Character transformations and their functional significance as a key to the evolution of hystricognath Rodentia

Hystricognathi represent a monophyletic taxon within Rodentia. Since phylogenetically analyzed morphological systems are essential for revealing evolutionary processes, this study identifies evolutionary character transformations on the stem lineage of Hystricognathi as derived from the author's own work and the literature. Data so far indicate that evolutionary transformations in the rostral head region, the loss of tactile ability in the outer nasal skin and the mobile arrangement of the associated cartilage, were allied with a switch from omnivorous to herbivorous and fiber-rich nutrition. Additional character transformations in the skull assist in digesting such food. Structures associated with reproduction and placentation show a remarkable pro portion of derived character conditions: the chorioallantoic placenta has a ring-shaped organization and growth structure which optimizes the capacity for passive diffusion, a subplacenta occurred as a specialized region responsible for placental invasion and the inverted yolk sac facilitates substance exchange with the main placenta. Finally, precocial newborns evolved as a derived condition within Rodentia. All things considered, a mode of reproduction is indicated, which does not demand excessive additional energy intake by the mother and is in accordance with her low energetic diet. Hystricognathi possess major character transformations that represent prerequisites for their successful radiation at the time when more open ecosystems and grasslands evolved during Earth history. The analysis resulted in the reconstruction of a life-near picture of the hystricognath stem species pattern with high explanatory power in terms of changes in space and time and their interdependence with biodiversity.

The key practices of customer portfolio management (CPM) process in the medical and healthcare B2B industry

The goal of this study is to deepen the understanding of the customer portfolio management process. There are many models for the process, and they are not necessarily exclusive of each other. Consequently, the inclusion of many models might even prove out to be beneficial. Other theoretical framework include the current economical situation and its propose on customer portfolio management. With an understanding of the theoretical models as a background, the empirical part of this study compares Finnish multinational medical and healthcare technology companies’ customer portfolio management practices. The empirical research was carried out with theme interviews held with 11 sales and marketing managers or directors from four different companies. The goal was to discover the most essential practices of the process steps in the companies. The result of this study is that there is a lack of systematic customer portfolio management, but most companies are aiming to improve this in the near future. The most essential practices are analysis of sales, communication level, learning, and commitment to strategy of the focal company. Special characteristics of this industry include large business networks that include customers, professional end-users, institutions, universities, researchers, and key opinion leaders. The management and analysis of this comprehensive network has been seen to be extremely important for this industry.

