisäävä vaikutus? Tätä tutkimusta varten haastateltiin 402 maanviljelijäperhettä Väli-Amerikassa, Panaman tasavallan Herreran läänissä. Näiden perheiden hyvinvointia mitattiin heidän kulutuksensa mukaan, ja paikalliset köyhyysrajat laskettiin paikallisen ruoan hinnan mukaan. Herrerassa ihminen tarvitsee keskimäärin 494 dollaria vuodessa saadakseen riittävän ravinnon, tai 876 dollaria vuodessa voidakseen ravinnon lisäksi kattaa muitakin välttämättömiä menoja. Ruoka- eli äärimmäisen köyhyyden rajan alle jäi 15,4% tutkituista perheistä, ja 33,6% oli jokseenkin köyhiä, eli saavutti kyllä riittävän ravitsemuksen, muttei kyennyt kustantamaan muita perustarpeitaan. Molempien köyhyysrajojen yläpuolelle ylsi siis 51% tutkituista perheistä. Näiden köyhyysryhmien välillä on merkittäviä eroavaisuuksia ei vain perheiden varallisuuden, tulojen ja investointistrategioiden välillä, mutta myös perheiden rakenteessa, elinympäristössä ja mahdollisuuksissa saada palveluja. Investointiköyhyyden mittaaminen osoittautui haastavaksi. Herrerassa viljelijät eivät tee investointeja puhtaasti ympäristönsuojeluun, eikä maankäytön kestävyyttä muutenkaan pystytty yhdistämään perheiden hyvinvoinnin tasoon. Siksi investointiköyhyyttä etsittiin sellaisena hyvinvoinnin tasona, jonka alapuolella elävien perheiden parissa tuottavat maanparannusinvestoinnit eivät enää ole suorassa suhteessa hyvinvointiin. Tällaisia investointeja ovat mm. istutetut aidat, lannoitus ja paranneltujen laiduntyyppien viljely. Havaittiin, että jos perheen hyvinvointi putoaa alle 1000 dollarin/henkilö/vuosi, tällaiset tuottavat maanparannusinvestoinnit muuttuvat erittäin harvinaisiksi. Investointiköyhyyden raja on siis noin kaksi kertaa riittävän ravitsemuksen hinta, ja sen ylitti 42,3% tutkituista perheistä. Heille on tyypillistä, että molemmat puolisot käyvät työssä, ovat korkeasti koulutettuja ja yhteisössään aktiivisia, maatila tuottaa paremmin, tilalla kasvatetaan vaativampia kasveja, ja että he ovat kerryttäneet enemmän omaisuutta kuin investointi-köyhyyden rajan alla elävät perheet. Tässä tutkimuksessa kyseenalaistettiin yleinen oletus, että omaisuudesta olisi poikkeuksetta hyötyä viljelijäperheelle. Niinpä omaisuuden vaikutusta perheiden hyvinvointiin tutkittiin selvittämällä, mitä reittejä pitkin perheiden omistama maa, karja, koulutus ja työikäiset perheenjäsenet voisivat lisätä perheen hyvinvointia. Näiden hyvinvointi-mekanismien ajateltiin myös riippuvan monista väliin tulevista tekijöistä. Esimerkiksi koulutus voisi lisätä hyvinvointia, jos sen avulla saataisiin paremmin palkattuja töitä tai perustettaisiin yritys; mutta näihin mekanismeihin saattaa vaikuttaa vaikkapa etäisyys kaupungeista tai se, omistaako perhe ajoneuvon. Köyhimpien perheiden parissa nimenomaan koulutus olikin ainoa tutkittu omaisuuden muoto, joka edisti perheen hyvinvointia, kun taas maasta, karjasta tai työvoimasta ei ollut apua köyhyydestä nousemiseen. Varakkaampien perheiden parissa sen sijaan korkeampaa hyvinvointia tuottivat koulutuksen lisäksi myös maa ja työvoima, joskin monesta väliin tulevasta muuttujasta, kuten tuotantopanoksista riippuen. Ei siis ole automaatiota, jolla omaisuus parantaisi perheiden hyvinvointia. Vaikka rikkailla onkin yleensä enemmän karjaa kuin köyhemmillä, ei tässä aineistossa löydetty yhtään mekanismia, jota kautta karjan määrä tuottaisi korkeampaa hyvinvointia viljelijäperheille. Omaisuuden keräämisen ja hyödyntämisen strategiat myös muuttuvat hyvinvoinnin kasvaessa ja niihin vaikuttavat monet ulkoiset tekijät. Ympäristön ja köyhyyden suhde on siis edelleen epäselvä. Köyhyyden voittaminen vaatii pitkällä tähtäimellä sitä, että viljelijäperheet nousisivat investointiköyhyyden rajan yläpuolelle. Näin heillä olisi varaa alkaa kartuttaa omaisuutta ja investoida kestävämpään maankäyttöön. Tällä hetkellä kuitenkin isolle osalle herreralaisia perheitä tuo raja on kaukana tavoittamattomissa. Miten päästä yli tuhannen dollarin kulutukseen perheenjäsentä kohden, mikäli elintaso ei yllä edes riittävään ravitsemukseen? Ja sittenkin, vaikka hyvinvointi kohenisi, ei ympäristön kannalta parannuksia ole välttämättä odotettavissa, mikäli karjalaumat kasvavat ja eroosioalttiit laitumet leviävät.

