System-level characterization of Th2 cell development and immune cell responses to ZnO and TiO2 nanoparticles

Asthma and allergy are common diseases and their prevalence is increasing. One of the hypotheses that explains this trend is exposure to inhalable chemicals such as traffi c-related air pollution. Epidemiological research supports this theory, as a correlation between environmental chemicals and allergic respiratory diseases has been found. In addition to ambient airborne particles, one may be exposed to engineered nanosized materials that are actively produced due to their favorable physico-chemical properties compared to their bulk size counterparts. On the cellular level, improper activity of T helper (Th) cells has been connected to allergic reactions. Th cells can differentiate into functionally different effector subsets, which are identifi ed according to their characteristic cytokine profi les resulting in specifi c ability to communicate with other cells. Th2 cells activate humoral immunity and stimulate eradication of extracellular pathogens. However, persistent predominance of Th2 cells is involved in a development of number of allergic diseases. The cytokine environment at the time of antigen recognition is the major factor determining the polarization of a naïve Th cell. Th2 cell differentiation is initiated by IL4, which signals via transcription factor STAT6. Although the importance of this pathway has been evaluated in the mouse studies, the signaling components involved have been largely unknown. The aim of this thesis was to identify molecules, which are under the control of IL4 and STAT6 in Th cells. This was done by using system-level analysis of STAT6 target genes at genome, mRNA and protein level resulting in identifi cation of various genes previously not connected to Th2 cell phenotype acquisition. In the study, STAT6-mediated primary and secondary target genes were dissection from each other and a detailed transcriptional kinetics of Th2 cell polarization of naïve human CD4+ T cells was collected. Integration of these data revealed the hierarchy of molecular events that mediates the differentiation towards Th2 cell phenotype. In addition, the results highlighted the importance of exploiting proteomics tools to complement the studies on STAT6 target genes identifi ed through transcriptional profi ling. In the last subproject, the effects of the exposure with ZnO and TiO2 nanoparticles was analyzed in Jurkat T cell line and in primary human monocyte-derived macrophages and dendritic cells to evaluate their toxicity and potential to cause infl ammation. Identifi cation of ZnO-derived gene expression showed that the same nanoparticles may elicit markedly distinctive responses in different cell types, thus underscoring the need for unbiased profi ling of target genes and pathways affected. The results gave additional proof that the cellular response to nanosized ZnO is due to leached Zn2+ ions. The approach used in ZnO and TiO2 nanoparticle study demonstrated the value of assessing nanoparticle responses through a toxicogenomics approach. The increased knowledge of Th2 cell signaling will hopefully reveal new therapeutic nodes and eventually improve our possibilities to prevent and tackle allergic infl ammatory diseases.

Safety and outcome of coronary interventions with special reference to anticoagulation and stent type