The Influence of Network Competence on Internationalization of SMEs

This study focuses on the relationship between organizational network competence and the internationalization process of small- and medium sized enterprises (SMEs). Over recent decades, the global business environment has become increasingly conducive to internationalization of small firms. A central facilitating factor in the process has been the emergence of networked business relationships between internationalizing firms. Research on SME internationalization has found that certain types of structures and dynamics of business networks allow SMEs access to the resources they need to enter foreign markets. This consequently means that their internationalization often becomes to depend on the networks they are embedded in. However, research so far has mostly ignored the possibility that the organizational ability to develop and manage business network relationships, network competence, may be a major underlying factor in determining how well SMEs can leverage their network relationships to enter foreign markets and consequently may determine in large part how successful their internationalization process turns out to be. This study aims to respond to those gaps, by empirically examining how the development of network competence in internationalizing SMEs influences the internationalization outcomes that they can expect, and how such network competence is conceptualized and developed. Using a mixed methods approach, survey data collected from 298 Finnish SMEs across five industry sectors is first used to examine how levels of network competence are related to internationalization propensity of SMEs and their subsequent international performance, growth and profitability as internationally operating firms. In order to illustrate in more detail the ways in which network competence is conceptualized and how it develops during the internationalization process of an SME, qualitative data from internationally operating Finnish SMEs are used. Longitudinal interview data of an internationalizing Finnish SME is accompanied by data gathered through a series of semistructured interviews of Finnish and Russian managers involved in mutual business relationship dyads. Structurally, this thesis examines the research issue as an article-based dissertation, consisting of five journal and conference publications. Three of these publications are based on the quantitative data, and the remaining two apply the qualitative interview data. The results find several aspects where network competence has a positive influence on the success of internationalizing SMEs, how it develops and what it entails conceptually in this context. Quantitatively, the level of network competence is found to have a positive relationship to various internationalization outcomes, including the propensity of SMEs to enter foreign markets and on their subsequent international performance, their growth and their profitability. Additionally, the positive relationship is divided between the relationship-specific and cross-relational dimension of network competence, in that the influence of the former is relevant for the propensity to internationalize, while the latter is for the growth and profitability of the already internationalized SMEs. Qualitatively, the results suggest, firstly, that the development process of network competence does not necessarily precede the start of the internationalization process, but may occur through a gradual learning process alongside it. And secondly, the results also imply that the conceptualization of network competence by Finnish managers of internationally operating Finnish SMEs is structurally distinct from that of their culturally distinct partner managers in Russia. This study contributes to the literature on SME internationalization in several ways. Firstly, it introduces operationalized organizational competencies to the literature on internationalization of SMEs, which has so far mainly examined the influence of business networking on the internationalization process without having such an organizational viewpoint. Furthermore, this study provides a multi-level analysis of the determinants of successful SME internationalization, by examining various strategic and performance outcomes across the process. These results also contribute to the literature on organizational strategy of internationalizing SMEs, by clarifying how different dimensions of business networking may be optimal in different phases of the internationalization process. Conceptually, the results of this study contribute to the literature on competence development and SME internationalization, by illustrating how the development process of network competence may occur during internationalization process. Thus, they also contribute to the discussion on how SMEs are able to influence the dynamics and structures of their business networks over time. Finally, this study contributes to the literature on the role of culture in the internationalization process, by implying that the cultural background of the manager of the SME may determine whether business networking and network competence is seen as an organizational-level or an individual level capability. The study also includes some additional contributions to the literature on dynamic capabilities in strategic management, and on that of strategic business networks. These include further clarifying the exact nature and tangibility of dynamic capabilities, and being one of the first studies to introduce constructs from both dynamic capabilities and business network literature to the field of international entrepreneurship. And finally, the study also has some contribution on the two streams of literature, in illustrating how both dyadic and network-level capabilities may be relevant, depending on the current strategic goals and market position of the firm. Keywords: network competence, internationalizatio

Osaamisen johtaminen ja kehittäminen asiantuntijaorganisaatiossa - case Itä-Suomen yliopiston opinto- ja opetuspalvelut

Tutkielman tavoitteena on luoda kokonaisvaltainen kuvaus osaamisen johtamisesta ja kehittämisestä tutkielman kohdeorganisaatiossa. Lisäksi halutaan selvittää, millaista osaamista kohdeorganisaatiosta löytyy ja mikä motivoi asiantuntijoita oman osaamisen kehittämiseen. Teoreettinen tarkastelu pohjautuu kolmeen keskeiseen käsitteeseen: osaamiseen, osaamisen johtamiseen ja osaamisen kehittämiseen. Kirjallisuuskatsauksessa pyritään myös selkeyttämään näiden käsitteiden määritelmien kirjavaa kenttää. Tutkimus toteutettiin kvalitatiivisena tapaustutkimuksena. Empiirinen aineisto kerättiin sähköisten kyselylomakkeiden avulla. Tutkielman kohdeorganisaatio on kokenut muutama vuosi sitten suuren organisaatiorakenteen muutoksen, mikä on tuonut omat haasteensa osaamisen johtamiseen ja toisaalta korostanut sen tärkeyttä. Tutkimuksen tulokset osoittavat, että kohdeorganisaatiossa on vahvaa monialaista osaamista ja oman osaamisen kehittämiseen motivoituneita työntekijöitä. Kuitenkin useimmilla osaamisen kehittäminen jää päivittäisten työtehtävien varjoon, joten kouluttautumiselle ja työssä oppimiselle toivottiin lisää mahdollisuuksia.

