Male mutation bias and possible long-term effects of human activities.

The ability of a population to adapt to changing environments depends critically on the amount and kind of genetic variability it possesses. Mutations are an important source of new genetic variability and may lead to new adaptations, especially if the population size is large. Mutation rates are extremely variable between and within species, and males usually have higher mutation rates as a result of elevated rates of male germ cell division. This male bias affects the overall mutation rate. We examined the factors that influence male mutation bias, and focused on the effects of classical life-history parameters, such as the average age at reproduction and elevated rates of sperm production in response to sexual selection and sperm competition. We argue that human-induced changes in age at reproduction or in sexual selection will affect male mutation biases and hence overall mutation rates. Depending on the effective population size, these changes are likely to influence the long-term persistence of a population.

Structure of the extracellular domains of human and Xenopus Fn14: implications in the evolution of TWEAK and Fn14 interactions.

TWEAK (TNF homologue with weak apoptosis-inducing activity) and Fn14 (fibroblast growth factor-inducible protein 14) are members of the tumor necrosis factor (TNF) ligand and receptor super-families. Having observed that Xenopus Fn14 cross-reacts with human TWEAK, despite its relatively low sequence homology to human Fn14, we examined the conservation in tertiary fold and binding interfaces between the two species. Our results, combining NMR solution structure determination, binding assays, extensive site-directed mutagenesis and molecular modeling, reveal that, in addition to the known and previously characterized β-hairpin motif, the helix-loop-helix motif makes an essential contribution to the receptor/ligand binding interface. We further discuss the insight provided by the structural analyses regarding how the cysteine-rich domains of the TNF receptor super-family may have evolved over time. DATABASE: Structural data are available in the Protein Data Bank/BioMagResBank databases under the accession codes 2KMZ, 2KN0 and 2KN1 and 17237, 17247 and 17252. STRUCTURED DIGITAL ABSTRACT: TWEAK binds to hFn14 by surface plasmon resonance (View interaction) xeFn14 binds to TWEAK by enzyme linked immunosorbent assay (View interaction) TWEAK binds to xeFn14 by surface plasmon resonance (View interaction) hFn14 binds to TWEAK by enzyme linked immunosorbent assay (View interaction).

Implementation of Customer Relationship Management Strategy in Pulp Company

Työn tarkoituksena oli löytää Asiakkuuksienhallintastrategian käyttöönoton ongelmakohtia asiakkuuksienhallintaan erikoistuneen konsulttiyrityksen asiakasyrityksen taholta. Lisäksi työssä etsitään ratkaisuja asiakkuusteorian viemiseksi käytäntöön. Työn anti on asiakkuusstrategian käytäntöön panon ongelmakohtien paikallistaminen, prosessin vaiheiden kuvaaminen sekä asiakkuuksienhallinnan tutkiminen lähtökohtana asiakkaalle tuotettu arvo. Asiakkuusstrategian implementoinnin ongelmakohtien ja kriittisten menestystekijöiden kuvaus ja vertailu käsitellään empiirisessä osassa suhteuttaen teoriaosuuden materiaaliin. CRM Group:n kannalta työ mahdollistaa osaltaan asiakasprojektien kehitystyön.Kirjallisuusosan pohjalta implementoinnin kannalta kriittisiksi menestystekijöiksi nousivat tietoteknisten ratkaisujen sulauttaminen osaksi asiakkuusstrategiaa tukevia toimintoja, aidon synergian löytäminen asiakas – toimittaja –suhteeseen sekä asiakkuusstrategiaa kehittävän organisaation sisäinen resursointi ja henkilöstön sitouttaminen.

