Kodin ja työn rajavyöhykkeellä - yhteensovittamisen jännitteitä ja ratkaisuja arjessa

The aim of this research is to study the boundary zone of home and work and the tensions people experience while reconciling home and work? How are the requirements of the family, the home and the work taken care of in everyday life? What kind of difficulties does the individual experience when reconciling home activities and job requirements together? What kind of activity policies have families created to ease the everyday life? What kind of goals and requirements do families feel behind the difficulties in adjusting home and work? What kind of changes would make the adjusting of home and work easier? The changing family life, everyday home activities and the changing Finnish working life are studied to describe the adjusting of home and work. In addition the boundary zone of home and work and its tensions are studied. 337 research persons who find reconciling home and work challenging were elected from different sectors of the working life. Research persons were gathered from the public, private and third sectors. The research material was gathered with a semi-structured qualitative questionnaire published in internet. Contents analysis was the analysis method of the research material. The tensions of adjusting home and work are various. Several activity systems meet on the boundary zone of home and work causing boundary zones to expand and tensions to increase and expand like a network. In the everyday life of an individual the boundary zone fades out and home and work overlap. Tensions can be examined as internal conflicts of the individual through the activity system of everyday life. Individuals balance between individualism and familism, feeling bad, suffering from lack of time and struggling with childcare organizing problems and inflexible employers. The solutions to reconciling home and work difficulties are situational. Often is the help of family and friends required without any solid solutions. The conflict of the goals, requirements and the reality is behind the problems as well as the tightening terms of the working life and its growing expectations. Change requests are proposed on the levels of individual, home, work and the society. Reconciling home and work is not only a challenge between the employee and the employer. It s a problem that needs multilateral solutions and changes on the levels of individual, home, work and society. The challenge remaining is to find out if it would be successful to take the everyday life as starting point to negotiate the reconciling of home and work and how the possible family, social and work political solutions appear in everyday life.

Lapsi ulkomailta – vanhempien rooli adoptiolapsen identiteetin kehityksessä

The importance of open discussion with the adopted child and his parents about adoption and ethnicity is often emphasized in adoption literature (Kirk 1964; Grotevant 1999; Carli & Dalen 1999). The child should have the possibility of constructing a harmonious view of himself, which consists of his history before adoption, ethnicity and the social environment’s conception of him. The purpose of this study was to examine the Finnish adoptive parents’ supportive role in relation to their child’s adoptive and ethnic identity and the social environment’s disposition to the child as witnessed by the parents. The first research problem was to find out how the parents support their child’s adoptive identity formation. The second problem was to find out if the parents want to support the child’s ethnic identity. The third problem was regarding the environment’s disposition to the child and family. The hypothesis was that Finnish adoptive parents are well aware of the problems of adoption and they have been well selected, so they have the aspirations and skills to help their child with his identity formation. The focus of this study was on Finnish parents who had adopted internationally, from whom 58 answers were obtained. The data was collected with an Internet based questionnaire. The questions were mostly qualitative. The analysis was directed by the theory, so that the analysis units were obtained from the main questions of international adoption and identity formation. The results expressed that the adoptive parents want to support their child’s adoption identity. They accept their child’s questions regarding his history, and that they did not want to conceal any details about their child’s life, even if they felt that it was a sensitive issue for them. The main problem was that there was no information available on the child’s history. Contact with the biological parents was almost impossible because there was hardly any information on them. Instead the parents were in contact with the children’s home because they felt that it had an important role as the child’s former home. The parents felt that the child’s birth culture was of importance and they mainly offered aspects of it informally daily. Parents who stressed their child’s Finnish identity were concerned that their child would not form a feeling of being Finnish. However, the majority wished that their child would have a multicultural identity. The parents felt that the environment regarded the child positively and the possibility of upcoming problems was tackled by discussing them beforehand with the child and environment.

