Lattice dynamics of hexagonal ice

The lattice dynamics of hexagonal ice is worked out with the force constants deduced from the experimental elastic constants.

Tammen alueellisen levinneisyyden rajoitteet : Tapaustutkimus Länsi-Turunmaalla

Elinympäristön vaikutusta eliölajien esiintymiseen voidaan tutkia habitaattimallinnuksen keinoin. Havainnot lajin esiintymisestä ja puuttumisesta eri kohdissa maisemaa suhteutetaan tilastollisen mallin avulla ympäristötekijöihin, jolloin saadaan kuva lajin elinympäristövaatimuksista. Tällöin oletetaan, että laji esiintyy kaikkialla siellä, missä sen elinympäristövaatimukset täyttyvät. Metapopulaatioteorian valossa näin ei kuitenkaan aina ole: maisemassa voi olla runsaasti lajille soveltuvia mutta asuttamattomia kasvupaikkoja, koska uusien yksilöiden leviäminen ja vanhojen häviäminen eivät välttämättä ole yksittäisten kasvupaikkojen tasolla tasapainossa. Siten myös lajin leviämiskyky vaikuttaa siihen, millaiseksi sen levinneisyyskuvio maisematasolla muodostuu. Tässä työssä keskityn tammen (Quercus robur) alueellisen levinneisyyden mallintamiseen. Tammen suhteellinen harvinaisuus Suomessa sekä sen rooli luonnon monimuotoisuuden merkittävänä tukipilarina tekevät siitä mielenkiintoisen kohdelajin ekologiselle tutkimukselle. Tutkimuskohteekseni valitsin Wattkastin saaren, n. 5 km2:n alueen Länsi-Turunmaalta. Wattkastissa on tutkittu kahdeksan vuoden ajan tammella elävien hyönteisyhteisöjen rakennetta ja kannanvaihteluita, ja saaressa kasvaa yli 1800 luonnonvaraista tammea, joiden tarkat sijainnit tiedetään. Tässä ympäristössä tutkin, rajoittaako tammen alueellista levinneisyyttä ensisijaisesti sopivien elinympäristöjen tilajakauma vai pikemminkin sen leviämiskyky. Yhdistin tammen esiintymiskuviota kuvaavaan habitaattimalliin kokeellisen aineiston, jonka avulla arvioin tammen paikallisen esiintymiskuvion ja tammelle soveltuvien elinympäristöjen tilajakauman vastaavuutta. Kokeellisen aineiston muodostivat 104 Wattkastiin vuonna 2004 istutettua pikkutammea, joiden selviytymisen ja kasvupaikkaolot kartoitin syksyllä 2009. Tutkin yleistetyillä lineaarisilla malleilla puiden menestymiseen siis selviytymiseen ja kuntoon vaikuttavia tekijöitä. Etsin potentiaalisia selittäjiä tammen menestymiselle kasvupaikan ympäristötekijöistä sekä istutetun puun sijainnista suhteessa luontaisiin tammikasvustoihin. Lisäksi tutkin habitaattimallin avulla, selittävätkö ympäristötekijät tammen nykyisen esiintymiskuvion Wattkastissa. Havaitsin, että istutetut puut olivat selviytyneet keskimäärin hyvin ja ettei niiden menestyminen riippunut sijainnista suhteessa luontaisiin tammikasvustoihin. Habitaattimallin selitysaste oli vain 19 %, eli kasvupaikkatekijät selittivät heikosti tammen nykyisen esiintymiskuvion Wattkastissa. Tulosten perusteella tammen paikallinen esiintymiskuvio ei vastaa sille soveltuvien elinympäristöjen jakaumaa maisemassa, joten tammen levinneisyyttä Wattkastissa rajoittaa ilmeisesti sen leviämiskyky. Tulokseni viittaavat siihen, ettei tammen elinympäristön laadussa ole suuria vaihteluita Wattkastin sisällä, koska sopivia kasvupaikkoja on tarjolla tammen nykyesiintymiseen nähden runsaasti. Tämä on tammihyönteistutkimusten kannalta kiinnostava tulos, koska se tarkoittaa, että aiemmat havainnot isäntäpuun sijainnin ja hyönteisten kannanvaihteluiden välisestä yhteydestä edustavat todellisia, tilaan sidottuja populaatioprosesseja eivätkä isäntäpuun välittämiä eroja elinympäristön laadussa. Lisäksi tutkimukseni osoittaa, että yhdistämällä habitaattimallinnukseen kokeellinen lähestymistapa saadaan realistisempi kuva lajin levinneisyyttä rajoittavista tekijöistä kuin tutkimalla pelkästään ympäristötekijöiden vaikutusta lajin esiintymiseen. Jos lajin rajoittunut leviämiskyky on vaikuttanut sen esiintymiskuvion syntyyn, pelkästään ympäristötekijöihin perustuva levinneisyysmalli liioittelee levinneisyyttä. Kokeellisen tutkimuksen avulla on tällaisessa tapauksessa mahdollista paljastaa myös leviämiskyvyn rooli esiintymiskuvion taustalla.

Sairaanhoitajat työn imussa? Palkkatyön sisällön ja kulttuuristen lähtökohtien tasapainossa

