Respiratory health effects of fifteen years of improved collective protection in a wheat-processing worker population.

INTRODUCTION: Occupational exposure to grain dust causes respiratory symptoms and pathologies. To decrease these effects, major changes have occurred in the grain processing industry in the last twenty years. However, there are no data on the effects of these changes on workers' respiratory health. OBJECTIVES: The aim of this study was to evaluate the respiratory health of grain workers and farmers involved in different steps of the processing industry of wheat, the most frequently used cereal in Europe, fifteen years after major improvements in collective protective equipment due to mechanisation. MATERIALS AND METHOD: Information on estimated personal exposure to wheat dust was collected from 87 workers exposed to wheat dust and from 62 controls. Lung function (FEV1, FVC, and PEF), exhaled nitrogen monoxide (FENO) and respiratory symptoms were assessed after the period of highest exposure to wheat during the year. Linear regression models were used to explore the associations between exposure indices and respiratory effects. RESULTS: Acute symptoms - cough, sneezing, runny nose, scratchy throat - were significantly more frequent in exposed workers than in controls. Increased mean exposure level, increased cumulative exposure and chronic exposure to more than 6 mg.m (-3) of inhaled wheat dust were significantly associated with decreased spirometric parameters, including FEV1 and PEF (40 ml and 123 ml.s (-1) ), FEV1 and FVC (0.4 ml and 0.5 ml per 100 h.mg.m (-3) ), FEV1 and FVC (20 ml and 20 ml per 100 h at >6 mg.m (-3) ). However, no increase in FENO was associated with increased exposure indices. CONCLUSIONS: The lung functions of wheat-related workers are still affected by their cumulative exposure to wheat dust, despite improvements in the use of collective protective equipment.

Acceptance and Use of Information Technology among Nurses in Psychiatric Hospitals

Hoitajien informaatioteknologian hyväksyntä ja käyttö psykiatrisissa sairaaloissa Informaatioteknologian (IT) käyttö ei ole ollut kovin merkittävässä roolissa psykiatrisessa hoitotyössä, vaikka IT sovellusten on todettu vaikuttaneen radikaalisti terveydenhuollon palveluihin ja hoitohenkilökunnan työprosesseihin viime vuosina. Tämän tutkimuksen tavoitteena on kuvata psykiatrisessa hoitotyössä toimivan hoitohenkilökunnan informaatioteknologian hyväksyntää ja käyttöä ja luoda suositus, jonka avulla on mahdollista tukea näitä asioita psykiatrisissa sairaaloissa. Tutkimus koostuu viidestä osatutkimuksesta, joissa on hyödynnetty sekä tilastollisia että laadullisia tutkimusmetodeja. Tutkimusaineistot on kerätty yhdeksän akuuttipsykiatrian osaston hoitohenkilökunnan keskuudessa vuosien 2003-2006 aikana. Technology Acceptance Model (TAM) –teoriaa on hyödynnetty jäsentämään tutkimusprosessia sekä syventämään ymmärrystä saaduista tutkimustuloksista. Tutkimus osoitti kahdeksan keskeistä tekijää, jotka saattavat tukea psykiatrisessa sairaalassa toimivien hoitajien tietoteknologiasovellusten hyväksyntää ja hyödyntämistä, kun nämä tekijät otetaan huomioon uusia sovelluksia käyttöönotettaessa. Tekijät jakautuivat kahteen ryhmään; ulkoiset tekijät (resurssien suuntaaminen, yhteistyö, tietokonetaidot, IT koulutus, sovelluksen käyttöön liittyvä harjoittelu, potilas-hoitaja suhde), sekä käytön helppous ja sovelluksen käytettävyys (käytön ohjeistus, käytettävyyden varmistaminen). TAM teoria todettiin käyttökelpoiseksi tulosten tulkinnassa. Kehitetty suositus sisältää ne toimenpiteet, joiden avulla on mahdollista tukea sekä organisaation johdon että hoitohenkilökunnan sitoutumista ja tätä kautta varmistaa uuden sovelluksen hyväksyntä ja käyttö hoitotyössä. Suositusta on mahdollista hyödyntää käytännössä kun uusia tietojärjestelmiä implementoidaan käyttöön psykiatrisissa sairaaloissa.