Tilausompelijan ja asiakkaan näkemyksiä laadusta

The aim of the study was to find out what kind of view on product quality dressmaker and customer have, how the views differ from each other and how the difference affects dressmaker s work as an entrepreneur. The research data consists of eight thematic interviews: four dressmakers and four customers were interviewed for the study. In the core of customised dressmaking is arelationship between a maker and a client. The product of a dressmaker, a unique dress, is created in an immediate interaction between a dressmaker and a client. Also the quality of a unique dress derives from this interaction. In the results of this study, the views on quality are linked with six themes: dress, process, dressmaker, customer, interaction and enterprise. The dressmakers and the customers agree that the quality of a custom-made dress is based on unique fit. Describing the process the dressmakers insist on the quality of manufacturing. The clients' view on process insists on those phases where they themselves take part: designing and fitting. The personality of the dressmaker is part of quality in both the dressmakers' and the customers' points of view. The dressmakers and the customers are also aware of the customers impact on fulfilling the expectations. The immediate interaction between dressmaker and customer is a key to the unique dressmaking. At its best the interaction is followed by a trusting relationship. Entrustment derives also from a good reputation, which is essential in dressmaker-entrepreneurs marketing strategy. The dressmakers views on quality are product- and manufacturing-based. According to the results of the study there can be seen different types of dressmakers, that emphasise different aspects of quality. At the other end is a manufacturing-based, even transcendent view on quality, which rests on the values of the dressmaker. At the other end lies a customer- and value-based approach, which is founded on fulfilling the expectations and needs of the customer. In their views on quality the customers emphasise the immediate interaction between dressmaker and client. Keywords: quality, dressmaker, customer, entrepreneur

Saako terveysuskoja synninpäästön? : Naispappien käsityksiä laihdutus- ja terveyskulttuurista nykyisessä mediayhteiskunnassa

Background and aims. Fatness and dieting have been the object of interest between many fields for a long time. Home economics as a discipline enables a comprehensive inspection of fatness and dieting reviewing different disciplines. In addition to the aspect where the pursuit of dieting and health is seen from the perspective of medical and health science it is also been reviewd as a social and cultural phenomena. This study contemplates the influence of history, religion, medicalization and media on dieting and health culture. The objective is to find out if the modern dieting and health culture has gathered influences from centuries ago and absorbed religious features. The stress deriving from appereance has been discussed in the public and there are many solutions conserning weight issues. The purpose of this study is to find out what personal experiences and thoughts female pastors have conserning these questions. The media – which is one of the most influential systems nowadays – has undeniably a great effect on the consumer. The goal is furthermore to estimate the effect of the media on the changing of dieting and health culture. The three main research questions are: 1. What kind of conseptions do female pastors have of dieting and health culture and of its religious features? 2. What kind of personal experiences and conseptions do female pastors have of dieting and strivines of health? 3. How do female pastors regard the image the media has supplied of dieting and health culture? Material and methods. The qualitative data was gathered in year 2009 using the halfstructured theme interview -method. The data consists of interviews conducted with specialists of spiritual matters, i.e. ten female pastors who are between 35 and 60 years old and live in the metropolitan area. The analytical procedure used is called a theory based context analysis. Results and conclusions. Results of this study show that the idealization of slimness and healthiness is a matter discussed in the public on a daily basis. The problem faced was that the media provided contradictory information regarding fatness and dieting and the standard of slimness in commercials focused on females. The pursuit of dieting and healthiness was believed to include also religious elements. In the Middle Ages and the era after that the fatness, overeating and the pleasure one gets from eating was still seen as a condemnable matter in our culture. One could say this was like a sin. The respondents believed that healthiness, healthy living, optimal eating and good looks were a matter more or less equal than a religion. This was a derivative from the fact that treasuring health has become a life stearing value for many people. In the priest’s profession dieting and the pursuit of health was seen in the light of problems arising from weight issues. In ones profession for example the unhealthy eating in festive situations was seen as a matter that leads to unnecessary weight. Another aspect was the job circumstances that limited the degree of movement. The belief was that the female pastors would in a decreasing fashion confront stress deriving from appearence in their job. Keywords: dieting, fatness, healthiness, slimness, female pastors, religion, medicalization, media

Intergenerational Transfer of Sabbath Observance : How is Religious Tradition Transferred to Children among Finnish Seventh-day Adventists?

