The Molecular Basis of Hydrolethalus Syndrome

Hydrolethalus syndrome (HLS) is a severe fetal malformation syndrome that is inherited by an autosomal recessive manner. HLS belongs to the Finnish disease heritage, an entity of rare diseases that are more prevalent in Finland than in other parts of the world. The phenotypic spectrum of the syndrome is wide and it is characterized by several developmental abnormalities, including hydrocephalus and absent midline structures in the brain, abnormal lobation of the lungs, polydactyly as well as micrognathia and other craniofacial anomalies. Polyhydramnios are relatively frequent during pregnancy. HLS can nowadays be effectively identified by ultrasound scan already at the end of the first trimester of pregnancy. One of the main goals in this study was to identify and characterize the gene defect underlying HLS. The defect was found from a previously unknown gene that was named HYLS1. Identification of the gene defect made it possible to confirm the HLS diagnosis genetically, an aspect that provides valuable information for the families in which a fetus is suspected to have HLS. Neuropathological findings of mutation confirmed HLS cases were described for the first time in detail in this study. Also, detailed general pathological findings were described. Since HYLS1 was an unknown gene with no relatives in the known gene families, many functional studies were performed in order to unravel the function of the gene and of the protein it codes for. Studies showed, for example, that the subcellular localization of the HYLS1 protein was different when the normal and the defective forms were compared. In addition, HYLS1 was shown to possess transactivation potential which was significantly diminished in the defective form. According to the results of this study it can be stated that HYLS1 most likely participates in transcriptional regulation and also in the regulation of cholesterol metabolism and that the function of HYLS1 is critical for normal fetal development.

Functional and cellular analysis of autoimmune regulator (AIRE) protein

Autoimmune diseases are a major health problem. Usually autoimmune disorders are multifactorial and their pathogenesis involves a combination of predisposing variations in the genome and other factors such as environmental triggers. APECED (autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy) is a rare, recessively inherited, autoimmune disease caused by mutations in a single gene. Patients with APECED suffer from several organ-specific autoimmune disorders, often affecting the endocrine glands. The defective gene, AIRE, codes for a transcriptional regulator. The AIRE (autoimmune regulator) protein controls the expression of hundreds of genes, representing a substantial subset of tissue-specific antigens which are presented to developing T cells in the thymus and has proven to be a key molecule in the establishment of immunological tolerance. However, the molecular mechanisms by which AIRE mediates its functions are still largely obscure. The aim of this thesis has been to elucidate the functions of AIRE by studying the molecular interactions it is involved in by utilizing different cultured cell models. A potential molecular mechanism for exceptional, dominant, inheritance of APECED in one family, carrying a glycine 228 to tryptophan (G228W) mutation, was described in this thesis. It was shown that the AIRE polypeptide with G228W mutation has a dominant negative effect by binding the wild type AIRE and inhibiting its transactivation capacity in vitro. The data also emphasizes the importance of homomultimerization of AIRE in vivo. Furthermore, two novel protein families interacting with AIRE were identified. The importin alpha molecules regulate the nuclear import of AIRE by binding to the nuclear localization signal of AIRE, delineated as a classical monopartite signal sequence. The interaction of AIRE with PIAS E3 SUMO ligases, indicates a link to the sumoylation pathway, which plays an important role in the regulation of nuclear architecture. It was shown that AIRE is not a target for SUMO modification but enhances the localization of SUMO1 and PIAS1 proteins to nuclear bodies. Additional support for the suggestion that AIRE would preferably up-regulate genes with tissue-specific expression pattern and down-regulate housekeeping genes was obtained from transactivation studies performed with two models: human insulin and cystatin B promoters. Furthermore, AIRE and PIAS activate the insulin promoter concurrently in a transactivation assay, indicating that their interaction is biologically relevant. Identification of novel interaction partners for AIRE provides us information about the molecular pathways involved in the establishment of immunological tolerance and deepens our understanding of the role played by AIRE not only in APECED but possibly also in several other autoimmune diseases.