On the Connectivity of the Julia sets of meromorphic functions

We prove that every transcendental meromorphic map $f$ with disconnected Julia set has a weakly repelling fixed point. This implies that the Julia set of Newton's method for finding zeroes of an entire map is connected. Moreover, extending a result of Cowen for holomorphic self-maps of the disc, we show the existence of absorbing domains for holomorphic self-maps of hyperbolic regions, whose iterates tend to a boundary point. In particular, the results imply that periodic Baker domains of Newton's method for entire maps are simply connected, which solves a well-known open question.

Is there a relationship between bilingual language switching and executive functions in bilingualism? Introducing a within-group analysis approach

Several studies have suggested a bilingual advantage in executive functions, presumably due to bilinguals' massive practice with language switching that requires executive resources, but the results are still somewhat controversial. Previous studies are also plagued by the inherent limitations of a natural groups design where the participant groups are bound to differ in many ways in addition to the variable used to classify them. In an attempt to introduce a complementary analysis approach, we employed multiple regression to study whether the performance of 30- to 75-year-old FinnishSwedish bilinguals (N = 38) on tasks measuring different executive functions (inhibition, updating, and set shifting) could be predicted by the frequency of language switches in everyday life (as measured by a language switching questionnaire), L2 age of acquisition, or by the self-estimated degree of use of both languages in everyday life. Most consistent effects were found for the set shifting task where a higher rate of everyday language switches was related to a smaller mixing cost in errors. Mixing cost is thought to reflect top-down management of competing task sets, thus resembling the bilingual situation where decisions of which language to use has to be made in each conversation. These findings provide additional support to the idea that some executive functions in bilinguals are affected by a lifelong experience in language switching and, perhaps even more importantly, suggest a complementary approach to the study of this issue.

Prevalence of Problematic Mobile Phone Use in British Adolescents

The problematic use of mobile phones among adolescents has not been widely studied. There are very few instruments for assessing potential technological addiction to mobile phones, or for categorizing different types of users or uses. The most widely used scale is the Mobile Phone Problem Use Scale (MPPUS), which is used to study adult populations, and has been applied in various forms in international contexts. The aims of this study were to adapt the Spanish version of this scale (MPPUSA) to British adolescents, and then to estimate the prevalence of possible problematic users. A questionnaire was administered to a sample of 1,529 secondary school pupils aged between 11 and 18 years, with 1,026 completed questionnaires being collected. The analysis showed that the factor and construct validity and reliability were comparable to those obtained in previous studies. The prevalence of problematic users among the students was 10%, and the typical problematic user tended to be an adolescent between 11 and 14 years old, studying in a public school, who considered themselves to be an expert user of this technology, who made extensive use of his/her mobile phone, and who attributed the same problem of use among their peers. These users presented notable scores in all the symptoms covered by the scale used to assess problematic use. In conclusion, the adaptation of the MPPUSA as a screening scale for British adolescents presents good sensitivity and specificity for detecting the main addictive symptoms proposed in this validated version.

The purpose and use of passenger ships in 2058 - Future scenarios generated by the Delphi method

The purpose of the thesis is to generate scenarios of future purposes and of use of ships, suitable for STX Finland Cruise Oy to design and build, over a 50 year time span by applying the Delphi method and an open innovation approach in a future workshop. The scenarios were mapped out with help of two Delphi survey rounds and one future workshop. The number of participants in both surveys and the workshop was some twenty experts in each, representing various fields. On the basis of the first survey round, four different subject areas were selected for analysis: purposes for the use of ships; energy efficiency of cruises and ships; cost efficiency of sea transportation and vacation; and the views and expectations of the customers in the future. As a result of the future workshop, four different themes were established, which were studied further during the second Delphi round. The themes are future service and operation concepts; versatile uses of the space in ships; communication of environmental benefits of ships, future energy solutions and social interaction between passengers onboard. In addition to generating the scenarios, further aim of the thesis is to implement the Delphi method and workshop activity as foresight tools for STX Europe and to produce a chart of a future shipbuilding foresight community to can serve the open innovation processes in the maritime cluster as a whole.

