Fluorescence in situ hybridization of potato somatohaploids and their somatic hybrid donors using two Solanum brevidens specific sequences

Selostus: Perunan somaattisten hybridien ja niiden somatohaploidien fluoresenssi in situ -hybridisaatio Solanum brevidens -lajin spesifisten sekvenssien avulla

Raakamaidon solupitoisuus Suomessa vuonna 1995

Osmo Myllykangas

R&D Performance Analysis: Case Studies on the Challenges and Promotion of the Evaluation and Measurement of R&D

Due to the intense international competition, demanding, and sophisticated customers, and diverse transforming technological change, organizations need to renew their products and services by allocating resources on research and development (R&D). Managing R&D is complex, but vital for many organizations to survive in the dynamic, turbulent environment. Thus, the increased interest among decision-makers towards finding the right performance measures for R&D is understandable. The measures or evaluation methods of R&D performance can be utilized for multiple purposes; for strategic control, for justifying the existence of R&D, for providing information and improving activities, as well as for the purposes of motivating and benchmarking. The earlier research in the field of R&D performance analysis has generally focused on either the activities and considerable factors and dimensions - e.g. strategic perspectives, purposes of measurement, levels of analysis, types of R&D or phases of R&D process - prior to the selection of R&Dperformance measures, or on proposed principles or actual implementation of theselection or design processes of R&D performance measures or measurement systems. This study aims at integrating the consideration of essential factors anddimensions of R&D performance analysis to developed selection processes of R&D measures, which have been applied in real-world organizations. The earlier models for corporate performance measurement that can be found in the literature, are to some extent adaptable also to the development of measurement systemsand selecting the measures in R&D activities. However, it is necessary to emphasize the special aspects related to the measurement of R&D performance in a way that make the development of new approaches for especially R&D performance measure selection necessary: First, the special characteristics of R&D - such as the long time lag between the inputs and outcomes, as well as the overall complexity and difficult coordination of activities - influence the R&D performance analysis problems, such as the need for more systematic, objective, balanced and multi-dimensional approaches for R&D measure selection, as well as the incompatibility of R&D measurement systems to other corporate measurement systems and vice versa. Secondly, the above-mentioned characteristics and challenges bring forth the significance of the influencing factors and dimensions that need to be recognized in order to derive the selection criteria for measures and choose the right R&D metrics, which is the most crucial step in the measurement system development process. The main purpose of this study is to support the management and control of the research and development activities of organizations by increasing the understanding of R&D performance analysis, clarifying the main factors related to the selection of R&D measures and by providing novel types of approaches and methods for systematizing the whole strategy- and business-based selection and development process of R&D indicators.The final aim of the research is to support the management in their decision making of R&D with suitable, systematically chosen measures or evaluation methods of R&D performance. Thus, the emphasis in most sub-areas of the present research has been on the promotion of the selection and development process of R&D indicators with the help of the different tools and decision support systems, i.e. the research has normative features through providing guidelines by novel types of approaches. The gathering of data and conducting case studies in metal and electronic industry companies, in the information and communications technology (ICT) sector, and in non-profit organizations helped us to formulate a comprehensive picture of the main challenges of R&D performance analysis in different organizations, which is essential, as recognition of the most importantproblem areas is a very crucial element in the constructive research approach utilized in this study. Multiple practical benefits regarding the defined problemareas could be found in the various constructed approaches presented in this dissertation: 1) the selection of R&D measures became more systematic when compared to the empirical analysis, as it was common that there were no systematic approaches utilized in the studied organizations earlier; 2) the evaluation methods or measures of R&D chosen with the help of the developed approaches can be more directly utilized in the decision-making, because of the thorough consideration of the purpose of measurement, as well as other dimensions of measurement; 3) more balance to the set of R&D measures was desired and gained throughthe holistic approaches to the selection processes; and 4) more objectivity wasgained through organizing the selection processes, as the earlier systems were considered subjective in many organizations. Scientifically, this dissertation aims to make a contribution to the present body of knowledge of R&D performance analysis by facilitating dealing with the versatility and challenges of R&D performance analysis, as well as the factors and dimensions influencing the selection of R&D performance measures, and by integrating these aspects to the developed novel types of approaches, methods and tools in the selection processes of R&D measures, applied in real-world organizations. In the whole research, facilitation of dealing with the versatility and challenges in R&D performance analysis, as well as the factors and dimensions influencing the R&D performance measure selection are strongly integrated with the constructed approaches. Thus, the research meets the above-mentioned purposes and objectives of the dissertation from the scientific as well as from the practical point of view.