On gravitational fields of stars in f(R) gravity theories

Einstein's general relativity is a classical theory of gravitation: it is a postulate on the coupling between the four-dimensional, continuos spacetime and the matter fields in the universe, and it yields their dynamical evolution. It is believed that general relativity must be replaced by a quantum theory of gravity at least at extremely high energies of the early universe and at regions of strong curvature of spacetime, cf. black holes. Various attempts to quantize gravity, including conceptually new models such as string theory, have suggested that modification to general relativity might show up even at lower energy scales. On the other hand, also the late time acceleration of the expansion of the universe, known as the dark energy problem, might originate from new gravitational physics. Thus, although there has been no direct experimental evidence contradicting general relativity so far - on the contrary, it has passed a variety of observational tests - it is a question worth asking, why should the effective theory of gravity be of the exact form of general relativity? If general relativity is modified, how do the predictions of the theory change? Furthermore, how far can we go with the changes before we are face with contradictions with the experiments? Along with the changes, could there be new phenomena, which we could measure to find hints of the form of the quantum theory of gravity? This thesis is on a class of modified gravity theories called f(R) models, and in particular on the effects of changing the theory of gravity on stellar solutions. It is discussed how experimental constraints from the measurements in the Solar System restrict the form of f(R) theories. Moreover, it is shown that models, which do not differ from general relativity at the weak field scale of the Solar System, can produce very different predictions for dense stars like neutron stars. Due to the nature of f(R) models, the role of independent connection of the spacetime is emphasized throughout the thesis.

Kuntoutusosallisuuden diagnoosi : Tutkimus entisten rappiokäyttäjien kuntoutumisen muodoista, mekanismeista ja mahdollisuuksista

The main theme of the research centres on the idea that social inclusion can be analysed as inclusions and exclusions. The research is focused on the phenomenon of inclusion that is defined as widely understood social relationships and social binds emerging in a rehabilitation process. Information was gathered from 13 ex substance abusers, who had a background of heavy substance abuse for appr. 15 years and who have been sober for about 7 years. Also 34 persons who helped them to rehabilitate by the helped persons’ perspectives, were interviewed. The speciality of the research is that 5 of the ex abusers were also physically or mentally disabled. A Simmelian interaction process analysis was applied for the narrative analysis of the collected data. The aim of the analysis was to define different kinds of configurations of social relations and social binds. According to the research 3 different forms of inclusion are emerged in rehabilitation. At the early stage rehabilitation leans towards controlling the new sober life style (inclusion of life control). When people begin to rely on their temperance, they begin to make decisions about an own way of living (life political inclusion) and can also dissociate from the institutional thought patterns. People must also find a way into the circles of social relationships to develop own esteemed individual settings of codes for their action (inclusion of life orientation). The main result of the research represents the ‘mechanism of the social’ of rehabilitation. It is composed of the forms of inclusion mentioned above, their contents and the specific reflection mechanism of inclusion. It consists of the heavy structure of the disciplines of the rehabilitation system and the light structure of social worlds. Finally rehabilitation in the long run seems to lean on aesthetic of social relationships – how the person is connected to the circle of social relationships in this reflection. The conclusions are the following. The role of institutional disciplines is an important social resource for controlling life. Other institutions, i.e. the institutions of adult education offer opportunities to organize the abuser’s life. Unfortunately, the institutional rehabilitation seems to offer feeble help, especially to those who are actualising a kind of life orientation that does not comply with legitimated institutional thought patterns. If the helpers cannot define the need for aid in this situation, the helped easily becomes perversely socially excluded. In a discreet way the institutional rehabilitation is shaping subjectivities of the ex abusers by transferring responsibilities for them. This incident already increases the uncertainty of life of ex abuser, who is disposed towards feeling shame and inferiority. It is more secure to strengthen social binds with the institutional rehabilitation and its membership. Thus, getting individually responsible increases addictive behaviours.