Nursing Ethics Education in Finland from the Perspective of Codes of Ethics

The purpose of this study was to analyze nursing ethics education from the perspective of nurses’ codes of ethics in the basic nursing education programmes in polytechnics in Finland with the following research questions: What is known about nurses’ codes in practice and education, what contents of the codes are taught, what teaching and evaluation methods are used, which demographic variables are associated with the teaching, what is nurse educators’ adequacy of knowledge to teach the codes and nursing students’ knowledge of and ability to apply the codes, and what are participants’ opinions of the need and applicability of the codes, and their importance in nursing ethics education. The aim of the study was to identify strengths and possible problem areas in teaching of the codes and nursing ethics in general. The knowledge gained from this study can be used for developing nursing ethics curricula and teaching of ethics in theory and practice. The data collection was targeted to all polytechnics in Finland providing basic nursing education (i.e. Bachelor of Health Care). The target groups were all nurse educators teaching ethics and all graduating nursing students in the academic year of 2006. A total of 183 educators and 214 students from 24 polytechnics participated. The data was collected using a structured questionnaire with four open-ended questions, designed for this study. The data was analysed by SPSS (14.0) and the open-ended questions by inductive content analysis. Descriptive statistics were used to summarize the data. Inferential statistics were used to estimate the differences between the participant groups. The reliability of the questionnaire was estimated with Cronbach’s coefficient alpha. The literature review revealed that empirical research on the codes was scarce, and minimal in the area of education. Teaching of nurses’ codes themselves and the embedded ethical concepts was extensive, teaching of the functions of the codes and related laws and agreements was moderate, but teaching of the codes of other health care professions was modest. Issues related to the nurse-patient relationship were emphasised. Wider social dimensions of the codes were less emphasized. Educators’ and students’ descriptions of teaching emphasized mainly the same teaching contents, but there were statistically significant differences between the groups in that educators assessed their teaching to be more extensive than what students had perceived it had been. T he use of teaching and evaluation methods was rather narrow and conventional. However, educators’ and students’ descriptions of the used methods differed statistically significantly. Students’ knowledge of the codes and their ability to apply them in practice was assessed as mediocre by educators and by students themselves. Most educators assessed their own knowledge of the codes as adequate to teach the codes, as did most of the students. Educators who regarded their knowledge as adequate taught the codes more extensively than those who assessed their knowledge as less adequate. Also students who assessed their educators’ knowledge as adequate perceived the teaching of the codes to be more extensive. Otherwise educators’ and students’ demographic variables had little association with their descriptions of the teaching. According to the participants, nurses need their own codes, and they are also regarded as applicable in practice. The codes are an important element in nursing ethics education, but their teaching needs development. Further research should focus on the organization of ethics teaching in the curricula, the teaching process, and on the evaluation of the effectiveness of ethics education and on educators’ competence. Also the meaning and functions of the codes at all levels of nursing deserve attention. More versatile use of research methods would be beneficial in gaining new knowledge.

Development of a project control procedure

The aim of this study is to develop a suitable project control procedure for a target company that can be used in engineering, procurement, and construction or con-struction management contracts. This procedure contains suitable project control software and a model for the use of the software in practice. This study is divided into two main sections. Theoretical part deals with project management, focusing on cost and time dimensions in projects. Empirical part deals with the development of the project control procedure for the target compa-ny. This development takes place in two parts. In the first part, semi-structured interviews are used to find out the company’s employees’ demands and desires for the project control software which will then be used in the developed procedure. These demands and desires are compared to available software in the market and the most suitable one will be chosen. Interview results show that important factors are cost tracking, integration with other software, English language availability, references, helpdesk, and no need for regular updates. The most suitable one is CMPro5 cost control software. The chosen software is used in a pilot project, where its functions and use are analyzed. Project control procedure which will be used in the future is developed based on these procedures. The five steps in developed procedure include employment of a cost engineer, whose task is to maintain the procedure in the target company.

Integration in project business : mechanisms for integrating customers and the project network during the life-cycle of industrial projects

