Cognitive Functions After Traumatic Brain Injury. A 30-year Follow-up Study

Many cognitive deficits after TBI (traumatic brain injury) are well known, such as memory and concentration problems, as well as reduced information-processing speed. What happens to patients and cognitive functioning after immediate recovery is poorly known. Cognitive functioning is flexible and may be influenced by genetic, psychological and environmental factors decades after TBI. The general aim of this thesis was to describe the long-term cognitive course after TBI, to find variables that may contribute to it, and how the cognitive functions after TBI are associated with specific medical factors and reduced survival. The original study group consisted of 192 patients with TBI who were originally assessed with the Mild Deterioration Battery (MDB) on average two years after the injury, during the years 1966 – 1972. During a 30-year follow-up, we studied the risks for reduced survival, and the mortality of the patients was compared with the general population using the Standardized Mortality Ratio (SMR). Sixty-one patients were re-assessed during 1998-2000. These patients were evaluated with the MDB, computerized testing, and with various other neuropsychological methods for attention and executive functions. Apolipoprotein-E (ApoE) genotyping and magnetic resonance imaging (MRI) based on volumetric analysis of the hippocampus and lateral ventricles were performed. Depressive symptoms were evaluated with the short form of the Beck depression inventory. The cognitive performance at follow-up was compared with a control group that was similar to the study group in regard to age and education. The cognitive outcome of the patients with TBI varied after three decades. The majority of the patients showed a decline in their cognitive level, the rest either improved or stayed at the same level. Male gender and higher age at injury were significant risk factors for the decline. Whereas most cognitive domains declined during the follow-up, semantic memory behaved in the opposite way, showing recovery after TBI. In the follow-up assessment, the memory decline and impairments in the set-shifting domain of executive functions were associated with MRI-volumetric measures, whereas reduction in information-processing speed was not associated with the MRI measures. The presence of local contusions was only weakly associated with cognitive functions. Only few cognitive methods for attention were capable of discriminating TBI patients with and without depressive symptoms. On the other hand, most complex attentional tests were sensitive enough to discriminate TBI patients (non-depressive) from controls. This means that complex attention functions, mediated by the frontal lobes, are relatively independent of depressive symptoms post-TBI. The presence of ApoE4 was associated with different kinds of memory processes including verbal and visual episodic memory, semantic memory and verbal working memory, depending on the length of time since TBI. Many other cognitive processes were not affected by the presence of ApoE4. Age at injury and poor vocational outcome were independent risk factors for reduced survival in the multivariate analysis. Late mortality was higher among younger subjects (age < 40 years at death) compared with the general population which should be borne in mind when assessing the need for rehabilitation services and long-term follow-up after TBI.