Lapset, media ja symbolinen vuorovaikutus : Suomalaisten, englantilaisten ja saksalaisten lasten mediasuhteen tarkastelua

Tämän hetken mediaympäristölle on ominaista intensiivisyys ja jatkuva läsnäolo. Medialla on merkittävä rooli myös pienten lasten jokapäiväisessä elämässä, sillä he aloittavat median säännöllisen seuraamisen keskimäärin kolmen vuoden iässä. Mediasisällöt, mediavälineet ja mediaan liittyvät sosiaaliset suhteet muodostavatkin lapsille mediaympäristön, jossa lapset rakentavat identiteettejään, oppivat sosiaalista kanssakäymistä ja kehittävät näkemyksiään yhteiskunnasta ja kulttuurista. Tutkimuksessa on selvitetty 4-6-vuotiaitten suomalaisten, englantilaisten ja saksalaisten lasten audiovisuaalisen median tulkintaa ja median roolia heidän elämässään. Tutkimuksen tavoitteena on ollut syventää tutkimuksellista tietoa median sosiaalisesta ja kulttuurisesta merkityksestä pienten lasten elämässä ja sitä, miten he tulkitsevat mediasisältöä. Tutkimuksessa lasten mediasuhdetta on tarkasteltu välineellisenä, sosiaalisena, symbolisena ja kulttuurisena tulkintaympäristönä. Edellisten lisäksi tutkimuksessa on arvioitu harvemmin viestinnän tutkimuksessa käytetyn symbolisen interaktionismin teorian tarjoamia mahdollisuuksia lasten mediasuhteen tarkasteluun. Suomessa, Englannissa ja Saksassa kootun kansainvälisen aineiston pohjalta on tarkasteltu myös vertailuryhmien välillä olevia mediaan liittyviä kulttuurisia eroja. Eri vertailumaiden melko samankaltaisesta mediaympäristöstä huolimatta tutkimus antaa viitteitä mediatulkinnoissa olevista kulttuurisista eroista. Media mahdollistaa lapsen erilaistan taitojensa kehittymistä ja voi siten muodostaa heille sosiaalisia, symbolisia ja kulttuurisia resursseja, joilla on merkitystä lapsen kehittymisen kannalta. Lapsen ja median suhde on kaksisuuntainen vuorovaikutussuhde ja mediainformaation tulkinnassa ovat mukana lapsen aiemmat tiedolliset ja sosiaaliset kokemukset. Aktiivisessa mediatulkintasuhteessaan lapsi kehittää sanavarastoaan, havainnointiaan, ajatteluaan ja tunne-elämäänsä. Median käyttö sosiaalisena tapahtumana kehittää osaltaan lapsen sosiaalisia valmiuksia. Siten esimerkiksi perheen median käyttöön liittyvät säännöt ja ohjeet ohjaavat perheen sisäistä toimintaa ja määrittävät lapsen asemaa perheessä. Median sisällöt ja niihin liittyvät erilaiset oheistuotteet toimivat osaltaan lapsen kulttuuristen koodistojen ja luokittelujen muodostajana. Tutkimus osoittaa myös symbolisen interaktionismin teorian tarjoavan varsin poikkitieteellisen tutkimuksellisen viitekehyksen lapsia ja mediaa koskevalle tutkimukselle ja mahdollistaa lasten mediasuhteen tutkimisen ja ymmärtämisen useiden, erilaisten tekijöiden suhteena.

Search for R-Parity Violating Decays of Sneutrinos to eμ, μτ, and eτ Pairs in pp̅ Collisions at √s=1.96 TeV

We present a search for tau sneutrino production using the Tevatron ppbar collision data collected with the CDF II detector and corresponding to an integrated luminosity of 1 fb^-1. We focus on the scenarios predicted by the R-parity violating (RPV) supersymmetric models in which tau sneutrinos decay to two charged leptons of different flavor. With the data consistent with the standard model expectations, we set the upper limits on sigma(ppbar -> tau sneutrino)*BR(tau sneutrino ->emu,mutau,etau) and use these results to constrain the RPV couplings as a function of tau sneutrino mass.

