Ranking RegionalInnovation Policies: DEA-based Benchmarking in an European Setting

Seudullinen innovaatio on monimutkainen ilmiö, joka usein sijaitsee paikallisten toimijoiden keskinäisen vuorovaikutuksen kentässä. Täten sitä on perinteisesti pidetty vaikeasti mitattavana ilmiönä. Työssä sovellettiin Data Envelopment Analysis menetelmää, joka on osoittautunut aiemmin menestyksekkääksi tapauksissa, joissa mitattavien syötteiden ja tuotteiden väliset suhteet eivät ole olleet ilmeisiä. Työssä luotiin konseptuaalinen malli seudullisen innovaation syötteistä ja tuotteista, jonka perusteella valittiin 12 tilastollisen muuttujan mittaristo. Käyttäen Eurostat:ia datalähteenä, lähdedata kahdeksaan muuttujsta saatiin seudullisella tasolla, sekä mittaristoa täydennettiin yhdellä kansallisella muuttujalla. Arviointi suoritettiin lopulta 45 eurooppalaiselle seudulle. Tutkimuksen painopiste oli arvioida DEA-menetelmän soveltuvuutta innovaatio-järjestelmän mittaamiseen, sillä menetelmää ei ole aiemmin sovellettu vastaavassa tapauksessa. Ensimmäiset tulokset osoittivat ylipäätään liiallisen korkeita tehok-kuuslukuja. Korjaustoimenpiteitä erottelutarkkuuden parantamiseksi esiteltiin ja sovellettiin, jonka jälkeen saatiin realistisempia tuloksia ja ranking-lista arvioitavista seuduista. DEA-menetelmän todettiin olevan tehokas ja kiinnostava työkalu arviointikäytäntöjen ja innovaatiopolitiikan kehittämiseen, sikäli kun datan saatavuusongelmat saadaan ratkaistua sekä itse mallia tarkennettua.

Ranking Regional Innovation Policies: DEA-based Benchmarking in an European Setting

Seudullinen innovaatio on monimutkainen ilmiö, joka usein sijaitsee paikallisten toimijoiden keskinäisen vuorovaikutuksen kentässä. Täten sitä on perinteisesti pidetty vaikeasti mitattavana ilmiönä. Työssä sovellettiin Data Envelopment Analysis menetelmää, joka on osoittautunut aiemmin menestyksekkääksi tapauksissa, joissa mitattavien syötteiden ja tuotteiden väliset suhteet eivät ole olleet ilmeisiä. Työssä luotiin konseptuaalinen malli seudullisen innovaation syötteistä ja tuotteista, jonka perusteella valittiin 12 tilastollisen muuttujan mittaristo. Käyttäen Eurostat:ia datalähteenä, lähdedata kahdeksaan muuttujsta saatiin seudullisella tasolla, sekä mittaristoa täydennettiin yhdellä kansallisella muuttujalla. Arviointi suoritettiin lopulta 45 eurooppalaiselle seudulle. Tutkimuksen painopiste oli arvioida DEA-menetelmän soveltuvuutta innovaatiojärjestelmän mittaamiseen, sillä menetelmää ei ole aiemmin sovellettu vastaavassa tapauksessa. Ensimmäiset tulokset osoittivat ylipäätään liiallisen korkeita tehokkuuslukuja. Korjaustoimenpiteitä erottelutarkkuuden parantamiseksi esiteltiin ja sovellettiin, jonka jälkeen saatiin realistisempia tuloksia ja ranking-lista arvioitavista seuduista. DEA-menetelmän todettiin olevan tehokas ja kiinnostava työkalu arviointikäytäntöjen ja innovaatiopolitiikan kehittämiseen, sikäli kun datan saatavuusongelmat saadaan ratkaistua sekä itse mallia tarkennettua.

