Lipid assisted membrane entry in specific phospholipid targeted protein systems

The purpose of this thesis project is to study changes in the physical state of cell membranes during cell entry, including how these changes are connected to the presence of ceramide. The role of enzymatical manipulation of lipids in bacterial internalization is also studied. A novel technique, where a single giant vesicle is chosen under the microscope and an enzyme coupled-particle attached to the micromanipulator pipette towards the vesicle, is used. Thus, the enzymatic reaction on the membrane of the giant vesicle can be followed in real-time. The first aim of this study is to develop a system where the localized sphingomyelinase membrane interaction could be observed on the surface of the giant vesicle and the effects could be monitored with microscopy. Domain formation, which resembles acid sphingomyelinase (ASMase), causes CD95 clustering in the cell membrane due to ceramide production (Grassmé et al., 2001a; Grassmé et al., 2001b) and the formation of small vesicles inside the manipulated giant vesicle is observed. Sphingomyelinase activation has also been found to be an important factor in the bacterial and viral invasion process in nonphagocytic cells (Grassmé et al., 1997; Jan et al., 2000). Accordingly, sphingomyelinase reactions in the cell membrane might also give insight into bacterial or viral cellular entry events. We found sphingomyelinase activity in Chlamydia pneumonia elementarybodies (EBs). Interestingly, the bacterium enters host cells by endocytosis but the internalization mechanism of Chlamydia is unknown. The hypothesis is that sphingomyelin is needed for host cell entry in the infection of C. pneumonia. The second project focuses on this subject. The goal of the third project is to study a role of phosphatidylserine as a target for a membrane binding protein. Phosphatidylserine is chosen because of its importance in fusion processes. This will be another example for the importance of lipids in cell targeting, internalization, and externalization.

Outcome of singleton pregnancy after assisted reproductive treatment

Singleton pregnancies achieved by means of assisted reproductive treatment (ART) are associated with increased obstetric and neonatal risks in comparison with spontaneously conceived singleton pregnancies. The impact of infertility- and treatment-related factors on these risks is not properly understood. In addition, the psychological effects of infertility and its treatment on the experience of pregnancy have scarcely been studied. Thus, the aim of the present study was to evaluate the importance of infertility- and treatment-related factors on prediction of pregnancy outcome, obstetric and neonatal risks, fear-of-childbirth and pregnancy-related anxiety. The subjects consisted of infertile women who achieved a singleton pregnancy by means of in vitro fertilisation (IVF) or intracytoplasmic sperm injection (ICSI). The control groups comprised spontaneously conceiving women with singleton gestations. Early pregnancy outcome was assessed by means of assay of serum human chorionic gonadoptrophin (hCG) in single samples. Other outcome data were collected from patient records, national Health Registers and via prospective questionnaire surveys. Viable pregnancies were associated with significantly higher serum hCG levels 12 days after embryo transfer than non-viable pregnancies. Among singleton pregnancies, aetiological subgroup, treatment type or the number of transferred embryos did not impair the predictive value of single hCG assessment. According to the register-based data, age-, parity- and socioeconomic status- adjusted risks of gestational hypertension, preterm contractions and placenta praevia were more frequent in the ART pregnancies than in the control pregnancies. Significantly higher rates of induction of delivery and Caesarean section occurred in the ART group than in the control group. The risks of preterm birth and low birth weight (LBW) were increased after ART pregnancy. Duration or aetiology of infertility, treatment type (fresh or frozen IVF or ICSI) or rank of treatment did not contribute to the risks of preterm birth or LBW. In addition, the risks of preterm birth and LBW remained elevated in spite of of the number of transferred embryos. Although mean duration of pregnancy was shorter and mean birth weight lower in the ART pregnancies than in the control pregnancies, these differences were hardly of clinical significance. Fear-of-childbirth and pregnancy-related anxiety were equally common to women conceiving by means of ART, or spontaneously. Partnership of five to ten years appeared to be protective as regards severe fear-of-childbirth, whereas long preceding infertility (≥ seven years) had the opposite effect. In conclusion, an early hCG assessment maintained its good predictive value regardless of infertility- or patient-related factors. Further, we did not recognise any infertility- or patient-related factors that would expose infertile women to increased obstetric or neonatal risks. However, a long period of infertility was associated with severe fear-of-childbirth.

Transition to parenthood after assisted reproductive treatment: Follow-up study of singleton pregnancies