University of Turku, Faculty of Medicine, Department of Cardiology and Cardiovascular Medicine, Doctoral Programme of Clinical Investigation, Heart Center, Turku University Hospital, Turku, Finland Division of Internal Medicine, Department of Cardiology, Seinäjoki Central Hospital, Seinäjoki, Finland Heart Center, Satakunta Central Hospital, Pori, Finland Annales Universitatis Turkuensis Painosalama Oy, Turku, Finland 2015 Antithrombotic therapy during and after coronary procedures always entails the challenging establishment of a balance between bleeding and thrombotic complications. It has been generally recommended to patients on long-term warfarin therapy to discontinue warfarin a few days prior to elective coronary angiography or intervention to prevent bleeding complications. Bridging therapy with heparin is recommended for patients at an increased risk of thromboembolism who require the interruption of anticoagulation for elective surgery or an invasive procedure. In study I, consecutive patients on warfarin therapy referred for diagnostic coronary angiography were compared to control patients with a similar disease presentation without warfarin. The strategy of performing coronary angiography during uninterrupted therapeutic warfarin anticoagulation appeared to be a relatively safe alternative to bridging therapy, if the international normalized ratio level was not on a supratherapeutic level. In-stent restenosis remains an important reason for failure of long-term success after a percutaneous coronary intervention (PCI). Drug-eluting stents (DES) reduce the problem of restenosis inherent to bare metal stents (BMS). However, a longer delay in arterial healing may extend the risk of stent thrombosis (ST) far beyond 30 days after the DES implantation. Early discontinuation of antiplatelet therapy has been the most important predisposing factor for ST. In study II, patients on long-term oral anticoagulant (OAC) underwent DES or BMS stenting with a median of 3.5 years’follow-up. The selective use of DESs with a short triple therapy seemed to be safe in OAC patients, since late STs were rare even without long clopidogrel treatment. Major bleeding and cardiac events were common in this patient group irrespective of stent type. In order to help to predict the bleeding risk in patients on OAC, several different bleeding risk scorings have been developed. Risk scoring systems have also been used also in the setting of patients undergoing a PCI. In study III, the predictive value of an outpatient bleeding risk index (OBRI) to identify patients at high risk of bleeding was analysed. The bleeding risk seemed not to modify periprocedural or long-term treatment choices in patients on OAC after a percutaneous coronary intervention. Patients with a high OBRI often had major bleeding episodes, and the OBRI may be suitable for risk evaluation in this patient group. Optical coherence tomography (OCT) is a novel technology for imaging intravascular coronary arteries. OCT is a light-based imaging modality that enables a 12–18 µm tissue axial resolution to visualize plaques in the vessel, possible dissections and thrombi as well as, stent strut appositions and coverage, and to measure the vessel lumen and lesions. In study IV, 30 days after titanium-nitride-oxide (TITANOX)-coated stent implantation, the binary stent strut coverage was satisfactory and the prevalence of malapposed struts was low as evaluated by OCT. Long-term clinical events in patients treated with (TITANOX)-coated bio-active stents (BAS) and paclitaxel-eluting stents (PES) in routine clinical practice were examined in study V. At the 3-year follow-up, BAS resulted in better long-term outcome when compared with PES with an infrequent need for target vessel revascularization. Keywords: anticoagulation, restenosis, thrombosis, bleeding, optical coherence tomography, titanium

Collectiveness within startup teams – Leading the way to initiating and managing collective pursuit of opportunities in organizational contexts

While traditional entrepreneurship literature addresses the pursuit of entrepreneurial opportunities to a solo entrepreneur, scholars increasingly agree that new ventures are often founded and operated by entrepreneurial teams as collective efforts especially in hightechnology industries. Researchers also suggest that team ventures are more likely to survive and succeed than ventures founded by the individual entrepreneur although specific challenges might relate to multiple individuals being involved in joint entrepreneurial action. In addition to new ventures, entrepreneurial teams are seen central for organizing work in established organizations since the teams are able to create major product and service innovations that drive organizational success. Acknowledgement of the entrepreneurial teams in various organizational contexts has challenged the notion on the individual entrepreneur. However, considering that entrepreneurial teams represent a collective-level phenomenon that bases on interactions between organizational members, entrepreneurial teams may not have been studied as indepth as could be expected from the point of view of the team-level, rather than the individual or the individuals in the team. Many entrepreneurial team studies adopt the individualized view of entrepreneurship and examine the team members’ aggregate characteristics or the role of a lead entrepreneur. The previous understandings might not offer a comprehensive and indepth enough understanding of collectiveness within entrepreneurial teams and team venture performance that often relates to the team-level issues in particular. In addition, as the collective-level of entrepreneurial teams has been approached in various ways in the existing literatures, the phenomenon has been difficult to understand in research and practice. Hence, there is a need to understand entrepreneurial teams at the collective-level through a systematic and comprehensive perspective. This study takes part in the discussions on entrepreneurial teams. The overall objective of this study is to offer a description and understanding of collectiveness within entrepreneurial teams beyond individual(s). The research questions of the study are: 1) what collectiveness within entrepreneurial teams stands for, what constitutes the basic elements of it, and who are included in it, 2) why, how, and when collectiveness emerges or reinforces within entrepreneurial teams, and 3) why collectiveness within entrepreneurial teams matters and how it could be developed or supported. In order to answer the above questions, this study bases on three approaches, two set of empirical data, two analysis techniques, and conceptual study. The first data set consists of 12 qualitative semi-structured interviews with business school students who are seen as prospective entrepreneurs. The data is approached through a social constructionist perspective and analyzed through discourse analysis. The second data set bases on a qualitative multiplecase study approach that aims at theory elaboration. The main data consists of 14 individual and four group semi-structured thematic interviews with members of core entrepreneurial teams of four team startups in high-technology industries. The secondary data includes publicly available documents. This data set is approached through a critical realist perspective and analyzed through systematic thematic analysis. The study is completed through a conceptual study that aims at building a theoretical model of collective-level entrepreneurship drawing from existing literatures on organizational theory and social-psychology. The theoretical work applies a positivist perspective. This study consists of two parts. The first part includes an overview that introduces the research background, knowledge gaps and objectives, research strategy, and key concepts. It also outlines the existing knowledge of entrepreneurial team literature, presents and justifies the choices of paradigms and methods, summarizes the publications, and synthesizes the findings through answering the above mentioned research questions. The second part consists of five publications that address independent research questions but all enable to answer the research questions set for this study as a whole. The findings of this study suggest a map of relevant concepts and their relationships that help grasp collectiveness within entrepreneurial teams. The analyses conducted in the publications suggest that collectiveness within entrepreneurial teams stands for cognitive and affective structures in-between team members including elements of collective entity, collective idea of business, collective effort, collective attitudes and motivations, and collective feelings. Collectiveness within entrepreneurial teams also stands for specific joint entrepreneurial action components in which the structures are constructed. The action components reflect equality and democracy, and open and direct communication in particular. Collectiveness emerges because it is a powerful tool for overcoming individualized barriers to entrepreneurship and due to collectively oriented desire for, collective value orientation to, demand for, and encouragement to team entrepreneurship. Collectiveness emerges and reinforces in processes of joint creation and realization of entrepreneurial opportunities including joint analysis and planning of the opportunities and strategies, decision-making and realization of the opportunities, and evaluation, feedback, and sanctions of entrepreneurial action. Collectiveness matters because it is relevant for potential future entrepreneurs and because it affects the ways collective ventures are initiated and managed. Collectiveness also matters because it is a versatile, dynamic, and malleable phenomenon and the ideas of it can be applied across organizational contexts that require team work in discovering or creating and realizing new opportunities. This study further discusses how the findings add to the existing knowledge of entrepreneurial team literature and how the ideas can be applied in educational, managerial, and policy contexts.