Temporomandibular Disorders and Headache in Adolescents

13-16-vuotiaiden purentaelimistön toimintahäiriöt ja päänsärky Tutkimuksen tarkoituksena oli selvittää purentaelimistön toimintahäiriöihin (TMD) liittyvien oireiden ja kliinisten löydösten esiintyvyyttä ja muutosta kolmen vuoden seurannan aikana päänsärystä kärsivillä nuorilla ja heidän verrokeillaan, TMD-löydösten yhteyttä eri tyyppisiin päänsärkyihin ja päänsärkyyn liittyviin tekijöihin, TMD-löydöksiä ennustavia tekijöitä sekä perhetaustan osuutta TMD-löydösten esiintyvyyteen. Tutkimus perustui kahteen laajaan koululaismateriaaliin Turun seudulla. Ensimmäinen 13-vuotiaiden nuorten ryhmä (n = 311) osallistui myös 16-vuotiaana seuranta-tutkimukseen. Toisen 13-vuotiaiden nuorten ryhmän (n = 154) äidit (n = 154) osallistuivat myös tutkimukseen, jossa selvitettiin tapaus-verrokkiasetelmassa TMD-löydösten ja päänsärkyjen esiintyvyyttä kahdessa sukupolvessa. Nuoret jaettiin päänsärkyryhmiin ja terveisiin kontrolleihin IHS (1988) päänsärky-kriteerien mukaisesti kyselykaavakkeen ja lääkärin suorittaman haastattelun ja kliinisen tutkimuksen antamien tietojen perusteella. Lääkäri määritteli äitien päänsärkydiagnoosin kyselykaavakkeen tietojen perusteella. Kaikki nuoret ja heidän äitinsä haastateltiin ja heille tehtiin kliininen purentafysiologinen tutkimus sokkoutetusti. Tutkimuksen tulokset osoittivat, että tytöillä esiintyi TMD-löydöksiä selvästi enemmän kuin pojilla sekä ennen puberteettia että sen jälkeen. Tutkimuksessa havaittiin selkeä yhteys TMD-löydösten ja molempien päänsärkytyyppien, migreenin ja episodisen tensiotyyppisen päänsäryn, välillä. Kolmen vuoden seurannan aikana TMD-löydöksissä havaittiin runsasta muutosta ja iän myötä vähenemistä, mutta TMD-oireiden kohdalla ei vastaavaa muutosta todettu. TMD-löydösten ja niska-hartiaseudun lihaskipujen välillä havaittiin yhteys 13-vuotiailla nuorilla. Mikään päänsärkyyn liittyvistä tekijöistä 13-vuotiailla ei osoittautunut ennustavaksi taustatekijäksi myöhemmille TMD-löydöksille. TMD-löydösten suhteen ei todettu perheyhteyttä. Päänsäryistä kärsivillä nuorilla on enemmän myös muita kiputiloja, kuten purentaelimistön toimintahäiriöitä ja niska-hartiaseudun kipuja, kuin heidän terveillä verrokeillaan. 1316 vuoden iässä nämä löydökset ovat valtaosaltaan lieviä ja vaihtelevia.

