Muscarinic toxins : characterization of adrenoceptor binding and applicability of membrane anchoring via glycosylphosphatidylinositol tail

Adrenoceptors (ARs), G-protein coupled receptors (GPCRs) at the plasma membrane, respond to endogenous catecholamines noradrenaline and adrenaline. These receptors mediate several important physiological functions being especially important in the cardiovascular system and in the regulation of smooth muscle contraction. Impairments in the function of these receptors can thus lead to severe diseases and disorders such as to cardiovascular diseases and benign prostatic hyperplasia. The Eastern green mamba (Dendroaspis angusticeps) venom has been shown to contain toxins that can antagonize the functions of GPCRs. The most well-known are muscarinic toxins (MTs) targeting muscarinic acetylcholine receptors (mAChRs) with high affinity and selectivity. However, some reports have indicated that these toxins might also act on the α1- and α2-ARs which can be divided into various subtypes; the α1-ARs to α1A-, α1B- and α1D-ARs and α2-ARs to α2A-, α2B- and α2C-ARs. In this thesis, the interaction of four common MTs (MT1, MT3, MT7 and MTα) with the adrenoceptors was characterized. It was also evaluated whether these toxins could be anchored to the plasma membrane via glycosylphosphatidylinositol (GPI) tail. Results of this thesis reveal that muscarinic toxins are targeting several α-adrenoceptor subtypes in addition to their previously identified target receptors, mAChRs. MTα was found to interact with high affinity and selectivity with the α2B-AR whereas MT7 confirmed its selectivity for the M1 mAChR. Unlike MTα and MT7, MT1 and MT3 have a broad range of target receptors among the α-ARs. All the MTs characterized were found to behave as non-competitive antagonists of receptor action. The interaction between MTα and the α2B-AR was studied more closely and it was observed that the second extracellular loop of the receptor functions as a structural entity enabling toxin binding. The binding of MTα to the α2B-AR appears to be rather complex and probably involves dimerized receptor. Anchoring MTs to the plasma membrane did not interfere with their pharmacological profile; all the GPI-anchored toxins created retained their ability to block their target receptors. This thesis shows that muscarinic toxins are able to target several subtypes of α-ARs and mAChRs. These toxins offer thus a possibility to create new subtype specific ligands for the α-AR subtypes. Membrane anchored MTs on the other hand could be used to block α-AR and mAChR actions in disease conditions such as in hypertension and in gastrointestinal and urinary bladder disorders in a cell-specific manner and to study the physiological functions of ARs and mAChRs in vivo in model organisms.

Older Consumers’ Adoption of Online Shopping

The thesis is concerned with the online shopping behavior of older adults, who in this study are at least 60 years old. At the moment, the population is ageing and consumers are buying more and more via the Internet. The objective of the thesis is to understand the large group of older adults in Finland as online customers.The study explores older consumers’ adoption of online shopping with a qualitative research, and it is situated in the research tradition of hermeneutic phenomenology. Phenomenology focuses on the life-world of people. The empirical data was collected by three focus groups with 13 participants altogether. The focus group conversations brought forth that there is not tremendous difference in the motives of older consumers to shop online compared to other age groups. The study strengthened the previous conception of a change toward more ageless market. However, online stores should be designed to accommodate some special needs of older consumers as they occasionally struggle with the logic of websites. Finnish older consumers have adopted online shopping because of perceived convenience and because of tolerable perceived risk during first online shopping experience. Positive experiences strengthen positive attitude toward electronic channel.