Targeted ablation of gonadotropin dependent endocrine tumors in transgenic mice through their luteinizing hormone receptor (LHR)

Gonadal somatic cell and adrenocortical endocrine tumors are rare. The incidence of adrenocortical carcinomas is only 1-2/1000000 a year. However, they are aggressive, especially in adulthood and currently surgery is the only curative treatment. Cytotoxic agents are in use in advanced cancers, but side effects and multidrug resistance are often problems. Thus there is a need for novel curative treatment methods. In contrast, ovarian granulosa cell tumors and testicular Leydig cell tumors are usually benign, especially at a younger age. The aim of the present thesis was to study a novel targeted treatment method through luteinizing hormone/chorionic gonadotropin receptor (LHCGR) in a transgenic mouse tumor model. The cytotoxic agent was lytic peptide Hecate-CGbeta conjugate where 23 amino acid Hecate, a synthetic form of honeybee venom melittin, was conjugated to 15 amino acid fragment of human chorionic gonadotropin β subunit. Lytic peptides are known to act only on negatively charged cells, such as bacteria and cancer cells and hereby, due to hCGbeta fragment, the conjugate is able to bind directly to LHCGR bearing cancer cells, saving the healthy ones. The experiments were carried out in inhibin-alpha-Simian Virus 40-T-antigen transgenic mice that are known to express LHCGR-bearing gonadal tumors, namely Leydig and granulosa cell tumors by 100% penetrance. If the mice are gonadectomized prepubertally they form adrenocortical tumors instead. Transgenic and wild type mice were treated for three consecutive weeks with control vehicle, Hecate or Hecate-CGbeta conjugate. GnRH antagonist or estradiol was given to a group of mice with or without Hecate-CGbeta conjugate to analyze the additive role of gonadotropin blockage in adrenocortical tumor treatment efficacy. Hecate-CGbeta conjugate was able to diminish the gonadal and adrenal tumor size effectively in males. No treatment related side effects were found. Gonadotropin blockage through GnRH antagonist was the best treatment in female adrenal tumors. The mode of cell death by Hecate-CGbeta conjugate was proven to be through necrosis. LHCGR and GATA-4 were co-expressed in tumors, where the treatment down-regulated their expression simultaneously, suggesting their possible use as tumor markers. In conclusion, the present thesis showed that Hecate-CGbeta conjugate targets its action selectively through LHCGR and selectively kills the LHCGR bearing tumor cells. It works both in gonadal somatic and in ectopic LHCGR bearing adrenal tumors. These results establish a more general principle that receptors expressed ectopically in malignant cells can be exploited in targeted cytotoxic therapies without affecting the normal healthy cells.

Leaf-Targeted Ferredoxin-NADP+-Oxidoreductase (FNR): Electron Transfer Properties and Thylakoid Association in Arabidopsis thaliana

Photosynthetic reactions are divided in two parts: light-driven electron transfer reactions and carbon fixation reactions. Electron transfer reactions capture solar energy and split water molecules to form reducing energy (NADPH) and energy-carrying molecules (ATP). These end-products are used for fixation of inorganic carbon dioxide into organic sugar molecules. Ferredoxin-NADP⁺ oxidoreductase (FNR) is an enzyme that acts at the branch point between the electron transfer reactions and reductive metabolism by catalyzing reduction of NADP+ at the last step of the electron transfer chain. In this thesis, two isoforms of FNR from A rabidopsis thaliana, FNR1 and FNR2, were characterized using the reverse genetics approach. The fnr1 and fnr2 mutant plants resembled each other in many respects. Downregulation of photosynthesis protected the single fnr mutant plants from excess formation of reactive oxygen species (ROS), even without significant upregulation of antioxidative mechanisms. Adverse growth conditions, however, resulted in phenotypic differences between fnr1 and fnr2. While fnr2 plants showed downregulation of photosynthetic complexes and upregulation of antioxidative mechanisms under low-temperature growth conditions, fnr1 plants had the wild-type phenotype, indicating that FNR2 may have a specific role in redistribution of electrons under unfavorable conditions. The heterozygotic double mutant (fnr1xfnr2) was severely devoid of chloroplastic FNR, which clearly restricted photosynthesis. The fnr1xfnr2 plants used several photoprotective mechanisms to avoid oxidative stress. In wild-type chloroplasts, both FNR isoforms were found from the stroma, the thylakoid membrane, and the inner envelope membrane. In the absence of the FNR1 isoform, FNR2 was found only in the stroma, suggesting that FNR1 and FNR2 form a dimer, by which FNR1 anchors FNR2 to the thylakoid membrane. Structural modeling predicted formation of an FNR dimer in complex with ferredoxin. In this thesis work, Tic62 was found to be the main protein that binds FNR to the thylakoid membrane, where Tic62 and FNR formed high molecular weight complexes. The formation of such complexes was shown to be regulated by the redox state of the chloroplast. The accumulation of Tic62-FNR complexes in darkness and dissociation of complexes from the membranes in light provide evidence that the complexes may have roles unrelated to photosynthesis. This and the high viability of fnr1 mutant plants lacking thylakoid-bound FNR indicate that the stromal pool of FNR is photosynthetically active.