NADPH-Dependent Thioredoxin System In Regulation of Chloroplast Functions

Photosynthesis, the process in which carbon dioxide is converted into sugars using the energy of sunlight, is vital for heterotrophic life on Earth. In plants, photosynthesis takes place in specific organelles called chloroplasts. During chloroplast biogenesis, light is a prerequisite for the development of functional photosynthetic structures. In addition to photosynthesis, a number of other metabolic processes such as nitrogen assimilation, the biosynthesis of fatty acids, amino acids, vitamins, and hormones are localized to plant chloroplasts. The biosynthetic pathways in chloroplasts are tightly regulated, and especially the reduction/oxidation (redox) signals play important roles in controlling many developmental and metabolic processes in chloroplasts. Thioredoxins are universal regulatory proteins that mediate redox signals in chloroplasts. They are able to modify the structure and function of their target proteins by reduction of disulfide bonds. Oxidized thioredoxins are restored via the action of thioredoxin reductases. Two thioredoxin reductase systems exist in plant chloroplasts, the NADPHdependent thioredoxin reductase C (NTRC) and ferredoxin-thioredoxin reductase (FTR). The ferredoxin-thioredoxin system that is linked to photosynthetic light reactions is involved in light-activation of chloroplast proteins. NADPH can be produced via both the photosynthetic electron transfer reactions in light, and in darkness via the pentose phosphate pathway. These different pathways of NADPH production enable the regulation of diverse metabolic pathways in chloroplasts by the NADPH-dependent thioredoxin system. In this thesis, the role of NADPH-dependent thioredoxin system in the redox-control of chloroplast development and metabolism was studied by characterization of Arabidopsis thaliana T-DNA insertion lines of NTRC gene (ntrc) and by identification of chloroplast proteins regulated by NTRC. The ntrc plants showed the strongest visible phenotypes when grown under short 8-h photoperiod. This indicates that i) chloroplast NADPH-dependent thioredoxin system is non-redundant to ferredoxinthioredoxin system and that ii) NTRC particularly controls the chloroplast processes that are easily imbalanced in daily light/dark rhythms with short day and long night. I identified four processes and the redox-regulated proteins therein that are potentially regulated by NTRC; i) chloroplast development, ii) starch biosynthesis, iii) aromatic amino acid biosynthesis and iv) detoxification of H₂O₂. Such regulation can be achieved directly by modulating the redox state of intramolecular or intermolecular disulfide bridges of enzymes, or by protecting enzymes from oxidation in conjunction with 2-cysteine peroxiredoxins. This thesis work also demonstrated that the enzymatic antioxidant systems in chloroplasts, ascorbate peroxidases, superoxide dismutase and NTRC-dependent 2-cysteine peroxiredoxins are tightly linked up to prevent the detrimental accumulation of reactive oxygen species in plants.

Making Sense of Shared Leadership. A case study of leadership processes and practices without formal leadership structure in the team context

Leadership is essential for the effectiveness of the teams and organizations they are part of. The challenges facing organizations today require an exhaustive review of the strategic role of leadership. In this context, it is necessary to explore new types of leadership capable of providing an effective response to new needs. The presentday situations, characterized by complexity and ambiguity, make it difficult for an external leader to perform all leadership functions successfully. Likewise, knowledge-based work requires providing professional groups with sufficient autonomy to perform leadership functions. This study focuses on shared leadership in the team context. Shared leadership is seen as an emergent team property resulting from the distribution of leadership influence across multiple team members. Shared leadership entails sharing power and influence broadly among the team members rather than centralizing it in the hands of a single individual who acts in the clear role of a leader. By identifying the team itself as a key source of influence, this study points to the relational nature of leadership as a social construct where leadership is seen as social process of relating processes that are co-constructed by several team members. Based on recent theoretical developments concerned with relational, practice-based and constructionist approaches to the study of leadership processes, this thesis proposes the study of leadership interactions, working processes and practices to focus on the construction of direction, alignment and commitment. During the research process, critical events, activities, working processes and practices of a case team have been examined and analyzed with the grounded theory –approach in the terms of shared leadership. There are a variety of components to this complex process and a multitude of factors that may influence the development of shared leadership. The study suggests that the development process of shared leadership is a common sense -making process and consists of four overlapping dimensions (individual, social, structural, and developmental) to work with as a team. For shared leadership to emerge, the members of the team must offer leadership services, and the team as a whole must be willing to rely on leadership by multiple team members. For these individual and collective behaviors to occur, the team members must believe that offering influence to and accepting it from fellow team members are welcome and constructive actions. Leadership emerges when people with differing world views use dialogue and collaborative learning to create spaces where a shared common purpose can be achieved while a diversity of perspectives is preserved and valued. This study also suggests that this process can be supported by different kinds of meaning-making and process tools. Leadership, then, does not reside in a person or in a role, but in the social system. The built framework integrates the different dimensions of shared leadership and describes their relationships. This way, the findings of this study can be seen as a contribution to the understanding of what constitutes essential aspects of shared leadership in the team context that can be of theoretical value in terms of advancing the adoption and development process of shared leadership. In the real world, teams and organizations can create conditions to foster and facilitate the process. We should encourage leaders and team members to approach leadership as a collective effort that the team can be prepared for, so that the response is rapid and efficient.