This study examined religious home education in educational, psychological, and sociological context. Growing up within a religious denomination is a process of learning the rules, norms, opinions, and attitudes, which serve to make the individual an active member of the group. It is a process of transferring the cultural inheritance between generations. Sabbathkeeping can be regarded as a strong indicator of the Seventh-day Adventist value system, which is also why I have concentrated on this specific issue in my study. The purpose of the study was to find out, how the Sabbath is transferred from parents to children among Finnish Adventists. It was also examined how parents could make the day of rest positively exceptional for children, and how the parental authoritativeness affects the process of transference. According to Bull & Lockhart s (1989) theory, the amount of Adventist generations in family history influences the transfer of religious tradition. This study aimed to find out whether or not this theory would apply to the present-day Finland. The nature of religious development among Adventist young people was also one of the interests of the research. The methods used in the study were in-depth interviews (n = 10) and a survey (n = 106). The majority of the interviewees was young adults (age 15-30) grown up in Adventist families. The interviews were taped and transcribed for the study, and survey answers were analysed with SPSS-data analysis program. The amount of survey questionnaires evaluated was 106, whole population of 15-30 year-old Finnish Adventists being about one thousand. Democratic relationship between parents and children, parents' example, encouragement to own thinking, and positive experiences of Sabbath and the whole religion, including the social dimension of the Adventism, seem to be some of the most significant factors in transference of religious tradition. Both too severe and too permissive education were considered to lead to similar results: unsuccessful transfer of values, or even rebellion and adopting a totally opposite way of life than that of the parents. In this study the amount of Adventist generations in family history does not correlate significantly with the end results of value transference. Keywords: Sabbath, intergenerational, value transference, religious home education Avainsanat: sapatti, arvojen siirtyminen vanhemmilta lapsille, uskonnollinen kotikasvatus

Pyhä Kolminaisuus vai pilven reunalla istuva partasuu? : Jumalakuva evankelisluterilaisissa ja ortodoksissa 1.–4.-luokan uskonnon oppikirjoissa 1970–80- ja 2000-luvuilla

A concept of god is a wholeness that an individual experiences as God. The Christian concept of god is based on triune God: Father, Son, and the Holy Spirit. The concept of god is examined in different kinds of contexts particularly between the 1940's and the 1970's. Many researches of school books have widely been made in Finland, but, however, only a few from the point of view of the concept of god. Considering this, the concept of god in the school books of Evangelical Lutheran and Orthodox religion from first to fourth grade in 1970–80 and 2000 is examined in this survey. Additionally, the concept of god in curricula between years 1970 and 2004 is studied. The perspective on the concept of god is the change in the course of time and denominational emphasis. As a first hypothesis, God the Father is represented in books in 21st century as a kind and loving figure. As a second hypothesis, the Trinity and the Holy Spirit get more space in Orthodox books comparing with the Lutheran books. Twelve school books of Evangelical Lutheran and Orthodox religion from first to fourth grade were used as a research material. The books were from four different series between the years 1978 and 2005. Teacher's guidebooks and student's exercise books were left outside of this survey. The research material was analyzed by using abductive content analysis and methodological triangulation. This study included both qualitative and quantitative aspects. The classification system which defined the classifying of concept of god from the research material was consisted of the basis of research material, former reseach, and subtext of used theories. The number of mentions in concept of god was higher in books from the 21st century. In Lutheran books, the change was seen as a growth of the category of God the Father. In Orthodox books, the trend was opposite: the category of Jesus the Son had grown. Differing from the presupposition, the features of loving God in new books had less emphasis than in older books in both churces. The mentions of the Holy Spirit and Trinity were marginal. In the Orthodox books, the categories were bigger, as it was presupposed. It could be seen, that the books confirmed the legalistic period of the concept of god on 3rd and 4th grades. The mentions of concept of god in curriculas have diminished and generalized. The diminution was seen most radically in the curriculum from the year 1994. The results tell something about social changes and views of innovation in curricula. In books the change was not perceived that bright. The idea of the concept of god getting shrank and decreased during the time can be refused.

