Pluripotency and genetic stability of human pluripotent stem cells

Pluripotent cells have the potential to differentiate into all somatic cell types. As the adult human body is unable to regenerate various tissues, pluripotent cells provide an attractive source for regenerative medicine. Human embryonic stem cells (hESCs) can be isolated from blastocyst stage embryos and cultured in the laboratory environment. However, their use in regenerative medicine is restricted due to problems with immunosuppression by the host and ethical legislation. Recently, a new source of pluripotent cells was established via the direct reprogramming of somatic cells. These human induced pluripotent stem cells (hiPSCs) enable the production of patient specific cell types. However, numerous challenges, such as efficient reprogramming, optimal culture, directed differentiation, genetic stability and tumor risk need to be solved before the launch of therapeutic applications. The main objective of this thesis was to understand the unique properties of human pluripotent stem cells. The specific aims were to identify novel factors involved in maintaining pluripotency, characterize the effects of low oxygen culture on hESCs, and determine the high resolution changes in hESCs and hiPSCs during culture and reprogramming. As a result, the previously uncharacterized protein L1TD1 was determined to be specific for pluripotent cells and essential for the maintenance of pluripotency. The low oxygen culture supported undifferentiated growth and affected expression of stem cell associated transcripts. High resolution screening of hESCs identified a number of culture induced copy number variations and loss of heterozygosity changes. Further, screening of hiPSCs revealed that reprogramming induces high resolution alterations. The results obtained in this thesis have important implications for stem cell and cancer biology and the therapeutic potential of pluripotent cells.

Hiperaldosteronismo primário: relato de dois casos

The authors present two cases of Primary Hiperaldosteronism, caused by functioning adenoma of the adrenal's cortex. The two females patients presented classic symptoms of the Conn's disease, especially hypocalemia and hypertension. Both were operated and unilateral adrenalectomy was done, with excelent outcome in one and satisfactory in the other one. It is discussed many aspects related to the incidence, the problems with the diagnosis, indication and surgery treatment.

Qualitative Characteristics and Quantitative Measures of Solution's Reliability in Discrete Optimization: Traditional Analytical Approaches, Innovative Computational Methods and Applicability

The purpose of this thesis is twofold. The first and major part is devoted to sensitivity analysis of various discrete optimization problems while the second part addresses methods applied for calculating measures of solution stability and solving multicriteria discrete optimization problems. Despite numerous approaches to stability analysis of discrete optimization problems two major directions can be single out: quantitative and qualitative. Qualitative sensitivity analysis is conducted for multicriteria discrete optimization problems with minisum, minimax and minimin partial criteria. The main results obtained here are necessary and sufficient conditions for different stability types of optimal solutions (or a set of optimal solutions) of the considered problems. Within the framework of quantitative direction various measures of solution stability are investigated. A formula for a quantitative characteristic called stability radius is obtained for the generalized equilibrium situation invariant to changes of game parameters in the case of the H¨older metric. Quality of the problem solution can also be described in terms of robustness analysis. In this work the concepts of accuracy and robustness tolerances are presented for a strategic game with a finite number of players where initial coefficients (costs) of linear payoff functions are subject to perturbations. Investigation of stability radius also aims to devise methods for its calculation. A new metaheuristic approach is derived for calculation of stability radius of an optimal solution to the shortest path problem. The main advantage of the developed method is that it can be potentially applicable for calculating stability radii of NP-hard problems. The last chapter of the thesis focuses on deriving innovative methods based on interactive optimization approach for solving multicriteria combinatorial optimization problems. The key idea of the proposed approach is to utilize a parameterized achievement scalarizing function for solution calculation and to direct interactive procedure by changing weighting coefficients of this function. In order to illustrate the introduced ideas a decision making process is simulated for three objective median location problem. The concepts, models, and ideas collected and analyzed in this thesis create a good and relevant grounds for developing more complicated and integrated models of postoptimal analysis and solving the most computationally challenging problems related to it.

Russia’s WTO membership and its effects on global wood sourcing

The aim of the thesis was to find the effects of World Trade Organization and economic integration on the wood sourcing process from Russia to Finland and to the European Union. Also, the fo reign direct investments to Russian forest industry are studied within the WTO and Economic integration framework. Qualitative interviews were carried out as primary data (total of 5 interviews). Research studies and articles regarding the same subject were used as secondary data. Results show that companies may increase their volumes of imported timber from Russia due to the reduction of custom tariffs. Russian companies are becoming more productive, but there are still several problems with legislation, infrastructure, availability and harvesting profitability in some areas. These suggest that sourcing process may not be profitable in the future. The Russian forest industry sector will not gain significant foreign direct investments in the recent years because of the infrastructure and overall atmosphere of investments. Forest industry is not seen as profitable enough. The demand for cellulose and paper in Russia is not increasing fast enough and the cost inflation is cutting the profits made from producing in Russia.

