Study of ligand-based virtual screening tools in computer-aided drug design

Virtual screening is a central technique in drug discovery today. Millions of molecules can be tested in silico with the aim to only select the most promising and test them experimentally. The topic of this thesis is ligand-based virtual screening tools which take existing active molecules as starting point for finding new drug candidates. One goal of this thesis was to build a model that gives the probability that two molecules are biologically similar as function of one or more chemical similarity scores. Another important goal was to evaluate how well different ligand-based virtual screening tools are able to distinguish active molecules from inactives. One more criterion set for the virtual screening tools was their applicability in scaffold-hopping, i.e. finding new active chemotypes. In the first part of the work, a link was defined between the abstract chemical similarity score given by a screening tool and the probability that the two molecules are biologically similar. These results help to decide objectively which virtual screening hits to test experimentally. The work also resulted in a new type of data fusion method when using two or more tools. In the second part, five ligand-based virtual screening tools were evaluated and their performance was found to be generally poor. Three reasons for this were proposed: false negatives in the benchmark sets, active molecules that do not share the binding mode, and activity cliffs. In the third part of the study, a novel visualization and quantification method is presented for evaluation of the scaffold-hopping ability of virtual screening tools.

Saksalainen laulu

Soitinnus: piano.

Sinivuokko

Soitinnus: lauluääni, piano.

Davviduovdagat : ”Eurohpálaš duovddaoktasašsoahpamuša ollašuhttin Davvikalohta gielddain” Konfereansa čakčamánu 7.-9. beaivve 2011, Anár, Suopma

Kansainvälinen Eurooppalaisen maisemayleissopimuksen tavoitteiden saavuttamista edistävä konferenssi järjestettiin Inarissa 7.-9.9.2011. Konferenssissa käsiteltiin maisemasopimuksen tavoitteita, tarpeita ja mahdollisuuksia Pohjois-Kalotin alueella. Tähän raporttiin on koottu konferenssissa esiintyneiden asiantuntijoiden laatimat artikkelit aiheesta. Raportin toivotaan helpottavan alueiden käytön suunnittelijoita käytännön työssään ja rohkaisevan kuntia toteuttamaan tulevaisuuden suunnittelua Eurooppalaisen maisemayleissopimuksen tavoitteiden mukaisesti. Raportti on saatavissa viidellä eri kielellä: suomeksi, ruotsiksi, norjaksi, pohjoissaameksi ja englanniksi. Pohjois-Kalotin aluetta yhdistää yhteinen tunnusomainen maisema. Saamelaiskulttuurin sekä poronhoidon muovaamat tunturimaisemat ja upeat jokivarsimaisemat heijastuvat ympäristössä laaja-alaisesti. Alueen maisemalle haasteita tuovat sen moninaiset maankäyttömuodot ja elinkeinot, kuten matkailu, kaivosteollisuus ja energiantuotanto. Arvokkaiden maisemapiirteiden säilyttäminen vaatii erityistä tuntemusta ja tietämystä alueen kunnissa. Maisemansuojelua ja -hoitoa toteutetaan alueiden- ja maankäytön suunnittelun kautta, pääasiallisesti kaavoituksella ja maisemanhoitosuunnitelmilla. Pohjois-Kalotin alueen kunnissa on erilaiset osin toisistaan poikkeavat toimintatavat ja käytännöt maisemanhoidossa. Kuitenkin alueen asukkailla on yhtäläisiä intressejä elinympäristönsä suojeluun ja säilyttämiseen. Maisema nähdään vetovoimatekijänä, jota ei haluta menettää. Lisääntyvät maankäyttötarpeet kunnissa luovat tarpeen entistä moniulotteisemmalle suunnittelulle. Paikallisten tahojen osallistaminen suunnitteluprosesseihin aikaisessa vaiheessa ja monimuotoinen vuorovaikutus, niin toimijoiden, kansalaisten kuin viranomaisten välillä vähentää konfliktien muodostumista. Tutkimustiedon tehokkaampi hyödyntäminen ja valtiorajat ylittävä yhteistyö helpottaa päätöksentekoa ja luo yhteisiä linjoja maisemansuojelutyöhön. Yhteiset kokemukset, käytännöt ja tietotaidon jakaminen sekä laajemman maisemakokonaisuuden hahmottaminen parantaa eurooppalaisen maisemayleissopimuksen tavoitteiden toteutumista. Työn jatkuvuuden varmistamiseksi Pohjois-Kalotin alueelle suunnitellaan perustettavaksi maisemayhteistyöryhmä, jonka tehtävä on maisemapolitiikan kehittäminen ja eteenpäin vieminen.