Selectivity of glyphosate in tank mixtures for RR soybean in sequential applications with mixtures only in the first or second application

Tank mixtures among herbicides of different action mechanisms might increase weed control spectrum and may be an important strategy for preventing the development of resistance in RR soybean. However, little is known about the effects of these herbicide combinations on soybean plants. Hence, two experiments were carried out aiming at evaluating the selectivity of glyphosate mixtures with other active ingredients applied in postemergence to RR soybean. The first application was carried out at V1 to V2 soybean stage and the second at V3 to V4 (15 days after the first one). For experiment I, treatments (rates in g ha-1) evaluated were composed by two sequential applications: the first one with glyphosate (720) in tank mixtures with cloransulam (30.24), fomesafen (125), lactofen (72), chlorimuron (12.5), flumiclorac (30), bentazon (480) and imazethapyr (80); the second application consisted of isolated glyphosate (480). In experiment II, treatments also consisted of two sequential applications, but tank mixtures as described above were applied as the second application. The first one in this experiment consisted of isolated glyphosate (720). For both experiments, sequential applications of glyphosate alone at 720/480, 960/480, 1200/480 and 960/720 (Expt. I) or 720/480, 720/720, 720/960 and 720/1200 (Expt. II) were used as control treatments. Applications of glyphosate tank mixtures with other herbicides are more selective to RR soybean when applied at younger stages whereas applications at later stages might cause yield losses, especially when glyphosate is mixed with lactofen and bentazon.

Selectivity of glyphosate tank mixtures for RR soybean

An active ingredients mixture of different action mechanisms is an essential tool to prevent or manage areas with resistant weeds. However, it is important that such a mixture provides adequate selectivity to the crop. The aim of this work was to evaluate glyphosate selectivity to glyphosate-resistant (RR) soybean, and also verify if there is selectivity in mixtures with other active ingredients applied postemergence aimed at new control strategies, which might be used in RR soybean cultivation. The herbicides and respective rates (g ha-1) evaluated were: glyphosate (720, 960, 1,200, and 1,440), and the mixtures of glyphosate (960) with cloransulam-methyl (30.24), fomesafen (125), lactofen (72), chlorimuron-ethyl (12.5), flumiclorac-pentyl (30), bentazon (480), or imazethapyr (80). All treatments were applied in postemergence when the soybean crop was at V2 to V3 stage. Treatments with glyphosate or in mixtures with postemergent herbicides showed visual effects of phytotoxicity when applied to the glyphosate-resistant soybean. Effects such as reduction in plant height, crop closure, number of pods per plant, and hundred grain weight could be observed. However, the effects related to plant development were mostly transient and did not persist during the crop cycle. Among the studied treatments, only the mixture of glyphosate and lactofen was not selective to the crop, promoting negative effects on most characteristics analyzed and consequently reducing grain yield.

Helluntailaiset luokkakuvassa. uskontokulttuuri ja yksikön luokka-asema Turun Helluntaiseurakunnassa

Tässä tutkimuksessa analysoin sitä, miten helluntailainen uskontokulttuuri vaikuttaa yksilön valintoihin ja sen kautta siihen, mihin luokka-asemiin seurakuntalaiset ovat päätyneet Turun Helluntaiseurakunnassa. Tutkimus on uskontoantropologinen ja kuuluu uskontotieteen alaan. Siinä yhdistetään sosiologista luokkatutkimusta sekä rationaalisen valinnan ja toiminnan teorioita uskontoantropologisessa viitekehyksessä. Pääasialliseksi aineistoksi keräsin laajan etnografisen aineiston, joka koostuu systemaattisesta havainnoinnista, kyselyistä ja haastatteluista. Lisäksi olen tutkinut seurakunnan ja helluntailaisuutta koskevia arkistoja sekä kirjallisuutta. Tutkimuksen kohde on Turun helluntaiseurakunta, joka muodostaa tutkimusongelman kannalta mielekkään tutkimusasetelman. Tutkimus kertoo olennaista tietoa siitä, miten uskonto vaikuttaa yksilön valintoihin ja hänen yhteiskunnalliseen asemaansa. Tutkimusaineiston pohjalta laadin selittävän mallin kuvaamaan sitä prosessia, miten yksilöt tekevät valintojaan rationaalisina toimijoina eri kulttuurien vaikutuspiireissä. Antropologisena pohjana selitykselle toimii uskonnon rajojen rakentumisen, muuttamisen ja ylittämisen logiikka. Pyhän kategorisoinnin jäsentämä uskontokulttuuri ohjaa yksilöä suosimaan toisia kulttuureja, luokkakulttuureja ja tyylejä sekä vierastamaan toisia. Jos yksilö haluaa tehdä valinnan, joka nähdään arveluttavana, täytyy hänen oikeuttaa se kulttuurinsa sisäisillä symboleilla ja rituaaleilla. Turun Helluntaiseurakunnassa korostuvat auttamisen ja sivistämisen ammatit, kuten lääkäri, sairaanhoitaja ja opettaja. Nämä voidaan edelleen jäljittää seurakunnan opetuksiin sekä seurakuntalaisten käyttämiin diskursseihin ja oletuksiin hyväksytyistä elämäntyyleistä. Lisäksi diskursseissa korostuvat näkemykset ammatista kutsumuksena, koulutuksen itsestäänselvyys sekä asemaan liittyvän radikalismin välttäminen. Seurakunnan uskontokulttuurin keskiluokkaistava vaikutus näkyy ennen kaikkea toisen ja useamman polven helluntailaisissa, jotka sijoittuvat korkeampiin asemiin kuin ulkopuolelta kääntyneet. Seurakunnan uskontokulttuuri vähentää luokkatietoisuuden syntyä ja voi osaltaan ylläpitää yhteiskunnan luokkarakennetta, koska uskonnon ensisijaiset päämäärät eivät kohdistu yhteiskunnan rakenteen muuttamiseen Suomessa. Tutkimuksen mukaan yksilön omat ja häneen kohdistetut oletukset ja arvot, jotka hän kulttuurissa omaksuu, ohjaavat häntä myös kulttuurinsa näkökulmasta suosiollisiin asemiin.

