The Structure and Function of αI Domains in Collagen Receptor and Leukocyte Integrins

Integrins are heterodimeric, signaling transmembrane adhesion receptors that connect the intracellular actin microfilaments to the extracellular matrix composed of collagens and other matrix molecules. Bidirectional signaling is mediated via drastic conformational changes in integrins. These changes also occur in the integrin αI domains, which are responsible for ligand binding by collagen receptor and leukocyte specific integrins. Like intact integrins, soluble αI domains exist in the closed, low affinity form and in the open, high affinity form, and so it is possible to use isolated αI domains to study the factors and mechanisms involved in integrin activation/deactivation. Integrins are found in all mammalian tissues and cells, where they play crucial roles in growth, migration, defense mechanisms and apoptosis. Integrins are involved in many human diseases, such as inflammatory, cardiovascular and metastatic diseases, and so plenty of effort has been invested into developing integrin specific drugs. Humans have 24 different integrins, four of which are collagen receptor (α1β1, α2β1, α10β1, α11β1) and five leukocyte specific integrins (αLβ2, αMβ2, αXβ2, αDβ2, αEβ7). These two integrin groups are quite unselective having both primary and secondary ligands. This work presents the first systematic studies performed on these integrin groups to find out how integrin activation affects ligand binding and selectivity. These kinds of studies are important not only for understanding the partially overlapping functions of integrins, but also for drug development. In general, our results indicated that selectivity in ligand recognition is greatly reduced upon integrin activation. Interestingly, in some cases the ligand binding properties of integrins have been shown to be cell type specific. The reason for this is not known, but our observations suggest that cell types with a higher integrin activation state have lower ligand selectivity, and vice versa. Furthermore, we solved the three-dimensional structure for the activated form of the collagen receptor α1I domain. This structure revealed a novel intermediate conformation not previously seen with any other integrin αI domain. This is the first 3D structure for an activated collagen receptor αI domain without ligand. Based on the differences between the open and closed conformation of the αI domain we set structural criteria for a search for effective collagen receptor drugs. By docking a large number of molecules into the closed conformation of the α2I domain we discovered two polyketides, which best fulfilled the set structural criteria, and by cell adhesion studies we showed them to be specific inhibitors of the collagen receptor integrins.

Doplervelocimetria das artérias oftálmica e central da retina em gestantes normais

OBJETIVOS: avaliar os padrões dos índices doplervelocimétricos das artérias oftálmica e central da retina durante o segundo e terceiro trimestres da gestação normal e comparar os valores obtidos do olho direito e esquerdo das gestantes. MÉTODOS: estudo transversal no qual se avaliaram seis índices doplervelocimétricos das artérias central da retina e oftálmica em 51 gestantes normais, com idades gestacionais entre a 20ª e a 38ª semana. As variáveis analisadas foram os índices de resistência e pulsatilidade (IR, IP), os picos de velocidade sistólica e diastólica (PVS, PVD) e a razão entre picos de velocidade (RPV). A análise dos índices doplervelocimétricos dos olhos direito e esquerdo foi realizada utilizando-se a mediana dos valores. Para a comparação dos valores dos índices entre os dois olhos das gestantes, utilizou-se o teste t de Student para dados pareados. A associação entre a idade gestacional e os índices foi testada empregando-se o coeficiente de correlação linear de Pearson. Adotou-se o nível de significância de 5% para os testes estatísticos. RESULTADOS: a mediana dos índices doplervelocimétricos das artérias oftálmica e central da retina foram, respectivamente: IP=1,83; IR=0,78; PVS=34,20; PVD=6,80; RPV=0,48 e IP=1,34; IR=0,70; PVS=7,40; PVD=2,10. Não houve diferenças na análise comparativa dos índices doplervelocimétricos entre os olhos direito e esquerdo das gestantes normais. O coeficiente de correlação linear entre a idade gestacional e os índices de ambas as artérias não mostrou diferença significante durante a gestação normal. CONCLUSÃO: é factível a análise unilateral dos índices doplervelocimétricos das artérias oftálmica e central da retina no estudo de doenças maternas sistêmicas. Não há mudança significativa dos índices doplervelocimétricos das artérias oftálmica e central da retina ao longo da gestação normal entre a 20ª e a 38ª semana.