Paper Surface Image Processing for Roughness Quality Measurement

Diplomityössä on käsitelty paperin pinnankarkeuden mittausta, joka on keskeisimpiä ongelmia paperimateriaalien tutkimuksessa. Paperiteollisuudessa käytettävät mittausmenetelmät sisältävät monia haittapuolia kuten esimerkiksi epätarkkuus ja yhteensopimattomuus sileiden papereiden mittauksissa, sekä suuret vaatimukset laboratorio-olosuhteille ja menetelmien hitaus. Työssä on tutkittu optiseen sirontaan perustuvia menetelmiä pinnankarkeuden määrittämisessä. Konenäköä ja kuvan-käsittelytekniikoita tutkittiin karkeilla paperipinnoilla. Tutkimuksessa käytetyt algoritmit on tehty Matlab® ohjelmalle. Saadut tulokset osoittavat mahdollisuuden pinnankarkeuden mittaamiseen kuvauksen avulla. Parhaimman tuloksen perinteisen ja kuvausmenetelmän välillä antoi fraktaaliulottuvuuteen perustuva menetelmä.

Evaluation of Implementation of BSc IT Curriculum at Tumaini University

In Tanzania computer knowledge is vital to supplement the pace fast growing economic and development activities, which demands high and reliable level of expertise in com- puting field. In 2006, a research carried out at Tumaini University with purpose to design and implement a contextualized curriculum that can supplement for such needs hence facilitate development in Tanzanian context. A contextualized curriculum took advantage of six principles namely curriculum contex- tualization, projects, practical, interdisciplinary orientation, international recognition and continuous research for the program’s formative and development. Implementation of the curriculum followed the CATI (Contextualize, Apply, Transfer, and Import) model with emphasis on students to identify societal expectations at the early stage in learning process, in which case the graduates will potentially cater for societal expertise needs on ICT. This study adopts an emergent exploratory cross-section research design, while employ- ing a qualitative approach. This study was conducted at Tumaini University in Iringa where by purposeful sampling was used to obtain participants such as students, teach- ers, administrators and employers who participated in several focus group discussions, in-depth interviews and participant observation. The study reveals that six principles are satisfactorily met,despite of bottlenecks such as incompatibility in pedagogical thinking and technology availability for e-learning, learning attitudes, insufficient experts with actual skills and experience,in academic field among the others. The study recommends that iterative longitudinal study should be car- ried out to design for proper intervention in response to these problems which will help in improving and stabilize the curriculum.

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.