Business Development Efforts and Performance Improvements in SMEs Case Study of Business Development Projects Implemented in SME

Under the circumstances of the increasing market pressure, enterprises try to improve their competitive position by development efforts, and a business development project is one tool for that. There are not many answers to the question of how the development projects launched to improve the business performance in SMEs have succeeded. Theacademic interest in the business development project success has mainly focused on projects implemented in larger organisations rather than in SMEs. The previous studies on the business success of SMEs have mainly focused on new business ventures rather than on existing SMEs. However, nowadays a large number of business development projects are undertaken in existing SMEs, where they can pose a great challenge. This study focuses on business development success in SMEs thathave already established their business. The objective of the present study is to gain a deep understanding on business development project success in the SME-context and to identify the dimensions and factors affecting the project success. Further, the aim is to clarify how the business development projects implemented in SMEs have affected their performance. The empirical evidence is based on multiple case study. This study builds a framework for a generic theory of business development success in the SME-context, based on literature from the areas ofproject and change management, entrepreneurship and small business management, as well as performance measurement, and on empirical evidence from SMES. The framework consists of five success dimensions: entrepreneurial, project preparation, change management, project management and project success. The framework provides a systematic way for analysing the business development project and its impact on the performance and on the performing company. This case evidence indicates that successful business development projects have a balanced, high performance concerning all the dimensions. Good performance in one dimension is not enoughfor the project success, but it gives a good ground for the other dimensions. The other way round, poor performance in one success dimension affects the others, leading to poor performance of the project. In the SME-context the business development project success seems to be dependent on several interrelated dimensions and factors. Success in one area leads to success in other areas, and so creates an upward success spiral. Failure in one area seems to lead to failure in other areas, creating a downward failure spiral. The study indicates that the internal business development projects have affected the SMEs' performance widely also on areas and functions not initially targeted. The implications cover all thesuccess categories: the project efficiency, the impact on the customer, the business success and the future potentiality. With successful cases, the success tends to spread out to areas and functions not mentioned as the project goals, andwith unsuccessful cases the failure seems to spread out widely to the SMEs' other functions. This study also indicates that the most important key factors for successful business development project implementation are the strength of intention, business ability, knowledge, motivation and participation of the employees, as well as adequate and well-timed training provided to the employees.