Computational studies on new chemical species in the gas-phase and the solid-state.

There is intense activity in the area of theoretical chemistry of gold. It is now possible to predict new molecular species, and more recently, solids by combining relativistic methodology with isoelectronic thinking. In this thesis we predict a series of solid sheet-type crystals for Group-11 cyanides, MCN (M=Cu, Ag, Au), and Group-2 and 12 carbides MC2 (M=Be-Ba, Zn-Hg). The idea of sheets is then extended to nanostrips which can be bent to nanorings. The bending energies and deformation frequencies can be systematized by treating these molecules as an elastic bodies. In these species Au atoms act as an 'intermolecular glue'. Further suggested molecular species are the new uncongested aurocarbons, and the neutral Au_nHg_m clusters. Many of the suggested species are expected to be stabilized by aurophilic interactions. We also estimate the MP2 basis-set limit of the aurophilicity for the model compounds [ClAuPH_3]_2 and [P(AuPH_3)_4]^+. Beside investigating the size of the basis-set applied, our research confirms that the 19-VE TZVP+2f level, used a decade ago, already produced 74 % of the present aurophilic attraction energy for the [ClAuPH_3]_2 dimer. Likewise we verify the preferred C4v structure for the [P(AuPH_3)_4]^+ cation at the MP2 level. We also perform the first calculation on model aurophilic systems using the SCS-MP2 method and compare the results to high-accuracy CCSD(T) ones. The recently obtained high-resolution microwave spectra on MCN molecules (M=Cu, Ag, Au) provide an excellent testing ground for quantum chemistry. MP2 or CCSD(T) calculations, correlating all 19 valence electrons of Au and including BSSE and SO corrections, are able to give bond lengths to 0.6 pm, or better. Our calculated vibrational frequencies are expected to be better than the currently available experimental estimates. Qualitative evidence for multiple Au-C bonding in triatomic AuCN is also found.

Synthesis of Isoflavone Conjugates

During this study different approaches were studied to obtain isoflavone sulphates, glucuronides and sulphoglucuronides. Three isoflavone disulphates (daidzein-di-O-sulphate, genistein-di-O-sulphate and glycitein-di-O-sulphate) and three isoflavonoid disulphates (dihydrodaidzein-di-O-sulphate, dihydrogenistein-di-O-sulphate and equol-di-O-sulphate) were synthesised in moderate yields by using in situ prepared pyridine sulphur trioxide complex, made from chlorosulphonic acid and pyridine. These disulphated compounds can be used to develop analytical procedures and study the biological activity of disulphated products. As the use of the HPLC-MS methods in the field of isoflavones has increased its popularity, deuterated isoflavone disulphates were synthesised. A new microwave assisted deuteration method, using CF3COOD, was developed for this purpose. Three polydeuterated isoflavone disulphates (daidzein-d6-di-O-sulphate, genistein-d4-di-O-sulphate and glycitein-d6-di-O-sulphate) were obtained in moderate yields with high isotopic purity. A synthetic method was developed for daidzein sulphoglucuronide (daidzein-7-O-b-D-glucuronide-4´-O-sulphate), which is a major metabolite in rat bile. By using protection/deprotection steps, the desired product was finally obtained in moderate yield. The method developed can be used in further studies of synthesis of isoflavonoid mixed conjugates. As a part of this study, the structure of naturally occurring daidzein-4´-O-b-glucoside was verified. Different glycosidation methods are reviewed and possible factors affecting the stereoselectivity are discussed. The study of the selective chlorination of isoflavones was a consequence of the observed unexpected chlorination during the synthesis of isoflavone acid chlorides by thionyl chloride. This fascinating phenomenon was investigated further with various isoflavones and as a result a method for producing isoflavone chlorides (8-chlorogenistein, 6,8-dichlorogenistein and 6,8-dichlorobiochanin A) was developed. Protecting groups played a great role during this study, which led to an intensive study on them. A regioselective protection method was developed by using direct introduction of the protecting group (Benzyl and Benzoyl) to positions 7-O or 4´-O in daidzein, genistein and glycitein with t-BuOK as a base in DMF in moderate yields. The possibility of exploiting the transesterification was also investigated. It was observed that by using K2CO3 as a base in DMF, daidzein, genistein and glycitein could be benzoylated at position 4´-O selectively, in the presence of the more acidic 7 hydroxy group. Transesterification also proved to be useful in the glycosidation of isoflavones at position 7-O, starting from 7-O-benzoylated isoflavones. Different carboxylic acid derivatives were synthesised for use either in the development of radioimmunoassay (7-O-carboxymethylglycitein and 4´-O-carboxymethylglycitein) or synthesis of daunorubicin isoflavone derivative for biological testing (7-O-carboxypropylbiochanin A and 7-O-carboxypropylgenistein).