Key factors in transforming university internationalization into commercial activity in Finland. Case of University of Turku

Globalization, developments in ICT, emergence of knowledge society and other changes have reformed the environment for international higher education during the past few decades. Consequently, higher education sector has moved towards more marketing-oriented system, and universities have started to undertake commercial activities as part of their internationalization. This development has emerged to Finland as well, which forms the basis for this study. The purpose is to examine commercialization in Finnish university landscape and to investigate the ways Finnish university could capitalize its international activities and educational knowledge for export. The research question of the study is: What are the key factors in transforming university internationalization into commercial activity in the Finnish university landscape? The main problem is further divided into three sub-questions: 1) How can a university internationalize; 2) what are the motivational factors behind university internationalization and commercialization; and 3) how can higher education be developed into export services and products? The research was conducted as a qualitative case study of University of Turku. Methods used for gathering and examining data were interviewing and document analysis. Primary data was collected through four individual semi-structured interviews, which were conducted face-to-face. Secondary data that included reports, articles and electronic materials such as university web pages, was used to complement the primary data. The results were analyzed by theming the data into three broader categories of internationalization activities; drivers and motivations and; education export activities. After the data was organized in themes, analysis continued by comparing different parts of data and finding patterns that would explain the phenomenon in Finnish universities. According to the empirical data, University of Turku is currently on the growth state of internationalization with strategies such as internationalization of curriculum, establishment of international research groups, mobility of students and academics, international networking and support services. Commercialization phenomenon is still rather new to the case university, but it has already developed educational products and services for export. The study concludes that university internationalization cannot be directly transformed into commercial activities in the Finnish context, but the universities need to be active in actually creating educational products. The key factors found in this study include: 1) the Finnish government policies behind the current hype of export education; 2) the potential and knowledge capacity of universities for exports; 3) need for additional profits; 4) further internationalization through commercial activities; 5) recognizing and exploiting the specific areas of strength and 6) establishing of cooperative partnerships for better products.

Mythology as a key to historical ways of thinking

Kirjallisuusarvostelu

Interoperability specifications and an automatic validation tool as a key factor for the support of a repository ecosystem

Presentation at Open Repositories 2014, Helsinki, Finland, June 9-13, 2014

Alpha- and gamma-melanocyte stimulating hormones in obesity. A study of the key central areas of metabolic regulation

The melanocortin system is an important regulator of feeding, energy metabolism,and cardiovascular function and it consists of the pro-opiomelanocortin (POMC) derived melanocyte stimulating hormones (α-, β- and γ-MSH) and their endogenous melanocortin receptors, MC1R to MC5R. In the hypothalamus, α-MSH reduces food intake, and increases energy expenditure and sympathetic tone by binding to MC4R. Mutations affecting the MC4R gene lead to obesity in mammals. On the other hand, the metabolic effects of MC3R stimulation using agonists such as the endogenously expressed γ-MSH have been less extensively explored. The main objective of this study was to investigate the long-term effects of increased melanocortin tone in key areas of metabolic regulation in the central nervous system (CNS) in order to investigate the sitespecific roles of both α-MSH and γ-MSH. The aim was to stereotaxically induce local overexpression of single melanocortin peptides using lentiviral vectors expressing α-MSH (LVi-α-MSH-EGFP) and γ-MSH (LVi-γ-MSH-EGFP). The lentiviral vectors were shown to produce a long-term overexpression and biologically active peptides in cell-based assays. The LVi-α-MSHEGFP was targeted to the arcuate nucleus in the hypothalamus of diet induced obese mice where it reduced weight gain and adiposity independently of food intake. When the nucleus tractus solitarus in the brainstem was targeted, the LVi-α-MSH-EGFP treatment was shown to cause a small decrease in adiposity, which did not impact weight development. However, the α-MSH treatment increased heart rate, which was attenuated by adrenergic receptor blockade indicative of increased sympathetic activity. The LVi-γ-MSH-EGFP was targeted to the hypothalamus where it decreased fat mass in mice eating the standard diet, but the effect was abated if animals consumed a high-fat Western type diet. When the diet induced obese mice were subjected again to the standard diet, the LVi-γ-MSH-EGFP treated animals displayed increased weight loss and reduced adiposity. These results indicate that the long-term central anti-obesity effects of α-MSH are independent of food intake. In addition, overexpression of α-MSH in the brain stem efficiently blocked the development of adiposity, but increased sympathetic tone. The evidence presented in this thesis also indicates that selective MC3R agonists such as γ-MSH could be potential therapeutics in combination with low fat diets.