Tutkimuksen tavoitteena on selvittää, mikä saa pitkän työuran tehneet sairaanhoitajat innostumaan työstään. Taustalla on yhteiskunnallinen tilanne, jossa työelämän vetovoimaisuuden lisääminen ja ikääntyvien työntekijöiden työssä jaksaminen ovat keskeisiä poliittisia tavoitteita. Aihetta lähestytään positiivisesta psykologiasta lähtöisin olevan työn imun käsitteen avulla. Se on määritelty pysyväksi, ”myönteiseksi, tunne- ja motivaatiotäyttymyksen tilaksi, jota luonnehtivat tarmokkuus, omistautuminen ja uppoutuminen työhön” (Hakanen 2009a, 9). Tutkimuksessa kysytään, voidaanko työn imua ymmärtää myös sosiologisesta näkökulmasta. Oletuksena on, että käsitteen taustalla on muutakin kuin psykologisesta perinteestä käsin jäsentyvää vaihtelua. Empiirisen aineiston muodostavan 11 sairaanhoitajan koko työuraa ja nykyistä työtä koskevat tiettyihin teemoihin ankkuroidut syvähaastattelut. Otosta poimittaessa on etsitty sellaisia haastateltavia, jotka kokevat kantavansa työn imua. Aineiston analyysitapana on käytetty matriisin avulla sovellettua kvalitatiivista sisällönanalyysiä. Työn imua hahmotetaan analyysissä henkilöhistoriallisten haastatteluiden – menneen, nykyisen ja tulevan – kautta. Pyrkimyksenä on etsiä tarinoita mahdollisesti yhdistävää kulttuurista muotoa ja ymmärtää, mihin se perustuu. Analyysin nojalla vastuurationaalisuuden käsite (esim. Korvajärvi 1986) näyttäisi jäsentävän osan haastateltavien suhteesta työhönsä. Avain työn imun löytymiseen näissä tarinoissa on kuitenkin se, kuinka haastateltavilla on ollut henkilökohtainen halu mennä eteenpäin ja kykyä ratkaista ongelmia työuransa aikana ja nykyisessä työssään. Tämä havainto tulkitaan Max Weberin (1922, 1980) käsitteiden – arvorationaalisen ja päämäärärationaalisen toiminnan väliseen suhteen – avulla. Tulokseksi syntyy oletus siitä, että analyysin kohteena olevissa tarinoissa on kyse yhteisestä kulttuurisesta tarinasta siitä, millainen on hyvä ihminen, miten hyvä ihminen toteuttaa itseään työssä ja miten hän tekee työtään: tarmokkaasti, omistautuen ja uppoutuen. Henkilökohtainen halu mennä eteenpäin ja kyky ratkaista ongelmia nojaa sairaanhoitajien erityiseen eetokseen, kutsumustyöhön ja hoivan moraaliin tavalla, joka on rakenteellisesti yhtäläinen protestanttisuutta leimaavan yksilöllisen jumalasuhteen kanssa. Lisäksi analyysin perusteella esitetään, että työn imun edellytys on arvorationaalisen eetoksen lisäksi oikeanlainen, riittävät työn voimavarat sisältävä ympäristö, jossa hoitotyön keskeiset palkinnot on mahdollista saavuttaa. Tällöin palkkatyön sisältö kohtaa kulttuuriset lähtökohdat, ja tulos näkyy työn imuna. Keskeisimmät taustoittavat lähteet ovat Henriksson, Lea & Wrede, Sirpa (toim.) (2004a). Hyvinvointityön ammatit ja Hakanen, Jari (2009a). Työn imun arviointimenetelmä (Utrecht Work Engagement Scale). Sosiologisen tulkinnan kannalta tärkein teoreettinen lähde on Weber, Max (1980): Protestanttinen etiikka ja kapitalismin henki.

Humanitaarisuuden varjossa : Poliittiset tekijät lastensiirroissa Ruotsiin sotiemme aikana ja niiden jälkeen