Development of Russian Ports in The Gulf of Finland

Russia has been one of the fastest developing economic areas in the world. Based on the GDP, the Russian economy grew evenly since the crisis in 1998 up till 2008. The growth in the gross domestic product has annually been some 5–10%. In 2007, the growth reached 8.1%, which is the highest figure after the 10% growth in 2000. Due to the growth of the economy and wage levels, purchasing power and consumption have been strongly increasing. The growing consumption has especially increased the imports of durables, such as passenger cars, domestic appliances and electronics. The Russian ports and infrastructure have not been able to satisfy the growing needs of exports and imports, which is why quite a large share of Russian foreign trade is going through third countries as transit transports. Finnish ports play a major role in transit transports to and from Russia. About 15% of the total value of Russian imports was transported through Finland in 2008. The economic recession that started in autumn 2008 and continues to date has had an impact on the economic development of Russia. The export income has decreased, mainly due to the reduced world market prices of energy products (oil and gas) and raw minerals. Investments have been postponed, getting credit is more difficult than before, and the ruble has weakened in relation to the euro and the dollar. The imports are decreasing remarkably, and are not forecast to reach the 2008 volumes even in 2012. The economic crisis is reflected in Finland's transit traffic. The volume of goods transported through Finland to and from Russia has decreased almost in the same proportion as the imports of goods to Russia. The biggest risk threatening the development of the Russian economy over long term is its dependence on export income from oil, gas, metals, minerals and forest products, as well as the trends of the world market prices of these products. Nevertheless, it is expected that the GDP of Russia will start to grow again in the forthcoming years due to the increased demand for energy products and raw minerals in the world. At the same time, it is obvious that the world market prices of these products will go up with the increasing demand. The increased income from exports will lead to a growth of imports, especially those of consumer goods, as the living standard of Russian citizens rises. The forecasts produced by the Russian Government concerning the economic development of Russia up till 2030 also indicate a shift in exported goods from raw materials to processed products, which together with energy products will become the main export goods of Russia. As a consequence, Russia may need export routes through third countries, which can be seen as an opportunity for increased transit transports through the ports of Finland. The ports competing with the ports of Finland for Russian foreign trade traffic are the Russian Baltic Sea ports and the ports of the Baltic countries. The strongest competitors are the Baltic Sea ports handling containers. On the Russian Baltic Sea, these ports include Saint Petersburg, Kaliningrad and, in the near future, the ports of Ust-Luga and possibly Vyborg. There are plans to develop Ust-Luga and Vyborg as modern container ports, which would become serious competitors to the Finnish ports. Russia is aiming to redirect as large a share as possible of foreign trade traffic to its own ports. The ports of Russia and the infrastructure associated with them are under constant development. On the other hand, the logistic capacity of Russia is not able to satisfy the continually growing needs of the Russian foreign trade. The capacity problem is emphasized by a structural incompatibility between the exports and imports in the Russian foreign trade. Russian exports can only use a small part of the containers brought in with imports. Problems are also caused by the difficult ice conditions and narrow waterways leading to the ports. It is predicted that Finland will maintain its position as a transit route for the Russian foreign trade, at least in the near future. The Russian foreign trade is increasing, and Russia will not be able to develop its ports in proportion with the increasing foreign trade. With the development of port capacity, cargo flows through the ports of Russia will grow. Structural changes in transit traffic are already visible. Firms are more and more relocating their production to Russia, for example as regards the assembly of cars and warehousing services. Simultaneously, an increasing part of transit cargoes are sent directly to Russia without unloading and reloading in Finland. New product groups have nevertheless been transported through Finland (textile products and tools), replacing the lost cargos. The global recession that started in autumn 2008 has influenced the volume of Russian imports and, consequently, the transit volumes of Finland, but the recession is not expected to be of long duration, and will thus only have a short-term impact on transit volumes. The Finnish infrastructure and services offered by the logistic chain should also be ready to react to the changes in imported product groups as well as to the change in Russian export products in the future. If the development plans of the Russian economy are realized, export products will be more refined, and the share of energy and raw material products will decrease. The other notable factor to be taken into consideration is the extremely fast-changing business environment in Russia. Operators in the logistic chain should be flexible enough to adapt to all kinds of changes to capitalise on business opportunities offered by the Russian foreign trade for the companies and for the transit volumes of Finnish ports, also in the future.