Infertility treatments are relatively easily available in most Western countries today, but the psychological consequences of these high-tech treatments have scarcely been addressed. The purpose of this controlled longitudinal study was to explore the early environment of the infant born by assisted reproductive treatment (ART). We focused on the parents mental well-being, marital relations and experience of parenting. In addition to this, we assessed parent child interaction and parents mental representations of their child after long-standing infertility and several unsuccessful ART attempts. The subjects were infertile couples who achieved a singleton pregnancy by in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI). The control group comprised of spontaneously conceiving couples with singleton pregnancies. ART women showed fewer depressive symptoms than controls during pregnancy and after delivery, but the difference vanished by the end of the child s first year. ART men consistently had lower levels of anxiety symptoms, sleeping difficulties, and social dysfunction than control men. Control women experienced a decrease in dyadic consensus during the child s first year, which did not happen among ART women. After the child was born, ART men reported a higher level of sexual affection compared with control men. Psychic symptoms and stressful life events were differently related to marital relations in ART and control groups. The parenting experiences of ART mothers were in general at a higher level, compared with controls, and they changed in a positive direction during the child s first year. Fathering experiences were at the same level in both groups, and they changed positively in both groups by the end of the child s first year. The parenting experiences of ART mothers and fathers were more resilient to certain child-related stressors than those of control group. Both mothers and fathers with long-term infertility showed more sensitive behaviour with their child in toddler-age than in infancy. Correspondingly, children s cooperation increased. Mothers often mentioned a fear of miscarriage and difficulty in creating representations of the child during pregnancy. Descriptions of the infants were mainly rich, vivid and loaded with positive features. In conclusion, ART parents in general seem to adapt well to the transition to parenthood. Former infertility and ART do not seem to constitute a risk for parents mental health, marital relations or experience of parenting. Even longstanding infertility with several unsuccessful treatment attempts did not create a risk as regards parenting behaviour or parents mental representations of their child. In this group, however, women were found to have fear for losing the child and difficulty in creating representations of the child during pregnancy, which in some cases may indicate need for psychosocial support. Even though our results are encouraging, infertility and infertility treatments are generally considered as a stressful experience. It is a challenge for health authorities to recognize those couples who need professional help to overcome the distressing experiences of infertility and ART.

Vanhustenhuolto + living lab = mahdollinen yhtälö?

Työ on laajaan dokumenttiaineistoon, haastatteluihin ja havaintoihin perustuva living lab - tyyppisen tuotekehitysprosessin yksityiskohtainen kuvaus. Hankehistoriallisessa tapaustutkimuksessa on käytetty historiantutkimuksen menetelmiä. Vanhustenkeskuksessa toteutetun living lab -hankkeen lopputuloksena syntyi vanhusten liikkeitä monitoroiva hoitotyön apuväline: turvalattia. Living lab -tyyppisessä tuotekehittämisessä on keskeistä teknologian kehittäminen tuotteen todellisessa käyttöympäristössä siten, että käyttäjät osallistuvat aktiivisesti kehitystyön kaikkiin vaiheisiin. Tutkimuksessa hankkeen etenemistä ja turvalattiateknologian rakentumista tarkastellaan toimijaverkostoteorian ja yhteisöllisen oppimisen käsitteen tarjoamista näkökulmista. Tutkimuksessa kiinnitetään erityisesti huomiota siihen, minkälaisia intressejä teknologian kehittämiseen osallistuvilla ryhmillä on ja minkälaisia konflikteja näiden intressien pohjalta syntyy. Lisäksi tarkastelun keskiössä on käyttäjien ja tuotekehittäjien välinen oppiminen, jonka mahdollistaminen ja edistäminen on living lab -kehittämisen päämäärä. Tutkimuksen keskeinen johtopäätös on, että käyttäjiltä saatu palaute on välttämätöntä käyttökelpoisen sosiaali- ja terveydenhuollon alan teknologian aikaansaamiseksi, ja turvalattian tapauksessa käyttäjäpalaute myös uudelleensuuntasi teknologisen järjestelmän innovaatioprosessia. Käyttäjien ja tuotekehittäjien yhteistyön myötä turvalattiaan kehitettiin joukko uusia toiminnallisuuksia ja käsitys tuotteen ydinominaisuuksista sekä hyötylupauksesta muuttuivat. Turvalattian tapaus osoittaa lisäksi yhteisöllisen oppimisen merkityksen innovaatioprosessissa sekä living lab -tyyppisen tuotekehittämisen potentiaalin näiden oppimisprosessien mahdollistajana ja kiihdyttäjänä. Tapaus myös valottaa sitä, kuinka monimutkainen toimintakenttä vanhustenhuolto on teknologian kehittämisen ja sen käyttöönoton näkökulmasta. Näyttäisi kuitenkin siltä, että living lab -metodologian avulla voidaan ylittää joitakin geronteknologian kehittämiseen ja myös käyttöönottoon liittyviä haasteita.

A model Integrating the Facilities Management Process with the Building End User’s Business Process (ProFacil)

The ProFacil model is a generic process model defined as a framework model showing the links between the facilities management process and the building end user’s business process. The purpose of using the model is to support more detailed process modelling. The model has been developed using the IDEF0 modelling method. The ProFacil model describes business activities from the generalized point of view as management-, support-, and core processes and their relations. The model defines basic activities in the provision of a facility. Examples of these activities are “operate facilities”, “provide new facilities”, “provide re-build facilities”, “provide maintained facilities” and “perform dispose of facilities”. These are all generic activities providing a basis for a further specialisation of company specific FM activities and their tasks. A facilitator can establish a specialized process model using the ProFacil model and interacting with company experts to describe their company’s specific processes. These modelling seminars or interviews will be done in an informal way, supported by the high-level process model as a common reference.