Variação do fluxo sanguíneo da artéria central da retina durante as diferentes fases do ciclo menstrual ovulatório

OBJETIVO: avaliar a resistência vascular da artéria central da retina, por meio do fluxo Doppler, nas diferentes fases do ciclo menstrual ovulatório. MÉTODOS: estudo observacional, longitudinal e prospectivo com avaliação de 34 mulheres saudáveis, submetidas a estudo dopplerfluxométrico do fundo do olho para avaliação da resistência vascular da artéria central da retina nas posições sentada e deitada, durante quatro fases do ciclo menstrual: fase folicular inicial, fase folicular média, fase periovulatória e fase lútea média. A confirmação da ovulação no ciclo de estudo foi feita pela dosagem de progesterona sérica na fase lútea média. Foram avaliados os índices de pulsatilidade (IP) e de resistência, e as velocidades máxima, mínima e média. RESULTADOS: a idade média foi de 29,7 anos. Não foram observadas diferenças entre os índices obtidos para ambos os olhos; assim, utilizamos as médias dos índices para realizar o cálculo estatístico. Quando comparadas às posições de realização do exame, detectou-se um IP maior na posição sentada; assim, as análises foram avaliadas em separado, respeitando-se a posição da paciente. O IP da artéria central da retina, avaliado com a paciente deitada, variou durante o ciclo menstrual, apresentando-se significativamente mais baixo nas fases folicular média (1,5±0,3) e periovulatória (1,5±0,3) quando comparadas às fases folicular precoce (1,7±0,4) e lútea média (1,7±0,4). Quando a avaliação foi feita com a paciente sentada não foram observadas diferenças para as diferentes fases do ciclo. CONCLUSÕES: num ciclo menstrual ovulatório ocorre diminuição da resistência vascular na artéria central da retina e posterior reversão do efeito, como demonstrado pelas variações do IP.

Developing raster bands computed from LiDAR to improve forest

This study examines the use of di erent features derived from remotely sensed data in segmentation of forest stands. Surface interpolation methods were applied to LiDAR points in order to represent data in the form of grayscale images. Median and mean shift ltering was applied to the data for noise reduction. The ability of di erent compositions of rasters obtained from LiDAR data and an aerial image to maximize stand homogeneity in the segmentation was evaluated. The quality of forest stand delineations was assessed by the Akaike information criterion. The research was performed in co-operation with Arbonaut Ltd., Joensuu, Finland.

DEVELOPING SOCIAL CAPITAL WITHIN COMPANIES THROUGH ENTERPRISE 2.0

Whereas external social media has been studied, hyped and integrated into companies´ strategies, an insignificant concentration has been put on internal social solutions, which companies provide increasingly to their personnel. An enterprise focusing solely on the benefits of external social media might end up underestimating the true potential embedded in social business. The purpose of this thesis was to examine how social collaboration can be depicted as a structuration process in an Enterprise 2.0 environment. Furthermore, this thesis sought to reveal the benefits, challenges and possibilities of social business. This thesis focused on researching Enterprise 2.0 at the workplace. The studied Enterprise 2.0 solution was IBM Connections. The qualitative research methodology was an extensive case study. Three companies took part into this thesis and all in all 12 employees were interviewed. Additionally, seven IBM Social Business Experts were interviewed in order to receive a better understanding of the phenomenon. Three research questions were designed to fulfill the purpose of this thesis. The research questions were: 1. How are the dimensions of social capital structured through collaboration? 2. How does agency form in Enterprise 2.0? 3. How does social collaboration emerge as a result of the interplay between agency and dimensions of social capital in an Enterprise 2.0 environment and creates outcomes such as trust, identification and knowledge? The main research findings indicate that social collaboration increases trust, identification and knowledge by giving employees more capabilities to do their work. Consequently, social collaboration increases company performance by making individuals and groups more effective. The support of top management is crucial in making Enterprise 2.0 successful, because it is more a cultural than a technological change. Power agency, the lack of top management support and old established work ways such as email and databases work as barriers to social collaboration.