Ironi som forskningsobjekt. Är det möjligt att forska i det som finns mellan raderna?

Abstract (Irony as object of research: Is it possible to explore what is between the lines?): The main concern of this article is the interpretation of irony: how is it brought about and how can it be investigated? The method applied is based on authentic texts and their elicited interpretations − a method referred to in this article response analysis. Interpretation of irony in the approach taken is seen as being crucially dependent on the notion of coherence. A text is perceived as being coherent if it (a) makes sense and if it(b) hangs together. Incoherent texts can result in an ironic interpretation; however, the incoherence must also be perceived as being intentional, and intentionality in turn is a sign of the edge of the ironist. Ironic interpretation is defined as a combination of five factors: (1) an ironic edge that (2) reflects the intention of the ironist, and (3) has a target and (4) a victim too. Essential to irony is its fifth factor, the fact that one or more of these four factors must be inferred from co(n)text. This definition of irony is crucial in distinguishing irony from non-irony, and it also helps to discern the differences as well as the similarities between irony and related phenomena.

Moral Professionalism in Interaction : Educators' Relational Moral Voices in Urban Schools

The aim of this study was to investigate educators relational moral voices in urban schools and to listen to what they told about moral professionalism and moral practices in challenging urban schools. Their relational moral voices were investigated through the following three questions: 1. What are the educators moral voices in relation to themselves and other people? 2. What are the educators moral voices in relation to their work and society? 3. What kind of interaction process lies between the educators moral voices and the urban school context? The research data of this study were gathered in four urban schools in Jyväskylä and Helsinki. The research schools were chosen for this study according to the criteria of the international Socrates Comenius project called Leading Schools Successfully in Challenging Urban Context: Strategies for Improvement. This study formed part of this project, which investigated successful urban schools as challenging learning environments in nine European countries and explored the principals success in leadership in particular. The data, which included 37 narratively constructed interviews with four principals and key informants selected by the principals, were gathered in interviews conducted in 2006. In other words, the data comprised three interviews with each of four principals, and interviews with two teachers, two parents, and two pupils from each school. In addition, the school deacon from one school was also interviewed. Furthermore, part of the data from one of the research schools included a medium report of the school deacon s work. This study combined the case study method, the narrative approach and the critical incident technique as the methodological framework. In addition, all of these methods served as practical tools for both analyzing and reporting the data. The educators' narrations and the results of the study appear in the original articles (Hanhimäki & Tirri 2008; Hanhimäki 2008b; Hanhimäki & Tirri 2009; Hanhimäki 2008a). The educators moral voices in relation to themselves and other people emerged through the main themes of moral leadership, the development and evaluation process, moral sensitivity, gender, values, and student well-being. The educators moral voices in relation to their work and society emerged through the main themes of multiprofessional cooperation, families and parental involvement, and moral school culture. The idea of moral interaction connected moral professionalism and the methodological combination of this study, which together emphasized social interaction and the creation of understanding and meaning in this interaction. The main point of this study was to state that the educators moral voices emerged in the interaction between the educators themselves and the urban school context. In this interaction, the educators moral professionalism was constructed and shaped in relation to themselves, other people, their work and society. The loudest relational moral voices heard through the main themes were those of caring, cooperation, respect, commitment, and professionalism. When the results were compared to the codes of ethics which guided these educators moral professional work, the ethical principles and values of the codes were clearly visible in their moral practices. The loudest message from the educators narration could be summarized in the words caring, respect and cooperation: at its best, there is just a human being and a human being with caring, respect and cooperation between them. The results of this study emphasize the need for practical approaches such as case studies and the narrative approach in teacher education to encourage educators to become moral professionals capable of meeting the needs of people of varied backgrounds. In addition, opportunities for moral, religious and spiritual education should be noticed and utilized in the plural interaction of urban schools when nurturing pupils and creating a moral school culture. Furthermore, multiprofessional cooperation and parents as the school s primary cooperation partner are needed to carry out the shared duty of moral education in urban schools. Keywords: moral professionalism, educator, relational moral voice, interaction, urban school