"Monesti on tullut ajateltua, että ihana, kamala kakara!" : Huomioidaanko päiväkodissa kansainvälisesti adoptoituun lapseen ja adoptioon liittyviä erityispiirteitä?

The purpose of this study was to examine the conceptions adoptive parents and kindergarten teachers have of adopted children in day care. Earlier Finnish research concerning international adoption has discussed adoption, adopted children and adoptive parents from the point of view of identity, racism and school. There has hardly been any research in Finland concerning adoption from the point of view of day care. The study focuses on how the special characteristics of adopted children are taken into consideration in day care. The ecological theory, in which a child's growth and learning environments are studied as part of the broader environment, provided the theoretical framework for the study. The study was based also on a second theory: intercultural competence or the capacity to interact with different people taking into consideration their individual characteristics and situations so that one understands and is understood. The first research problem consisted of describing the conceptions adoptive parents and day care teachers have of the special characteristics of adopted children. The second research problem was to examine adopted parents' expectations of kindergarten and of kindergarten teachers. The third research problem was to find out what kind of support day care teachers think they need when working with adopted children. The study focused on 20 adoptive parents and 15 kindergarten teachers. Research material was collected in the form of essay writings amounting to a total of 73 pages. The respondents wrote about their experiences with the help of a supporting questionnaire. The research method was qualitative and narrative. The results of the study show that adoptive parents have similar conceptions of adopted children's special characteristics concerning their character, social competence, adaptation and appearance. Adoptive parents had a better understanding of the dynamics of attachment than kindergarten teachers, in this study. When describing the special characters of adopted children, the teachers regarded adopted children in particular as needing special support. According to the results of the study, adoptive parents feel adoption matters and adoptive parenthood are something quite new and bewildering to day care teachers. Adoptive parents did not feel they got any support from the kindergarten in their parenthood. Adoptive parents regarded as particularly important the start of day care and the familiarisation process during which adopted children need time and special support due to earlier experiences of separation and abandonment. The findings of the study show that kindergarten teachers have little knowledge of adoption and the significance of adoption for a child's growth and development. Kindergarten teachers felt at a loss in dealing with adoption issues and clearly need additional support in the matter.

"Sitte se menee koulus" : Eri kieli- ja kulttuuritaustaisen lapsen suomen kielen taito esiopetuksen päättövaiheessa

A child learns new things, creates social relationships and participates in play with the help of language. How can a child overcome these challenges if the surrounding language is not his mother tongue? The objective of learning a new language in the Pre-school education is an active bilingualism in all fields of the language. Theoretical context of the research rises from bilingualism, learning a language, language skills and evaluating them. Object of the research was to understand language skills of a child from a different linguistic and cultural background in the final stage of Pre-school education and to clarify how learning Finnish was supported during the Pre-school year. Answers to the research issues will be searched with the following questions: 1) What kind of language skills does a child from a different linguistic and cultural backgrounds have at the final stage of Pre-school education?, 1.1) What kind of listening comprehension skills?, 1.2) What kind of speech and vocabulary skills?, 1.3) What kind of structural skills?, 2) What kind of individual differences are there in language skills of children from different linguistic and cultural backgrounds?, and 3) How has a child from a different linguistic and cultural background been supported in learning Finnish during the Pre-school education? The view of language skills in this research is holistic even though it will be analysed in separate fields. The aim of this research is to form an overall impression of Finnish skills of the children participating in the research. Eight Pre-school-aged children with different linguistic and cultural backgrounds and their kindergarten teachers participated in this research. The children had taken part in Finnish activities for about three years. The research material consists of the test series (KITA), which evaluate children’s language skills – and of the questionnaire to the kindergarten teachers. The purpose of the questionnaire was to provide additional information on children’s language skills in Pre-school teaching situations and on supporting Finnish in Pre-school education. This research is qualitative and processing of the material is based on content analysis. According to the kindergarten teachers, the children’s social language skills were sufficient to cope in everyday life but children needed assistance with longer instructions. The same phenomenon could also be seen with the KITA tests – in which long and abstract instructions turned out to be difficult. Individual differences of the children were perceived in productivity skills, which were realised in fluent or influent speech. The children were supported in learning Finnish individually, in small-groups and in the activities of a whole group. ‘Finnish as the second language’ small-groups were the most common form of support in learning the language. The support at understanding activities was emphasized in whole group situations as well as in individual situations while assisting the child’s language skills. Generally, the children’s language skills were in the same level with developing basic language skills. The data of this research help to understand children’s language skills after three years of adopting Finnish. The results can be utilised in planning and evaluation of teaching another language.