Targeting Adenoviral Gene Therapy Vectors to Head and Neck Squamous Cell Carcinoma and Heart

Gene therapy aims to treat diseases by introducing genetic material to the diseased tissue. For cancer treatment it is important to destroy cancerous cells; this can be achieved by introducing a gene, which induces cell death or by allowing viral vectors to replicate, which also results in destruction of cancerous cells. For cardiac diseases the approach is more like the former, except the gene produces beneficial effects, like angiogenesis. Adenoviruses have many beneficial qualities, which make the virus an interesting gene therapy vector; it can be produced relatively easily, its manipulation is quite easy and it has naturally broad tropism. By removing or replacing certain genes in the adenoviral genome, it can be made non-replicative. In this study, adenoviral receptor expression patterns were characterized in both head and neck squamous cell carcinoma and the human heart. Adenovirus serotype 5 receptor expression in head and neck cancer cell lines was found to be highly variable between cell lines and overall at lower levels, while Ad35 receptor expression was more uniform and at higher levels in all analyzed cell lines. It was also shown that a hybrid virus Ad5/35 is able to infect cells refractory to Ad5, which correlates with receptor expression in these cells. Furthermore, this difference in infection properties extends to cell killing efficiency in case of conditionally replicative viruses. Expression levels of adenoviral receptors CAR, CD46, CD86 and αv-integrins were found to be high both in normal and dilated cardiomyopathy heart tissue. The receptor levels also correlate with transduction efficiency after intracardiac injection. Ad5 showed superior transduction ability compared with Ad5/35, but evoked also a more profound immune reaction when administered this way. Adenoviral gene therapy vectors are the most used delivery vehicles in clinical trials to date. These vectors have proven to be well tolerated and positive results have been obtained when combined with traditional treatments, although poor transduction efficiency has often been reported due to low-level expression of viral receptors on target cells. In spite of this, the results are encouraging and merit for further research.

Bonding of Composite Resin to Alumina and Zirconia Ceramics with Special Emphasis on Surface Conditioning and Use of Coupling Agents

Dental oxide ceramics have been inspired by their biocompability and mechanical properties which have made durable all-ceramic structures possible. Clinical longevity of the prosthetic structures is dependent on effective bonding with luting cements. As the initial shear bond strength values can be comparable with several materials and procedures, long-term durability is affected by ageing. Aims of the current study were: to measure the shear bond strength of resin composite-to-ceramics and to evaluate the longevity of the bond; to analyze factors affecting the bond, with special emphasis on: the form of silicatization of the ceramic surface; form of silanization; type of resin primer and the effect of the type of the resin composite luting cement; the effect of ageing in water was studied regarding its effect to the endurance of the bond. Ceramic substrates were alumina and yttrium stabilized zirconia. Ceramic conditioning methods included tribochemical silicatization and use of two silane couplings agents. A commercial silane primer was used as a control silane. Various combinations of conditioning methods, primers and resin cements were tested. Bond strengths were measured by shear bond strength method. The longevity of the bond was generally studied by thermocycling the materials in water. Additionally, in one of the studies thermal cycling was compared with long-term water storaging. Results were analysed statistically with ANOVA and Weibull analysis. Tribochemical treatment utilizing air pressure of 150 kPa resulted shear bond strengths of 11.2 MPa to 18.4 MPa and air pressure of 450 kPa 18.2 MPa to 30.5 MPa, respectively. Thermocycling of 8000 cycles or four years water storaging both decreased shear bond strength values to a range of 3.8 MPa to 7.2 MPa whereas initial situation varied from 16.8. Mpa to 23.0 MPa. The silane used in studies had no statistical significance. The use of primers without 10-MDP resulted spontaneous debonding during thermocycling or shear bond strengths below 5 MPa. As conclusion, the results showed superior long-term bonding with primers containing 10-MDP. Silicatization with silanizing showed improved initial shear bond strength values which considerably decreased with ageing in water. Thermal cycling and water storing for up to four years played the major role in reduction of bond strength, which could be due to thermal fatigue of the bonding interface and hydrolytic degradation of the silane coupled interface.