DEVELOPING A CROWDSOURCED VIDEOGRAPHIC RESEARCH METHOD FOR CONSUMER CULTURE RESEARCH

The purpose of this study is to develop a crowdsourced videographic research method for consumer culture research. Videography provides opportunities for expressing contextual and culturally embedded relations. Thus, developing new ways to conduct videographic research is meaningful. This study develops the crowdsourced videographic method based on a literature review and evaluation of a focal study. The literature review follows a qualitative systematic review process. Through the literature review, based on different methodological, crowdsourcing and consumer research related literature, this study defines the method, its application process and evaluation criteria. Furthermore, the evaluation of the focal study, where the method was applied, completes the study. This study applies professional review with self-evaluation as a form of evaluation, drawing from secondary data including research task description, screenshots of the mobile application used in the focal study, videos collected from the participants, and self-evaluation by the author. The focal study is analyzed according to its suitability to consumer culture research, research process and quality. Definitions and descriptions of the research method, its process and quality criteria form the theoretical contribution of this study. Evaluating the focal study using these definitions underlines some best practices of this type of research, generating the practical contribution of this study. Finally, this study provides ideas for future research. First, defining the boundaries of the use of crowdsourcing in various parts of conducting research. Second, improving the method by applying it to new research contexts. Third, testing how changes in one dimension of the crowdsourcing models interact with other dimension. Fourth, comparing the quality criteria applied in this study to various other quality criteria to improve the method’s usefulness. Overall, this study represents a starting point for further development of the crowdsourced videographic research method.

Exploring Customer-Oriented Service Offerings in Public Health: Developing Integrated Health Care Services for Rural Areas

Väestön ikääntyminen pakottaa yhteiskunnan ja julkisen terveydenhuollon muutoksiin. Jotta ikääntyvien ihmisten kotona asuminen voidaan mahdollistaa, palvelujärjestelmän pitää mukautua muuttuvaan tilanteeseen. Tämän diplomityön tarkoituksena on tunnistaa asiakaslähtöisiä lähellä asiakasta tarjottavia palvelukokonaisuuksia. Tutkimuksen teoreettinen viitekehys muodostuu asiakasarvon luomisesta ja palvelutarjoamista. Tarkasteluryhmänä on Etelä-Karjalan alueen 60–90-vuotiaat ja käytetty aineisto on kerätty vastaajilta postitse lähetetyllä kyselyllä. Tutkimus on eksploratiivinen ja tulosten tulkinnassa on hyödynnetty määrällisen tutkimuksen ja verkostoanalyysin menetelmiä. Työn keskeisimmät tulokset ovat tunnistetut asiakassegmentit ja heidän tarpeidensa pohjalta muodostetut palvelupaketit. Tulokset indikoivat asiakkaiden tarpeita ja tuloksia on analysoitu myös tuottajan näkökulmasta. Empiiristen tulosten lisäksi teoriaviitekehystä on kehitetty eteenpäin, jotta palvelukeskeiset teoriat voidaan ymmärtää yritysten näkökulman lisäksi asiakkaan näkökulmasta.

The Changing Role of the CIO: Developing Skills by Means of Postgraduate Educational Programs

The objective of this research was to identify the skills and competences required by Chief Information Officers in their professional life and whether these skills can be developed by means of postgraduate education pro-grams. Although the changing role of the CIO has been studied for years by the academia, the ways of necessary skills development have not been paid significant attention. In order to obtain understanding of the topic and its main issues qualitative method was implemented and questionnaires and interviews were conducted with CIOs and other C-level executives to-gether with analysis of the curricula of postgraduate educational programs in the field of business designed for executives. Business skills and knowledge along with developed communication and leadership skills are among the most discussed and required from CIOs. According to the collected data and its further analysis, although the most important competences of an IT executive are technological, the im-portance of business related skills is emphasized by the majority of re-spondents and supported by the existing theory. Postgraduate educational programs have curricula that can develop the required competences, alt-hough not equally.