Photochemistry and photobiology of actinic erythema: defensive and reparative cutaneous mechanisms

Sunlight is part of our everyday life and most people accept it as beneficial to our health. With the advance of our knowledge in cutaneous photochemistry, photobiology and photomedicine over the past four decades, the terrestrial solar radiation has become a concern of dermatologists and is considered to be a major damaging environmental factor for our skin. Most photobiological effects (e.g., sunburn, suntanning, local and systemic immunosuppression, photoaging or dermatoheliosis, skin cancer and precancer, etc.) are attributed to ultraviolet radiation (UVR) and more particularly to UVB radiation (290-320 nm). UVA radiation (320-400 nm) also plays an important role in the induction of erythema by the photosensitized generation of reactive oxygen species (singlet oxygen (1O2), superoxide (O2.-) and hydroxyl radicals (.OH)) that damage DNA and cellular membranes, and promote carcinogenesis and the changes associated with photoaging. Therefore, research efforts have been directed at a better photochemical and photobiological understanding of the so-called sunburn reaction, actinic or solar erythema. To survive the insults of actinic damage, the skin appears to have different intrinsic defensive mechanisms, among which antioxidants (enzymatic and non-enzymatic systems) play a pivotal role. In this paper, we will review the basic aspects of the action of UVR on the skin: a) photochemical reactions resulting from photon absorption by endogenous chromophores; b) the lipid peroxidation phenomenon, and c) intrinsic defensive cutaneous mechanisms (antioxidant systems). The last section will cover the inflammatory response including mediator release after cutaneous UVR exposure and adhesion molecule expression

The insulin receptor substrate 1 associates with phosphotyrosine phosphatase SHPTP2 in liver and muscle of rats

Insulin stimulates the tyrosine kinase activity of its receptor resulting in the phosphorylation of its cytosolic substrate, insulin receptor substrate-1 (IRS-1) which, in turn, associates with proteins containing SH2 domains. It has been shown that IRS-1 associates with the tyrosine phosphatase SHPTP2 in cell cultures. While the effect of the IRS-1/SHPTP2 association on insulin signal transduction is not completely known, this association may dephosphorylate IRS-1 and may play a critical role in the mitogenic actions of insulin. However, there is no physiological demonstration of this pathway of insulin action in animal tissues. In the present study we investigated the ability of insulin to induce association between IRS-1 and SHPTP2 in liver and muscle of intact rats, by co-immunoprecipitation with anti-IRS-1 antibody and anti-SHPTP2 antibody. In both tissues there was an increase in IRS-1 association with SHPTP2 after insulin stimulation. This association occurred when IRS-1 had the highest level of tyrosine phosphorylation and the decrease in this association was more rapid than the decrease in IRS-1 phosphorylation levels. The data provide evidence against the participation of SHPTP2 in IRS-1 dephosphorylation in rat tissues, and suggest that the insulin signal transduction pathway in rat tissues is related mainly to the mitogenic effects of the hormone.

