Type II aromatic polyketide biosynthetic tailoring enzymes: diversity and adaptation in Streptomyces secondary metabolism.

Members of the bacterial genus Streptomyces are well known for their ability to produce an exceptionally wide selection of diverse secondary metabolites. These include natural bioactive chemical compounds which have potential applications in medicine, agriculture and other fields of commerce. The outstanding biosynthetic capacity derives from the characteristic genetic flexibility of Streptomyces secondary metabolism pathways: i) Clustering of the biosynthetic genes in chromosome regions redundant for vital primary functions, and ii) the presence of numerous genetic elements within these regions which facilitate DNA rearrangement and transfer between non-progeny species. Decades of intensive genetic research on the organization and function of the biosynthetic routes has led to a variety of molecular biology applications, which can be used to expand the diversity of compounds synthesized. These include techniques which, for example, allow modification and artificial construction of novel pathways, and enable gene-level detection of silent secondary metabolite clusters. Over the years the research has expanded to cover molecular-level analysis of the enzymes responsible for the individual catalytic reactions. In vitro studies of the enzymes provide a detailed insight into their catalytic functions, mechanisms, substrate specificities, interactions and stereochemical determinants. These are factors that are essential for the thorough understanding and rational design of novel biosynthetic routes. The current study is a part of a more extensive research project (Antibiotic Biosynthetic Enzymes; www.sci.utu.fi/projects/biokemia/abe), which focuses on the post-PKS tailoring enzymes involved in various type II aromatic polyketide biosynthetic pathways in Streptomyces bacteria. The initiative here was to investigate specific catalytic steps in anthracycline and angucycline biosynthesis through in vitro biochemical enzyme characterization and structural enzymology. The objectives were to elucidate detailed mechanisms and enzyme-level interactions which cannot be resolved by in vivo genetic studies alone. The first part of the experimental work concerns the homologous polyketide cyclases SnoaL and AknH. These catalyze the closure of the last carbon ring of the tetracyclic carbon frame common to all anthracycline-type compounds. The second part of the study primarily deals with tailoring enzymes PgaE (and its homolog CabE) and PgaM, which are responsible for a cascade of sequential modification reactions in angucycline biosynthesis. The results complemented earlier in vivo findings and confirmed the enzyme functions in vitro. Importantly, we were able to identify the amino acid -level determinants that influence AknH and SnoaL stereoselectivity and to determine the complex biosynthetic steps of the angucycline oxygenation cascade of PgaE and PgaM. In addition, the findings revealed interesting cases of enzyme-level adaptation, as some of the catalytic mechanisms did not coincide with those described for characterised homologs or enzymes of known function. Specifically, SnoaL and AknH were shown to employ a novel acid-base mechanism for aldol condenzation, whereas the hydroxylation reaction catalysed by PgaM involved unexpected oxygen chemistry. Owing to a gene-level fusion of two ancestral reading frames, PgaM was also shown to adopt an unusual quaternary sturucture, a non-covalent fusion complex of two alternative forms of the protein. Furthermore, the work highlighted some common themes encountered in polyketide biosynthetic pathways such as enzyme substrate specificity and intermediate reactivity. These are discussed in the final chapters of the work.

The cultural dimension in focus : promoting awareness of diversity and respect for difference in a Finland-Swedish EFL classroom