The evacuation of Finnish children to Sweden during WW II has often been called a small migration . Historical research on this subject is scarce, considering the great number of children involved. The present research has applied, apart from the traditional archive research, the framework of history-culture developed by Rüsen in order to have an all-inclusive approach to the impact of this historical event. The framework has three dimensions: political, aesthetic and cognitive. The collective memory of war children has also been discussed. The research looks for political factors involved in the evacuations during the Winter War and the Continuation War and the post-war period. The approach is wider than a purely humanitarian one. Political factors have had an impact in both Finland and Sweden, beginning from the decision-making process and ending with the discussion of the unexpected consequences of the evacuations in the Finnish Parliament in 1950. The Winter War (30.11.1939 13.3.1940) witnessed the first child transports. These were also the model for future decision making. The transports were begun on the initiative of Swedes Maja Sandler, the wife of the resigned minister of foreign affairs Rickard Sandler, and Hanna Rydh-Munck af Rosenschöld , but this activity was soon accepted by the Swedish government because the humanitarian help in the form of child transports lightened the political burden of Prime Minister Hansson, who was not willing to help Finland militarily. It was help that Finland never asked for and it was rejected at the beginning. The negative response of Minister Juho Koivisto was not taken very seriously. The political forces in Finland supporting child transports were stronger than those rejecting them. The major politicians in support belonged to Finland´s Swedish minority. In addition, close to 1 000 Finnish children remained in Sweden after the Winter War. No analysis was made of the reasons why these children did not return home. A committee set up to help Finland and Norway was established in Sweden in 1941. Its chairman was Torsten Nothin, an influential Swedish politician. In December 1941 he appealed to the Swedish government to provide help to Finnish children under the authority of The International Red Cross. This plea had no results. The delivery of great amounts of food to Finland, which was now at war with Great Britain, had automatically caused reactions among the allies against the Swedish imports through Gothenburg. This included the import of oil, which was essential for the Swedish navy and air force. Oil was later used successfully to force a reduction in commerce between Sweden and Finland. The contradiction between Sweden´s essential political interests and humanitarian help was solved in a way that did not harm the country´s vital political interests. Instead of delivering help to Finland, Finnish children were transported to Sweden through the organisations that had already been created. At the beginning of the Continuation War (25.6.1941 27.4.1945) negative opinion regarding child transports re-emerged in Finland. Karl-August Fagerholm implemented the transports in September 1941. In 1942, members of the conservative parties in the Finnish Parliament expressed their fear of losing the children to the Swedes. They suggested that Finland should withdraw from the inter-Nordic agreement, according to which the adoptions were approved by the court of the country where the child resided. This initiative failed. Paavo Virkkunen, an influential member of the conservative party Kokoomus in Finland, favoured the so-called good-father system, where help was delivered to Finland in the form of money and goods. Virkkunen was concerned about the consequences of a long stay in a Swedish family. The risk of losing the children was clear. The extreme conservative party (IKL, the Patriotic Movement of the Finnish People) wanted to alienate Finland from Sweden and bring Finland closer to Germany. Von Blücher, the German ambassador to Finland, had in his report to Berlin, mentioned the political consequences of the child transports. Among other things, they would bring Finland and Sweden closer to each other. He had also paid attention to the Nordic political orientation in Finland. He did not question or criticize the child transports. His main interest was to increase German political influence in Finland, and the Nordic political orientation was an obstacle. Fagerholm was politically ill-favoured by the Germans, because he had a strong Nordic political disposition and had criticised Germany´s activities in Norway. The criticism of child transports was at the same time criticism of Fagerholm. The official censorship organ of the Finnish government (VTL) denied the criticism of child transports in January 1942. The reasons were political. Statements made by members of the Finnish Parliament were also censored, because it was thought that they would offend the Swedes. In addition, the censorship organ used child transports as a means of active propaganda aimed at improving the relations between the two countries. The Finnish Parliament was informed in 1948 that about 15 000 Finnish children still remained in Sweden. These children would stay there permanently. In 1950 the members of the Agrarian Party in Finland stated that Finland should actively strive to get the children back. The party on the left (SKDL, the Democratic Movement of Finnish People) also focused on the unexpected consequences of the child transports. The Social Democrats, and largely Fagerholm, had been the main force in Finland behind the child transports. Members of the SKDL, controlled by Finland´s Communist Party, stated that the war time authorities were responsible for this war loss. Many of the Finnish parents could not get their children back despite repeated requests. The discussion of the problem became political, for example von Born, a member of the Swedish minority party RKP, related this problem to foreign policy by stating that the request to repatriate the Finnish children would have negative political consequences for the relations between Finland and Sweden. He emphasized expressing feelings of gratitude to the Swedes. After the war a new foreign policy was established by Prime Minister (1944 1946) and later President (1946 1956) Juho Kusti Paasikivi. The main cornerstone of this policy was to establish good relations with the Soviet Union. The other, often forgotten, cornerstone was to simultaneously establish good relations with other Nordic countries, especially Sweden, as a counterbalance. The unexpected results of the child evacuation, a Swedish initiative, had violated the good relations with Sweden. The motives of the Democratic Movement of Finnish People were much the same as those of the Patriotic Movement of Finnish People. Only the ideology was different. The Nordic political orientation was an obstacle to both parties. The position of the Democratic Movement of Finnish People was much better than that of the Patriotic Movement of Finnish People, because now one could clearly see the unexpected results, which included human tragedy for the many families who could not be re-united with their children despite their repeated requests. The Swedes questioned the figure given to the Finnish Parliament regarding the number of children permanently remaining in Sweden. This research agrees with the Swedes. In a calculation based on Swedish population registers, the number of these children is about 7 100. The reliability of this figure is increased by the fact that the child allowance programme began in Sweden in 1948. The prerequisite to have this allowance was that the child be in the Swedish population register. It was not necessary for the child to have Swedish nationality. The Finnish Parliament had false information about the number of Finnish children who remained in Sweden in 1942 and in 1950. There was no parliamentary control in Finland regarding child transports, because the decision was made by one cabinet member and speeches by MPs in the Finnish Parliament were censored, like all criticism regarding child transports to Sweden. In Great Britain parliamentary control worked better throughout the whole war, because the speeches regarding evacuation were not censored. At the beginning of the war certain members of the British Labour Party and the Welsh Nationalists were particularly outspoken about the scheme. Fagerholm does not discuss to any great extent the child transports in his memoirs. He does not evaluate the process and results as a whole. This research provides some possibilities for an evaluation of this sort. The Swedish medical reports give a clear picture of the physical condition of the Finnish children when arriving in Sweden. The transports actually revealed how bad the situation of the poorest children was. According to Titmuss, similar observations were made in Great Britain during the British evacuations. The child transports saved the lives of approximately 2 900 children. Most of these children were removed to Sweden to receive treatment for illnesses, but many among the healthy children were undernourished and some suffered from the effects of tuberculosis. The medical inspection in Finland was not thorough. If you compare the figure of 2 900 children saved and returned with the figure of about 7 100 children who remained permanently in Sweden, you may draw the conclusion that Finland as a country failed to benefit from the child transports, and that the whole operation was a political mistake with far-reaching consequenses. The basic goal of the operation was to save lives and have all the children return to Finland after the war. The difficulties with the repatriation of the children were mainly psychological. The level of child psychology in Finland at that time was low. One may question the report by Professor Martti Kaila regarding the adaptation of children to their families back in Finland. Anna Freud´s warnings concerning the difficulties that arise when child evacuees return are also valid in Finland. Freud viewed the emotional life of children in a way different from Kaila: the physical survival of a small child forces her to create strong emotional ties to the person who is looking after her. This, a characteristic of all small children, occurred with the Finnish children too, and it was something the political decision makers in Finland could not see during and after the war. It is a characteristic of all little children. Yet, such experiences were already evident during the Winter War. The best possible solution had been to limit the child transports only to children in need of medical treatment. Children from large and poor families had been helped by organising meals and by buying food from Denmark with Swedish money. Assisting Finland by all possible means should have been the basic goal of Fagerholm in September 1941, when the offer of child transports came from Sweden. Fagerholm felt gratitude towards the Swedes. The risks became clear to him only in 1943. The war children are today a rather scattered and diffuse group of people. Emotionally, part of these children remained in Sweden after the war. There is no clear collective memory, only individual memories; the collective memory of the war children has partly been shaped later through the activities of the war child associations. The main difference between the children evacuated in Finland (for example from Karelia to safer areas with their families) and the war children, who were sent abroad, is that the war children lack a shared story and experience with their families. They were outsiders . The whole matter is sensitive to many of such mothers and discussing the subject has often been avoided in families. The war-time censorship has continued in families through silence and avoidance and Finnish politicians and Finnish families had to face each other on this issue after the war. The lack of all-inclusive historical research has also prevented the formation of a collective awareness among war children returned to Finland or those remaining permanently abroad.. Knowledge of historical facts will help war-children by providing an opportunity to create an all-inclusive approach to the past. Personal experiences should be regarded as part of a large historical entity shadowed by war and where many political factors were at work in both Finland and Sweden. This means strengthening of the cognitive dimension discussed in Rüsen´s all-inclusive historical approach.