Transition management and the sustainable nutrients economy in the Netherlands; positioning paper

In this positioning paper transition management (TM) and the sustainable nutrient economy are addressed. We discuss TM from its scholarly origins in the 1990’s to its implementation as a comprehensive sector-wide policy program on sustainability in The Netherlands during the first decade of the 2000´s. Although the program was innovative and provoked a new approach to environmental policy and governance, the program at large failed to set the right conditions under which sustainable transition take place. Lessons from the Netherlands, both successful and less successful, are addressed in this positioning paper to inform Finnish governmental and knowledge institutes on how (not) to implement TM on environmental issues. When looking at sustainable nutrient economy the paper takes a historical view at how problems with nutrients (especially phosphates) were dealt with in the Netherlands during the post World War II era. This transition did not occur easily. In the agricultural sector environmental policies to prevent nutrient problems were not easily accepted, as large agricultural economic interests were at stake and the sector’s main actors were generally opposed to (radical) environmental transition. Currently, sustainable nutrient economy initiatives are starting to receive attention on the political agenda once again. In 2011 a sector- and chain-wide covenant was signed, showing that sustainable nutrient transition goals get commitment from stakeholders throughout the nutrient chain. We judge that TM provides useful elements that are applicable to Finnish governance modes to support sustainable nutrient economy transition. However, the Finnish government should be careful when implementing TM to prevent making the same mistakes the Dutch government made in previous years.

Tertiary Treatment and Re-use of Kraft Pulp Mill Effluent

The efficient use of materials and natural recourses, for ecological and economic reasons, has become more and more important in all industries. In the forest industries this means higher levels of closure in the material circulations of the mills. One possibility to reduce wastewater discharge is to re-use part of the 2nd clarifier effluent as process water. The main target of this thesis was to evaluate the technical suitability of several mechanical and chemical tertiary treatment methods for water re-use. Some of the tested methods seemed to have high potential for the removal of some specific constituents from the wastewater. Tertiary treatment is needed because higher levels of closure may cause problems with increasing amounts of non-process elements in different points of kraft pulp process. The aspect of sustainable development was taken into account by evaluating positive and negative environmental effects of the treatment processes. Environmental benefits can be gained by using some of the tertiary treatment methods tested. These methods should still be researched more for system optimization.

Talousveden tuotannon ja jakelun tietohuollon kehittäminen julkisomisteisessa vesilaitoksessa

Vesilaitokset kuluttavat merkittäviä määriä energiaa, johon on alettu kiinnittää huomiota viime vuosina. Energiatehokkuuden edistämisen hidasteeksi on noussut puutteellinen tietohuolto sekä vesilaitosten yhteisten tunnuslukujen ja kriteerien puuttuminen. Diplomityön tavoitteena on selvittää tietohuollon ongelmia Tampereen Vedellä. Työn tavoitteena on myös tutkia veden tuotannon ja jakelun energiatehokkaiden ohjaustapojen löytämistä tietohuollon ja tunnuslukujen avulla. Työssä käytetyt metodologiat ovat Tampereen Veden työntekijöiden haastattelut, prototyypin analysointi sekä vedenottamoiden ominaisenergiaan liittyvien mittauspisteiden läpikäynti. Diplomityön tuloksena saatiin laaja kuva Tampereen Veden tietohuoltoon liittyvistä ongelmista. Merkittävimmät tietohuollon haasteet liittyvät työntekijöihin, järjestelmiin sekä mittauspisteiden puuttumiseen. Mittauspisteet ja niiden tallentuminen ovat edellytys tunnuslukujen luomiselle. Tunnuslukuja voidaan hyödyntää energiatehokkaiden ohjaustapojen löytämiseksi, mutta vesilaitosten yhteiset kriteerit tunnusluvuille puuttuvat. Energiatehokkuustunnuslukuja on tarve tutkia lisää ja kehittää yhteistyötä vesilaitosten välillä tunnuslukujen luomiseksi sekä vertailutietojen saamiseksi.