This thesis focuses on integration in project business, i.e. how projectbased companies organize their product and process structures when they deliver industrial solutions to their customers. The customers that invest in these solutions run their businesses in different geographical, political and economical environments, which should be acknowledged by the supplier when providing solutions comprising of larger and more complex scopes than previously supplied to these customers. This means that the suppliers are increasing their supply range by taking over some of the activities in the value chain that have traditionally been handled by the customer. In order to be able to provide the functioning solutions, including more engineering hours, technical equipment and a wider project network, a change is needed in the mindset in order to be able to carry out and take the required responsibility that these new approaches bring. For the supplier it is important to be able to integrate technical products, systems and services, but the supplier also needs to have the capabilities to integrate the cross-functional organizations and departments in the project network, the knowledge and information between and within these organizations and departments, along with inputs from the customer into the product and process structures during the lifecycle of the project under development. Hence, the main objective of this thesis is to explore the challenges of integration that industrial projects meet, and based on that, to suggest a concept of how to manage integration in project business by making use of integration mechanisms. Integration is considered the essential process for accomplishing an industrial project, whereas the accomplishment of the industrial project is considered to be the result of the integration. The thesis consists of an extended summary and four papers, that are based on three studies in which integration mechanisms for value creation in industrial project networks and the management of integration in project business have been explored. The research is based on an inductive approach where in particular the design, commissioning and operations functions of industrial projects have been studied, addressing entire project life-cycles. The studies have been conducted in the shipbuilding and power generation industries where the scopes of supply consist of stand-alone equipment, equipment and engineering, and turnkey solutions. These industrial solutions include demanding efforts in engineering and organization. Addressing the calls for more studies on the evolving value chains of integrated solutions, mechanisms for inter- and intra-organizational integration and subsequent value creation in project networks have been explored. The research results in thirteen integration mechanisms and a typology for integration is proposed. Managing integration consists of integrating the project network (the supplier and the sub-suppliers) and the customer (the customer’s business purpose, operations environment and the end-user) into the project by making use of integration mechanisms. The findings bring new insight into research on industrial project business by proposing integration of technology and engineering related elements with elements related to customer oriented business performance in contemporary project environments. Thirteen mechanisms for combining products and the processes needed to deliver projects are described and categorized according to the impact that they have on the management of knowledge and information. These mechanisms directly relate to the performance of the supplier, and consequently to the functioning of the solution that the project provides. This thesis offers ways to promote integration of knowledge and information during the lifecycle of industrial projects, enhancing the development towards innovative solutions in project business.

The Structure and Function of αI Domains in Collagen Receptor and Leukocyte Integrins

Integrins are heterodimeric, signaling transmembrane adhesion receptors that connect the intracellular actin microfilaments to the extracellular matrix composed of collagens and other matrix molecules. Bidirectional signaling is mediated via drastic conformational changes in integrins. These changes also occur in the integrin αI domains, which are responsible for ligand binding by collagen receptor and leukocyte specific integrins. Like intact integrins, soluble αI domains exist in the closed, low affinity form and in the open, high affinity form, and so it is possible to use isolated αI domains to study the factors and mechanisms involved in integrin activation/deactivation. Integrins are found in all mammalian tissues and cells, where they play crucial roles in growth, migration, defense mechanisms and apoptosis. Integrins are involved in many human diseases, such as inflammatory, cardiovascular and metastatic diseases, and so plenty of effort has been invested into developing integrin specific drugs. Humans have 24 different integrins, four of which are collagen receptor (α1β1, α2β1, α10β1, α11β1) and five leukocyte specific integrins (αLβ2, αMβ2, αXβ2, αDβ2, αEβ7). These two integrin groups are quite unselective having both primary and secondary ligands. This work presents the first systematic studies performed on these integrin groups to find out how integrin activation affects ligand binding and selectivity. These kinds of studies are important not only for understanding the partially overlapping functions of integrins, but also for drug development. In general, our results indicated that selectivity in ligand recognition is greatly reduced upon integrin activation. Interestingly, in some cases the ligand binding properties of integrins have been shown to be cell type specific. The reason for this is not known, but our observations suggest that cell types with a higher integrin activation state have lower ligand selectivity, and vice versa. Furthermore, we solved the three-dimensional structure for the activated form of the collagen receptor α1I domain. This structure revealed a novel intermediate conformation not previously seen with any other integrin αI domain. This is the first 3D structure for an activated collagen receptor αI domain without ligand. Based on the differences between the open and closed conformation of the αI domain we set structural criteria for a search for effective collagen receptor drugs. By docking a large number of molecules into the closed conformation of the α2I domain we discovered two polyketides, which best fulfilled the set structural criteria, and by cell adhesion studies we showed them to be specific inhibitors of the collagen receptor integrins.