Käsityötä, kotiteollisuutta ja sosiaalihuoltoa : Työtupa Aunuksessa 1941-1944

When Finland occupied East Karelian territories in Soviet Union during The Continuation War (1941 1944) Finnish people had also to take care of the inhabitants of the occupied East Karelia. For example there was a lack of clothes and shoes during the wartime. In order to facilitate clothing situation and to provide more opportunities to work for women, Finnish people founded some workshops in East Karelia. Workshops also helped to collect East Karelian craft products. One of the workshops was founded in the city of Olonets in October 1941 and it was in operation until June 1944. This workshop is the subject of this thesis. The aim of this thesis is to find out with the microhistorical approach what kind of functions the workshop of Olonets had during The Continuation War and who worked in the workshop. In this thesis I also examine women s crafts in the Olonets workshop and their meaning during the wartime. I collected the material of this thesis from different places. In February 2010 I interviewed Talvikki Lausala, the leader of the Olonets workshop, who worked in the Olonets from May 1942 to June 1944. From the Virkki Käsityömuseo I looked for objects which have been made in the workshop of Olonets. Tyyne-Kerttu Virkki collected crafts from the East Karelia when she was working in the area and in the workshop from 1941 to 1944. Archive material I found from the Finnish National archive and from the archive of the Tyyne-Kerttu Virkki -Foundation. East Karelian women and girls who were not able to do anything else came to work in the Olonets workshop. If women could not go to work outside of home, they had an option to do the same crafts at home. There were three Finnish women, Tyyne-Kerttu Virkki, Talvikki Lausala and Sofi Nyrkkö, who worked and led in the workshop of Olonets. In addition to the workshop, there was a dress maker s atelier in which clothes were made to order and soldiers uniforms were repaired, a small museum and a shop to sell products of the workshop. Craft products were also exported to Finland. Courses were organized in which Finnish women taught East Karelian crafts.

Oikein, nurin - miten Suomessa kudin : Tutkimus neulonnan työotteista.

The aim of this work was to study what kind of working grips people use to knit in Finland and decide if one grip is superior to others. I investigated how knitters have adopted their grips and how they experience their knitting. I also explored whether it is possible to change one's grip. To provide a theoretical basis for the research I observed knitting in terms of culture, skill and ergonomics. The first part of the study material comprised video recordings of the grips of 95 knitters together with background information collected via a questionnaire during the education of craft teachers at the University of Helsinki in spring 2004, 2005 and 2006. Using the data obtained I focused on three knitters, whose grip of the knitting needles clearly differed from the ergonomically good grip. In addition to them I interviewed one student, who had changed over to more ergonomic way of knitting after participating in the first part of this study. In this respect my study is a several events' case study. In order to analyse my data I used both qualitative and quantitative content analysis methods to complement each other. Most of my research participants had learned to knit in first years of elementary school or comprehensive school. Almost everyone had adopted the basics of knitting by imitating, and many of them had corrected "incorrect" positions from verbal instructions. Through practice the imitated position had gradually become the style unique to each knitter. The findings showed that students' background in knitting is quite varied due to the diverse level of craft teaching. This is reflected in their knitting grips and their interest in knitting. Students do not think that there is one right working grip. The most important thing is that working seems as fluent and relaxed as possible, at which point knitting is easy and flows freely. They often consider their own style so pleasing and well-functioning that they do not think there could be any room for improvement. This study pointed out that, while it is possible to change a knitter's working grip, there is a bigger challenge in acknowledging weaknesses in one's know how. According to the results of my research, the most common working grip among Finnish knitters' corresponds with the grip that has been described as ergonomically good. Over one third of all participants knitted this way. Hands keep the knitting firmly but without tension. The forefinger that guides the yarn from the ball rests gently against the knitting needle, and the yarn goes in front of the first joint of the forefinger. The position of the hands and loops is the same as in the ergonomically good grip, i.e. the fingertips of both hands and the loops are near the tips of the knitting needles, so that the fingers only have to move small distances. When knitters purl and plain, they commonly pick up the yarn from the back of the knitting needle in the same way as when knitting. While researching the common features of working grips I have learned what abnormal grips are like. Although I recognized many different ways to knit, all the peculiar grips were modifications of the continental way of knitting. The results of this study give a clear picture of those points knitters should focus their attention on in order to gain a good hold of the needles.