Stochastic approximation methods in stochastic optimization

Stochastic approximation methods for stochastic optimization are considered. Reviewed the main methods of stochastic approximation: stochastic quasi-gradient algorithm, Kiefer-Wolfowitz algorithm and adaptive rules for them, simultaneous perturbation stochastic approximation (SPSA) algorithm. Suggested the model and the solution of the retailer's profit optimization problem and considered an application of the SQG-algorithm for the optimization problems with objective functions given in the form of ordinary differential equation.

Laajeneva ohjelmointiesimerkkikokoelma Ohjelmoinnin perusteet -kurssille

Lappeenrannan teknillisen yliopiston Ohjelmoinnin perusteet -kurssin osallistujilla on ollut vaikeuksia aloittelevan ohjelmoijan kannalta laajojen ohjelmien tuottamisessa ja tällaisten ohjelmien jäsentelemisessä aliohjelmiksi. Kurssin harjoitustyö on kuitenkin vaatinut tällaisen laajan ja jäsennellyn ohjelman tuottamista ja osallistujien ongelmat edellä mainittujen asioiden suhteen ovat ilmenneet palautetuista harjoitustöistä. Tässä työssä pyritään tuottamaan ratkaisu edellä kuvattuun ongelmaan konstruktiivisen tutkimuksen keinoin. Työssä tuotettava konstruktio on ohjelmointiesimerkkikokoelma ja sen avulla kurssin osallistujille voidaan esitellä kuinka laajoja ohjelmia voidaan tuottaa vaiheittain ja kuinka tällaisia ohjelmia voidaan jäsennellä aliohjelmiksi.

Professionalization of controllers in Finland

Professions are a special category of occupations that possesses exclusive rights over its domain of expertise. Professions apply expert knowledge in their work by using professional discretion and judgment to solve their clients’ problems. With control over their expert knowledge base, professions are able to control the supply of practitioners in their field and regulate the practice in their market. Professionalization is the process during which occupations attempt to gain the status of a profession. The benefits of becoming a profession are extensive – professional autonomy, social and financial rewards, prestige, status, and an exclusive community are only a few of the privileges that established professions possess. Many aspiring occupations have tried and failed to gain the status of a profession and one of these groups is the occupation of controllers in Finland. The objective of this study to uncover, why controllers have not professionalized, which properties of the occupation correspond with the elements generally regarded to pertain to professions, and which aspects of the occupational group may hinder the professionalization project. The professionalization project of controllers is analyzed using a multi-actor model of professionalization, in which practitioners, clients, the state, training institutions, and employing organizations are considered to affect the project. The properties of the occupation of controllers are compared to features generally associated with professions. The research methodology for this thesis is qualitative, and the study is conducted as an exploratory research. The data is primarily gathered using semi-structured interviews, which were conducted between March and May 2013 lasting from 40 minutes to an hour. In total, four controllers were interviewed, who worked for different companies operating in different industries, and whose experience of working as a controller varied between a few years to nearly 15 years. The data in this study indicates that although controllers possess qualities that distinguish professions from other occupational groups, the professionalization of controllers may not be plausible. Controllers enjoy considerable autonomy in organizations, and they possess a strong orientation towards serving their clients. The more profound problem with the occupation is its non-exclusive, indistinct knowledge base that does not rely solely on a single knowledge base. Controllers’ expertise is relatively organization-specific and built on several different fields of knowledge and not just management accounting, which could be considered as their primary knowledge base. In addition, controllers have not organized themselves, which is a quintessential, but by no means a sufficient prerequisite for professionalization.