Intellectual Property Management in a Small Company

Opinnäytetyö keskittyi kriittisiin tapahtumiin, joita on tullut yhtiön tai sen edeltävän yhtiön, joka oli Mobile Screen TV – 4 ALL, tekemien aikaisempien patenttihakemusten yhteydessä . Tutkimus vertasi ja evaluoi yhtiön aikaisemmin tekemien keksintöjen suojausta. Toisaalta opinnäytetyön päämäärä oli tutkia ja selvittää monitapaus-menetelmällä yhtiön aikaisempia keksintöjä ja miten aineettoman oikeuden suojaus toteutui prosessien eri vaiheissa. Tämä päättötyötutkielma vei loppuun asti erittäin suuren patenttien ja hyödyllisyysmallien hakemusten tutkimuksen. LH Communications Oy on tehnyt monia niistä, mutta tutkimus sisälsi myös joitakin kilpailijoiden hakemuksia. Tässä tutkimuksessa oli kaksi pääkysymystä. Miten pieni yhtiö voisi suojella heidän uusia ideoitaan ja keksintöjään ja myös samalla pitää yhtiön talouden hyvällä tasolla. Tämä tutkimus käytti The Critical Incidents Technique (CIT), joka keskittyy kriittisiin tapahtumiin, selvittääkseen sopivia menetelmiä pienelle yhtiölle siitä, miten suojella uusia ajatuksia, ideoita ja keksintöjä ja samanaikaisesti olla tuottava niiden kanssa. Tutkimuksemme käsitteli kaikenlaisia tarvittavia käytäntöjä pienessä yhtiössä ja päähuomio pienessä yhtiössä tulee olla omien keksintöjen suojaamisessa. Paras suojaus on tehdä patentteja, mutta se tulee maksamaan hyvin paljon koko tapahtumasarjan aikana.

Creating possibilities for collective creativity : Brokerage Functions in Practice-Based Innovation

In the network era, creative achievements like innovations are more and more often created in interaction among different actors. The complexity of today‘s problems transcends the individual human mind, requiring not only individual but also collective creativity. In collective creativity, it is impossible to trace the source of new ideas to an individual. Instead, creative activity emerges from the collaboration and contribution of many individuals, thereby blurring the contribution of specific individuals in creating ideas. Collective creativity is often associated with diversity of knowledge, skills, experiences and perspectives. Collaboration between diverse actors thus triggers creativity and gives possibilities for collective creativity. This dissertation investigates collective creativity in the context of practice-based innovation. Practice-based innovation processes are triggered by problem setting in a practical context and conducted in non-linear processes utilising scientific and practical knowledge production and creation in cross-disciplinary innovation networks. In these networks diversity or distances between innovation actors are essential. Innovation potential may be found in exploiting different kinds of distances. This dissertation presents different kinds of distances, such as cognitive, functional and organisational which could be considered as sources of creativity and thus innovation. However, formation and functioning of these kinds of innovation networks can be problematic. Distances between innovating actors may be so great that a special interpretation function is needed – that is, brokerage. This dissertation defines factors that enhance collective creativity in practice-based innovation and especially in the fuzzy front end phase of innovation processes. The first objective of this dissertation is to study individual and collective creativity at the employee level and identify those factors that support individual and collective creativity in the organisation. The second objective is to study how organisations use external knowledge to support collective creativity in their innovation processes in open multi-actor innovation. The third objective is to define how brokerage functions create possibilities for collective creativity especially in the context of practice-based innovation. The research objectives have been studied through five substudies using a case-study strategy. Each substudy highlights various aspects of creativity and collective creativity. The empirical data consist of materials from innovation projects arranged in the Lahti region, Finland, or materials from the development of innovation methods in the Lahti region. The Lahti region has been chosen as the research context because the innovation policy of the region emphasises especially the promotion of practice-based innovations. The results of this dissertation indicate that all possibilities of collective creativity are not utilised in internal operations of organisations. The dissertation introduces several factors that could support collective creativity in organisations. However, creativity as a social construct is understood and experienced differently in different organisations, and these differences should be taken into account when supporting creativity in organisations. The increasing complexity of most potential innovations requires collaborative creative efforts that often exceed the boundaries of the organisation and call for the involvement of external expertise. In practice-based innovation different distances are considered as sources of creativity. This dissertation gives practical implications on how it is possible to exploit different kinds of distances knowingly. It underlines especially the importance of brokerage functions in open, practice-based innovation in order to create possibilities for collective creativity. As a contribution of this dissertation, a model of brokerage functions in practice-based innovation is formulated. According to the model, the results and success of brokerage functions are based on the context of brokerage as well as the roles, tasks, skills and capabilities of brokers. The brokerage functions in practice-based innovation are also possible to divide into social and cognitive brokerage.