This study addresses the role of EFL education, its potential and shortcomings, and the challenges the future of EFL education will bring. It is argued that new societal demands and the limited time we have at our disposal in the classroom make it necessary to rethink goals and content and move away from the transmissionof limited sets of facts and information to helping students develop awareness and competences that can be applied in many different situations, also in a perspective of lifelong learning. The overall aim of the current study is to problematize and increase understanding of the implementation of cultural aspects in the language classroom by addressing the interrelated what, why and how of the cultural dimension within EFL education. This has been conducted by means of theoretical explorations into the area, alongside an attempt at promoting intercultural competence (IC) in a more systematic and insightful manner within my own educational praxis. The focus of the intercultural work in the classroom was on the promotion of awareness of difference and diversity, as well as respect for such difference through the ability to decenter from cultural norms and behavior that previously have been taken for granted. These are two elements that have been suggested as fundamental for other work with IC in the classroom and for the realization of important aspects of the underlying values of basic education. In the context of this study, IC comprises several interconnected components supportingeach other in a variety of ways, with the further aim being interaction with and respect for difference in general, not only concerning e.g. representatives ofcertain English-speaking communities. The methodology was informed by action research, with myself in the role of the teacher-researcher or the reflective practitioner. For the purpose of the project I was authorized to take on the EFL education for the three years of upper comprehensive school of one random class of students originally assigned to one of the language teachers of the selected Finland-Swedish school. Thus, the class of 17 students was not specifically chosen for the project, and the aims and contents chosen for the development project were placed within the framework of the ordinary curriculum. By exploring the students¿ insights concerning different English-speaking cultural groups, mainly through a set of questionnaires, it was possible to outline the work with the cultural dimension in the classroom for the following three years. Work progress was evaluated at specific stages, and the final project evaluations were conducted through individual student interviews in grade 9. The interviews were focused on possible development of students¿ insights concerning different aspects of the cultural dimension. In particular this concerned awareness of difference and diversity, including modification of stereotypes, as well as the ability to decenterin order to be better able to respect such difference. I also explored students¿ awareness and views of the activities and approaches used in class, as well asaffordances both inside and outside the EFL classroom in relation to these intended insights. A further focus area was the perceived relevance to students of different aspects of the cultural dimension. The frameworks and approaches adopted for the work in the classroom all have in common that they are based on a constructivist framework, where knowledge is constructed and reconstructed through interaction with one¿s social and cultural environment, including interaction with others. Reflective processes precede or are simultaneous with the learning of basic factual knowledge. This entails a view of learning as a progression from simple to more complex models rather than as a progression from facts to understanding and analysis. Here, the development of intercultural competence is seen asa cyclical process, or along a spiral curriculum, from simple to more complex levels through a combination of cognitive, affective and behavioral elements within a framework of experiential learning. This project has shown one possible wayforward concerning the development of intercultural competence within EFL education through a more systematic and comprehensive approach regarding linguistic and cultural aspects. The evaluation of the educational process explored in the study suggests the possibilities for work with the promotion of awareness of difference and diversity concerning some specific context that, based on students¿ prior knowledge and preconceptions, would benefit from further work. In this case, the specific context primarily concerned different aspects of both cultural and linguistic conditions in the UK. It is also suggested that many students developed the ability to decenter, described in the study as integral to being able to respect otherness. What still remains to be explored are more individualized approaches considering students¿ different levels of departure. Further work alsoneeds to be put into how to apply insights gained in these specific situations to more general contexts. It is also necessary to explore the use of the suggested approaches in a wider range of different contexts.

Information exchange and disruption risk in multimodal maritime supply chains

Supply chains are becoming increasingly dependent on information ex-change in today’s world, and any disruption can cause severe repercus-sions to the flow of materials in the chain. The speed, accuracy and amount of information are key factors. The aim in this thesis is to address a gap in the research by focusing on information exchange and the risks related to it in a multimodal wood supply chain operating between the Baltic States and Finland. The study involved interviewing people engaged in logistics management in the supply chain in question. The main risk the interviewees identified arose from the sea logistics system, which held a lot of different kinds of information. The threat of breakdown in the Internet connection was also found to hinder the operations significantly. A vulnerability analysis was carried out in order to identify the main actors and channels of infor-mation flow in the supply chain. The analysis revealed that the most important and therefore most vulnerable information-exchange channels were those linking the terminal superintendent, the operative managers and the mill managers. The study gives a holistic picture of the investigated supply chain. Information-exchange-related risks varied greatly. One of the most frequently mentioned was the risk of information inaccuracy, which was usually due to the fact that those in charge of the various functions did not fully understand the consequences for the entire chain.

Cultural Diversity, Social Cohesion, Religion: Core Values and Educational Policies in Four European Nations

In my doctoral thesis I evaluate strategies designed to cope with the multicultural nature of four European nations: Great Britain, The Netherlands, Sweden, and Denmark. I also analyse and clarify the question of the place of religion in present-day Europe. The empirical material analysed in the study consists of politicians’ statements and policy documents dealing with immigration policy and religious and values education in the four countries. In addition, I analyse statements issued by the Council of Europe regarding religious education, along with all cases relevant to religious education brought before the United Nations Human Rights Committee or the European Court of Human Rights. The theoretical framework is formed by the scholarly debate – among philosophers, sociologists and scholars of religion in education – concerning the question of a just society. Special emphasis is given to philosophical theories that are in favour of granting special group rights to religious minorities in the name of equal treatment. With regard to the question of the appropriate place of religion, I apply Kim Knott’s methodological model for locating religion in secular contexts, and Émile Durkheim’s theory as to the significance of religion and collective sentiments in uniting adherents or members of a group into a single moral community. The study shows that even when the positive side of immigration, as a potential force for the enrichment of the public culture, is acknowledged, there is anxiety as to the successful integration of immigrants. The premises and goals of immigration policies have also been questioned. One central problem is the incommensurability between the values upheld by Western liberal democracies and certain religious traditions, above all those of Islam. Great Britain, The Netherlands, Sweden, and Denmark have tightened control over their citizens’ ethical attitudes and want to regulate these as well. In coping with cultural diversity, the significance of education, especially religious education, plays a significant role; as future citizens, pupils are expected to internalise the society’s core values as well as gaining an understanding of different cultures and ways of life. It is also worth noting that both the Council of Europe and the European Court of Human Rights have recently expressed the view that one important goal of religious education is to enable pupils to be critical and autonomous with regard to different religions and moral positions. The study shows that religion is not seen as purely a personal matter. Religion is closely linked to individual and national identity, and religious traditions thus have a place in the public domain. It should be noted, however, that a religious tradition – more precisely, an interpretation of religious tradition – qualifies as a legitimate partner in the democratic decision-making process only if it shares similar values with Western European nations.