JNK, a versatile regulator of kinesin-1 transport and cytoskeleton dynamics

C-Jun N-terminal kinase (JNK) is traditionally recognized as a crucial factor in stress response and inducer of apoptosis upon various stimulations. Three isoforms build the JNK subfamily of MAPK; generally expressed JNK1 and JNK2 and brain specific JNK3. Degenerative potency placed JNK in the spotlight as potential pharmacological option for intervention. Unfortunately, adverse effects of potential drugs and observation that expression of only JNK2 and JNK3 are induced upon stress, restrained initial enthusiasm. Notably, JNK1 demonstrated atypical high constitutive activity in neurons that is not responsive to cellular stresses and indicated existence of physiological activity. This thesis aimed at revealing the physiological functions of JNK1 in actin homeostasis through novel effector MARCKS-Like 1 (MARCKSL1) protein, neuronal trafficking mediated by major kinesin-1 motor protein and microtubule (MT) dynamics via STMN2/SCG10. The screen for novel physiological JNK substrates revealed specific phosphorylation of C-terminal end of MARCKSL1 at S120, T148 and T183 both ex vivo and in vitro. By utilizing site-specific mutagenesis, various actin dynamics and migrations assays we were able to demonstrate that JNK1 phosphorylation specifically facilitates F-actin bundling and thus filament stabilisation. Consecutively, this molecular mechanism was proved to enhance formation of filopodia; cell surface projections that allow cell sensing surrounding environment and migrate efficiently. Our results visualize JNK dependent and MARCKSL1 executed induction of filopodia in neurons and fibroblast indicating general mechanism. Subsequently, inactivation of JNK action on MARCKSL1 shifts cellular actin machinery into lamellipodial dynamic arrangement. Tuning of actin cytoskeleton inevitably melds with cell migration. We observed that both active JNK and JNK pseudo-phosphorylated form of MARCKSL1 reduce actin turnover in intact cells leading to overall diminished cell motility. We demonstrate that tumour transformed cells from breast, prostate, lung and muscle-derived cancers upregulate MARCKSL1. We showed on the example of prostate cancer PC-3 cell line that JNK phosphorylation negatively controls MARCKSL1 ability to induce migration, which precedes cancer cell metastasis. The second round of identification of JNK physiological substrates resulted in detection of predominant motor protein kinesin-1 (Kif5). Mass spectrometry detailed analysis showed evident endogenous phosphorylation of kinesin-1 on S176 within motor domain that interacts with MT. In vitro phosphorylation of bacterially expressed kinesin heavy chain by JNK isoforms displayed higher specificity of JNK1 when compared to JNK3. Since, JNK1 is constitutively active in neurons it signified physiological aspect of kinesin-1 regulation. Subsequent biochemical examination revealed that kinesin-1, when not phosphorylated on JNK site, exhibits much higher affinity toward MTs. Expression of the JNK non-phosphorable kinesin-1 mutant in intact cells as well as in vitro single molecule imaging using total internal reflection fluorescence microscopy indicated that the mutant loses normal speed and is not able to move processively into proper cellular compartments. We identify novel kinesin-1 cargo protein STMN2/SCG10, which along with known kinesin-1 cargo BDNF is showing impaired trafficking when JNK activity is inhibited. Our data postulates that constitutive JNK activity in neurons is crucial for unperturbed physiologically relevant transport of kinesin-1 dependant cargo. Additionally, my work helps to validate another novel physiological JNK1 effector STMN2/SCG10 as determinant of axodendritic neurites dynamics in the developing brain through regulation of MT turnover. We show successively that this increased MT dynamics is crucial during developmental radial migration when brain layering occurs. Successively, we are able to show that introduction of JNK phosphorylation mimicking STMN2/SCG10 S62/73D mutant rescues completely JNK1 genetic deletion migration phenotype. We prove that STMN2/SCG10 is predominant JNK effector responsible for MT depolymerising activity and neurite length during brain development. Summarizing, this work describes identification of three novel JNK substrates MARCKSL1, kinesin-1 and STMN2/SCG10 and investigation of their roles in cytoskeleton dynamics and cargo transport. This data is of high importance to understand physiological meaning of JNK activity, which might have an adverse effect during pharmaceutical intervention aiming at blocking pathological JNK action.

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.

Regulation of self-renewal and detection of karyotypic changes of pluripotent human embryonic stem cells