The Forms and Functions of Multilingual Practices in Early Modern School Drama from the King‟s School, Canterbury

Käsittelen tutkimuksessani monikielisyyden ilmenemistä Canterburyn katedraalikoulun oppilaiden 1600-luvun loppupuoliskolla esittämissä näytelmissä, jotka löytyvät käsikirjoituksesta Lit.Ms.E41 (Canterburyn katedraalin arkisto). Tämä käsikirjoitus sisältää puheita ja näytelmiä, joiden kielinä ovat englanti, latina ja vähemmissä määrin myös kreikka. Useissa näytelmissä esiintyy koodinvaihtoa näiden kielten välillä, ja tutkielmassani selvitän, millaisia syntaktisia ilmenemismuotoja ja pragmaattisia merkityksiä koodinvaihdolla on. Teoreettinen viitekehykseni on yhdistelmä filologista ja lingvististä lähestymistapaa. Olen sisällyttänyt tutkielmaani aiemman koodinvaihdon tutkimuksen lisäksi Brownin ja Levinsonin kohteliaisuusteorian, jonka avulla erityisesti puhujien välisiin sosiaalisiin suhteisiin liittyviä koodinvaihdon funktioita voidaan luokitella. Koska historiallinen koodinvaihto on tutkimusaiheena vielä melko tuore, käsittelen perusteellisesti erilaisia metodologisia ratkaisuja. Valitsemani metodi yhdistää perinteisen filologisen lähiluvun pragmaattiseen analyysiin, jonka kautta työssäni vaikuttavat muun muassa rationaalisuuden ja empatian käsitteet. Analyysini perusteella kävi ilmi, että erityisen yleinen koodinvaihdon funktio on mahdollistaa intertekstuaalisuus, jolla edelleen voidaan ilmaista esimerkiksi solidaarisuutta eli sosiaalista läheisyyttä tai loukata puhuteltavaa. Solidaarisuus oli myös ilman intertekstuaalisuutta yleinen koodinvaihdon funktio. Näiden lisäksi koodinvaihdon funktioita olivat muun muassa kasvoja uhkaavat teot, eufemismit, stilistiset efektit sekä diskurssin avustaminen. Syntaktisten ilmenemismuotojen osalta keskeisin havainto oli, että koodinvaihdon ja lainaamisen erottaminen ei ole tarpeellista tai edes kannattavaa kaikissa tilanteissa. Lisäksi voitiin todeta, että valittu metodi soveltui hyvin aineiston analysoimiseen, ja sitä tulisi soveltaa mahdollisuuksien mukaan laajempaan materiaaliin sekä muiden pragmaattisten ilmiöiden tutkimiseen.