Transport Resource Management within UMTS Radio Network Subsystem

Tällä hetkellä haastavin telekommunikaatioteollisuuden tutkimus – ja kehitystoiminta on keskittynyt kolmannen sukupolven matkapuhelinjärjestelmien ympärille. Järjestelmien standardointityössä on saatu aikaiseksi ensimmäiset vakaat spesifikaatioversiot ja kaupallista toimintaa ollaan parhaillaan aloittelemassa Japanissa ja Euroopassa. Eräs kolmannen sukupolven järjestelmistä on UMTS (Universal Mobile Telecommunications System). Tämä diplomityö antaa yleiskuvan UMTS järjestelmästä ja sen eri verkkoelementtien toiminnallisuuksista. Päähuomio on kiinnitetty radioverkkojärjestelmään (UMTS Terrestrial Radio Access Network) ja erityisesti sen radioaliverkkojärjestelmään (Radio Network Subsystem), joka koostuu radioverkonohjaimesta (Radio Network Controller) ja joukosta siihen kuuluvia tukiasemia (Node B). Radioverkonohjain ja tukiasemat on yhdistetty avoimen rajapinnan kautta jota kutsutaan Iub -rajapinnaksi. Rajapinta tarjoaa radioverkonohjaimelle mahdollisuuden kontrolloida tukiasemia signalointiviestien avulla ja mahdollistaa tehokkaan ja luotettavan käyttäjätiedon siirron radioaliverkkojärjestelmän sisällä. Tämän diplomityön pääasiallinen sisältö on siirtoresurssien hallinta Iub -rajapinnan ylitse. Työssä esitellään ja selitetään siirtoverkon arkkitehtuuri. Myös kaikki Iub:ssä sijaitsevat protokollat ja toiminnalliset yksiköt jotka vaikuttavat siirtoresurssien hallintaan esitellään ja kuvataan yksityiskohtaisesti. Päähuomio on kiinnitetty sovellusprotokolliin sekä rajapinnan siirtoverkko- että radioverkkokerroksella sekä näiden protokollien väliseen vuorovaikutukseen. Kyseiset protokollat ovat Node B Application Part (NBAP) ja Access Link Control Application Part (ALCAP). Työn toteutusosassa käydään lävitse NBAP –protokollan prototyypin ja Node B Manager –toiminnallisen yksikön prototyypin implementaatio.

Integrating Group Support Systems to innovation process of a forest company

The objective of this study was to analyze the effects of Group Support Systems (GSS) to overall efficiency of innovation process. Overall efficiency was found to be a sum of meeting efficiency, product effectiveness, and learning efficiency. These components were studied in various working situations common in early stages of innovation process. In the empirical part of this study, the suitability of GSS at the forest company was assessed. The basics for this study were idea generation meetings held at LUT and results from the surveys done after the sessions. This data combined with the interviews and theoretical background was used to analyze suitability of this technology to organizational culture at the company. The results of this study are divided to theory and case level. On theory level GSS was found to be a potentially valuable tool for innovation managers, especially at the first stages of the process. On case level, GSS was found to be a suitable tool at Stora Enso for further utilization. A five step implementation proposal was built to illustrate what would be the next stages of GSS implementation, if technology was chosen for further implementation.

Human Capital Questionnaire (PHCQ): Assessment of European nurses' perception as indicators of human capital quality

Healthcare accreditation models generally include indicators related to healthcare employees' perceptions (e.g. satisfaction, career development, and health safety). During the accreditation process, organizations are asked to demonstrate the methods with which assessments are made. However, none of the models provide standardized systems for the assessment of employees. In this study, we analyzed the psychometric properties of an instrument for the assessment of nurses' perceptions as indicators of human capital quality in healthcare organizations. The Human Capital Questionnaire was applied to a sample of 902 nurses in four European countries (Spain, Portugal, Poland, and the UK). Exploratory factor analysis identified six factors: satisfaction with leadership, identification and commitment, satisfaction with participation, staff well-being, career development opportunities, and motivation. The results showed the validity and reliability of the questionnaire, which when applied to healthcare organizations, provide a better understanding of nurses' perceptions, and is a parsimonious instrument for assessment and organizational accreditation. From a practical point of view, improving the quality of human capital, by analyzing nurses and other healthcare employees' perceptions, is related to workforce empowerment.

Johdon ja keskijohdon rekrytointiprosessin kehittäminen Suomessa Case: UPM-Kymmene Oyj

Tutkielman tarkoituksena on olla kehittämässä UPM-Kymmenen johdon ja keskijohdon rekrytointiprosessia. Tavoitteena on tutkia osaamisniukkuuden aiheuttaman riskin minimoimista, hyvien työntekijöiden palkkaamista ja kuinka työntekijät saadaan pysymään yhtiön palveluksessa. Tutkimusmenetelmä on kvalitatiivinen. Se perustuu muun muassa rekrytointiryhmän kokousten materiaaleihin ja muihin sisäisiin raportteihin sekä haastatteluun. Johdon ja keskijohdon kohdalla mahdollisia rekrytoitavia on vähän, joten heidän pysyvyytensä yrityksen palveluksessa tulee varmistaa. Uuden työntekijän löytäminen on usein vaikeaa ja rekrytointikustannukset ovat suuria. Osaamisniukkuutta voidaan välttää hyvällä henkilöstösuunnittelulla.