Developing Service-based Solutions for Water Treatment in Finnish Mining Industry

The aim of this master’s thesis is to analyze the mining industry customers' current and future needs for the water treatment services and discover new business development opportunities in the context of mine water treatment. In addition, the study focuses on specifying service offerings needed and evaluate suitable revenue generation models for them. The main research question of the study is: What kind of service needs related to water treatment can be identified in the Finnish mining industry? The literature examined in the study focused on industrial service classification and new service development process as well as the revenue generation of services. A qualitative research approach employing a case study method was chosen for the study. The present study uses customer and expert interviews as primary data source, complemented by archival data. The primary data was gathered by organizing total of 13 interviews, and the interviews were analyzed by using qualitative content analysis. The abductive-logic was chosen as the way of conducting scientific reasoning in this study. As a result, new service proposals were developed for Finnish mine industry suppliers. The main areas of development were on asset efficiency services and process support services. The service needs were strongly associated with suppliers’ know-how of water treatment process optimization, cost-effectiveness as well as on alternative technologies. The study provides an insight for managers that wish to pursue a water treatment services as a part of their business offering.

Microbusiness: A new social business model to alleviate poverty in developing countries?

Poverty alleviation views have shifted from seeing the poor as victims or as potential consumers, to seeing them as gainers. Social businesses include microfinancing and microfranchising, which engage people at the bottom of the pyramid using business instead of charity. There are, however, social business firms that do not fit to the existing social business model theory. These firms provide markets to poor producers and mix traditional, local craftsmanship with western design. Social business models evolve faster than the academic literature can study them. This study contributes to filling this gap. The purpose of this Master’s thesis is to develop the concept of social business as poverty alleviation method in developing countries. It also aims; 1) to describe the means for poverty alleviation in developing countries; 2) to introduce microbusiness as a social business model; and 3) to examine the challenges of microbusinesses. Qualitative case study is used as a research strategy and theme interviews as a data collecting method. The empirical data is gathered from four interviews of Finnish or Finnish-owned firms that employ microbusiness – Mifuko, Tensira, Mangomaa and Tikau – and this is supported with secondary data including articles on case companies. The results show that microbusiness is a valid new social business model that aims at poverty alleviation by engaging the poor at the bottom of the pyramid. It is possible to map the value proposition, value constellation, and economic and social profit equations of the case firms. Two major types of firms emerge from the results; the first consists of design-oriented firms that emphasize the quality and design of the products, and the second consists of bazaar-like firms whose product portfolio is less sophisticated and who promote more the stories of the products – not the design. All microbusiness firms provide markets, promote traditional handicrafts, form close relationships to their producers, and aim at enhancing lives through their businesses. The attitudes towards social businesses are sometimes negative, but this is changing for the better. In conclusion, microbusiness answers to two different needs at the same time – consumers’ needs for ethical products and the social needs of the producers – but the social need is the ultimate reason why the entrepreneurs started business. Microbusiness continues as a poverty alleviation tool that sees the poor as gainers; by providing them steady employment, microbusiness increases the poor’s self-esteem and enables them for a better living. Academic literature has not been able to offer enough alternative business models to cover all social businesses; the current study contributes to this by concluding that microbusiness is another social business model.

Understanding, Managing And Developing A Well-Being Service Brand

The aim of this study is to analyze and understand a well-being service brand. Brands most definitely are a hot topic of today’s business world. Companies have started to realize the importance of branding, especially when talking about product related industries. Branding of services is a relatively new concept, which has gained less attention within academic literature. Though there is no legal distinction between product and service brands, they both have their own characteristics and qualities. The focus of the study is especially on the current brand images of both internal and external stakeholder groups. Understanding these brand perceptions will help in managing and developing the brand, so that it becomes even stronger, more recognized, and unified. This study is a quantitative, semi hypothetic-deductive single case study. The data for this study was collected throughout an online survey. The respondents represent both internal stakeholders, in direct contact with the service, as well as external stakeholders, who have no previous history with the service brand. The respondents represent a wide age spread, and are also geographically diverse. The study relies on a Finnish context. The study provides numerous managerial takeaways, especially because of its wide scope, on a topic that has never before been studied. All findings strongly reflected existing service brand theory, in addition with making the findings implementable for the case company.