Management of commercial property derived risks in the market context of the Russian Federation

The objective of the thesis is to examine the current state of risk management and to determine an appropriate risk management policy for commercial property derived risks in the Russian branch of a Finnish retail trade company. The employed research methodologies are comparative in-depth interviews and empirical value at risk analysis, including portfolio risk decomposition to determine the inter-currency characteristics. For a multinational retail trade company, the commercial property derived risks open up as a diverse combination of financial and non-financial risks with four distinctive interest groups. The research results indicate that geographical diversification across currency regimes provides diversification benefits. The Russian ruble is the most significant single risk component when considering the net investments outside the euro-zone. Decreasing the Russian ruble and Swedish krona exposures are the most effective methods to reduce translation derived risk. Exchange rate volatility varies over time according to idiosyncratic currency regime characteristics, and cost-effective risk management requires comprehensive analysis of the business environment. Profound and proactive risk management methods are found to be pivotal for companies with cross-border operations in order to succeed among international competitors.

TR(i)P, TR(i)P, hooray : new functions for TRPC2 and TRPC3

Kalciumjonen påverkar många aspekter av cellbiologi, från fertiliseringen av äggcellen till tillväxt och differentiering av alla typer av celler. Störningar i hur kalciumjonerna transporteras in och friges i cellerna kan ha stor betydelse för hur sjukdomar framskrider. På grund av detta är det viktigt att studera hur kalciumtransportörer såsom kalciumkanaler fungerar och hur de påverkar cellernas funktioner. I avhandlingen har klassiska transient receptorpotential (TRPC) katjonkanaler studerats. Dessa kanaler är permeabla för kalcium och aktiveras nedströms av G-proteinkopplade receptorer. Resultaten som presenteras i avhandlingen visar på nya funktioner för TRPC2- och TRPC3-kanalerna. Utöver TRPC3-kanalens roll i plasmamembranen, där den medverkar i receptorreglerat kalciuminflöde, tyder våra resultat på att TRPC3 har en potentiell intracellulär roll. Vid överuttryck av kanalen lokaliserade kanalen till endoplasmatiska nätverket där kanalen friger intracellulärt kalcium. TRPC2 har en viktig funktion i möss där kanalen reglerar hur djuret reagerar på feromoner. Våra resultat tyder på att TRPC2 är involverad i autokrin sfingosin-1-fosfat (S1P)-signalering. S1P som produceras i cellerna transporterades ut från cellerna varpå det aktiverade S1P2-receptorer på plasmamembranen. Diacylglycerol som bildas som en följd av aktivering av S1P2-receptorn aktiverade i sin tur inflöde av extracellulärt kalcium. Våra resultat indikerar att TRPC2 är kanalen som förmedlar detta kalciuminflöde. I sköldkörtelceller studerades nedströms effekter för TRPC2. Kanalen reglerade negativt cAMP-produktionen i cellerna vilket hämmar extracellulärt signalreglerat kinas 1/2 (ERK1/2). När uttrycket för TRPC2 minskades i cellerna, ökades produktionen av cAMP och fosforyleringen av ERK1/2, vilket resulterade i ökat uttryck för receptorn för sköldkörtelstimulerande hormon. Slutligen, presenterar vi resultat som tyder på att TRPC2 är viktigt för sekretion av prekursorn till sköldkörtelhormon.

Influence of distal ileum exclusion on hepatic and renal functions in presence of extrahepatic cholestasis

OBJECTIVE: To verify whether the ileal exclusion interferes with liver and kidney functional changes secondary to extrahepatic cholestasis.METHODS: We studied 24 rats, divided into three groups with eight individuals each: Group 1 (control), Group 2 (ligation of the hepatic duct combined with internal biliary drainage), and Group 3 (bile duct ligation combined with internal biliary drainage and exclusion of the terminal ileum). Animals in Group 1 (control) underwent sham laparotomy. The animals of groups 2 and 3 underwent ligation and section of the hepatic duct and were kept in cholestasis for four weeks. Next, they underwent an internal biliary bypass. In Group 3, besides the biliary-enteric bypass, we associated the exclusion of the last ten centimeters of the terminal ileum and carried out an ileocolic anastomosis. After four weeks of monitoring, blood was collected from all animals of the three groups for liver and kidney biochemical evaluation (albumin, ALT, AST, direct and indirect bilirubin, alkaline phosphatase, cGT, creatinine and urea).RESULTS: there were increased values of ALT, AST, direct bilirubin, cGT, creatinine and urea in rats from Group 3 (p < 0.05).CONCLUSION: ileal exclusion worsened liver and kidney functions in the murine model of extrahepatic cholestasis, being disadvantageous as therapeutic procedure for cholestatic disorders.