Adenoviral Gene Therapy for Advanced Head and Neck Cancer

Advanced stage head and neck cancers (HNC) with distant metastasis, as well as prostate cancers (PC), are devastating diseases currently lacking efficient treatment options. One promising developmental approach in cancer treatment is the use of oncolytic adenoviruses, especially in combination therapy with conventional cancer therapies. The safety of the approach has been tested in many clinical trials. However, antitumor efficacy needs to be improved in order to establish oncolytic viruses as a viable treatment alternative. To be able to test in vivo the effects on anti-tumor efficiency of a multimodal combination therapy of oncolytic adenoviruses with the standard therapeutic combination of radiotherapy, chemotherapy and Cetuximab monoclonal antibody (mAb), a xenograft HNC tumor model was developed. This model mimics the typical clinical situation as it is initially sensitive to cetuximab, but resistance develops eventually. Surprisingly, but in agreement with recent findings for chemotherapy and radiotherapy, a higher proportion of cells positive for HNC cancer stem cell markers were found in the tumors refractory to cetuximab. In vitro as well as in vivo results found in this study support the multimodal combination therapy of oncolytic adenoviruses with chemotherapy, radiotherapy and monoclonal antibody therapy to achieve increased anti-tumor efficiency and even complete tumor eradication with lower treatment doses required. In this study, it was found that capsid modified oncolytic viruses have increased gene transfer to cancer cells as well as an increased antitumor effect. In order to elucidate the mechanism of how oncolytic viruses promote radiosensitization of tumor cells in vivo, replicative deficient viruses expressing several promising radiosensitizing viral proteins were tested. The results of this study indicated that oncolytic adenoviruses promote radiosensitization by delaying the repair of DNA double strand breaks in tumor cells. Based on the promising data of the first study, two tumor double-targeted oncolytic adenoviruses armed with the fusion suicide gene FCU1 or with a fully human mAb specific for human Cytotoxic T Lymphocyte-Associated Antigen 4 (CTLA-4) were produced. FCU1 encodes a bifunctional fusion protein that efficiently catalyzes the direct conversion of 5-FC, a relatively nontoxic antifungal agent, into the toxic metabolites 5-fluorouracil and 5-fluorouridine monophosphate, bypassing the natural resistance of certain human tumor cells to 5-fluorouracil. Anti-CTLA4 mAb promotes direct killing of tumor cells via apoptosis and most importantly immune system activation against the tumors. These armed oncolytic viruses present increased anti-tumor efficacy both in vitro and in vivo. Furthermore, by taking advantage of the unique tumor targeted gene transfer of oncolytic adenoviruses, functional high tumor titers but low systemic concentrations of the armed proteins were generated. In addition, supernatants of tumor cells infected with Ad5/3-24aCTLA4, which contain anti-CTLA4 mAb, were able to effectively immunomodulate peripheral blood mononuclear cells (PBMC) of cancer patients with advanced tumors. -- In conclusion, the results presented in this thesis suggest that genetically engineered oncolytic adenoviruses have great potential in the treatment of advanced and metastatic HNC and PC.