The Strategic Intent and Launching of a Knowledge Management Tool in a Complex Organisation, case Stora Enso Consumer Boards

Informaatiotulva ja organisaation monimutkaisuus luoneet tarpeen tietämyksen hallinnalle. Tämän tutkimuksen tavoitteena on tunnistaa muutostarpeet, jotka portaalin käyttöönotto tietämyksenhallintatyökaluna luo. Tutkimuksessa verrataan myös uusia työkaluja olemassa oleviin sekä arvioidaan organisaation kykyä siirtää tietämystä virtuaalisesti. Kirjallisuutta vastaavanlaisista projekteista ei ole ollut saatavilla, sillä käyttöönotettava teknologia on melko uutta. Samaa teknologiaa on käytössä hieman eri alueella, kuin tässä projektissa on tavoitteena. Tutkimus on tapaustutkimus, jonka pääasialliset lähteet ovat erilaisissa kokouksissa tuotettuja dokumentteja. Tutkija on osallistunut aktiivisesti projektityöhön, joten osa taustatiedoista perustuu tutkijan huomioihin sekä vielä keskusteluihin. Teoriaosassa käsitellään tietämyksen jakamista tietämyksen hallinnan ja virtuaalisuuden näkökulmasta. Muutoksen hallintaa on käsitelty lyhyesti tietämyksenhallintatyökalun käyttöönotossa. Tutkimus liittyy Stora Enso Consumer Boardsin tietämyksen hallintaprojektiin.

Safety of human immunisation with a live-attenuated Mycobacterium tuberculosis vaccine: a randomised, double-blind, controlled phase I trial.

BACKGROUND: Tuberculosis remains one of the world's deadliest transmissible diseases despite widespread use of the BCG vaccine. MTBVAC is a new live tuberculosis vaccine based on genetically attenuated Mycobacterium tuberculosis that expresses most antigens present in human isolates of M tuberculosis. We aimed to compare the safety of MTBVAC with BCG in healthy adult volunteers. METHODS: We did this single-centre, randomised, double-blind, controlled phase 1 study at the Centre Hospitalier Universitaire Vaudois (CHUV; Lausanne, Switzerland). Volunteers were eligible for inclusion if they were aged 18-45 years, clinically healthy, HIV-negative and tuberculosis-negative, and had no history of active tuberculosis, chemoprophylaxis for tuberculosis, or BCG vaccination. Volunteers fulfilling the inclusion criteria were randomly assigned to three cohorts in a dose-escalation manner. Randomisation was done centrally by the CHUV Pharmacy and treatments were masked from the study team and volunteers. As participants were recruited within each cohort, they were randomly assigned 3:1 to receive MTBVAC or BCG. Of the participants allocated MTBVAC, those in the first cohort received 5 × 10(3) colony forming units (CFU) MTBVAC, those in the second cohort received 5 × 10(4) CFU MTBVAC, and those in the third cohort received 5 × 10(5) CFU MTBVAC. In all cohorts, participants assigned to receive BCG were given 5 × 10(5) CFU BCG. Each participant received a single intradermal injection of their assigned vaccine in 0·1 mL sterile water in their non-dominant arm. The primary outcome was safety in all vaccinated participants. Secondary outcomes included whole blood cell-mediated immune response to live MTBVAC and BCG, and interferon γ release assays (IGRA) of peripheral blood mononuclear cells. This trial is registered with ClinicalTrials.gov, number NCT02013245. FINDINGS: Between Jan 23, 2013, and Nov 6, 2013, we enrolled 36 volunteers into three cohorts, each of which consisted of nine participants who received MTBVAC and three who received BCG. 34 volunteers completed the trial. The safety of vaccination with MTBVAC at all doses was similar to that of BCG, and vaccination did not induce any serious adverse events. All individuals were IGRA negative at the end of follow-up (day 210). After whole blood stimulation with live MTBVAC or BCG, MTBVAC was at least as immunogenic as BCG. At the same dose as BCG (5×10(5) CFU), although no statistical significance could be achieved, there were more responders in the MTBVAC group than in the BCG group, with a greater frequency of polyfunctional CD4+ central memory T cells. INTERPRETATION: To our knowledge, MTBVAC is the first live-attenuated M tuberculosis vaccine to reach clinical assessment, showing similar safety to BCG. MTBVAC seemed to be at least as immunogenic as BCG, but the study was not powered to investigate this outcome. Further plans to use more immunogenicity endpoints in a larger number of volunteers (adults and adolescents) are underway, with the aim to thoroughly characterise and potentially distinguish immunogenicity between MTBVAC and BCG in tuberculosis-endemic countries. Combined with an excellent safety profile, these data support advanced clinical development in high-burden tuberculosis endemic countries. FUNDING: Biofabri and Bill & Melinda Gates Foundation through the TuBerculosis Vaccine Initiative (TBVI).