Developing the Product Return Process of a Service Center With Lean Methods

Today lean-philosophy has gathered a lot of popularity and interest in many industries. This customer-oriented philosophy helps to understand customer’s value creation which can be used to improve efficiency. A comprehensive study of lean and lean-methods in service industry were created in this research. In theoretical part lean-philosophy is studied in different levels which will help to understand its diversity. To support lean, this research also presents basic concepts of process management. Lastly theoretical part presents a development model to support process development in systematical way. The empirical part of the study was performed by performing experimental measurements during the service center’s product return process and by analyzing this data. Measurements were used to map out factors that have a negative influence on the process flow. Several development propositions were discussed to remove these factors. Problems mainly occur due to challenges in controlling customers and due to the lack of responsibility and continuous improvement on operational level. Development propositions concern such factors as change in service center’s physical environment, standardization of work tasks and training. These factors will remove waste in the product return process and support the idea of continuous improvement.

Developing Bioimage Informatics – from Microscopy to Software Solutions – with alpha2beta1 Integrin as a Case Study

Biokuvainformatiikan kehittäminen – mikroskopiasta ohjelmistoratkaisuihin – sovellusesimerkkinä α2β1-integriini Kun ihmisen genomi saatiin sekvensoitua vuonna 2003, biotieteiden päätehtäväksi tuli selvittää eri geenien tehtävät, ja erilaisista biokuvantamistekniikoista tuli keskeisiä tutkimusmenetelmiä. Teknologiset kehitysaskeleet johtivat erityisesti fluoresenssipohjaisten valomikroskopiatekniikoiden suosion räjähdysmäiseen kasvuun, mutta mikroskopian tuli muuntua kvalitatiivisesta tieteestä kvantitatiiviseksi. Tämä muutos synnytti uuden tieteenalan, biokuvainformatiikan, jonka on sanottu mahdollisesti mullistavan biotieteet. Tämä väitöskirja esittelee laajan, poikkitieteellisen työkokonaisuuden biokuvainformatiikan alalta. Väitöskirjan ensimmäinen tavoite oli kehittää protokollia elävien solujen neliulotteiseen konfokaalimikroskopiaan, joka oli yksi nopeimmin kasvavista biokuvantamismenetelmistä. Ihmisen kollageenireseptori α2β1-integriini, joka on tärkeä molekyyli monissa fysiologisissa ja patologisissa prosesseissa, oli sovellusesimerkkinä. Työssä saavutettiin selkeitä visualisointeja integriinien liikkeistä, yhteenkeräytymisestä ja solun sisään siirtymisestä, mutta työkaluja kuvainformaation kvantitatiiviseen analysointiin ei ollut. Väitöskirjan toiseksi tavoitteeksi tulikin tällaiseen analysointiin soveltuvan tietokoneohjelmiston kehittäminen. Samaan aikaan syntyi biokuvainformatiikka, ja kipeimmin uudella alalla kaivattiin erikoistuneita tietokoneohjelmistoja. Tämän väitöskirjatyön tärkeimmäksi tulokseksi muodostui näin ollen BioImageXD, uudenlainen avoimen lähdekoodin ohjelmisto moniulotteisten biokuvien visualisointiin, prosessointiin ja analysointiin. BioImageXD kasvoi yhdeksi alansa suurimmista ja monipuolisimmista. Se julkaistiin Nature Methods -lehden biokuvainformatiikkaa käsittelevässä erikoisnumerossa, ja siitä tuli tunnettu ja laajalti käytetty. Väitöskirjan kolmas tavoite oli soveltaa kehitettyjä menetelmiä johonkin käytännönläheisempään. Tehtiin keinotekoisia piidioksidinanopartikkeleita, joissa oli "osoitelappuina" α2β1-integriinin tunnistavia vasta-aineita. BioImageXD:n avulla osoitettiin, että nanopartikkeleilla on potentiaalia lääkkeiden täsmäohjaussovelluksissa. Tämän väitöskirjatyön yksi perimmäinen tavoite oli edistää uutta ja tuntematonta biokuvainformatiikan tieteenalaa, ja tämä tavoite saavutettiin erityisesti BioImageXD:n ja sen lukuisten julkaistujen sovellusten kautta. Väitöskirjatyöllä on merkittävää potentiaalia tulevaisuudessa, mutta biokuvainformatiikalla on vakavia haasteita. Ala on liian monimutkainen keskimääräisen biolääketieteen tutkijan hallittavaksi, ja alan keskeisin elementti, avoimen lähdekoodin ohjelmistokehitystyö, on aliarvostettu. Näihin seikkoihin tarvitaan useita parannuksia,