Vanhustenhuolto + living lab = mahdollinen yhtälö? Tutkimus geronteknologisen järjestelmän tuotekehitysprosessista

Työ on laajaan dokumenttiaineistoon, haastatteluihin ja havaintoihin perustuva living lab - tyyppisen tuotekehitysprosessin yksityiskohtainen kuvaus. Hankehistoriallisessa tapaustutkimuksessa on käytetty historiantutkimuksen menetelmiä. Vanhustenkeskuksessa toteutetun living lab -hankkeen lopputuloksena syntyi vanhusten liikkeitä monitoroiva hoitotyön apuväline: turvalattia. Living lab -tyyppisessä tuotekehittämisessä on keskeistä teknologian kehittäminen tuotteen todellisessa käyttöympäristössä siten, että käyttäjät osallistuvat aktiivisesti kehitystyön kaikkiin vaiheisiin. Tutkimuksessa hankkeen etenemistä ja turvalattiateknologian rakentumista tarkastellaan toimijaverkostoteorian ja yhteisöllisen oppimisen käsitteen tarjoamista näkökulmista. Tutkimuksessa kiinnitetään erityisesti huomiota siihen, minkälaisia intressejä teknologian kehittämiseen osallistuvilla ryhmillä on ja minkälaisia konflikteja näiden intressien pohjalta syntyy. Lisäksi tarkastelun keskiössä on käyttäjien ja tuotekehittäjien välinen oppiminen, jonka mahdollistaminen ja edistäminen on living lab -kehittämisen päämäärä. Tutkimuksen keskeinen johtopäätös on, että käyttäjiltä saatu palaute on välttämätöntä käyttökelpoisen sosiaali- ja terveydenhuollon alan teknologian aikaansaamiseksi, ja turvalattian tapauksessa käyttäjäpalaute myös uudelleensuuntasi teknologisen järjestelmän innovaatioprosessia. Käyttäjien ja tuotekehittäjien yhteistyön myötä turvalattiaan kehitettiin joukko uusia toiminnallisuuksia ja käsitys tuotteen ydinominaisuuksista sekä hyötylupauksesta muuttuivat. Turvalattian tapaus osoittaa lisäksi yhteisöllisen oppimisen merkityksen innovaatioprosessissa sekä living lab -tyyppisen tuotekehittämisen potentiaalin näiden oppimisprosessien mahdollistajana ja kiihdyttäjänä. Tapaus myös valottaa sitä, kuinka monimutkainen toimintakenttä vanhustenhuolto on teknologian kehittämisen ja sen käyttöönoton näkökulmasta. Näyttäisi kuitenkin siltä, että living lab -metodologian avulla voidaan ylittää joitakin geronteknologian kehittämiseen ja myös käyttöönottoon liittyviä haasteita.

Elämää keskustassa ja kaupunkiseudun reunoilla. Urbaani ja jälkiesikaupungillinen elämäntyyli asumisen valinnoissa ja arkiliikkumisessa Helsingin seudulla.

The lifestyles of people living in single-family housing areas on the outskirts of the Greater Helsinki Region (GHR) are different from those living in inner city area. The urban structure of the GHR is concentrated in the capital on the one hand, and spread out across the outskirts on the other. Socioeconomic spatial divisions are evident as well-paid and educated residents move to the inner city or the single-family house dominated suburban neighbourhoods depending on their housing preferences and life situations. The following thesis explores how these lifestyles have emerged through the housing choices and daily mobility of the residents living in the new single-family housing areas on the outskirts of the GHR and the inner city. The study shows that, when it comes to lifestyles, residents on the outskirts of the region have different housing preferences and daily mobility patterns when compared with their inner city counterparts. Based on five different case study areas my results show that these differences are related to residents values, preferences and attitudes towards the neighbourhood, on the one hand, and limited by urban structure on the other. This also confirms earlier theoretical analyses and findings from the GHR. Residents who moved to the outskirts of Greater Helsinki Region and the apartment buildings of the inner city were similar in the basic elements of their housing preferences: they sought a safe and peaceful neighbourhood close to the natural environment. However, where housing choices, daily mobility and activities vary different lifestyles develop in both the outskirts and the inner city. More specifically, lifestyles in the city apartment blocks were inherently urban. Liveliness and highest order facilities were appreciated and daily mobility patterns were supported by diverse modes of transportation for the purposes of work, shopping and leisure time. On the outskirts, by contrast, lifestyles were largely post-suburban and child-friendliness appreciated. Due to the heterachical urban structure, daily mobility was more car-dependent since work, shopping and free time activities of the residents are more spread around the region. The urban structure frames the daily mobility on the outskirts of the region, but this is not to say that short local trips replace longer regional ones. This comparative case study was carried out in the single-family housing areas of Sundsberg in Kirkkonummi, Landbo in Helsinki and Ylästö in Vantaa, as well as in the inner city apartment building areas of Punavuori and Katajanokka in Helsinki. The data is comprised of residential surveys, interviews, and statistics and GIS data sets that illustrate regional daily mobility, socio-economic structure and vis-à-vis housing stock.