Dominant-Negative Effects of Adult-Onset Huntingtin Mutations Alter the Division of Human Embryonic Stem Cells-Derived Neural Cells.

Mutations of the huntingtin protein (HTT) gene underlie both adult-onset and juvenile forms of Huntington's disease (HD). HTT modulates mitotic spindle orientation and cell fate in mouse cortical progenitors from the ventricular zone. Using human embryonic stem cells (hESC) characterized as carrying mutations associated with adult-onset disease during pre-implantation genetic diagnosis, we investigated the influence of human HTT and of an adult-onset HD mutation on mitotic spindle orientation in human neural stem cells (NSCs) derived from hESCs. The RNAi-mediated silencing of both HTT alleles in neural stem cells derived from hESCs disrupted spindle orientation and led to the mislocalization of dynein, the p150Glued subunit of dynactin and the large nuclear mitotic apparatus (NuMA) protein. We also investigated the effect of the adult-onset HD mutation on the role of HTT during spindle orientation in NSCs derived from HD-hESCs. By combining SNP-targeting allele-specific silencing and gain-of-function approaches, we showed that a 46-glutamine expansion in human HTT was sufficient for a dominant-negative effect on spindle orientation and changes in the distribution within the spindle pole and the cell cortex of dynein, p150Glued and NuMA in neural cells. Thus, neural derivatives of disease-specific human pluripotent stem cells constitute a relevant biological resource for exploring the impact of adult-onset HD mutations of the HTT gene on the division of neural progenitors, with potential applications in HD drug discovery targeting HTT-dynein-p150Glued complex interactions.

Regional variability in the impact of human capital on regional growth

The first objective of this study is to furnish new evidence concerning the aggregate profitability of the accumulation of human capital. In addition to the traditional measure of the return to human capital, combining the information on its shadow price with the social cost of providing education allows us to confirm the profitability of human capital investments as a tool for promoting economic growth. The possibility of obtaining estimations of these effects for each Spanish region enables us to empirically evaluate the amount of heterogeneity across economies in the effects of human capital. As a second objective, we provide evidence on the indirect effect of human capital in making private capital investment more attractive. Among the main explanations for this process, we observe that higher worker skill levels enable higher returns to be extracted from investment in physical capital.

Development of IT Service Management in a Large International Company

The purpose of this Master’s thesis is to examine the IT Service Management (ITSM) capabilities of a large international company and develop a design for the IT Service Management of the company. The thesis consists of two parts: a literature review and a case study. The first part is the literature review. It examines different aspects of IT Service Management. The purpose of the literature review is to increase the credibility of the case study. In the case study, the IT Service Management of a large industrial company is assessed, and an improved design for IT Service Management is created. The services are limited to common IT services, and management is limited to operative management. To assess and develop the case company’s IT Service Management, the IT organization and its ITSM capabilities are analyzed, and on the basis of the analyses, an improved IT Service Management model is created. As a result of the analyses, it was found out that the management of the IT organization is function-oriented. Therefore, the organization needs a management model that breaks the functional borders and brings services to the center of management. The designed model aspires to achieve this by defining IT services and modeling management processes from the service perspective.

Henkilöstöresurssien organisointi suuren alusöljyvahingon torjunnassa

Tässä pro gradu -tutkielmassa tarkastellaan henkilöstöresurssien organisointia suuren alusöljyvahingon torjuntatilanteessa. Tavoitteena on suunnitella Suomenlahden rannikon öljyntorjunnasta vastaavien viranomaisten käyttöön optimaalinen rekrytointistrategia pahimman todennäköisen alusöljyvahingon varalle. Tutkimuksessa selvitetään myös millainen työsopimus öljyntorjuntatyöntekijöiden kanssa voidaan sopia. Näiden lisäksi etsitään vastausta siihen,kuinka työvoima saadaan pidettyä. Tämän laadullisen tutkimuksen teoreettinen osuus toteutettiin kirjallisuuskatsauksena. Tutkimuksen empiirinen aineisto kerättiin haastattelemalla yhdeksää asiantuntijaa syksyn 2009 aikana. Haastattelut olivat muodoltaan puolistrukturoituja teemahaastatteluja. Tutkimustulosten mukaan merkittävin lisätyövoiman tarve ilmenee käsin tehtävässä rantapuhdistustyössä. Etenkin puhdistustyön pitkittyessä pelastusviranomaiset tarvitsevat avukseen ulkopuolista työvoimaa. Rekrytointi suoritetaan muutamien viikkojen kuluessa öljyvahingon aiheutumisen jälkeen. Alueellinen pelastuslaitos suorittaa rekrytoinnin käyttäen tehokkaita, laajan kohderyhmän tavoittavia rekrytointiviestinnän välineitä (esim. sanomalehdet, TV ja Internet). Työntekijöiden kanssa sovitaan määräaikainen, Kunnallista virkaja työehtosopimusta noudattava työsopimus. Tärkeimpinä puhdistustyöntekijöitä motivoivina tekijöinä nähdään työn merkitys yhteiskunnalle, selkeästi määritelty, saavutettavissa oleva tavoite sekä palaute tehdystä työstä.