Genetic regulatory networks in avian B cells

Biology is turning into an information science. The science of systems biology seeks to understand the genetic networks that govern organism development and functions. In this study the chicken was used as a model organism in the study of B cell regulatory factors. These studies open new avenues for plasma cell research by connecting the down regulation of the B cell gene expression program directly to the initiation of plasma cell differentiation. The unique advantages of the DT40 avian B cell model system, specifically its high homologous recombination rate, were utilized to study gene regulation in Pax5 knock out cell lines and to gain new insights into the B cell to plasma cell transitions that underlie the secretion of antibodies as part of the adaptive immune response. The Pax5 transcription factor is central to the commitment, development and maintenance of the B cell phenotype. Mice lacking the Pax5 gene have an arrest in development at the pro-B lymphocyte stage while DT40 cells have been derived from cells at a more mature stage of development. The DT40 Pax5-/- cells exhibited gene expression similarities with primary chicken plasma cells. The expression of the plasma cell transcription factors Blimp-1 and XBP-1 were significantly upregulated while the expression of the germinal centre factor BCL6 was diminished in Pax5-/- cells, and this alteration was normalized by Pax5 re-introduction. The Pax5-deficient cells further manifested substantially elevated secretion of IgM into the supernatant, another characteristic of plasma cells. These results for the first time indicated that the downregulation of the Pax5 gene in B cells promotes plasma cell differentiation. Cross-species meta-analysis of chicken and mouse Pax5 gene knockout studies uncovers genes and pathways whose regulatory relationship to Pax5 has remained unchanged for over 300 million years. Restriction of the hematopoietic stem cell fate to produce T, B and NK cell lineages is dependent on the Ikaros and its molecular partners, the closely related Helios and Aiolos. Ikaros family members are zinc finger proteins which act as transcriptional repressors while helping to activate lymphoid genes. Helios in mice is expressed from the hematopoietic stem cell level onwards, although later in development its expression seems to predominate in the T cell lineage. This study establishes the emergence and sequence of the chicken Ikaros family members. Helios expression in the bursa of Fabricius, germinal centres and B cell lines suggested a role for Helios in the avian B-cell lineage, too. Phylogenetic studies of the Ikaros family connect the expansion of the Ikaros family, and thus possibly the emergence of the adaptive immune system, with the second round of genome duplications originally proposed by Ohno. Paralogs that have arisen as a result of genome-wide duplications are sometimes termed ohnologs – Ikaros family proteins appear to fit that definition. This study highlighted the opportunities afforded by the genome sequencing efforts and somatic cell reverse genetics approaches using the DT40 cell line. The DT40 cell line and the avian model system promise to remain a fruitful model for mechanistic insight in the post-genomic era as well.

Det gyldne snitt : den estetiske dimensjon, en kilde til helse oget etisk anliggende

Within caring science, investigations and explorations have been carried out on the ontology of caring, and many aspects of the field have been the subject of scientific research. The main subject for this study is grounded on the human need for aesthetics. The purpose is to find how the aesthetic dimension is taken into consideration and how the aesthetic surroundings are evaluated and attended to, in the general hospitals in Norway. The theoretical perspective is founded basicly on the study of litterature from caring science and philosophy. The aim is to develop a disposition for a framework on the aesthetic surroundings in the hospitals, and to develop phenomenological and ontological knowledge and understanding of the aesthetic dimension. The study aspires to attain a deeper understanding of the aesthetic acknowledgment and of the aesthetic needs. The focus is how the aesthetic dimension can promote health and wellbeing, both for patients and for the caring staff, in the general hospitals and why the aesthetic dimension should be obligatory in `evident care¿. The study concentrates on 11 selected categories in the hospital environment, where aesthetics is of importance. The research is implemented on 5 part studies: 1. part is a study of caring science and philosophical theories about aesthetics, as a framework for the investigation. 2. part is a survey of the physical environment, in Norwegian somatic hospitals, with focus on aesthetics. This by analyzing the strategy plans for the hospitals. 3. and 4. part is questionnaires to patients and nurses to get their opinion and evaluation of the aesthetic environment in the hospitals they are connected to, and their opinion on how this influences the health and wellness for both patients and caring staff. 5. part is qualitative interviews with 16 experts, to get their opinion and evaluation of the aesthetic environment in hospitals they are or have been connected to. How would the experts like the aesthetic surroundings to be, and also their opinion on what influence they think aesthetics has on health and wellness. The main literature of caring science is rooted in K. Erikssons caring theory as well as philosophic literature; mainly I. Kant, Platon and Y. Hirn's theories on aesthetics. Various scientificresearchers of aesthetics have also been referred to. The methodological approach is a triangulation with a hermeneutic exploration, where H.G. Gadamer and Ricoeur provides the inspirational foundation. The findings and conclusions result in the development of new hypothesis for the caring science foundation and suggestions, a disposition for a framework related to future planning of the aesthetic environments in general hospitals. It might be said that a common thread arises/appears in the invariance's (invariables) that are discerned from the analysis and interpretation of the interviews and also important angles shows in the variances that crystallized. Based on the conclusions the study confirms that there is a clearconnection between health, wellness and aesthetics in the environment and that it is an ethical obligationfor those in the caring professions to be aware of and attend to the aesthetic dimension.