Developmental, functional brain imaging and electrophysiological evidence of visual and auditory working memory

Intact function of working memory (WM) is essential for children and adults to cope with every day life. Children with deficits in WM mechanisms have learning difficulties that are often accompanied by behavioral problems. The neural processes subserving WM, and brain structures underlying this system, continue to develop during childhood till adolescence and young adulthood. With functional magnetic resonance imaging (fMRI) it is possible to investigate the organization and development of WM. The present thesis aimed to investigate, using behavioral and neuroimaging methods, whether mnemonic processing of spatial and nonspatial visual information is segregated in the developing and mature human brain. A further aim in this research was to investigate the organization and development of audiospatial and visuospatial information processing in WM. The behavioral results showed that spatial and nonspatial visual WM processing is segregated in the adult brain. The fMRI result in children suggested that memory load related processing of spatial and nonspatial visual information engages common cortical networks, whereas selective attention to either type of stimuli recruits partially segregated areas in the frontal, parietal and occipital cortices. Deactivation mechanisms that are important in the performance of WM tasks in adults are already operational in healthy school-aged children. Electrophysiological evidence suggested segregated mnemonic processing of visual and auditory location information. The results of the development of audiospatial and visuospatial WM demonstrate that WM performance improves with age, suggesting functional maturation of underlying cognitive processes and brain areas. The development of the performance of spatial WM tasks follows a different time course in boys and girls indicating a larger degree of immaturity in the male than female WM systems. Furthermore, the differences in mastering auditory and visual WM tasks may indicate that visual WM reaches functional maturity earlier than the corresponding auditory system. Spatial WM deficits may underlie some learning difficulties and behavioral problems related to impulsivity, difficulties in concentration, and hyperactivity. Alternatively, anxiety or depressive symptoms may affect WM function and the ability to concentrate, being thus the primary cause of poor academic achievement in children.

Expression of cytochrome P450 enzymes and metabolism of timolol in human ocular tissue

Glaucoma is a group of progressive optic neuropathies causing irreversible blindness if not diagnosed and treated in the early state of progression. Disease is often, but not always, associated with increased intraocular pressure (IOP), which is also the most important risk factor for glaucoma. Ophthlamic timolol preparations have been used for decades to lower increased intraocular pressure (IOP). Timolol is locally well tolerated but may cause e.g. cardiovascular and pulmonary adverse effects due to systemic absorption. It has been reported that approximately 80% of a topically administered eye drop is systemically absorbed. However, only limited information is available on timolol metabolism in the liver or especially in the human eye. The aim of this work was to investigate metabolism of timolol in human liver and human ocular tissues. The expression of drug metabolizing cytochrome P450 (CYP) enzymes in the human ciliary epithelial cells was studied. The metabolism of timolol and the interaction potential of timolol with other commercially available medicines were investigated in vitro using different liver preparations. The absorption of timolol to the aqueous humor from two commercially available products: 0.1% eye gel and 0.5% eye drops and the presence of timolol metabolites in the aqueous humor were investigated in a clinical trial. Timolol was confirmed to be metabolized mainly by CYP2D6 as previously suggested. Potent CYP2D6 inhibitors especially fluoxetine, paroxetine and quinidine inhibited the metabolism of timolol. The inhibition may be of clinical significance in patients using ophthalmic timolol products. CYP1A1 and CYP1B1 mRNAs were expressed in the human ciliary epithelial cells. CYP1B1 was also expressed at protein level and the expression was strongly induced by a known potent CYP1B1 inducer 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). The CYP1B1 induction is suggested to be mediated by aryl hydrocarbon receptor (AHR). Low levels of CYP2D6 mRNA splice variants were expressed in the human ciliary epithelial cells and very low levels of timolol metabolites were detected in the human aqueous humor. It seems that negligible amount of CYP2D6 protein is expressed in the human ocular tissues. Timolol 0.1% eye gel leads to aqueous humor concentration high enough to achieve therapeutic effect. Inter-individual variation in concentrations is low and intraocular as well as systemic safety can be increased when using this product with lower timolol concentration instead of timolol 0.5% eye drops.