Cellular responses to stress and kinase signaling activation : apoptosis and differentiation

Stressignaler avkänns många gånger av membranbundna proteiner som översätter signalerna till kemisk modifiering av molekyler, ofta proteinkinaser Dessa kinaser överför de avkodade budskapen till specifika transkriptionsfaktorer genom en kaskad av sekventiella fosforyleringshändelser, transkriptionsfaktorerna aktiverar i sin tur de gener som behövs för att reagera på stressen. En av de mest kända måltavlorna för stressignaler är transkriptionsfaktor AP-1 familjemedlemen c-Jun. I denna studie har jag identifierat den nukleolära proteinet AATF som en ny regulator av c-Jun-medierad transkriptionsaktivitet. Jag visar att stresstimuli inducerar omlokalisering av AATF vilket i sin tur leder till aktivering av c-Jun. Den AATF-medierad ökningen av c-Jun-aktiviteten leder till en betydande ökning av programmerad celldöd. Parallellt har jag vidarekarakteriserat Cdk5/p35 signaleringskomplexet som tidigare har identifierats i vårt laboratorium som en viktig faktor för myoblastdifferentiering. Jag identifierade den atypiska PKCξ som en uppströms regulator av Cdk5/p35-komplexet och visar att klyvning och aktivering av Cdk5 regulatorn p35 är av fysiologisk betydelse för differentieringsprocessen och beroende av PKCξ aktivitet. Jag visar att vid induktion av differentiering fosforylerar PKCξ p35 vilket leder till calpain-medierad klyvning av p35 och därmed ökning av Cdk5-aktiviteten. Denna avhandling ökar förståelsen för de regulatoriska mekanismer som styr c-Jun-transkriptionsaktiviteten och c-Jun beroende apoptos genom att identifiera AATF som en viktig faktor. Dessutom ger detta arbete nya insikter om funktionen av Cdk5/p35-komplexet under myoblastdifferentiering och identifierar PKCξ som en uppströms regulator av Cdk5 aktivitet och myoblast differentiering.

Fe y esperanza : women's road to leadership and ministry in the Lutheran church of El Salvador 1952-2009

The Lutheran Church of El Salvador made a decision, in 1986, to open the ministry to women. How was it possible in the midst of a Latin American macho culture and after having been influenced by the theologically conservative, North American mission work? This research examines the kinds of internal and external factors which led women to leadership and ministry, and the context in which this development occurred. The roles of women have been scrutinised during several time periods. During 1952-1974 the focus was on women as missionary wives and fundadoras (founding mothers). Women’s roles as laywomen grew in 1975-1985. After the outburst of the civil war in 1980, women advanced to lay leaders. The ministry was opened for women and the first deacon pastors were installed in 1986 and the first presbyter pastors were ordained in 1994. In 2009, more women than ever were working in different levels – from laywomen to leaders – in the Lutheran Church of El Salvador. The research shows that the reasons for the development and changes concerning women’s positions and roles lie in the impact of significant individuals, liberation theology, the feminist and women’s movement, civil war and the theology of life.

Effects of obtained benefits on willingness to pay and word-of-mouth behavior in newspaper industry

The purpose of this master’s thesis was to investigate the effects which benefits obtained from reading a newspaper and using its website have on behavioral outcomes such as word-of-mouth behavior and willingness to pay. Several other antecedents of willingness to pay have been used as the control variables. However, their interrelations haven’t been hypothesized. The empirical part focused on a case company – Finnish regional newspaper. Empirical research has been conducted using a quantitative method and data was collected via online survey placed on newspaper’s website during 2010. 1001 responses have been collected. The results showed that benefits obtained both from traditional printed newspaper and from online one have positive effects on the word-of-mouth about this newspaper and its website. However, it has been revealed that benefits obtained from reading the newspaper don’t have effect on the willingness to pay for this newspaper. Additionally, only interpersonal and convenience benefits obtained from using the newspaper’s website influence on the willingness to pay for it. Finally, willingness to pay for the bundle of printed newspaper and its website access is affected positively only by the information/learning benefits obtained from reading the newspaper and by the interpersonal benefits obtained from using the newspaper’s website.