Implementation of a trauma registry in a brazilian public hospital: the first 1,000 patients

OBJECTIVE: Show the steps of a Trauma Registry (TR) implementation in a Brazilian public hospital and evaluate the initial data from the database.METHODS: Descriptive study of the a TR implementation in João XXIII Hospital (Hospital Foundation of the state of Minas Gerais) and analysis of the initial results of the first 1,000 patients.RESULTS: The project was initiated in 2011 and from January 2013 we began collecting data for the TR. In January 2014 the registration of the first 1000 patients was completed. The greatest difficulties in the TR implementation were obtaining funds to finance the project and the lack of information within the medical records. The variables with the lowest completion percentage on the physiological conditions were: pulse, blood pressure, respiratory rate and Glasgow coma scale. Consequently, the Revised Trauma Score (RTS) could be calculated in only 31% of cases and the TRISS methodology applied to 30.3% of patients. The main epidemiological characteristics showed a predominance of young male victims (84.7%) and the importance of aggression as a cause of injuries in our environment (47.5%), surpassing traffic accidents. The average length of stay was 6 days, and mortality 13.7%.CONCLUSION: Trauma registries are invaluable tools in improving the care of trauma victims. It is necessary to improve the quality of data recorded in medical records. The involvement of public authorities is critical for the successful implementation and maintenance of trauma registries in Brazilian hospitals.

Implementation of the trauma registry as a tool for quality improvement in trauma care in a brazilian hospital: the first 12 months

ABSTRACTObjective:to analyze the implementation of a trauma registry in a university teaching hospital delivering care under the unified health system (SUS), and its ability to identify points for improvement in the quality of care provided.Methods:the data collection group comprised students from medicine and nursing courses who were holders of FAPESP scholarships (technical training 1) or otherwise, overseen by the coordinators of the project. The itreg (ECO Sistemas-RJ/SBAIT) software was used as the database tool. Several quality "filters" were proposed to select those cases for review in the quality control process.Results:data for 1344 trauma patients were input to the itreg database between March and November 2014. Around 87.0% of cases were blunt trauma patients, 59.6% had RTS>7.0 and 67% ISS<9. Full records were available for 292 cases, which were selected for review in the quality program. The auditing filters most frequently registered were laparotomy four hours after admission and drainage of acute subdural hematomas four hours after admission. Several points for improvement were flagged, such as control of overtriage of patients, the need to reduce the number of negative imaging exams, the development of protocols for achieving central venous access, and management of major TBI.Conclusion: the trauma registry provides a clear picture of the points to be improved in trauma patient care, however, there are specific peculiarities for implementing this tool in the Brazilian milieu.

Intellectual Property Protection in China in the Cases of Outsourcing and own Manufacturing

The intellectual property (IP) environment in China is still very immature. There are several problems in legal, political, economic, social-cultural, competitive and labor environment which have hindered IP legal enforcement. Under such circumstances, IP misappropriation is a major concern especially for foreign small and medium-sized enterprises (SMEs) doing business in China. These circumstances require foreign companies, no matter whether they are multinational corporations (MNCs) or SMEs and have own manufacturing in China or not, to take strong IP actions. Therefore, the purpose of this study is to discuss how IP can be protected in China in the case of outsourcing and in the case of own manufacturing. The comparison will consider the process of outsourcing and own manufacturing consisting two stages: preparation stage and operation stage. In order to clarify the conceptual arguments, two illustrative case studies were studied. The case data bases on two semi-structured interviews of the managing directors, field notes and archival data. The findings propose that attention in IP protection should be given to following issues: integrating IP strategy into the company’s business strategy, protecting the most critical knowledge, regarding IP steps as a whole in the protection mechanism and making IP strategy as proactive as possible. The major difference between outsourcing and own manufacturing in IP protection is in the operation stage. Besides, the findings also provide managerial advice on IP protection, e.g. foreign managers should be prepared for IP risks in China, they should establish an own IP protection mechanism which matches the company’s situation and they should consider IP protection as an on-going process.