Semi-supervised learning of WLAN radio maps

In this thesis a manifold learning method is applied to the problem of WLAN positioning and automatic radio map creation. Due to the nature of WLAN signal strength measurements, a signal map created from raw measurements results in non-linear distance relations between measurement points. These signal strength vectors reside in a high-dimensioned coordinate system. With the help of the so called Isomap-algorithm the dimensionality of this map can be reduced, and thus more easily processed. By embedding position-labeled strategic key points, we can automatically adjust the mapping to match the surveyed environment. The environment is thus learned in a semi-supervised way; gathering training points and embedding them in a two-dimensional manifold gives us a rough mapping of the measured environment. After a calibration phase, where the labeled key points in the training data are used to associate coordinates in the manifold representation with geographical locations, we can perform positioning using the adjusted map. This can be achieved through a traditional supervised learning process, which in our case is a simple nearest neighbors matching of a sampled signal strength vector. We deployed this system in two locations in the Kumpula campus in Helsinki, Finland. Results indicate that positioning based on the learned radio map can achieve good accuracy, especially in hallways or other areas in the environment where the WLAN signal is constrained by obstacles such as walls.

Part I: Enzyme replacement versus neurotrophic factor viral vector-mediated gene therapy of Parkinson’s disease, Part II: The effects of orally dosed tolcapone and entacapone on dopamine metabolism in the dorsal striatum and nucleus accumbens in rats

Part I: Parkinson’s disease is a slowly progressive neurodegenerative disorder in which particularly the dopaminergic neurons of the substantia nigra pars compacta degenerate and die. Current conventional treatment is based on restraining symptoms but it has no effect on the progression of the disease. Gene therapy research has focused on the possibility of restoring the lost brain function by at least two means: substitution of critical enzymes needed for the synthesis of dopamine and slowing down the progression of the disease by supporting the functions of the remaining nigral dopaminergic neurons by neurotrophic factors. The striatal levels of enzymes such as tyrosine hydroxylase, dopadecarboxylase and GTP-CH1 are decreased as the disease progresses. By replacing one or all of the enzymes, dopamine levels in the striatum may be restored to normal and behavioral impairments caused by the disease may be ameliorated especially in the later stages of the disease. The neurotrophic factors glial cell derived neurotrophic factor (GDNF) and neurturin have shown to protect and restore functions of dopaminergic cell somas and terminals as well as improve behavior in animal lesion models. This therapy may be best suited at the early stages of the disease when there are more dopaminergic neurons for neurotrophic factors to reach. Viral vector-mediated gene transfer provides a tool to deliver proteins with complex structures into specific brain locations and provides long-term protein over-expression. Part II: The aim of our study was to investigate the effects of two orally dosed COMT inhibitors entacapone (10 and 30 mg/kg) and tolcapone (10 and 30 mg/kg) with a subsequent administration of a peripheral dopadecarboxylase inhibitor carbidopa (30 mg/kg) and L- dopa (30 mg/kg) on dopamine and its metabolite levels in the dorsal striatum and nucleus accumbens of freely moving rats using dual-probe in vivo microdialysis. Earlier similarly designed studies have only been conducted in the dorsal striatum. We also confirmed the result of earlier ex vivo studies regarding the effects of intraperitoneally dosed tolcapone (30 mg/kg) and entacapone (30 mg/kg) on striatal and hepatic COMT activity. The results obtained from the dorsal striatum were generally in line with earlier studies, where tolcapone tended to increase dopamine and DOPAC levels and decrease HVA levels. Entacapone tended to keep striatal dopamine and HVA levels elevated longer than in controls and also tended to elevate the levels of DOPAC. Surprisingly in the nucleus accumbens, dopamine levels after either dose of entacapone or tolcapone were not elevated. Accumbal DOPAC levels, especially in the tolcapone 30 mg/kg group, were elevated nearly to the same extent as measured in the dorsal striatum. Entacapone 10 mg/kg elevated accumbal HVA levels more than the dose of 30 mg/kg and the effect was more pronounced in the nucleus accumbens than in the dorsal striatum. This suggests that entacapone 30 mg/kg has minor central effects. Also our ex vivo study results obtained from the dorsal striatum suggest that entacapone 30 mg/kg has minor and transient central effects, even though central HVA levels were not suppressed below those of the control group in either brain area in the microdialysis study. Both entacapone and tolcapone suppressed hepatic COMT activity more than striatal COMT activity. Tolcapone was more effective than entacapone in the dorsal striatum. The differences between dopamine and its metabolite levels in the dorsal striatum and nucleus accumbens may be due to different properties of the two brain areas.