User Experience of Geocaching and Its Application to Tourism and Education

Advances in technology have provided new ways of using entertainment and game technology to foster human interaction. Games and playing with games have always been an important part of people’s everyday lives. Traditionally, human-computer interaction (HCI) research was seen as a psychological cognitive science focused on human factors, with engineering sciences as the computer science part of it. Although cognitive science has made significant progress over the past decade, the influence of people’s emotions on design networks is increasingly important, especially when the primary goal is to challenge and entertain users (Norman 2002). Game developers have explored the key issues in game design and identified that the driving force in the success of games is user experience. User-centered design integrates knowledge of users’ activity practices, needs, and preferences into the design process. Geocaching is a location-based treasure hunt game created by a community of players. Players use GPS (Global Position System) technology to find “treasures” and create their own geocaches; the game can be developed when the players invent caches and used more imagination to creations the caches. This doctoral dissertation explores user experience of geocaching and its applications in tourism and education. Globally, based on the Geocaching.com webpage, geocaching has been played about 180 countries and there are more than 10 million registered geocachers worldwide (Geocaching.com, 25.11.2014). This dissertation develops and presents an interaction model called the GameFlow Experience model that can be used to support the design of treasure hunt applications in tourism and education contexts. The GameFlow Model presents and clarifies various experiences; it provides such experiences in a real-life context, offers desirable design targets to be utilized in service design, and offers a perspective to consider when evaluating the success of adventure game concepts. User-centered game designs have adapted to human factor research in mainstream computing science. For many years, the user-centered design approach has been the most important research field in software development. Research has been focusing on user-centered design in software development such as office programs, but the same ideas and theories that will reflect the needs of a user-centered research are now also being applied to game design (Charles et al. 2005.) For several years, we have seen a growing interest in user experience design. Digital games are experience providers, and game developers need tools to better understand the user experience related to products and services they have created. This thesis aims to present what the user experience is in geocaching and treasure hunt games and how it can be used to develop new concepts for the treasure hunt. Engineers, designers, and researchers should have a clear understanding of what user experience is, what its parts are, and most importantly, how we can influence user satisfaction. In addition, we need to understand how users interact with electronic products and people, and how different elements synergize their experiences. This doctoral dissertation represents pioneering work on the user experience of geocaching and treasure hunt games in the context of tourism and education. The research also provides a model for game developers who are planning treasure hunt concepts.

Liquidity levels of Finnish SME’s from 2007 to 2013 and a closer analysis of the IC sector

TAVOITTEET: Tämän tutkielman tarkoitus on tarkastella eri toimialojen likviditeettitasoja vuosien 2007 ja 2013 välillä. Se tarkastelee myös kassanhallinnan ja likviditeetin kirjallisuutta, erilaisia likviditeettiä kuvaavia tunnuslukuja sekä asioita, joilla on vaikutusta likviditeettiin. Tämän lisäksi se tutkii informaatio ja kommunikaatio sektoria tarkemmin. DATA: Data on kerätty Orbis tietokannasta. Toimialakohtaiset keskiarvot on laskettu joko kappaleen 2 esittämillä kaavoilla tai noudettu suoraan tietokannasta. Hajonta kuvaajat on tehty Excelillä ja korrelaatio matriisi ja regressioanalyysit SAS EG:llä. TULOKSET: Tämä tutkimus esittää toimialakohtaiset keskiarvot liquidity ratiosta, solvency ratiosta sekä gearingista, kuten monista muista likviditeettiä kuvaavista tai siihen vaikuttavista tunnusluvuista. Tutkimus osoittaa, että keskimäärin likviditeetti ja maksuvalmius ovat säilyneet melko samana, mutta toimialakohtaiset muutokset ovat voimakkaita. IC sektorilla likviditeettiin vaikuttaa katetuotto, työntekijöiden määrä, liikevaihto, taseen määrä sekä maksuaika.