Nurse-led interpersonal counselling for depressive symptoms in patients with myocardial infarction

The broad interest of this intervention study is in two worldwide remarkable diseases, myocardial infarction and depression. The purpose of the 18-month follow-up study was to evaluate the outcomes of interpersonal counselling implemented by a psychiatric nurse, and to examine the recovery experienced by the patients after myocardial infarction. The interpersonal counseling consisted of a short-term (max 6 sessions) depression-focused intervention modified for myocardial infarction patients. The main principle of interpersonal counselling is that depressive symptoms relate to interpersonal relations. The measured outcomes of the intervention consisted of changes in depressive symptoms and distress, health-related quality of life and the use of health care services. The data consisted of 103 patients with acute myocardial infarction and with sufficient knowledge of Finnish language, and they were randomized into intervention group (n=51) and control group (n=52) with standard care. Depressive symptoms were measured using Beck Depression Inventory, and distress using Symptom Checklist-25. The instrument to measure health-related quality of life was EuroQol-5 Dimensions. All instruments were used at three measurements: in hospital, at 6 months and at 18 months after hospital discharge. The Use of Health Care Services questionnaire was used during the 6- and 18-month period after hospital discharge. In addition, satisfaction with the intervention and with information received from the health-care professional was evaluated during the follow-up. To examine recovery, the patients kept diaries during a 6-month period and they were interviewed at 18 months after myocardial infarction. The number of patients with depressive symptoms decreased significantly more in the intervention group compared with the control group during 18 months of follow-up. Distress decreased significantly more among patients under 60 years in the intervention group than in the control group, but the difference was not significant between the groups. No differences in the changes of health-related quality of life were found between the groups during follow-up. However, in the group of patients under 60 years, the improvement of health-related quality of life in the intervention was significantly better in the intervention group compared with the control group during the follow-up. During the follow-up period, there was even a decline in the use of somatic specialized health care services in the intervention group and among intervention patients who had no other long-term disease. Considering recovery experienced by the patients, main categories including many supporting and inhibiting factors and subcategories were identified: clinical and physical, psychological, social, functional and professional category. No differences between the groups were found in satisfaction with information received from the professionals. The brief and easy-to-learn intervention, with which the patients were satisfied, seems to decrease depressive symptoms after myocardial infarction. Interpersonal counselling seems to be beneficial especially with younger patients. These results justify adopting depression screening and interpersonal counselling as part of routine care after myocardial infarction. The first stage evaluation of the use of health care services is interesting, and calls for more studies. From the perspective of individual patients, recovery after myocardial infarction seems to consist of many supporting and inhibiting factors. This is something that is important to take into account in developing nursing practice. The results indicate a need for further studies in outcomes of interpersonal counselling and recovery experienced by the patients after myocardial infarction. In addition, the results encourage widening the research perspective to nursing administration and educational level.

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.