Designing sustainable industrial ecosystems : the case of a biogas-for-traffic solution

This thesis focuses on the development of sustainable industrial architectures for bioenergy based on the metaphors of industrial symbiosis and industrial ecosystems, which imply exchange of material and energy side-flows of various industries in order to improve sustainability of those industries on a system level. The studies on industrial symbiosis have been criticised for staying at the level of incremental changes by striving for cycling waste and by-flows of the industries ‘as is’ and leaving the underlying industry structures intact. Moreover, there has been articulated the need for interdisciplinary research on industrial ecosystems as well as the need to extend the management and business perspectives on industrial ecology. This thesis addresses this call by applying a business ecosystem and business model perspective on industrial symbiosis in order to produce knowledge on how industrial ecosystems can be developed that are sustainable environmentally and economically. A case of biogas business is explored and described in four research papers and an extended summary that form this thesis. Since the aim of the research was to produce a normative model for developing sustainable industrial ecosystems, the methodology applied in this research can be characterised as constructive and collaborative. A constructive research mode was required in order to expand the historical knowledge on industrial symbiosis development and business ecosystem development into the knowledge of what should be done, which is crucial for sustainability and the social change it requires. A collaborative research mode was employed through participating in a series of projects devoted to the development of a biogas-for-traffic industrial ecosystem. The results of the study showed that the development of material flow interconnections within industrial symbiosis is inseparable from larger business ecosystem restructuring. This included a shift in the logic of the biogas and traffic fuel industry and a subsequent development of a business ecosystem that would entail the principles of industrial symbiosis and localised energy production and consumption. Since a company perspective has been taken in this thesis, the role of an ecosystem integrator appeared as a crucial means to achieve the required industry restructuring. This, in turn, required the development of a modular and boundary-spanning business model that had a strong focus on establishing collaboration among ecosystem stakeholders and development of multiple local industrial ecosystems as part of business growth. As a result, the designed business model of the ecosystem integrator acquired the necessary flexibility in order to adjust to local conditions, which is crucial for establishing industrial symbiosis. This thesis presents a normative model for the development of a business model required for creating sustainable industrial ecosystems, which contributes to approaches at the policy-makers’ level, proposed earlier. Therefore, this study addresses the call for more research on the business level of industrial ecosystem formation and the implications for the business models of the involved actors. Moreover, the thesis increases the understanding of system innovation and innovation in business ecosystems by explicating how business model innovation can be the trigger for achieving more sustainable industry structures, such as those relying on industrial symbiosis.

Detection of somatic mutations of the PIG-A gene in Brazilian patients with paroxysmal nocturnal hemoglobinuria

Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired clonal syndrome characterized by intravascular hemolysis mediated by complement, thrombotic events and alterations in hematopoiesis. Basically, the molecular events which underlie the complexity of the syndrome consist of the absence of the glycosylphosphatidylinositol (GPI) anchor as a consequence of somatic mutations in the PIG-A gene, located on the X chromosome. The GPI group is responsible for the attachment of many proteins to the cytoplasmic membrane. Two of them, CD55 and CD59, have a major role in the inhibition of the action of complement on the cellular membrane of blood cells. The absence of GPI biosynthesis can lead to PNH. Since mutations in the PIG-A gene are always present in patients with PNH, the aim of this study was to characterize the mutations in the PIG-A gene in Brazilian patients. The analysis of the PIG-A gene was performed using DNA samples derived from bone marrow and peripheral blood. Conformation-sensitive gel electrophoresis was used for screening the mutation and sequencing methods were used to identify the mutations. Molecular analysis permitted the identification of three point mutations in three patients: one G->A transition in the 5' portion of the second intron, one T->A substitution in the second base of codon 430 (Leu430->stop), and one deletion deltaA in the third base of codon 63. This study represents the first description of mutations in the PIG-A gene in a Brazilian population.