Localization, Frequency, and Functions of Filled Pauses: Five American Politicians’ Use of er and erm in the Talk Show Larry King Live

Tämän pro gradu– tutkielman tavoitteena oli testata täytettyjen taukojen (er ja erm) esiintymistiheyttä, sijaintia kieliopillisessa rakenteessa sekä funktioita Kjellmerin (2003) korpus-tutkimuksessa. Materiaalina käytin viiden yhdysvaltalaisen poliitikon puhetta keskusteluohjelmasta Larry King Live. Tutkimuksessani sovelsin Kjellmerin tutkimusmenetelmiä, joita muokkasin huomattavasti suppeampaan materiaaliini sopiviksi. Lähestymistapani oli täten induktiivinen toisin kuin testatussa tutkimuksessa. Materiaalini oli tarkoituksellisesti rajattu, sillä halusin selvittää, kuvaavatko Kjellmerin laajaan materiaaliin perustuvat tutkimustulokset myös täytettyjen taukojen käyttöä suppeammassa materiaalissa. Materiaalini (kokonaisuudessaan 101 minuuttia) transkriboin ortografisesti. Analyysissäni arvioin täytettyjen taukojen esiintymistiheyden puhujakohtaisesti ja koko ryhmälle suhteuttamalla täytettyjen taukojen lukumäärän kokonaissanamäärään. Tämän jälkeen tein perinteisen kielioppianalyysin rakenteista, joita edeltää tai joissa esiintyy täytetty tauko, ja täytettyjen taukojen sijainnin perusteella luokittelin ne sana-, lauseke-, ja lausetasolle. Lopuksi analysoin täytettyjen taukojen käyttöä soveltaen Kjellmerin ehdottamia funktioita (hesitaatio, vuorottelujäsennyksen merkitseminen, huomion herättäminen ja kontaktin luominen, korostus ja korjaus) ja niiden piirteitä omaan materiaaliini. Tutkimukseni perusteella täytetyt tauot esiintyvät tutkitun viiden poliitikon puheessa suhteellisen usein. Puhujakohtaiset eroavaisuudet olivat kuitenkin huomattavat. Kieliopillisen luokitteluni mukaan sana-, lauseke- ja lausetasot eivät täysin kuvaa täytettyjen taukojen sijoittumista, sillä täytetyt tauot edelsivät mm. määre-lauseita, jotka eivät vastaa lausetasoa englannin kielessä. Materiaalini funktioanalyysi osoitti, että täytetyt tauot yleensä vastaavat yhtä tai useampaa Kjellmerin ehdottamaa funktioita. Lisäksi tutkimukseni mukaan täytetyillä tauoilla on ainakin yksi rakenteellinen funktio. Analyysini perusteella Kjellmerin tutkimustulokset ovat siis pääosin sovellettavissa suppeampaan materiaaliin. Puutteiksi hänen tutkimuksessaan osoittautuivat funktioanalyysille tärkeän kontekstuaalisen informaation puute sekä keskittyminen täytettyihin taukoihin, jotka esiintyvät vain tietyissä kielioppirakenteissa. Yleisesti voin tutkimukseni pohjalta todeta, että täytetyt tauot ovat vielä vajaasti tunnettuja ja että kieliopillisen sijoituksen ja funktioiden lisätutkimus on tarpeellista.