Targeted Therapy Possibilities for Metastatic Melanoma

The incidence of malignant melanoma of the skin has been steadily rising worldwide during the past decades. Most early detected primary tumors can be removed surgically and the prognosis is good. However, at the same time there still is no permanent cure for metastatic melanoma and its prognosis is poor, although lately new effective drugs have emerged. In this thesis, four different approaches of experimental therapy for metastatic melanoma were studied. Endogenous cis-Urocanic acid (UCA) is found in every individual’s skin, where exposure to UV light from the sun generates it from its inactive trans conformation. Cis- UCA was found to destroy malignant melanoma cells in culture under an acidified pH and sufficient concentration through caspase-3 mediated apoptosis. Furthermore, cis-UCA is able to considerably diminish the growth rate in human melanoma tumors on living SCID mice. Using replication-competent Semliki Forest viruses, human melanoma tumors grown in SCID mice were dramatically shrunken as the fulminant production of viruses in melanoma cells leads them to apoptosis within 72 hours. Small oligopeptides attaching to melanoma cells were identified using in vivo phage display. The melanoma-specific peptides found were further tested in vitro on adenoviruses. Ultimately, the adenoviral retargeting using the peptides was tested in vivo. One peptide homed to human transferring receptor upregulated on melanoma cells. In order to kill the malignant melanoma cells with the retargeted adenoviruses, the viruses should carry genetic material producing apoptotic proteins in the cancer tissue. TIMP-3 has been identified as a good candidate for such a protein, as it inhibits malignant cell adhesion as well as promotes apoptosis through a caspase-8 pathway. It is further shown here that adenovirally delivered TIMP-3 is even more potent, as it could kill non-adherent cancer cells, lacking the fully functional death receptor signalling pathway. Adenovirally delivered TIMP-2 also showed marked antitumor effects in human malignant melanoma xenografts on SCID mice both in ex vivo and systemic delivery.

Lethal weapons : novel approaches for receptor-targeted cancer cell elimination

The currently used forms of cancer therapy are associated with drug resistance and toxicity to healthy tissues. Thus, more efficient methods are needed for cancer-specific induction of growth arrest and programmed cell death, also known as apoptosis. Therapeutic forms of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) are investigated in clinical trials due to the capability of TRAIL to trigger apoptosis specifically in cancer cells by activation of cell surface death receptors. Many tumors, however, have acquired resistance to TRAIL-induced apoptosis and sensitizing drugs for combinatorial treatments are, therefore, in high demand. This study demonstrates that lignans, natural polyphenols enriched in seeds and cereal, have a remarkable sensitizing effect on TRAIL-induced cell death at non-toxic lignan concentrations. In TRAIL-resistant and androgen-dependent prostate cancer cells we observe that lignans repress receptor tyrosine kinase (RTK) activity and downregulate cell survival signaling via the Akt pathway, which leads to increased TRAIL sensitivity. A structure-activity relationship analysis reveals that the γ-butyrolactone ring of the dibenzylbutyrolactone lignans is essential for the rapidly reversible TRAIL-sensitizing activity of these compounds. Furthermore, the lignan nortrachelogenin (NTG) is identified as the most efficient of the 27 tested lignans and norlignans in sensitization of androgen-deprived prostate cancer cells to TRAIL-induced apoptosis. While this combinatorial anticancer approach may leave normal cells unharmed, several efficient cancer drugs are too toxic, insoluble or unstable to be used in systemic therapy. To enable use of such drugs and to protect normal cells from cytotoxic effects, cancer-targeted drug delivery vehicles of nanometer scale have recently been generated. The newly developed nanoparticle system that we tested in vitro for cancer cell targeting combines the efficient drug-loading capacity of mesoporous silica to the versatile particle surface functionalization of hyperbranched poly(ethylene imine), PEI. The mesoporous hybrid silica nanoparticles (MSNs) were functionalized with folic acid to promote targeted internalization by folate receptor overexpressing cancer cells. The presented results demonstrate that the developed carrier system can be employed in vitro for cancer selective delivery of adsorbed or covalently conjugated molecules and furthermore, for selective induction of apoptotic cell death in folate receptor expressing cancer cells. The tested carrier system displays potential for simultaneous delivery of several anticancer agents specifically to cancer cells also in vivo.