Effect of race, genetic population structure, and genetic models in two-locus association studies: clustering of functional renin-angiotensin system gene variants in hypertension association studies

Previous genetic association studies have overlooked the potential for biased results when analyzing different population structures in ethnically diverse populations. The purpose of the present study was to quantify this bias in two-locus association studies conducted on an admixtured urban population. We studied the genetic structure distribution of angiotensin-converting enzyme insertion/deletion (ACE I/D) and angiotensinogen methionine/threonine (M/T) polymorphisms in 382 subjects from three subgroups in a highly admixtured urban population. Group I included 150 white subjects; group II, 142 mulatto subjects, and group III, 90 black subjects. We conducted sample size simulation studies using these data in different genetic models of gene action and interaction and used genetic distance calculation algorithms to help determine the population structure for the studied loci. Our results showed a statistically different population structure distribution of both ACE I/D (P = 0.02, OR = 1.56, 95% CI = 1.05-2.33 for the D allele, white versus black subgroup) and angiotensinogen M/T polymorphism (P = 0.007, OR = 1.71, 95% CI = 1.14-2.58 for the T allele, white versus black subgroup). Different sample sizes are predicted to be determinant of the power to detect a given genotypic association with a particular phenotype when conducting two-locus association studies in admixtured populations. In addition, the postulated genetic model is also a major determinant of the power to detect any association in a given sample size. The present simulation study helped to demonstrate the complex interrelation among ethnicity, power of the association, and the postulated genetic model of action of a particular allele in the context of clustering studies. This information is essential for the correct planning and interpretation of future association studies conducted on this population.

The multicultural moment : the history of the idea and politics of multiculturalism in Sweden in comparative, transnational and biographical context, 1964–1975

The emergence of the idea of multiculturalism in Swedish public discourse and social science in the latter half of the 1960s and introduction of official multiculturalism in 1975 constituted a major intellectual and political shift in the post-war history of Sweden. The ambition of the 1975 immigrant and minority policy to enable the preservation of ethno-cultural minorities and to create a positive attitude towards the new multicultural society among the majority population was also incorporated into Swedish cultural, educational and media policies. The rejection of assimilationism and the new commitment to ethno-cultural diversity, the multicultural moment, has earned Sweden a place on the list of the early adopters of official multiculturalism, together with Canada and Australia. This compilation thesis examines the origins and early post-war history of the idea of multiculturalism as well as the interplay between idea and politics in the shift from a public ideal of homogeneity to an ideal of multiculturalism in Sweden. It does so from a range of conceptual, comparative, transnational, and biographical perspectives. The thesis consists of an introduction (Part I) and four previously published studies (Part II). The primary research result of the thesis concerns the agency involved in the break-through and formal establishment of the idea of multiculturalism in Sweden. Actors such as ethnic activists, experts and officials were instrumental in the introduction and establishment of multiculturalism in Sweden, as they also had been in Canada and in Australia. These actors have, however, not previously been recognized and analysed as significant idea-makers and political agents in the case of Sweden. The intertwined connections between activists, social scientists, linguists, and officials facilitated the transfer of the idea of multiculturalism from a publically contested idea to public policy via the way of The Swedish Trade Union Confederation, academia and the Royal Commission of Immigration. The thesis furthermore shows that the political success of the idea of multiculturalism, such as it was within the limits of the universalist social democratic welfare state, was dependent on whom the claims-makers were, the status and positions they held, and the way the idea of multiculturalism was conceptualised and used. It was also dependent on the migratory context of labour immigration in the 1960s and 1970s and on whose behalf the advocates of multiculturalism made their claims. The majority of the labour immigrants were Finnish citizens from the former eastern half of the kingdom of Sweden who were net contributors to the Swedish welfare state. This facilitated the recognition of their ethno-cultural difference, and, following the logic of universalism, the ethno-cultural difference of other minority groups in Sweden. The historical significance of the multicultural moment is still evident in the contemporary immigration and integration policies of Sweden. The affirmation of diversity continues to set Sweden apart from the rest of Europe, now more so than in the 1970s, even though the migratory context has changed radically in the last 40 years.