Immigration Strategy for Northern Ostrobothnia 2015

A strategy process was completed in the ESF project “Promotion of Work-related Immigration”, which was implemented at Centre for Economic Development, Transport and the Environment for North Ostrobothnia, and an immigration strategy was drawn up for Northern Ostrobothnia on the basis of the process. Information was collected about the situation in Northern Ostrobothnia from the point of view of immigration and the future availability of labour. The intention was to use the information as background material for the strategy. Employers’ need for support in recruiting foreign labour was investigated with a broad inquiry, to which 1000 respondents replied. The strategy process was carried out together with an outside consultant (Net Effect Oy) by arranging three workshops and a seminar where the workshop results were summarised. A large number of companies, authorities, municipalities, associations, project actors and immigrants engaged in immigration issues participated in the workshops. The draft strategy is based on their experiences about immigration and on statistical data, background inquiries and surveys. To ensure the accuracy of the draft strategy, comments were requested from several parties and received from 64 organisations. The core of the immigration strategy consists of an initial analysis, values, a vision and priorities. The strategy is composed of three priorities. The key aim of the priority Internationalisation and Supporting Diversity is to support diversity in schools, workplaces and people’s everyday lives e.g. through attitude development and by promoting internationalisation in companies and education institutions. The aim of the priority Supporting Entrepreneurship and Recruiting Foreign Labour is to promote entrepreneurship among immigrants and the recruitment of foreign labour and to develop the forecasting of educational needs. The priority Developing Integration Services, Regional Cooperation and Networks, in turn, seeks to develop the service structure and policies of immigrant integration and to increase cooperation and exchange of information between regional actors engaged in integration issues. The aim is to use the strategy as a guideline document for immigration issues in Northern Ostrobothnia. The strategy is used to coordinate the existing organisations and operations dealing with immigration issues. In addition, it contains a future-oriented focus and underlines the management of new immigration projects and operations. The main party responsible for the implementation of the strategy is the Immigration Committee. In addition, responsible parties have been assigned to each measure. The implementation of the immigration strategy will be monitored annually on the basis of indicators.