Finnish Institutional Innovation Support Policies from Russian Entrepreneurs' Perspective: Establishing Cross-Border Technology Oriented Start-Up Firm

The purpose of this thesis is to study how Russian entrepreneurs perceive Finnish institutional environment and innovation support policies provided in the country, as well as to present a practical example in form of a case study of one technology oriented start-up firm which was established in Finland by Russian entrepreneurs. The empirical research of the thesis is conducted qualitatively in two parts. First part is conducted through online questionnaire with open questions in order to review the perceptions of Russian entrepreneurs in general. Second part is based on personal interviews with case company’s founders with the focus on the process of establishing the company in Finland. In the first part of the empirical research, five Russian start-up firms were contacted, and four responses were received. All of these responses were qualified for further analysis. The findings of the first part of the research reveal that Russian entrepreneurs have rather positive attitudes towards Finnish institutional innovation support policies. However, most of the entrepreneurs stated that they are unlikely to create their presence in Finland. As an outcome of the second part of the research, the process of establishing a case company in Finland is illustrated. In order to be able to establish companies in Finland, Russian entrepreneurs who have a permanent residence outside European Economic Area (EEA) are required to apply for a permission to perform business operations in the country. In addition, the established company must engage in improving the economical stand of the country by creating new work places, raising tax revenues, develop technologies and generate innovations in the country.

Cultural Diversity, Social Cohesion, Religion: Core Values and Educational Policies in Four European Nations

In my doctoral thesis I evaluate strategies designed to cope with the multicultural nature of four European nations: Great Britain, The Netherlands, Sweden, and Denmark. I also analyse and clarify the question of the place of religion in present-day Europe. The empirical material analysed in the study consists of politicians’ statements and policy documents dealing with immigration policy and religious and values education in the four countries. In addition, I analyse statements issued by the Council of Europe regarding religious education, along with all cases relevant to religious education brought before the United Nations Human Rights Committee or the European Court of Human Rights. The theoretical framework is formed by the scholarly debate – among philosophers, sociologists and scholars of religion in education – concerning the question of a just society. Special emphasis is given to philosophical theories that are in favour of granting special group rights to religious minorities in the name of equal treatment. With regard to the question of the appropriate place of religion, I apply Kim Knott’s methodological model for locating religion in secular contexts, and Émile Durkheim’s theory as to the significance of religion and collective sentiments in uniting adherents or members of a group into a single moral community. The study shows that even when the positive side of immigration, as a potential force for the enrichment of the public culture, is acknowledged, there is anxiety as to the successful integration of immigrants. The premises and goals of immigration policies have also been questioned. One central problem is the incommensurability between the values upheld by Western liberal democracies and certain religious traditions, above all those of Islam. Great Britain, The Netherlands, Sweden, and Denmark have tightened control over their citizens’ ethical attitudes and want to regulate these as well. In coping with cultural diversity, the significance of education, especially religious education, plays a significant role; as future citizens, pupils are expected to internalise the society’s core values as well as gaining an understanding of different cultures and ways of life. It is also worth noting that both the Council of Europe and the European Court of Human Rights have recently expressed the view that one important goal of religious education is to enable pupils to be critical and autonomous with regard to different religions and moral positions. The study shows that religion is not seen as purely a personal matter. Religion is closely linked to individual and national identity, and religious traditions thus have a place in the public domain. It should be noted, however, that a religious tradition – more precisely, an interpretation of religious tradition – qualifies as a legitimate partner in the democratic decision-making process only if it shares similar values with Western European nations.