The interplay of JNK and SCG10 during cortical development and in excitotoxic responses in brain

Initially identified as stress activated protein kinases (SAPKs), the c-Jun Nterminal kinases (JNKs) are currently accepted as potent regulators of various physiologically important cellular events. Named after their competence to phosphorylate transcription factor c-Jun in response to UVtreatment, JNKs play a key role in cell proliferation, cell death or cell migration. Interestingly, these functions are crucial for proper brain formation. The family consists of three JNK isoforms, JNK1, JNK2 and JNK3. Unlike brain specific JNK3 isoform, JNK1 and JNK2 are ubiquitously expressed. It is estimated that ten splice variants exist. However, the detailed cellular functions of these remain undetermined. In addition, physiological conditions keep the activities of JNK2 and JNK3 low in comparison with JNK1, whereas cellular stress raises the activity of these isoforms dramatically. Importantly, JNK1 activity is constitutively high in neurons, yet it does not stimulate cell death. This suggests a valuable role for JNK1 in brain development, but also as an important mediator of cell wellbeing. The aim of this thesis was to characterize the functional relationship between JNK1 and SCG10. We found that SCG10 is a bona fide target for JNK. By employing differential centrifugation we showed that SCG10 co-localized with active JNK, MKK7 and JIP1 in a fraction containing endosomes and Golgi vesicles. Investigation of JNK knockout tissues using phosphospecific antibodies recognizing JNK-specific phosphorylation sites on SCG10 (Ser 62/Ser 73) showed that phosphorylation of endogenous SCG10 was dramatically decreased in Jnk1-/- brains. Moreover, we found that JNK and SCG10 co-express during early embryonic days in brain regions that undergo extensive neuronal migration. Our study revealed that selective inhibition of JNK in the cytoplasm significantly increased both the frequency of exit from the multipolar stage and radial migration rate. However, as a consequence, it led to ill-defined cellular organization. Furthermore, we found that multipolar exit and radial migration in Jnk1 deficient mice can be connected to changes in phosphorylation state of SCG10. Also, the expression of a pseudo-phosphorylated mutant form of SCG10, mimicking the JNK1- phopshorylated form, brings migration rate back to normal in Jnk1 knockout mouse embryos. Furthermore, we investigated the role of SCG10 and JNK in regulation of Golgi apparatus (GA) biogenesis and whether pathological JNK action could be discernible by its deregulation. We found that SCG10 maintains GA integrity as with the absence of SCG10 neurons present more compact fragmented GA structure, as shown by the knockdown approach. Interestingly, neurons isolated from Jnk1-/- mice show similar characteristics. Block of ER to GA is believed to be involved in development of Parkinson's disease. Hence, by using a pharmacological approach (Brefeldin A treatment), we showed that GA recovery is delayed upon removal of the drug in Jnk1-/- neurons to an extent similar to the shRNA SCG10-treated cells. Finally, we investigated the role of the JNK1-SCG10 duo in the maintenance of GA biogenesis following excitotoxic insult. Although the GA underwent fragmentation in response to NMDA treatment, we observed a substantial delay in GA disintegration in neurons lacking either JNK1 or SCG10.

Liiketoimintatiedonhallinnan hyödyntämisen esteet päätettäessä palveluista. Case: Kunnalliset pelastustoimen liikelaitokset ja eriytetyt taseyksiköt