Novel Functions of ErbB4 and NRG-1 in Development and Cancer

Cells communicate, or signal, with each other constantly to ensure proper functioning of tissues and organs. Cell signaling is often performed by interplay of receptors and ligands that bind these receptors. ErbB receptors (epidermal growth factor receptors, EGFR, HER) bind extracellular growth factors and transduce these signals inside of cells. ErbB dysfunction promotes carcinogenesis, and also results in numerous defects during normal development. This study focused on the functions of one member of the ErbB receptor family, ErbB4, and growth factor, neuregulin-1 (NRG-1), that can bind and activate ErbB4. This study aimed to find novel functions of ErbB4 and NRG-1. Hypoxia, or deficiency of oxygen, is common in cancer and ischemic conditions. One of the key findings of the work was the identification and characterization of a cross-talk between ErbB4 and Hypoxia-inducible factor 1α (HIF-1α), the central mediator of hypoxia signaling. ErbB4 activation by NRG-1 was found to increase HIF-1α activity. Interestingly, this regulation occurred in reciprocal manner as HIF-1α was also able to increase protein levels of NRG-1 and ErbB4. Moreover, expression of NRG-1 and ErbB4 was associated with HIF activity in vivo in human clinical samples and in mice. Reduction of functional ErbB4 in developing zebrafish embryos resulted in defects in development of the skeletal muscles. To study ErbB4 functions in pathological situation in humans, clinical samples of serous ovarian carcinoma were analyzed using tissue microarrays and real-time RT-PCR. A specific isoform of ErbB4, CYT-1, was associated with poor survival in serous ovarian cancer and increased anchorage independent growth of ovarian cancer cells in vitro. These observations demonstrate that ErbB4 and NRG-1 are essential regulators of cellular response to hypoxia, of development, and of ovarian carcinogenesis.

Training executive functions in the laboratory and in real life : cognitive consequences of computer-based exercises and bilingualism

The question of the trainability of executive functions and the impact of such training on related cognitive skills has stirred considerable research interest. Despite a number of studies investigating this, the question has not yet been solved. The general aim of this thesis was to investigate two very different types of training of executive functions: laboratory-based computerized training (Studies I-III) and realworld training through bilingualism (Studies IV-V). Bilingualism as a kind of training of executive functions is based on the idea that managing two languages requires executive resources, and previous studies have suggested a bilingual advantage in executive functions. Three executive functions were studied in the present thesis: updating of working memory (WM) contents, inhibition of irrelevant information, and shifting between tasks and mental sets. Studies I-III investigated the effects of computer-based training of WM updating (Study I), inhibition (Study II), and set shifting (Study III) in healthy young adults. All studies showed increased performance on the trained task. More importantly, improvement on an untrained task tapping the trained executive function (near transfer) was seen in Study I and II. None of the three studies showed improvement on untrained tasks tapping some other cognitive function (far transfer) as a result of training. Study I also used PET to investigate the effects of WM updating training on a neurotransmitter closely linked to WM, namely dopamine. The PET results revealed increased striatal dopamine release during WM updating performance as a result of training. Study IV investigated the ability to inhibit task-irrelevant stimuli in bilinguals and monolinguals by using a dichotic listening task. The results showed that the bilinguals exceeded the monolinguals in inhibiting task-irrelevant information. Study V introduced a new, complementary research approach to study the bilingual executive advantage and its underlying mechanisms. To circumvent the methodological problems related to natural groups design, this approach focuses only on bilinguals and examines whether individual differences in bilingual behavior correlate with executive task performances. Using measures that tap the three above-entioned executive functions, the results suggested that more frequent language switching was associated with better set shifting skills, and earlier acquisition of the second language was related to better inhibition skills. In conclusion, the present behavioral results showed that computer-based training of executive functions can improve performance on the trained task and on closely related tasks, but does not yield a more general improvement of cognitive skills. Moreover, the functional neuroimaging results reveal that WM training modulates striatal dopaminergic function, speaking for training-induced neural plasticity in this important neurotransmitter system. With regard to bilingualism, the results provide further support to the idea that bilingualism can enhance executive functions. In addition, the new complementary research approach proposed here provides some clues as to which aspects of everyday bilingual behavior may be related to the advantage in executive functions in bilingual individuals.