Käsinhitsauksen mekanisointiratkaisujen kehittäminen

Työn tavoitteena on kehittää asiakkaiden käsinhitsausta kartoittamalla heidän hitsaavaa tuotantoa, sekä sen mahdollisia ongelmia. Järjestettävän hitsauskokeen avulla mitataan mekanisoidun hitsauksen tuottavuutta, laatua ja työergonomiaa. Työ sisältää teoreettisen ja käytännöllisen osuuden. Teoreettinen osuus pohjautuu kirjallisuuteen ja käytännöllinen osuus eri yrityksien kyselyihin ja haastatteluihin sekä hitsauskokeeseen. Teoreettinen osuus käsittelee käsinhitsausta ja siihen liittyviä mekanisointiratkaisuja. Käsinhitsauksessa käsitellään yleisimmät käsinhitsausprosessit, käsinhitsattava tuote ja tuotanto sekä sen tuottavuutta. Mekanisointiratkaisuissa käsitellään yleisimmät mekanisointiratkaisut ja laitteet sekä käytännön toteutusta. Käytännöllisessä osuudessa yritykset pitivät nykyisin hitsauksessa tärkeimpänä hitsaajien ammattitaitoa, tuottavuutta, työn mielekkyyttä, laatua sekä työturvallisuutta. Yrityksien tulisi tarkastella tuotannossaan hitsaussolujen sisältöä, sisäistä logistiikkaa ja kappaleiden kiinnitystä. Kappaleenkäsittelijään yrityksiltä tuli paljon kehitysideoita, kuten kiinnitykseen valmiita ratkaisuja sekä pöytälevyyn erilaisia vaihtoehtoja. Hitsauskokeen perusteella kappaleenkäsittelijällä työaika oli 29,4 % pienempi kuin työpöydällä. Laadullisesti koe antoi myös positiivisia tuloksia, käsittelypöydässä hitsattuja rakenteita ei tarvinnut korjata, mutta normaalissa työpöydässä piti, jotta C –luokan vaatimukset täyttyivät. Työturvallisuuden ja ergonomian kannalta suurimmat hyödyt olivat hyvä työasento, huurujen ja kurkottelun vähentyminen, mahdollisten palovammojen vähentyminen sekä vähemmän vaaraa osien putoamisesta.

Occurrence of weed species in Jatropha curcas intercropping systems

This study aimed to evaluate the level of infestation by weed species in a consolidated Jatropha plantation, as a function of the plant species grown in interrows. The experiment was installed in 2006 at the district of Itahum, city of Dourados, state of Mato Grosso do Sul, Brazil, made possible through a partnership between Embrapa Western Agriculture and Paraiso Farm. Treatments consisted of (1) Jatropha in monocrop, with no plant at the interrrows; or the following plants cultivaded at the interrows of Jatropha: (2) Stylosanthes spp.; (3) Brachiaria ruziziensis; (4) Brachiaria ruziziensis + Stylosanthess pp.; (5) Brachiaria humidicola; (6) Panicum maximum cv. massai; (7) Cajanus cajan cv. anão; (8) Crotalaria spectabilis; (9) Crop rotation system 1 - (maize second crop -Crambe abyssinica - soybean - peanut); and (10) Crop rotation system 2 - (cowpea - radish - maize - cowpea) conducted for two years. Phytosociological characterization of weed species was accomplished in 2011 based on the Ecological Approach. Estimations of relative abundance, frequency, dominance and Importance Value Index were obtained. Areas were also characterized by the diversity coefficients of Simpson and modified Shannon-Weiner, and then grouped by cluster analysis. Areas with low soil coverage resulted in higher infestation levels; crop rotation in the interrows of Jatropha produced a significant reduction in weed infestation, but the lowest infestation levels were observed when grasses were grown intercropped with Jatropha. Lower diversity coefficients were associated with occurrence of the most troublesome weed species. In the first years after planting Jatropha, species of Brachiaria or a crop rotation involving species with high mulching ability and whose biomass exhibit a high C:N ratio, should be established in the interrows to avoid problems with weeds infestation.

Grey literature, green open access: the BLDS Digital Library

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

The site of self-incompatibility action in cupuassu (Theobroma grandiflorum)

Cupuassu (Theobroma grandiflorum (Willd. ex Spreng.) Schumann) is a fruit tree that is attracting attention in Brazil and also in other tropical countries. Its pulp is used to prepare ice-cream, juices, jellies and many other home-made sweets. This species has a very low fecundity, attributed to problems with pollination and self-incompatibility, noted as being restrictive to the agronomic productivity of the species. Controlled pollinations between compatible and incompatible parents were made and flowers were collected at three times: 24, 48 and 72 h after pollinations, during the floral seasons of 1995 and 1998. In flowers collected 24 h after pollination, in both compatible and incompatible crosses, around 70% of ovules showed egg apparatus without evidences of sperm cell delivery; nevertheless some pollen tubes had been observed. Ovaries collected at 48 h showed different behaviors according to the type of cross. In the compatibles, 35% of ovules did not show evidences of gamete fusion. In incompatible crosses this number rose to 50%. Collected ovaries with 72 h, from compatible and incompatible crosses, showed respectively 1.2% and 14.2% of the ovules with the egg apparatus and polar nuclei only. In these ovaries, for the two types of crosses, the presence of sperm nuclei was common and the zygote was still undivided. The incompatibility action is occurring after fertilization, in a late self-incompatibility action.

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.