Pelastuslaitosten liiketoimintatiedonhallinnalla, tietoperusteisuudella ja tietojohtamisella on tulevaisuudessa merkittävä rooli päätettäessä palveluista. Julkisen pelastustoimen kuntien liikelaitoksina ja eriytettyinä taseyksiköinä toimivien pelastuslaitosten haasteet tulevat olemaan jatkossa tehokkaiden ja vaikuttavien palveluiden strategisessa johtamisessa ja suunnittelussa. Näistä asioista päättäminen on kriittinen vaihe onnistumisen kannalta. Päätöksenteko eri tasoilla tarvitsee tuekseen toiminnasta ja palveluista kanavoitua analysoitua tietoa. Asiakastarpeesta lähtevä vaikuttavuus ja laatu korostuvat. Liiketoimintatiedonhallinta ja tietoperusteisuus haastavat pelastuslaitoksen johtamisjärjestelmän. Johtamisen kyvykkyys ja henkilöstön osaaminen ovat tietoperusteisuuden ja tiedonhallinnan keskiössä. Systemaattisen liiketoimintatiedonhallinnan ja tietoperusteisuuden erottaa perinteisestä virkamiehen tietojen hyväksikäytöstä käsitteen kokonaisvaltaisuus ja järjestelmällisyys kaikessa tiedollisessa toiminnassa. Tämä kattaa tietojärjestelmät, mittarit, prosessit, strategian suunnitelmat, asiakirjat, raportoinnin, kehittämisen ja tutkimuksen. Liiketoimin-tatiedonhallinta ja tietojohtaminen linkittävät kaiken toisiinsa muodostaen keskinäisriippuvaisen yhtenäisen järjestelmän ja kokonaisvaltaisen ymmärryksen. Tutkimukseni on laadullinen tutkimus jossa tiedon keruu ja analysointi on toteutettu toisiaan tukevilla tutkimusotteilla. Metodologia nojaa teorialähtöiseen systemaattiseen analyysiin, jossa on valikoituja osia sisällön analyysistä. Tutkimuksessa on käytetty aineisto- ja menetelmätriangulaatioita. Tutkimuksen aineisto on kerätty teemahaastatteluilla valittujen kohde pelastuslaitosten asiantuntijoilta palveluiden päätös- ja suunnittelutasolta, johtoryhmistä ja joh-tokunnista. Haastatteluja varten tutkija on tutustunut kohdepelastuslaitosten palveluita mää-rittävään tiedolliseen dokumentaatioon kuten palvelutasopäätöksiin ja riskianalyyseihin. Ai-neisto keruun kohteiksi valikoitui pääkaupunkiseudun alueen pelastuslaitokset: Helsingin kaupungin pelastuslaitos sekä Itä-, Keski- ja Länsi-Uudenmaan pelastuslaitokset. Tulosten mukaan pelastuslaitosten keskeiset liiketoimintatiedonhallinnan esteet muodostuvat johtamisen ongelmista, organisaation muutosvastarinnasta ja päätöksenteon tietoperusteen puutteesta. Nämä ilmenevät strategisen johtamisen puutteina, vaikuttavuuden mittaamisen sekä tiedon jalostamisen ongelmina. Keskeistä tiedollista yhdistävää ja linkittävää tekijää ei tunnisteta ja löydetä. Tiedollisessa liiketoimintatiedonhallinnan prosessityössä voisi olla tulos-ten mukaan mahdollisuuksia tämän tyhjiön täyttämiseen. Pelastuslaitoksille jää tulevaisuudessa valinta suunnasta johon ne haluavat edetä tiedonhal-linnan, tietojohtamisen ja tietoperusteisuuden kanssa. Tämä vaikuttaa kehitykseen ja tavoitteeseen keskeisistä palveluiden päätöksentekoa tukevista johtamis- ja tietojärjestelmistä, tietoa kokoavista ja luovista dokumenteista sekä organisaation joustavasta rakenteesta. Tietoprosessiin, tiedon prosessimaiseen johtamiseen ja systemaattiseen tiedonhallintaan meneminen vaikuttaa tutkimuksen tulosten mukaan lupaavalta mahdollisuudelta. Samalla se haastaa pelauslaitokset suureen kulttuuriseen muutokseen ja asettaa uusien vaikuttavuusmittareiden tuottaman tiedon ennakoivan hyväksynnän vaateen strategiselle suunnittelulle. Tämä vaatii pelastuslaitosten johdolta ja henkilöstöltä osaamista, yhteisymmärrystä, muutostarpeiden hyväksyntää sekä asiakkaan asettamista vaikuttavuuden keskiöön.