11β-Hydroxysteroid dehydrogenase inhibitors and selectivity modeling of 11β-HSDs

11β-hydroksisteroididehydrogenaasientsyymit (11β-HSD) 1 ja 2 säätelevät kortisonin ja kortisolin määrää kudoksissa. 11β-HSD1 -entsyymin ylimäärä erityisesti viskeraalisessa rasvakudoksessa aiheuttaa metaboliseen oireyhtymän klassisia oireita, mikä tarjoaa mahdollisuuden metabolisen oireyhtymän hoitoon 11β-HSD1 -entsyymin selektiivisellä estämisellä. 11β-HSD2 -entsyymin inhibitio aiheuttaa kortisonivälitteisen mineralokortikoidireseptorien aktivoitumisen, mikä puolestaan johtaa hypertensiivisiin haittavaikutuksiin. Haittavaikutuksista huolimatta 11β-HSD2 -entsyymin estäminen saattaa olla hyödyllistä tilanteissa, joissa halutaan nostaa kortisolin määrä elimistössä. Lukuisia selektiivisiä 11β-HSD1 inhibiittoreita on kehitetty, mutta 11β-HSD2-inhibiittoreita on raportoitu vähemmän. Ero näiden kahden isotsyymin aktiivisen kohdan välillä on myös tuntematon, mikä vaikeuttaa selektiivisten inhibiittoreiden kehittämistä kummallekin entsyymille. Tällä työllä oli kaksi tarkoitusta: (1) löytää ero 11β-HSD entsyymien välillä ja (2) kehittää farmakoforimalli, jota voitaisiin käyttää selektiivisten 11β-HSD2 -inhibiittoreiden virtuaaliseulontaan. Ongelmaa lähestyttiin tietokoneavusteisesti: homologimallinnuksella, pienmolekyylien telakoinnilla proteiiniin, ligandipohjaisella farmakoforimallinnuksella ja virtuaaliseulonnalla. Homologimallinnukseen käytettiin SwissModeler -ohjelmaa, ja luotu malli oli hyvin päällekäinaseteltavissa niin templaattinsa (17β-HSD1) kuin 11β-HSD1 -entsyymin kanssa. Eroa entsyymien välillä ei löytynyt tarkastelemalla päällekäinaseteltuja entsyymejä. Seitsemän yhdistettä, joista kuusi on 11β-HSD2 -selektiivisiä, telakoitiin molempiin entsyymeihin käyttäen ohjelmaa GOLD. 11β-HSD1 -entsyymiin yhdisteet kiinnittyivät kuten suurin osa 11β-HSD1 -selektiivisistä tai epäselektiivisistä inhibiittoreista, kun taas 11β-HSD2 -entsyymiin kaikki yhdisteet olivat telakoituneet käänteisesti. Tällainen sitoutumistapa mahdollistaa vetysidokset Ser310:een ja Asn171:een, aminohappoihin, jotka olivat nähtävissä vain 11β-HSD2 -entsyymissä. Farmakoforimallinnukseen käytettiin ohjelmaa LigandScout3.0, jolla ajettiin myös virtuaaliseulonnat. Luodut kaksi farmakoforimallia, jotka perustuivat aiemmin telakointiinkin käytettyihin kuuteen 11β-HSD2 -selektiiviseen yhdisteeseen, koostuivat kuudesta ominaisuudesta (vetysidosakseptori, vetysidosdonori ja hydrofobinen), ja kieltoalueista. 11β-HSD2 -selektiivisyyden kannalta tärkeimmät ominaisuudet ovat vetysidosakseptori, joka voi muodostaa sidoksen Ser310 kanssa ja vetysidosdonori sen vieressä. Tälle vetysidosdonorille ei löytynyt vuorovaikutusparia 11β-HSD2-mallista. Sopivasti proteiiniin orientoitunut vesimolekyyli voisi kuitenkin olla sopiva ratkaisu puuttuvalle vuorovaikutusparille. Koska molemmat farmakoforimallit löysivät 11β-HSD2 -selektiivisiä yhdisteitä ja jättivät epäselektiivisiä pois testiseulonnassa, käytettiin molempia malleja Innsbruckin yliopistossa säilytettävistä yhdisteistä (2700 kappaletta) koostetun tietokannan seulontaan. Molemmista seulonnoista löytyneistä hiteistä valittiin yhteensä kymmenen kappaletta, jotka lähetettiin biologisiin testeihin. Biologisien testien tulokset vahvistavat lopullisesti sen kuinka hyvin luodut mallit edustavat todellisuudessa 11β-HSD2 -selektiivisyyttä.

Encouragement and discouragement : Essays on taxation and government expenditure

This thesis consists of an introduction to a topic of optimal use of taxes and government expenditure and three chapters analysing these themes more in depth. Chapter 2 analyses to what extent a given amount of subsidies affects the labour supply of parents. Municipal supplement to the Finnish home care allowance provides exogenous variation to labour supply decision of a parent. This kind of subsidy that is tied to staying at home instead of working is found to have fairly large effect on labour supply decisions of parents. Chapter 3 studies theoretically when it is optimal to provide publicly private goods. In the set up of the model government sets income taxes optimally and provides a private good, if it is beneficial to do so. The analysis results in an optimal provision rule according to which the good should be provided when it lowers the participation threshold into labour force. Chapter 4 investigates what happened to prices and demand when hairdressers value added tax was cut in Finland from 22 per cent to 8 per cent. The pass-through to prices was about half of the full pass-through and no clear indication of increased demand for the services or better employment situation in the sector is found.

Adnominal Person in the Morphological System of Erzya : Adnominaalinen persoona ersän kielen morfologisessa järjestelmässä

This dissertation is a synchronic description of adnominal person in the highly synthetic morphological system of Erzya as attested in extensive Erzya-language written-text corpora consisting of nearly 140 publications with over 4.5 million words and over 285,000 unique lexical items. Insight for this description have been obtained from several source grammars in German, Russian, Erzya, Finnish, Estonian and Hungarian, as well as bounteous discussions in the understanding of the language with native speakers and grammarians 1993 2010. Introductory information includes the discussion of the status of Erzya as a lan- guage, the enumeration of phonemes generally used in the transliteration of texts and an in-depth description of adnominal morphology. The reader is then made aware of typological and Erzya-specifc work in the study of adnominal-type person. Methods of description draw upon the prerequisite information required in the development of a two-level morphological analyzer, as can be obtained in the typological description of allomorphic variation in the target language. Indication of original author or dialect background is considered important in the attestation of linguistic phenomena, such that variation might be plotted for a synchronic description of the language. The phonological description includes the establishment of a 6-vowel, 29-consonant phoneme system for use in the transliteration of annotated texts, i.e. two phonemes more than are generally recognized, and numerous rules governing allophonic variation in the language. Erzya adnominal morphology is demonstrated to have a three-way split in stem types and a three-layer system of non-derivative affixation. The adnominal-affixation layers are broken into (a) declension (the categories of case, number and deictic marking); (b) nominal conjugation (non-verb grammatical and oblique-case items can be conjugated), and (c) clitic marking. Each layer is given statistical detail with regard to concatenability. Finally, individual subsections are dedicated to the matters of: possessive declension compatibility in the distinction of sublexica; genitive and dative-case paradigmatic defectivity in the possessive declension, where it is demonstrated to be parametrically diverse, and secondary declension, a proposed typology modifiers without nouns , as compatible with adnominal person.