Electroactive ion exchange membranes based on conducting polymers

Ion exchange membranes are indispensable for the separation of ionic species. They can discriminate between anions and cations depending on the type of fixed ionic group present in the membrane. These conventional ion exchange membranes (CIX) have exceptional ionic conductivity, which is advantageous in various electromembrane separation processes such as electrodialysis, electrodeionisation and electrochemical ion exchange. The main disadvantage of CIX membranes is their high electrical resistance owing to the fact that the membranes are electronically non conductive. An alternative can be electroactive ion exchange membranes, which are ionically and electronically conducting. Polypyrrole (PPy) is a type of electroactive ion exchange material as well as a commonly known conducting polymer. When PPy membranes are repeatedly reduced and oxidised, ions are pumped through the membrane. The main aim of this thesis was to develop electroactive cation transport membranes based on PPy for the selective transport of divalent cations. Membranes developed composed of PPy films deposited on commercially available support materials. To carry out this study, cation exchange membranes based on PPy doped with immobile anions were prepared. Two types of dopant anions known to interact with divalent metal ions were considered, namely 4-sulphonic calix[6]arene (C6S) and carboxylated multiwalled carbon nanotubes (CNT). The transport of ions across membranes containing PPy doped with polystyrene sulphonate (PSS) and PPy doped with para-toluene sulphonate (pTS) was also studied in order to understand the nature of ion transport and permeability across PPy(CNT) and PPy(C6S) membranes. In the course of these studies, membrane characterisation was performed using electrochemical quartz crystal microbalance (EQCM) and scanning electron microscopy (SEM). Permeability of the membranes towards divalent cations was explored using a two compartment transport cell. EQCM results demonstrated that the ion exchange behaviour of polypyrrole is dependent on a number of factors including the type of dopant anion present, the type of ions present in the surrounding medium, the scan rate used during the experiment and the previous history of the polymer film. The morphology of PPy films was found to change when the dopant anion was varied and even when the thickness of the film was altered in some cases. In nearly all cases the permeability of the membranes towards metal ions followed the order K+ > Ca2+ > Mn2+. The one exception was PPy(C6S), for which the permeability followed the order Ca2+ ≥ K+ > Mn2+ > Co2+ > Cr3+. The above permeability sequences show a strong dependence on the size of the metal ions with metal ions having the smallest hydrated radii exhibiting the highest flux. Another factor that affected the permeability towards metal ions was the thickness of the PPy films. Films with the least thickness showed higher metal ion fluxes. Electrochemical control over ion transport across PPy(CNT) membrane was obtained when films composed of the latter were deposited on track-etched Nucleopore® membranes as support material. In contrast, the flux of ions across the same film was concentration gradient dependent when the polymer was deposited on polyvinylidene difluoride membranes as support material. However, electrochemical control over metal ion transport was achieved with a bilayer type of PPy film consisting of PPy(pTS)/PPy(CNT), irrespective of the type of support material. In the course of studying macroscopic charge balance during transport experiments performed using a two compartment transport cell, it was observed that PPy films were non-permselective. A clear correlation between the change in pH in the receiving solution and the ions transported across the membrane was observed. A decrease in solution pH was detected when the polymer membrane acted primarily as an anion exchanger, while an increase in pH occurred when it functioned as a cation exchanger. When there was an approximately equal flux of anions and cations across the polymer membrane, the pH in the receiving solution was in the range 6 - 8. These observations suggest that macroscopic charge balance during the transport of cations and anions across polypyrrole membranes was maintained by introduction of anions (OH-) and cations (H+) produced via electrolysis of water.

Exchange rate volatility and the use of foreign currency derivatives: Impact of 2008 global financial crisis

This thesis examines the impact of foreign exchange rate volatility to the extent of use of foreign currency derivatives. Especially the focus is on the impacts of 2008 global financial crisis. The crisis increased risk level in the capital markets greatly. The change in the currency derivatives use is analyzed by comparing means between different periods and in addition, by linear regression that enables to analyze the explanatory power of the model. The research data consists of financial statements figures from fiscal years 2006-2011 published by firms operating in traditional Finnish industrial sectors. Volatilities of the chosen three currency pairs is calculated from the daily fixing rates of ECB. Based on the volatility the sample period is divided into three sub-periods. The results suggest that increased FX market volatility did not increase the use foreign currency derivatives. Furthermore, the increased foreign exchange rate volatility did not increase the power of linear regression model to estimate the use foreign currency derivatives compared to previous studies.

The Anchoring Bias of Investors and the 52-Week High Momentum Strategy in the OMX Helsinki Stock Exchange: Psychological Approach to Market Efficiency

The behavioural finance literature expects systematic and significant deviations from efficiency to persist in securities markets due to behavioural and cognitive biases of investors. These behavioural models attempt to explain the coexistence of intermediate-term momentum and long-term reversals in stock returns based on the systematic violations of rational behaviour of investors. The study investigates the anchoring bias of investors and the profitability of the 52-week momentum strategy (GH henceforward). The relatively highly volatile OMX Helsinki stock exchange is a suitable market for examining the momentum effect, since international investors tend to realise their positions first from the furthest security markets by the time of market turbulence. Empirical data is collected from Thomson Reuters Datastream and the OMX Nordic website. The objective of the study is to provide a throughout research by formulating a self-financing GH momentum portfolio. First, the seasonality of the strategy is examined by taking the January effect into account and researching abnormal returns in long-term. The results indicate that the GH strategy is subject to significantly negative revenues in January, but the strategy is not prone to reversals in long-term. Then the predictive proxies of momentum returns are investigated in terms of acquisition prices and 52-week high statistics as anchors. The results show that the acquisition prices do not have explanatory power over the GH strategy’s abnormal returns. Finally, the efficacy of the GH strategy is examined after taking transaction costs into account, finding that the robust abnormal returns remain statistically significant despite the transaction costs. As a conclusion, the relative distance between a stock’s current price and its 52-week high statistic explains the profits of momentum investing to a high degree. The results indicate that intermediateterm momentum and long-term reversals are separate phenomena. This presents a challenge to current behavioural theories, which model these aspects of stock returns as subsequent components of how securities markets respond to relevant information.