Neural stem cell characteristics affected by oncogenic pathways and in a human motoneuron disease

Neural stem cell characteristics affected by oncogenic pathways and in a human motoneuron disease Stem cells provide the self-renewing cell pool for developing or regenerating organs. The mechanisms underlying the decisions of a stem or progenitor cell to either self-renew and maintain multipotentiality or alternatively to differentiate are incompletely understood. In this thesis work, I have approached this question by investigating the role of the proto-oncogene Myc in the regulatory functions of neural progenitor cell (NPC) self-renewal, proliferation and differentiation. By using a retroviral transduction technique to create overexpression models in embryonic NPCs cultured as neurospheres, I show that activated levels of Myc increase NPC self-renewal. Furthermore, several mechanisms that regulate the activity of Myc were identified. Myc induced self-renewal is signalled through binding to the transcription factor Miz-1 as shown by the inhibited capacity of a Myc mutant (MycV394D), deficient in binding to Miz-1, to increase self-renewal in NPCs. Furthermore, overexpression of the newly identified proto-oncogene CIP2A recapitulates the effects of Myc overexpression in NPCs. Also the expression levels and in vivo expression patterns of Myc and CIP2A were linked together. CIP2A stabilizes Myc protein levels in several cancer types by inhibiting its degradation and our results suggest the same function for CIP2A in NPCs. Our results also support the conception of self-renewal and proliferation being two separately regulated cellular functions. Finally, I suggest that Myc regulates NPC self-renewal by influencing the way stem and progenitor cells react to the environmental cues that normally dictate the cellular identity of tissues containing self-renewing cells. Neurosphere cultures were also utilised in order to characterise functional defects in a human disease. Neural stem cell cultures obtained post-mortem from foetuses of lethal congenital contracture syndrome (LCCS) were used to reveal possible cell autonomous differentiation defects of patient NPCs. However, LCCS derived NPCs were able to differentiate normally in vitro although several transcriptional differences were identified by using microarray analysis. Proliferation rate of the patient NPCs was also increased as compared to NPCs of age-matched control foetuses.

Levosimendan: Studies on its mechanisms of action and beyond

Acute heart failure syndrome represents a prominent and growing health problem all around the world. Ideally, medical treatment for patients admitted to hospital because of this syndrome, in addition to alleviating the acute symptoms, should also prevent myocardial damage, modulate neurohumoral and inflammatory activation, and preserve or even improve renal function. Levosimendan is a cardiac enhancer having both inotropic and vasodilatory effects. It is approved for the short-term treatment of acutely decompensated chronic heart failure, but it has been shown to have beneficial clinical effects also in ischemic heart disease and septic shock as well as in perioperative cardiac support. In the present study, the mechanisms of action of levosimendan were studied in isolated guinea-pig heart preparations: Langendorff-perfused heart, papillary muscle and permeabilized cardiomyocytes as well as in purified phosphodiesterase isoenzyme preparations. Levosimendan was shown to be a potent inotropic agent in isolated Langendorff-perfused heart and right ventricle papillary muscle. In permeabilized cardiomyocytes, it was demonstrated to be a potent calcium sensitizer in contrast to its enantiomer, dextrosimendan. It was additionally shown to be a very selective phosphodiesterase (PDE) type-3 inhibitor, the selectivity factor for PDE3 over PDE4 being 10000 for levosimendan. Irrespective of this very selective PDE3 inhibitory property in purified enzyme preparations, the inotropic effect of levosimendan was demonstrated to be mediated mainly through calcium sensitization in the isolated heart as well as the papillary muscle preparations at clinically relevant concentrations. In the isolated Lagendorff-perfused heart, glibenclamide antagonized the levosimendan-induced increase in coronary flow (CF). Therefore, the main vasodilatory mechanism in coronary veins is believed to be the opening of the ATP-sensitive potassium (KATP) channels. In the paced hearts, CF did not increase in parallel with oxygen consumption (MVO2), thus indicating that levosimendan had a direct vasodilatory effect on coronary veins. The pharmacology of levosimendan was clearly different from that of milrinone, which induced an increase in CF in parallel with MVO2. In conclusion, levosimendan was demonstrated to increase cardiac contractility by binding to cardiac troponin C and sensitizing the myofilament contractile proteins to calcium, and further to induce coronary vasodilatation by opening KATP channels in vascular smooth muscle. In addition, the efficiency of the cardiac contraction was shown to be more advantageous when the heart was perfused with levosimendan in comparison to milrinone perfusion.