Sterol-binding proteins in late endosomes : Regulation of endosome motility and lipid metabolism

Despite its bad reputation in the mass media, cholesterol is an indispensable constituent of cellular membranes and vertebrate life. It is, however, also potentially lethal as it may accumulate in the arterial intima causing atherosclerosis or elsewhere in the body due to inherited conditions. Studying cholesterol in cells, and research on how the cell biology of cholesterol affects on system level is essential for a better understanding of the disease states associated with cholesterol and for the development of new therapies for these conditions. On its way to the cell, exogenous cholesterol traverses through endosomes, transport vesicles involved in internalizing material to cells, and needs to be transported out of this compartment. This endosomal pool of cholesterol is important for understanding both the common disorders of metabolism and the more rare hereditary disorders of cholesterol metabolism. The study of cholesterol in cells has been hampered by the lack of bright fluorescent sterol analogs that would resemble cholesterol enough to be used in cellular studies. In the first study of my thesis, we present a new sterol analog, Boron-Dipyrromethene (BODIPY)-cholesterol for visualizing sterols in living cells and organism. This fluorescent cholesterol derivative is shown to behave similarly to cholesterol both by atomic scale computer simulations and biochemical experiments. We characterize its localization inside different types of living cells and show that it can be used to study sterol trafficking in living organisms. Two sterol binding proteins associated with the endosomal membrane; the Niemann-Pick type C disease protein 1 (NPC1) and the Oxysterol Binding Protein Related Protein 1 (ORP1) are the subjects of the rest of this study. Sensing cholesterol on endosomes, transporting lipids away from this compartment and the effects these lipids play on cellular metabolism are considered. In the second study we characterize how the NPC1 protein affects lipid metabolism. We show that this cholesterol binding protein affects synthesis of triglycerides and that genetic polymorphisms or a genetic defect in the NPC1 gene affect triglyceride on the whole body level. These effects take place via regulation of carbon fluxes to different lipid classes in cells. In the third part we characterize the effects of another endosomal sterol binding protein, ORP1L on the function and motility of endosomes. Specifically we elucidate how a mutation in the ability of ORP1L to bind sterols affects its behavior in cells, and how a change in ORP1L levels in cells affects the localization, degradative capacity and motility of endosomes. In addition we show that ORP1L manipulations affect cholesterol balance also in macrophages, a cell type important for the development of atherosclerosis.

Italian ja Veneton läänin kolmas sektori. Maaraportti maaseutualueiden palvelutuotannon haasteista ja hyvistä käytännöistä.