Pölymittausmenetelmien luotettavuuden arviointi ja prosessiolosuhteiden vaikutus pölyävyyteen

Pölyäminen aiheuttaa ongelmia sekä paperin valmistuksessa paperikoneella että asiakkaalla painokoneella. Pölyäminen painokoneella aiheuttaa kumulatiivisia kertymiä painokumeille, -levyille ja kostutusvesijärjestelmään. Pölykertymistä seuraa painojäljen heikkenemistä, pesukertojen lisääntymistä ja tuotantokatkoja. Lisääntynyt painaminen tahmeilla offsetväreillä ja täyteaineiden käyttö paperin raaka-aineena on aiheuttanut paperin pölyämisherkkyyden kasvamista. Paperin pölyävyyteen vaikuttavia tekijöitä valmistuksessa, jälkikäsittelyssä ja jatkojalostuksessa on useita, mikä tekee ilmiöstä monimutkaisen. Paperin painatuksessa esiintyvän pölyävyyden ennakoimiseksi tutkittiin erilaisten pölymittausmenetelmien käytettävyys ja luotettavuus. Työssä käytetyt menetelmät olivatMac Millan Bloedel pölytesteri, R.A. Emerson & Company:n pölymittalaite, Finntesteri, SOLA, Masuga, arkkipainatus sekä IGT ja Prüfbau laboratoriopainatukset. Menetelmien luotettavuus arvioitiin vertaamalla saatuja pölytuloksia testipainatuksesta saatuihin pölytuloksiin ja Gage R&R testiä käyttäen. Lisäksi työssä selvitettiin paperin pölyävyyteen vaikuttavia tekijöitä, ja tutkittiin prosessiolosuhteiden vaikutusta paperin pölyävyyteen. Tutkimus osoitti tuotantoprosessin olosuhteissa tehtyjen muutosten aiheuttavan oleellisia muutoksia paperin pölyävyyteen. Käytettävän massan ominaisuuksilla, tuotantoprosessin kemian hallinnalla sekä paperin ominaisuuksista etenkin lujuus- ja formaatio-ominaisuuksilla on selkeästi yhteyttä paperin pölyävyyteen painatuksessa. Pölymittauksilla paperin valmistuksen yhteydessä voidaan tasollisesti arvioida paperinpölyävyys painatuksessa, mutta absoluuttisten tulosten saaminen on ilmiön monimuotoisuudesta johtuen mahdotonta. Käytetyistä menetelmistä tähän tuotantoprosessiin toimivin pölyävyyden mittamenetelmä on R.A. Emerson & Company:n pölymittalaite. Laite on yksinkertainen ja nopea käyttää, eikä toteutus vaadi suuria investointeja.

Moment Operators of Observables in Quantum Mechanics, with Applications to Quantization and Homodyne Detection

The questions studied in this thesis are centered around the moment operators of a quantum observable, the latter being represented by a normalized positive operator measure. The moment operators of an observable are physically relevant, in the sense that these operators give, as averages, the moments of the outcome statistics for the measurement of the observable. The main questions under consideration in this work arise from the fact that, unlike a projection valued observable of the von Neumann formulation, a general positive operator measure cannot be characterized by its first moment operator. The possibility of characterizing certain observables by also involving higher moment operators is investigated and utilized in three different cases: a characterization of projection valued measures among all the observables is given, a quantization scheme for unbounded classical variables using translation covariant phase space operator measures is presented, and, finally, a mathematically rigorous description is obtained for the measurements of rotated quadratures and phase space observables via the high amplitude limit in the balanced homodyne and eight-port homodyne detectors, respectively. In addition, the structure of the covariant phase space operator measures, which is essential for the above quantization, is analyzed in detail in the context of a (not necessarily unimodular) locally compact group as the phase space.

Role of Membrane Transporters, P-Glycoprotein and Mrp1, in The Placental Transfer of Drugs With Special Reference to Saquinavir and Quetiapine