Kognitiiviset kartat operatiivisen ketjuliiketoimintajohtamisen taustalla

Tutkimuksen tavoitteena oli selvittää, millaiset ajattelumallit korostuvat menestyksekkäässä ketjuliiketoimintajohtamisessa tasapainotetun tuloskortin eri näkökulmien osalta. Tutkimuskohteena olivat kuusi päivittäistavarakaupan ketjuliiketoiminnan asiakasrajapinnassa työskentelevää Osuuskauppa Keskimaan S-marketpäällikköä. Ajattelua tutkittiin kognitiivisesta näkökulmasta. Tutkimus toteutettiin laadullista tutkimusmenetelmää, kognitiivista kartoitusta hyödyntäen. Karttojen rakentamiseen käytetty tutkimusaineisto hankittiin puolistrukturoitujen teemahaastattelujen avulla. Tutkimuksen teoreettinen viitekehys rakennettiin mielen sisäisten skeemojen ja kognitiivisten karttojen kautta päätöksenteonteorioihin. Tutkimuksen tulosten perusteella asiakasnäkökulmassa menestyminen edellyttää liikeideaa kunnioittavaa ja konseptin tinkimättömään toteuttamiseen keskittyvää johtamisajattelua. Henkilöstönäkökulmassa menestyminen korostaa kokonaisvaltaisen esimiestyön ja moniulotteisten vuorovaikutussuhteiden merkitystä, joiden ilmeneminen on kognitiivisia rakenteita ja prosesseja monimuotoisempi kokonaisuus. Prosessinäkökulmassa menestyminen edellyttää selkeiden ohjeiden vaalimiseen ja niiden johtamiseen keskittyvää ajattelutapaa. Menestys talousnäkökulmassa kokoaa tuloskortin eri näkökulmat yhteen, korostaen kokonaisuuden hahmottamisen tärkeyttä sekä toimialan ja ketjuliiketoiminnan business-logiikan ymmärtämisen merkitystä osana operatiivista ketjuliiketoimintajohtamista. Lisäksi tutkimus vahvistaa aiempien tutkimustulosten mukaisesti, että kognitiivisen kartan rikkaudella, yhtenäisyydellä, johdonmukaisuudella, kartan sisältämien suorituskykymittareihin viittaavien mainintojen määrällä sekä esimiehen kokemalla vaikutusmahdollisuudella on yhteys liiketoimintamenestyksen kanssa. Kokonaisuutena päivittäistavarakaupan ketjuliiketoiminnan menestyksekkäässä johtamisessa näyttää korostuvan rationaalisuutta ja loogisuutta korostava ajattelutapa, joka tukeutuu vahvasti ketjuliiketoiminnan perusprosesseihin.

The 5alpha-reductase type 1, but not type 2, gene is expressed in anagen hairs plucked from the vertex area of the scalp of hirsute women and normal individuals

The aim of the present study was to determine the expression of the genes for type 1 (SDR5A1) and type 2 (SDR5A2) 5alpha-reductase isoenzymes in scalp hairs plucked from 33 hirsute patients (20 with polycystic ovary syndrome and 13 with idiopathic hirsutism) and compare it with that of 10 men and 15 normal women. SDR5A1 and SDR5A2 expression was estimated by RT-PCR using the gene of the ubiquitously expressed protein ß2-microglobulin as an internal control. The results are expressed as arbitrary units in relation to ß2-microglobulin absorbance (mean ± SEM). SDR5A2 expression was not detected in any hair samples analyzed in this study. No differences were found in SDR5A1 mRNA levels between men and normal women (0.78 ± 0.05 vs 0.74 ± 0.06, respectively). SDR5A1 gene expression in the cells of hair plucked from the scalp of normal women (0.85 ± 0.04) and of women with polycystic ovary syndrome (0.78 ± 0.05) and idiopathic hirsutism (0.80 ± 0.06) was also similar. These results indicate that SDR5A1 gene expression in the follicular keratinocytes from the vertex area of the scalp seems not to be related to the differences in hair growth observed between normal men and women and hirsute patients. Further studies are needed to investigate the expression of the 5alpha-reductase genes in other scalp follicular compartments such as dermal papillae, and also in hair follicles from other body sites, in order to elucidate the mechanism of androgen action on the hair growth process and related diseases.