Five Baltic Ports Togehter: Forecasts, Trends and Recommendations

The ports of Stockholm, Tallinn, Helsinki, Naantali and Turku play key roles in making the Central Baltic region accessible. Effective, competitive, eco-friendly and safe port procedures and solutions for the transportation of goods are of major importance for trade in the Baltic Sea region. This report presents the most essential results and recommendations of the PENTA project, which focused on how ports could better comprehend and face current and future challenges facing carriage of goods by sea. Each of the four work packages (WPs) of the PENTA project analysed the changes from a different perspective. WP2 focused on traffic flows between the PENTA ports. Its main emphasis was on the ports, shipowners, and logistics companies that are the key parties in freight transport and on the changes affecting the economy of those ports. In WP3 noise as an environmental challenge for ports was investigated and the analysis also shed light on the relationship between the port and the city. In WP4 procedures related to safety, security and administrative procedures were researched. The main emphasis was on identifying the requirements for the harmonisation of those procedures. Collaboration is highlighted throughout this report. In order to prepare for the future, it was found that ports need to respond to growing competition, increasing costs and shifts in customer demand by strengthening their existing partnerships with other actors in the maritime cluster. Cargo and passenger transport are the main sources of income for most ports. Cargo traffic between the PENTA ports is expected to grow steadily in the future and the outlook for passenger traffic is positive. However, to prepare for the future, ports should not only secure the core activities which generate revenue but also seek alternative ways to make profit. In order to gain more transit traffic, it is suggested that ports conduct a more thorough study of the future requirements for doing business with Russia. The investigation of noise at ports revealed two specific dilemmas that ports cannot solve alone. Firstly, the noise made by vessels and, secondly, the relationship between the port and the surrounding city. Vessels are the most important single noise source in the PENTA ports and also one of the hardest noise sources to handle. Nevertheless, port authorities in Finland and Sweden are held responsible for all noise in the port area, including noise produced by vessels, which is noise the port authority can only influence indirectly. Building housing by waterfront areas close to ports may also initiate disagreements because inhabitants may want quiet areas, whereas port activities always produce some noise from their traffic. The qualitative aspects of the noise question, cooperating with the stakeholders and the communicating of issues related to noise are just as important. We propose that ports should follow the logic of continuous improvement in their noise management. The administrative barriers discussed in this report are mainly caused by differences in international and national legislation, variations in the customs procedures of each country, the incompatibility of the IT systems used in maritime transport, noncompliance with regulations regarding dangerous goods, and difficulties in applying Schengen regulations to vessels from non-EU countries. Improving the situation is out of the hands of the ports to do alone and requires joint action on a variety of levels, including the EU, national authorities and across administrative borders.

ERBB4 mutations in cancer and amyotrophic lateral sclerosis

ErbB receptor tyrosine kinases, epidermal growth factor receptor (EGFR, also known as ErbB1), ErbB2 (HER2 or NEU), ErbB3 (HER3), and ErbB4 (HER4), transduce signals borne by extracellular ligands into central cellular responses such as proliferation, survival, differentiation, and apoptosis. Mutations in ERBB genes are frequently detected in human malignant diseases of epithelial and neural origin, making ErbB receptors important drug targets. Targeting EGFR and ErbB2 has been successful in eg. lung and breast cancer, respectively, and mutations in these genes can be used to select patients that are responsive to the targeted treatment. Although somatic ERBB4 mutations have been found in many high-incidence cancers such as melanoma, lung cancer, and colorectal cancer and germ-line ERBB4 mutations have been linked to neuronal disorders and cancer, ErbB4 has generally been neglected as a potential drug target. Thus, the consequences of ERBB4 mutations on ErbB4 biology are largely unknown. This thesis aimed to elucidate the functional consequences and assess the clinical significance of somatic and germ-line ERBB4 mutations in the context of cancer and amyotrophic lateral sclerosis. The results of this study indicated that cancer-associated ERBB4 mutations can promote aberrant ErbB4 function by activating the receptor or inducing qualitative changes in ErbB4 signaling. ERBB4 mutations increased survival or decreased differentiation in vitro, suggesting that ERBB4 mutations can be oncogenic. Importantly, the potentially oncogenic mutations were located in various subdomains in ErbB4, possibly providing explanation for the characteristic scattered pattern of mutations in ERBB4. This study also demonstrated that hereditary variation in ERBB4 gene can have a significant effect on the prognosis of breast cancer. In addition, it was shown that hereditary or de novo germ-line ERBB4 mutations that predispose to amyotrophic lateral sclerosis inhibit ErbB4 activity. Together, these results suggest that ErbB4 should be considered as a novel drug target in cancer and amyotrophic lateral sclerosis.