Tiivistelmä Maaraportin tavoitteena on luoda yleiskatsaus Italian kolmanteen sektoriin ja tutkimus kohdistuu erityisesti Pohjois-Italiassa sijaitsevan Veneton läänin kolmannen sektorin palvelutuotantoon. Raportissa tarkastellaan erityisesti kolmannen sektorin ja julkisen palvelutuotantosektorin sekä julkishallinnon toiminnallisia suhteita. Kolmannen sektorin mahdollisuuksia vastata maaseutualueiden palvelujen tarjonnan haasteisiin on pyritty analysoimaan. Italia on julkishallinnon ja kolmannen sektorin palvelutuotannon kannalta tarkasteltuna nykytilanteessa mielenkiintoinen testilaboratorio koko Euroopan mittakaavassa johtuen maan historiallisista, kulttuuri-sista, kieli- ja maantieteellisistä sekä itse väestöpohjan tarjoamista haasteista. Italiasta ei voida puhua yhden homogeenisen valtiokäsitteen alla, koska maa toimii kulttuurisista perinteistään johtuen kolmella eri nopeudella. Itse valtio käsitettäkin tulkitaan Italiassa monin eri tavoin pohjautuen ”valtiona” nähdyn organisaation käytännön funktioon sitoutuneena alueellisiin ja kulttuurisiin tekijöihin. Teollinen, dynaaminen yritysten varakas Pohjois-Italia henkilöityneenä Milanoon, hallinnon ja kulttuurin leimaama Keski-Italia kiteytyneenä ikuiseen kaupunkiin Roomaan ja Napolin alapuolinen Etelä-Italia, joka painii ”järjestelmässä sisällä olevan järjestelmänsä” kanssa eivät ole koskaan muodos-taneet oikeasti yhtenäistä Italian valtiota. Italiassa erillisinä itsehallinnollisina alueina toimivat lääneiksi luettavat Sisilia, Trentino Alto-Adige, Val di Aosta, Sardegna ja Friuli-Venezia Giulia, mikä lisää hallinnollista kirjavuutta. Viimeisten vuosien aikana Italian julkishallinto on ollut jatkuvassa transitiotilassa yrittäessään kohdata uudistumisen vaateita globalisoituvassa maailmassa. Italiassa on meneillään hidas siirtyminen liittovaltiomaiseen järjestelmään ja jopa syvempään paikallisuuteen. Massiivinen ja raskas julkishallintokoneisto neljällä eri tasolla (valtio - lääninhallinnolliset alueet - vahvat maakunnat - kunnat) on erittäin hankalasti modernisoitavissa, mutta poliittinen tahtotila on vaihtumassa klassista vahvaa keskushallintoa kannattavasta ajattelutavasta hyväksymään federalistisia, alueellisia hallintoratkaisuja. Italiassa on herätty havaitsemaan, että ongelmien ratkaisu täytyy viedä itse alueille ja niiden ihmisille, koska unilateraalinen keskushallinnointitapa ei enää vastaa monikerroksisiin, moniulotteisiin alueellisiin haasteisiin. Jokaisella alueella on erilaiset lähtökohdat ongelmien ratkaisuihin myös globalisoitumisen asettamissa yhteisissä haasteissa. Kolmannen sektorin asema arvostettuna italialaisten kansalaispalvelujen täydentäjänä ja tuottajana alkaa olla nykypäivää. Kolmannen sektorin elintärkeä osuus uusien palvelutarpeiden tunnistamisessa on jo yleisesti tunnustettu tosiasia Italiassa. Vapaaehtoisjärjestöt toimivat eturivissä kansalaisten arkipäivässä ja pystyvät näin kanavoimaan ensimmäisinä sosiaalista kehityskulkua ja kohottamaan esiin erilaisia marginaalistenkin ryhmien tarpeita sekä vastaamaan niihin. Kolmas sektori laajentaa, tuottaa ja paikkaa paikallista julkista palvelutuotantoa. Ratkaiseva askel lainsäädännölliseltä kannalta on ollut rahoitusvirtojen ohjaaminen kolmannen sektorin ns. ONLUS-organisaatioille ja ONLUS-statuksen perustaminen vuonna 1997. Italiassa on 60 231.214 asukasta (31.7.2009) ja se on hallinnollisesti jakaantuneena 8 100 kuntaan. Suomessa vastaavat luvut ovat 5 350 712 asukasta ja 348 kuntaa (11/2009). Maantieteelliseltä kooltaan Italia ei eroa 301 338 km2:n pinta-alallaan paljonkaan Suomesta (338 424 km2). Väestömäärän erojen vuoksi Italiassa on keskimäärin 199,9 asukasta neliökilometrillä ja Suomessa 17,1. Maiden välinen suora vertailu ei ollut mittakaavaerojen vuoksi järkevää. Kuntien hallinnollinen rooli on Italiassa painotukseltaan erilainen kuin Suomessa. Suomessa kuntien vastuulla oleva sosiaali-, terveydenhuolto- ja koulutoimi eivät ole samassa laajuudessa italialaisten kuntien vastuulla vaan näiden toimialojen vastuulliset tahot ovat läänit terveydenhoitopiireineen sekä maakuntahallinto koulupiirien osalta. Italialaisten kuntien vastuualueet voivat myös vaihdella mittavasti perustuslaissa määriteltyjen perustoimien lisäksi. Tutkimuksen kohteeksi on rajattu Koillis-Italiassa sijaitseva Veneton läänin alue, koska se on väkimäärältään lähes yhtä suuri kuin Suomi, 4 893 309 asukasta (31.3.2009). Kuntien lukumäärä on huimaava 581 kpl. Veneto on maantieteelliseltä alueeltaan pieni ja harvaan asuttua maaseutua on pinta-alasta melko niukasti. Pohjoisen osan vuoristoalueet karuine olosuhteineen muodostavat palvelutuotannollisesti haas-teellisen ympäristön, joka on verrattavissa suomalaisten maaseutualueiden tilanteeseen. Venetossa on omaksuttu Italian mittakaavassa innovatiivisia ratkaisuja julkishallinnon palvelutuotannon ja kolmannen sektorin toiminnan osalta. Veneton alue on luokiteltu maailman pienyritysintensiivisimmäksi alueeksi, mikä heijastuu myös alueen palvelutuotantoratkaisuissa. Raportti esittelee ensin Italian hallintoa, keskushallinnon, paikallishallinnon ja tutkimuksen asettelulle olennaisten kolmannen sektorin toimijoiden osalta. Tämä on välttämätöntä, sillä kolmannen sektorin toiminta on Italiassa hyvin pitkälle lainsäädännöllä ohjattua ja rajattua. Kolmannen sektorin käsitteistöä, toimijoita, järjestäytymistä ja sen toimintaa säätelevää lainsäädäntöä esitellään tarkemmin. Veneton läänin osalta kolmanteen sektoriin perehdytään sekä hallinnon että toimijakentän näkökulmia tulkiten. Raportin lopussa esitellään kolmannen sektorin palvelutuotantoon ja hallinnointiin liittyviä case-esimerkkitapauksia.

The Path to a Porous Semiconductor Multilayer

Thin films are the basis of much of recent technological advance, ranging from coatings with mechanical or optical benefits to platforms for nanoscale electronics. In the latter, semiconductors have been the norm ever since silicon became the main construction material for a multitude of electronical components. The array of characteristics of silicon-based systems can be widened by manipulating the structure of the thin films at the nanoscale - for instance, by making them porous. The different characteristics of different films can then to some extent be combined by simple superposition. Thin films can be manufactured using many different methods. One emerging field is cluster beam deposition, where aggregates of hundreds or thousands of atoms are deposited one by one to form a layer, the characteristics of which depend on the parameters of deposition. One critical parameter is deposition energy, which dictates how porous, if at all, the layer becomes. Other parameters, such as sputtering rate and aggregation conditions, have an effect on the size and consistency of the individual clusters. Understanding nanoscale processes, which cannot be observed experimentally, is fundamental to optimizing experimental techniques and inventing new possibilities for advances at this scale. Atomistic computer simulations offer a window to the world of nanometers and nanoseconds in a way unparalleled by the most accurate of microscopes. Transmission electron microscope image simulations can then bridge this gap by providing a tangible link between the simulated and the experimental. In this thesis, the entire process of cluster beam deposition is explored using molecular dynamics and image simulations. The process begins with the formation of the clusters, which is investigated for Si/Ge in an Ar atmosphere. The structure of the clusters is optimized to bring it as close to the experimental ideal as possible. Then, clusters are deposited, one by one, onto a substrate, until a sufficiently thick layer has been produced. Finally, the concept is expanded by further deposition with different parameters, resulting in multiple superimposed layers of different porosities. This work demonstrates how the aggregation of clusters is not entirely understood within the scope of the approximations used in the simulations; yet, it is also shown how the continued deposition of clusters with a varying deposition energy can lead to a novel kind of nanostructured thin film: a multielemental porous multilayer. According to theory, these new structures have characteristics that can be tailored for a variety of applications, with precision heretofore unseen in conventional multilayer manufacture.