Drug transporting membrane proteins are expressed in various human tissues and blood-tissue barriers, regulating the transfer of drugs, toxins and endogenous compounds into or out of the cells. Various in vitro and animal experiments suggest that P-glycoprotein (P-gp) forms a functional barrier between maternal and fetal blood circulation in the placenta thereby protecting the fetus from exposure to xenobiotics during pregnancy. The multidrug resistance-associated protein 1 (MRP1) is a relatively less studied transporter protein in the human placenta. The aim of this study series was to study the role of placental transporters, apical P-gp and basal MRP1, using saquinavir as a probe drug, and to study transfer of quetiapine and the role of P-gp in its transfer in the dually perfused human placenta/cotyledon. Furthermore, two ABCB1 (encoding P-gp) polymorphisms (c.3435C>T, p.Ile1145Ile and c.2677G>T/A, p.Ala893Ser/Thr) were studied to determine their impact on P-gp protein expression level and on the transfer of the study drugs. Also, the influence of the P-gp protein expression level on the transfer of the study drugs was addressed. Because P-gp and MRP1 are ATP-dependent drug-efflux pumps, it was studied whether exogenous ATP is needed for the function of ATP-dependent transporter in the present experimental model. The present results indicated that the addition of exogenous ATP was not necessary for transporter function in the perfused human placental cotyledon. Saquinavir and quetiapine were both found to cross the human placenta; transplacental transfer (TPTAUC %) for saquinavir was <0.5% and for quetiapine 3.7%. Pharmacologic blocking of P-gp led to disruption of the blood-placental barrier (BPB) and increased the placental transfer of P-gp substrate, saquinavir, into the fetal circulation by 6- to 8-fold. In reversed perfusions P-gp, MRP1 and possibly OATP2B1 had a negligible role in the fetal-to-maternal transfer of saquinavir. The TPTAUC % of saquinavir was about 100-fold greater from the fetal side to the maternal side compared with the maternal-to-fetal transfer. P-gp activity is not likely to modify the placental transfer of quetiapine. Higher P-gp protein expression levels were associated with the variant allele 3435T, but no correlation was found between the TPTAUC % of saquinavir and placental P-gp protein expression. The present results indicate that P-gp activity drastically affects the fetal exposure to saquinavir, and suggest that pharmacological blockade of the P-gp activity during pregnancy may pose an increased risk for adverse fetal outcome. The blockade of P-gp activity could be used in purpose to obtain higher drug concentration to the fetal side, for example, in prevention (to decrease virus transfer to fetal side) or in treating sick fetus.

Improving oral healthcare in Scotland with special reference to sustainability and caries prevention

Brett Duane Improving oral healthcare in Scotland with special reference to sustainability and caries prevention University of Turku, Faculty of Medicine, Institute of Dentistry, Community Dentistry, Finnish Doctoral Program in Oral Sciences (FINDOS-Turku), Turku, Finland Annales Universitatis Turkuensis, Sarja- Ser. D, Medica-Odontologica. Painosalama Oy, Turku, Finland, 2015. Dentistry must provide sustainable, evidence-based, and prevention-focused care. In Scotland oral health prevention is delivered through the Childsmile programme, with an increasing use of high concentration fluoride toothpaste (HCFT). Compared with other countries there is little knowledge of xylitol prevention. The UK government has set strict carbon emission limits with which all national health services (NHS) must comply. The purpose of these studies was firstly to describe the Scottish national oral health prevention programme Childsmile (CS), to determine if the additional maternal use of xylitol (CS+X) was more effective at affecting the early colonisation of mutans streptococci (MS) than this programme alone; secondly to analyse trends in the prescribing and management of HCFT by dentists; and thirdly to analyse data from a dental service in order to improve its sustainability. In all, 182 mother/child pairs were selected on the basis of high maternal MS levels. Motherswere randomly allocated to a CS or CS+X group, with both groups receiving Childsmile. Theintervention group consumed xylitol three times a day, from when the child was 3 months until 24 months. Children were examined at age two to assess MS levels. In order to understand patterns of HCFT prescribing, a retrospective secondary data analysis of routine prescribing data for the years 2006-2012 was performed. To understand the sustainability of dental services, carbon accounting combined a top-down approach and a process analysis approach, followed by the use of Pollard’s decision model (used in other healthcare areas) to analyse and support sustainable service reconfiguration. Of the CS children, 17% were colonised with MS, compared with 5% of the CS+X group. This difference was not statistically significant (P=0.1744). The cost of HCFT prescribing increased fourteen-fold over five years, with 4% of dentists prescribing 70% of the total product. Travel (45%), procurement (36%) and building energy (18%) all contributed to the 1800 tonnes of carbon emissions produced by the service, around 4% of total NHS emissions. Using the analytical model, clinic utilisation rates improved by 56% and patient travel halved significantly reducing carbon emissions. It can be concluded that the Childsmile programme was effective in reducing the risk for MS transmission. HCFT is increasing in Scotland and needs to be managed. Dentistry has similar carbon emissions proportionally as the overall NHS, and the use of an analytic tool can be useful in helping identify these emissions. Key words: Sustainability, carbon emissions, xylitol, mutans streptococci, fluoride toothpaste, caries prevention.