Kirjallisuutta

Kirjallisuusarvostelu

Additional revenue opportunities in pulp mills and their impacts on the kraft process

Although the concept of multi-products biorefinery provides an opportunity to meet the future demands for biofuels, biomaterials or chemicals, it is not assured that its implementation would improve the profitability of kraft pulp mills. The attractiveness will depend on several factors such as mill age and location, government incentives, economy of scale, end user requirements, and how much value can be added to the new products. In addition, the effective integration of alternative technologies is not straightforward and has to be carefully studied. In this work, detailed balances were performed to evaluate possible impacts that lignin removal, hemicelluloses recovery prior to pulping, torrefaction and pyrolysis of wood residues cause on the conventional mill operation. The development of mill balances was based on theoretical fundamentals, practical experience, literature review, personal communication with technology suppliers and analysis of mill process data. Hemicelluloses recovery through pre-hydrolysis of chips leads to impacts in several stages of the kraft process. Effects can be observed on the pulping process, wood consumption, black liquor properties and, inevitably, on the pulp quality. When lignin is removed from black liquor, it will affect mostly the chemical recovery operation and steam generation rate. Since mineral acid is used to precipitate the lignin, impacts on the mill chemical balance are also expected. A great advantage of processing the wood residues for additional income results from the fact that the pulping process, pulp quality and sales are not harmfully affected. For pulp mills interested in implementing the concept of multi-products biorefinery, this work has indicated possible impacts to be considered in a technical feasibility study.

Understanding Online Game Players' Post-adoption Behavior: an Investigation of Social Network Games in China

Retaining players and re-attracting switching players has long been a central topic for SNG providers with regard to the post-adoption stage of playing an online game. However, there has not been much research which has explored players’ post-adoption behavior by incorporating the continuance intention and the switching intention. In addition, traditional IS continuance theories were mainly developed to investigate users’ continued use of utilitarian IS, and thus they may fall short when trying to explain the continued use of hedonic IS. Furthermore, compared to the richer literature on IS continuance, far too little attention has been paid to IS switching, leading to a dearth of knowledge on the subject, despite the increased incidence of the switching phenomenon in the IS field. By addressing the limitations of prior literature, this study seeks to examine the determinants of SNG players’ two different post-adoption behaviors, including the continuance intention and the switching intention. This study takes a positivist approach and uses survey research method to test five proposed research models based on Unified Theory of Acceptance and Use of Technology 2; Use and Gratification Theory; Push-Pull-Mooring model; Cognitive Dissonance Theory; and a self-developed model respectively with empirical data collected from the SNG players of one of the biggest SNG providers in China. A total of 3919 valid responses and 541 valid responses were used to examine the continuance intention and the switching intention, respectively. SEM is utilized as the data analysis method. The proposed research models are supported by the empirical data. The continuance intention is determined by enjoyment, fantasy, escapism, social interaction, social presence, social influence, achievement and habit. The switching intention is determined by enjoyment, satisfaction, subjective norms, descriptive norms, alternative attractiveness, the need for variety, change experience, and adaptation cost. This study contributes to IS theories in three important ways. Firstly, it shows IS switching should be included in IS post-adoption research together with IS continuance. Secondly, a modern IS is usually multi-functional and SNG players have multiple reasons for using a SNG, thus a player’s beliefs about the hedonic, social and utilitarian perceptions of their continued use of the SNG exert significant effects on the continuance intention. Thirdly, the determinants of the switch ing intention mainly exert push, pull, and mooring effects. Players’ beliefs about their current SNG and the available alternatives, as well as their individual characteristics are all significant determinants of the switching intention. SNG players combine these effects in order to formulate the switching intention. Finally, this study presents limitations and suggestions for future research.

Minun äitini: pienille lapsille

Värssyt kirj. J. Krohn.