Comparison of the homeostasis model assessment and quantitative insulin sensitivity check index with data from forearm metabolic studies for the in vivo assessment of insulin sensitivity

The present study was designed to compare the homeostasis model assessment (HOMA) and quantitative insulin sensitivity check index (QUICKI) with data from forearm metabolic studies of healthy individuals and of subjects in various pathological states. Fifty-five healthy individuals and 112 patients in various pathological states, including type 2 diabetes mellitus, essential hypertension and others, were studied after an overnight fast and for 3 h after ingestion of 75 g of glucose, by HOMA, QUICKI and the forearm technique to estimate muscle uptake of glucose combined with indirect calorimetry (oxidative and non-oxidative glucose metabolism). The patients showed increased HOMA (1.88 ± 0.14 vs 1.13 ± 0.10 pmol/l x mmol/l) and insulin/glucose (I/G) index (1.058.9 ± 340.9 vs 518.6 ± 70.7 pmol/l x (mg/100 ml forearm)-1), and decreased QUICKI (0.36 ± 0.004 vs 0.39 ± 0.006 (µU/ml + mg/dl)-1) compared with the healthy individuals. Analysis of the data for the group as a whole (patients and healthy individuals) showed that the estimate of insulin resistance by HOMA was correlated with data obtained in the forearm metabolic studies (glucose uptake: r = -0.16, P = 0.04; non-oxidative glucose metabolism: r = -0.20. P = 0.01, and I/G index: r = 0.17, P = 0.03). The comparison of QUICKI with data of the forearm metabolic studies showed significant correlation between QUICKI and non-oxidative glucose metabolism (r = 0.17, P = 0.03) or I/G index (r = -0.37, P < 0.0001). The HOMA and QUICKI are good estimates of insulin sensitivity as data derived from forearm metabolic studies involving direct measurements of insulin action on muscle glucose metabolism.

Identification of characteristics for successful university-company partnership development

The importance of university-company collaboration has increased during the last decades. The drivers for that are, on the one hand, changes in business logic of companies and on the other hand the decreased state funding of universities. Many companies emphasize joint research with universities as an enabling input to their development processes, which aim at creating new innovations, products and wealth. These factors have changed universities’ operations and they have adopted several practices of dynamic business organizations, such as strategic planning, monitoring and controlling methods of internal processes etc. The objective of this thesis is to combine different characteristics of successful university-company partnership and its development. The development process starts with identifying potential partners in the university’s interest group, which requires understanding the role of different partners in the innovation system. Next, in order to find a common development basis, matching the policy and strategy between partners is needed. The third phase is to combine the academic and industrial objectives of a joint project, which is a typical form of university-company collaboration. The optimum is a win-win situation where both partners, universities and companies, can get addedvalue. For the companies added value typically means access to new research results before their competitors. For the universities added value offers a possibility to carry on high level scientific work. The research output in the form of published scientific articles is evaluated by the international science community. Because the university-company partnership is often executed by joint projects, the different forms of this kind of projects is discussed in this study. The most challenging form of collaboration is a semi-open project model, which is not based on bilateral activities between universities and companies but on a consortium of several universities, research institutes and companies. The universities and companies are core actors in the innovation system. Thus the discussion of their roles and relations to public operators like publicly funded financiers is important. In the Finnish innovation system there are at least the following doers executing strategies and policies: EU, Academy of Finland and TEKES. In addition to these, Strategic Centres for Science, Technology and Innovation which are owned jointly by companies, universities and research organizations have a very important role in their fields of business. They transfer research results into commercial actions to generate wealth. The thesis comprises two parts. The first part consists of an overview of the study including introduction, literature review, research design, synthesis of findings and conclusions. The second part introduces four original research publications.