Control of the phosphorylation of the astrocyte marker glial fibrillary acidic protein (GFAP) in the immature rat hippocampus by glutamate and calcium ions: possible key factor in astrocytic plasticity

The present review describes recent research on the regulation by glutamate and Ca2+ of the phosphorylation state of the intermediate filament protein of the astrocytic cytoskeleton, glial fibrillary acidic protein (GFAP), in immature hippocampal slices. The results of this research are discussed against a background of modern knowledge of the functional importance of astrocytes in the brain and of the structure and dynamic properties of intermediate filament proteins. Astrocytes are now recognized as partners with neurons in many aspects of brain function with important roles in neural plasticity. Site-specific phosphorylation of intermediate filament proteins, including GFAP, has been shown to regulate the dynamic equilibrium between the polymerized and depolymerized state of the filaments and to play a fundamental role in mitosis. Glutamate was found to increase the phosphorylation state of GFAP in hippocampal slices from rats in the post-natal age range of 12-16 days in a reaction that was dependent on external Ca2+. The lack of external Ca2+ in the absence of glutamate also increased GFAP phosphorylation to the same extent. These effects of glutamate and Ca2+ were absent in adult hippocampal slices, where the phosphorylation of GFAP was completely Ca2+-dependent. Studies using specific agonists of glutamate receptors showed that the glutamate response was mediated by a G protein-linked group II metabotropic glutamate receptor (mGluR). Since group II mGluRs do not act by liberating Ca2+ from internal stores, it is proposed that activation of the receptor by glutamate inhibits Ca2+ entry into the astrocytes and consequently down-regulates a Ca2+-dependent dephosphorylation cascade regulating the phosphorylation state of GFAP. The functional significance of these results may be related to the narrow developmental window when the glutamate response is present. In the rat brain this window corresponds to the period of massive synaptogenesis during which astrocytes are known to proliferate. Possibly, glutamate liberated from developing synapses during this period may signal an increase in the phosphorylation

Interferon gamma is a key cytokine in lung phase immunity to schistosomes but what is its precise role?

Vaccination of mice with radiation-attenuated cercariae of Schistosoma mansoni induces a high level of protection against challenge with normal larvae. The immune effector mechanism, which operates in the lungs, is a cell-mediated delayed-type hypersensitivity response and involves the formation of a tight focus of mononuclear cells around embolised larvae. CD4+ T cells with Th1 characteristics are a major component of the infiltrate. They secrete abundant interferon gamma (IFNg) upon antigen stimulation in vitro, whilst in vivo neutralisation of the cytokine results in 90% abrogation of immunity. IFNg can induce a large number of genes and an attempt has been made to identify the ones which are essential components of the effector mechanism. Inducible nitric oxide synthase (iNOS) is such a candidate and nitric oxide (NO) is produced by cultures of airway leucocytes from the lungs of vaccinated mice post-challenge. However, the continued resistance of mice with a disrupted iNOS gene indicates that NO has only a minor role in the protective response. Mice with a disrupted IFNg receptor gene have been used to dissect the role of the cytokine. After vaccination and challenge, CD4+ T cells from the pulmonary interstitium have reduced levels of ICAM-1 and LFA-1 expression, compared to wild-type animals, which coincides with a reduced cohesiveness of foci. However, immunity is not significantly impaired in mice with a disrupted ICAM-1 gene, and focus formation is normal. Similarly, a role has not been found for CD2/CD48 interactions in cell aggregation. Possible IFNg-inducible molecules yet to be fully investigated include other ligand-receptor pairs, chemokines, and tumour necrosis factor a.

Galectins: a key intersection between glycobiology and immunology

Galectins are a family of evolutionarily conserved animal lectins, widely distributed from lower invertebrates to mammals. They share sequence and structure similarities in the carbohydrate recognition domain and specificity for polylactosamine-enriched glycoconjugates. In the last few years significant experimental data have been accumulated concerning their participation in different biological processes requiring carbohydrate recognition such as cell adhesion, cell growth regulation, inflammation, immunomodulation, apoptosis and metastasis. In the present review we will discuss some exciting questions and advances in galectin research, highlighting the significance of these proteins in immunological processes and their implications in biomedical research, disease diagnosis and clinical intervention. Designing novel therapeutic strategies based on carbohydrate recognition will provide answers for the treatment of autoimmune disorders, inflammatory processes, allergic reactions and tumor spreading.