Customer consciousness in the production process of a steel factory

The purpose of this thesis is to examine the level of customer consciousness of the production process employees in a steel factory and to investigate the methods of internal marketing in order to propose development practices to enhance the customer consciousness of the case company employees. The significance of the level of customer consciousness is discussed and practices already implemented affecting the level of customer consciousness in the company are examined. The literature review gives an insight to the role of customer consciousness in the CRM philosophy of a manufacturing company and examines the means of internal marketing in enhancing customer consciousness. In the empirical part of the study, the level and significance of customer consciousness is determined by conducting individual and focus group interviews. The interviews are also used to examine the practices that could function in enhancing the customer consciousness of the employees. Development suggestions to improve the level of customer consciousness in the production process are given based on the results. The level of customer consciousness is at a poor level in the production process and influences above all on work motivation and job satisfaction, but possibly on customer satisfaction as well. The enhancement of customer consciousness in the production process should be done e.g. by ensuring the distribution of right knowledge coherently to all of the employees, gathering large customer reference database to exploit in work and in training, using visual illustration in presenting the customer information, training proactively and letting the employees to participate in the customer oriented development activities. Customer satisfaction focused reward system can be considered.

The Process of Greening Cycle as Method of Operative Environmental

The structural change of society from product-based business to service- and further to need-based business has caused the fact that work for environmental issues has spread from conventional factories and environmentally harmful production to concern services and offices as well. Almost every company has an office, so a relatively small environmental burden caused by an individual office grows remarkable already at the state level and globally even more. Motivation to work for environmental issues in an individual office could be challenging even without the fact that wasted environmental impacts bound also wasted costs. Besides cost savings, a concretely greener image of a company has its value in the B2Cas well as in the B2B-field. Consumers and clients are more and more conscious of environmental issues and demand concrete actions instead of speeches, good thoughts and meaningless certifications. Internal work for environmental issues at a strategy level is not sufficient, so operational environmental management is needed for changing old practices. This research is about the effects of operative environmental management on the greening process of an office-based business. The research is outlined to concern the operative work in the office including field sales. Target was to concretely lower the environmental impacts of Lyreco Finland and to find cost savings directly by changing the operative practices in the office and also indirectly by affecting the level of environmental knowledge of the personnel. During the greening process, the aim was also to create concrete arguments for marketing as well. The circle of greening process, which was especially created for this diploma work, was used as a method. The circle divides a year to themes and sections separated by factors of environmental impacts. Separation is based on Brett Wills’ thoughts of seven green wastes (Wills, Brett. The Green Intensions. 2009) and follows it uneasily. The circle aimed at ensuring evolutionary growth of knowledge instead of being revolutionary in the changing process. Committing personnel to the process from its start by asking ideas from them and giving them clear directions was an important part of the research of operative management. Because of working from distance, communication with personnel was operated by frequent training days and weekly greening notes via emails and intranet. Also availability for communication was an important task because of the telecommuting. Research results of this work show that operative environmental management in an officebased business today is mostly management of change. When the strategic environmental friendliness is taken into a concrete level, the most important individual factor is motivating the operating personnel. Research shows that evolutionary change is found being an efficient way to make a change. Also understanding one´s own impact on the environmental burden and on the whole greening process clearly motivates the personnel. Results show that in the operative realization of the greening process, clear directions of new working practices, being as concrete as possible, and committing personnel to follow them make the process more effective. The operative environmental management and the cycle of the greening process decrease the environmental burden and save costs. The concrete results could be used as believable arguments in marketing and therefore exploited in communication with interest groups. Commitment of the management is also one of the key factors of success in the greening process. In this research, changes in the business field by a company trade took the focus of the management away from the greening process and made the process more inefficient by decreasing the amount of training days. The circle of greening process will be used as a tool in the future, as well, and therefore it will help observe environmental impacts of a company and increase sustainable development. Commitment of management to the evolutionary environmental work helps the operating personnel lower environmental impacts, decrease costs and build a concretely greener image.