Uutta tietoa Kainuun soista : Kainuun suoselvitys -projektin tulosraportti

Raportissa esitellään Kainuun suoselvitys -projektin keskeisimpiä tuloksia ja niistä vedettyjä johtopäätöksiä. Vuosina 2010–2012 toteutetun projektin tarkoituksena on ollut parantaa tietopohjaa Kainuun soista, ja sitä kautta luoda edellytyksiä soiden eri käyttömuotojen yhteensovittamiselle ja samalla nostaa esille Kainuun soihin liittyviä mahdollisuuksia. Soiden käyttö nähtiin projektissa laajasti, sisältäen paitsi erilaiset taloudellisen hyödyntämisen muodot myös soiden merkityksen ihmisten virkistykselle ja hyvinvoinnille sekä luonnon monimuotoisuudelle ja monille sääteleville toiminnoille. Taustana projektille on samaan aikaan laadittu kansallinen suostrategia. Sen mukaan soiden luonnontilaa muuttavien toimintojen, maa-, metsä- ja turvetalouden, tulisi jatkossa toimia jo ojitetuilla tai muuten merkittävästi muuttuneilla soilla. Näin soiden luonnontilaisuudesta hyötyville soiden käytön muodoille ja ekosysteemipalveluille jää paremmin tilaa toimia. Kainuu on Suomen kolmanneksi soisin maakunta. Suot ovat keskeinen osa sen luontoa ja maisemaa ja myös monipuolinen luonnonvara. Valtaosa Kainuun suopinta-alasta on ojitettu. Uutta tietoa on projektissa tuotettu paikkatietomenetelmin ja kohdennetuin maastoselvityksin. Raportin aihepiirejä ovat Kainuun soiden käyttö, jäljellä olevat ojittamattomat suot, suojeltujen soiden vesitaloudellinen eheys, metsätalouden käytöstä poistuvat ojitetut suot, soiden merkitys virkistyksen ja matkailun kannalta sekä maastossa tutkittujen 143 suon arviointi turpeennoston ja luonnon monimuotoisuuden kannalta. Raportissa esitetään, että kansallisen suostrategian tavoite soiden kestävästä ja vastuullisesta käytöstä ja suojelusta on mahdollista saavuttaa eri toimijoiden yhteistyön ja maankäytön ohjauksen avulla. Se edellyttää sitoutumista suostrategian linjauksiin sekä tietopohjan parantamista soista ja eri toimintojen vaikutuksista. Kainuun suoselvitys -projektissa on osaltaan tuotettu tätä tietoa ja myös kehitelty menetelmiä sen hankkimiseksi.

Iran's domestic and foreign policies

Iran has a reputation of being a problematic country. Right now, it is proceeding with its nuclear program despite the opposition of the West and neighboring countries and the massive sanctions inflicted upon it. The country is also struggling with domestic issues. Half of Iran’s population belongs to different ethnic or religious minorities. They have poor rights to express their culture in the country, which is a cause of dissatisfaction among non-Shiite and non-Persian citizens. After the Arab Spring, the situation in Iran is getting more topical than ever. In the Syrian conflict, the Shiite Iran is constantly giving support to al-Assad’s regime. These are all factors that have aggravated the already irritated relations between Iran and the West.

How is OpenAIRE supporting open access policies and infrastructures in Europe? A Nordic point of view!

Presentation at the Nordic Perspectives on Open Access and Open Science seminar, Helsinki, October 15, 2013

Open research data policies, what makes the difference?

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

Targeted Annotation of Scientific Literature and Data Resources in Invenio Digital Libraries

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