Human embryonic stem cells are pluripotent cells capable of renewing themselves and differentiating to specialized cell types. Because of their unique regenerative potential, pluripotent cells offer new opportunities for disease modeling, development of regenerative therapies, and treating diseases. Before pluripotent cells can be used in any therapeutic applications, there are numerous challenges to overcome. For instance, the key regulators of pluripotency need to be clarified. In addition, long term culture of pluripotent cells is associated with the accumulation of karyotypic abnormalities, which is a concern regarding the safe use of the cells for therapeutic purposes. The goal of the work presented in this thesis was to identify new factors involved in the maintenance of pluripotency, and to further characterize molecular mechanisms of selected candidate genes. Furthermore, we aimed to set up a new method for analyzing genomic integrity of pluripotent cells. The experimental design applied in this study involved a wide range of molecular biology, genome-wide, and computational techniques to study the pluripotency of stem cells and the functions of the target genes. In collaboration with instrument and reagent company Perkin Elmer, KaryoliteTM BoBsTM was implemented for detecting karyotypic changes of pluripotent cells. Novel genes were identified that are highly and specifically expressed in hES cells. Of these genes, L1TD1 and POLR3G were chosen for further investigation. The results revealed that both of these factors are vital for the maintenance of pluripotency and self-renewal of the hESCs. KaryoliteTM BoBsTM was validated as a novel method to detect karyotypic abnormalities in pluripotent stem cells. The results presented in this thesis offer significant new information on the regulatory networks associated with pluripotency. The results will facilitate in understanding developmental and cancer biology, as well as creating stem cell based applications. KaryoliteTM BoBsTM provides rapid, high-throughput, and cost-efficient tool for screening of human pluripotent cell cultures.

Muscarinic toxins : characterization of adrenoceptor binding and applicability of membrane anchoring via glycosylphosphatidylinositol tail

Adrenoceptors (ARs), G-protein coupled receptors (GPCRs) at the plasma membrane, respond to endogenous catecholamines noradrenaline and adrenaline. These receptors mediate several important physiological functions being especially important in the cardiovascular system and in the regulation of smooth muscle contraction. Impairments in the function of these receptors can thus lead to severe diseases and disorders such as to cardiovascular diseases and benign prostatic hyperplasia. The Eastern green mamba (Dendroaspis angusticeps) venom has been shown to contain toxins that can antagonize the functions of GPCRs. The most well-known are muscarinic toxins (MTs) targeting muscarinic acetylcholine receptors (mAChRs) with high affinity and selectivity. However, some reports have indicated that these toxins might also act on the α1- and α2-ARs which can be divided into various subtypes; the α1-ARs to α1A-, α1B- and α1D-ARs and α2-ARs to α2A-, α2B- and α2C-ARs. In this thesis, the interaction of four common MTs (MT1, MT3, MT7 and MTα) with the adrenoceptors was characterized. It was also evaluated whether these toxins could be anchored to the plasma membrane via glycosylphosphatidylinositol (GPI) tail. Results of this thesis reveal that muscarinic toxins are targeting several α-adrenoceptor subtypes in addition to their previously identified target receptors, mAChRs. MTα was found to interact with high affinity and selectivity with the α2B-AR whereas MT7 confirmed its selectivity for the M1 mAChR. Unlike MTα and MT7, MT1 and MT3 have a broad range of target receptors among the α-ARs. All the MTs characterized were found to behave as non-competitive antagonists of receptor action. The interaction between MTα and the α2B-AR was studied more closely and it was observed that the second extracellular loop of the receptor functions as a structural entity enabling toxin binding. The binding of MTα to the α2B-AR appears to be rather complex and probably involves dimerized receptor. Anchoring MTs to the plasma membrane did not interfere with their pharmacological profile; all the GPI-anchored toxins created retained their ability to block their target receptors. This thesis shows that muscarinic toxins are able to target several subtypes of α-ARs and mAChRs. These toxins offer thus a possibility to create new subtype specific ligands for the α-AR subtypes. Membrane anchored MTs on the other hand could be used to block α-AR and mAChR actions in disease conditions such as in hypertension and in gastrointestinal and urinary bladder disorders in a cell-specific manner and to study the physiological functions of ARs and mAChRs in vivo in model organisms.

Excessive functions, Appell polynomials and optimal stopping

The main topic of the thesis is optimal stopping. This is treated in two research articles. In the first article we introduce a new approach to optimal stopping of general strong Markov processes. The approach is based on the representation of excessive functions as expected suprema. We present a variety of examples, in particular, the Novikov-Shiryaev problem for Lévy processes. In the second article on optimal stopping we focus on differentiability of excessive functions of diffusions and apply these results to study the validity of the principle of smooth fit. As an example we discuss optimal stopping of sticky Brownian motion. The third research article offers a survey like discussion on Appell polynomials. The crucial role of Appell polynomials in optimal stopping of Lévy processes was noticed by Novikov and Shiryaev. They described the optimal rule in a large class of problems via these polynomials. We exploit the probabilistic approach to Appell polynomials and show that many classical results are obtained with ease in this framework. In the fourth article we derive a new relationship between the generalized Bernoulli polynomials and the generalized Euler polynomials.