Brain oscillatory responses, working memory and cognitive developmental stages in 11- and 14-year-old children: an ERD/ERS study

Aim: So far, most of the cognitive neuroscience studies investigating the development of brain activity in childhood have made comparisons between different age groups and ignored the individual stage of cognitive development. Given the wide variation in the rate of cognitive development, this study argues that chronological age alone cannot explain the developmental changes in brain activity. This study demonstrates how Piaget s theory and information on child s individual stage of development can complement the age-related evaluations of brain oscillatory activity. In addition, the relationship between cognitive development and working memory is investigated. Method: A total of 33 children (17 11-year-olds, 16 14-year-olds) participated in this study. The study consisted of behavioural tests and an EEG experiment. Behavioral tests included two Piagetian tasks (the Volume and Density task, the Pendulum task) and Raven s Standard Progressive Matrices task. During EEG experiment, subjects performed a modified version of the Sternberg s memory search paradigm which consisted of an auditorily presented memory set of 4 words and a probe word following these. The EEG data was analyzed using the event-related desynchronization / synchronization (ERD/ERS) method. The Pendulum task was used to assess the cognitive developmental stage of each subject and to form four groups based on age (11- or 14-year-olds) and cognitive developmental stage (concrete or formal operational stage). Group comparisons between these four groups were performed for the EEG data. Results and conclusions: Both age- and cognitive stage-related differences in brain oscillatory activity were found between the four groups. Importantly, age-related changes similar to those reported by previous studies were found also in this study, but these changes were modified by developmental stage. In addition, the results support a strong link between working memory and cognitive development by demonstrating differences in memory task related brain activity and cognitive developmental stages. Based on these findings it is suggested that in the future, comparisons of development of brain activity should not be based only on age but also on the individual cognitive developmental stage.

Spatial ecology of food webs : herbivore-parasitoid communities on the pedunculate oak

Herbivorous insects, their host plants and natural enemies form the largest and most species-rich communities on earth. But what forces structure such communities? Do they represent random collections of species, or are they assembled by given rules? To address these questions, food webs offer excellent tools. As a result of their versatile information content, such webs have become the focus of intensive research over the last few decades. In this thesis, I study herbivore-parasitoid food webs from a new perspective: I construct multiple, quantitative food webs in a spatially explicit setting, at two different scales. Focusing on food webs consisting of specialist herbivores and their natural enemies on the pedunculate oak, Quercus robur, I examine consistency in food web structure across space and time, and how landscape context affects this structure. As an important methodological development, I use DNA barcoding to resolve potential cryptic species in the food webs, and to examine their effect on food web structure. I find that DNA barcoding changes our perception of species identity for as many as a third of the individuals, by reducing misidentifications and by resolving several cryptic species. In terms of the variation detected in food web structure, I find surprising consistency in both space and time. From a spatial perspective, landscape context leaves no detectable imprint on food web structure, while species richness declines significantly with decreasing connectivity. From a temporal perspective, food web structure remains predictable from year to year, despite considerable species turnover in local communities. The rate of such turnover varies between guilds and species within guilds. The factors best explaining these observations are abundant and common species, which have a quantitatively dominant imprint on overall structure, and suffer the lowest turnover. By contrast, rare species with little impact on food web structure exhibit the highest turnover rates. These patterns reveal important limitations of modern metrics of quantitative food web structure. While they accurately describe the overall topology of the web and its most significant interactions, they are disproportionately affected by species with given traits, and insensitive to the specific identity of species. As rare species have been shown to be important for food web stability, metrics depicting quantitative food web structure should then not be used as the sole descriptors of communities in a changing world. To detect and resolve the versatile imprint of global environmental change, one should rather use these metrics as one tool among several.

Wood-inhabiting Basidiomycetes in the Caucasus Region : Systematics and Biogeography

The Caucasus region is a hotspot of biodiversity and is one of the few areas in the Northern Hemisphere which harbor Pleistocene glacial refugia. The region encompasses Armenia, Azerbaijan, Georgia, the southernmost European Russia, NE Turkey, and northern Iran. The study on fungal composition of the Caucasus region and its connection and possible contribution to the present mycota of Europe has largely escaped empirical scrutiny. Using taxonomic surveys, phylogenetic reconstruction methods, haplotype analysis, and similarity tests, this study has aimed to, 1) summarize the knowledge on the occurrence of corticioids and polypores in the Caucasus region, 2) resolve the phylogenetic relationships of selected, resupinate wood-inhabiting basidiomycetes for which the Caucasus region is currently the mere, or one of the noteworthy areas of distribution, and, 3) assess the similarity of Caucasian corticioid fungi to those of Europe and important areas in the Northern Hemisphere, and to examine the significance of the Caucasus region as a glacial refugium for these fungi. This study provides the first catalogue of corticioids and polypores (635 species) occurring in the Caucasus region. The phylogeny and systematics of the Caucasian resupinate taxa in focus has been resolved and the usefulness of some morphological characters has been re-evaluated. In this context, four new genera and two new species were described and five new combinations were proposed, two of which were supplemented with modern descriptions. The species composition of corticioids in the Caucasus region is found to be distinctly more similar to Europe and North America than to East Asia and India. The highest molecular diversity and within population pairwise distance for Peniophorella praetermissa has been detected in the Caucasus and East Asia, with the isolates of the latter area being highly divergent from the European ones. This, and the assignment of root haplotype to the Caucasian isolates in a haplotype network for Phlebia tuberucalta and P. livida, call attention to the role of the Caucasus region in shaping the current mycota of Europe.