Lojalitet i licensavtal

Loyalty in Licensing Agreements The purpose of the dissertation is to analyse the impact of the principle of loyalty on licensing agreements from the viewpoint of Finnish law using the traditional legal method (Rechtsdogmatik) combined with empirical data in the form of licensing agreements. The need for good licensing agreements is crucial. One should avoid mechanical and stereotyped agreements in favour of more conscious and goal-oriented ones. When the parties' will and goals have been made clear, the drafting technique should be chosen accordingly. The importance of the principle of loyalty in the interpretation of licensing agreements varies according to their degree of relationality. This is a concept originating in the relational contract theory, more precisely Ian Macneil's spectrum of contracts, where contracts can be placed on an axis according to their degree of relationality. In the dissertation different factors are used to conclude whether the licensing agreement at hand is to be placed on the axis closer to the transactional pole or closer to the relational pole. A conclusion of the dissertation is that few licensing agreements can be placed so close to the transactional pole, that the principle of loyalty lacks importance altogether. The impact of the principle of loyalty the main focus of which is on fostering the contracting parties to behave in accordance with best practices, not for example on altering contract terms is analysed in different situations where the parties' interests typically collide. These situations are discussed from the point of view of three patent and knowhow licensing agreements that differ as to their degree of relationality. A balance needs to be struck between freedom of contract and relational needs. Especially when interpreting more modern licensing agreements, one should not focus on the written document alone, as is often recommended in the literature on Nordic intellectual property law. Neither is the principle of caveat emptor a proper starting point. Moreover, where the parties are of equal bargaining power, one should not assume that the grants in licensing agreements are to be interpreted narrowly. Focus in the interpretation should instead be on the entirety of the circumstances.

Kateuden luonne ja erityispiirteet filosofisessa pohdinnassa

Kateuden tunnetta ei ole tarkasteltu käytännöllisessä filosofiassa huolimatta sen määräävästä asemasta ihmisen normaalissa päivittäisessä elämässä. Kateus liittyy moniin ilmiöihin yksilöllisenä tai jopa kollektiivisena ryhmätunteena, kun siihen yhdistyvät epäoikeudenmukaisuus ja itsepetoksellisuus. Tutkielma pyrki osoittamaan kateuden vääjäämättömän monipuolisuuden kilpailullisena ja eriarvoisuutta lisäävänä vertailevana kompleksisena negatiivisena tunteena. Jo antiikin Kreikassa kateus liitettiin ihmisten ja jumalien väliseen eriarvoisuuteen, nykypäivänä taas kateutta leimaa liberaalisen yhteiskuntapolitiikan keskiössä ”tietämättömyyden verhon” takana egalitaarisuuden ihanne ja oikeudenmukaisuuden ja reiluuden taju. Tunnekokemuksena kateus on impotenttinen toisen paremmuudesta ja inferioi näin kateuden episodisuuden irrationaaliseen tilanteeseensa nähden antagonistiseksi. Tutkielman neljästä pääluvussa ensimmäisessä kateus yhdistetään poliittisen liberaalin yhteiskuntafilosofian yhdysvaltalaiseen kannattajaan John Rawlsiin (1921−2002). Hänen ajattelussaan ja pääteoksessaan A Theory of Justice (1971) ja siinä erityisesti kateutta käsittelevässä luvussa IX kateus on yhteiskunnassa vaikuttavaa erityispsykologista taipumusta tavoitella parempiosaisten asemaa oikeudenmukaisuuden kontraktuaalisessa valintajärjestelmässä. Rawlsille kateus ei ole tabu, vaan kateuden ongelma koskee kaikkia abstraktissa alkuasetelmassa yhteiskuntasopimuksen piiriin liittyviä sopija−agentteja. Rationaalinen agentti ei kärsi kateudesta, kun epäoikeudenmukaisuutta ei ole hänen ja muiden samojen vapaus− ja eroperiaatteiden nojalla toimivien ihmisten välillä sietämättömästi. Rawls tekee kuitenkin jaon pahantahoisessa kateudessa (proper) yleiseen ja erityiseen ja erottaa sekä emulatiivisen (emulative) eli motivoivan esimerkin sysäämän kilvoittelevan kateuden varsinaisesta kateudesta (proper). Myös anteeksiannettava kateus (excusable general envy) on Rawlsin onnellisuutta ja reiluutta tasa–arvoistavassa sopimusteorian ideaalissa varsinaisen kateuden alaluokkana mukana. Kateus ja tasa-arvo tulevat esille paremmin kilpailullisessa kateudessa, mistä myös viime vuosien merkittävin kateustutkija amerikkalainen Kentuckyn yliopiston psykologian professori Richard H. Smith on ollut kiinnostunut. Hänelle kateus on inferiorisen kompleksista ja liittyy oman arvon tunteeseen ja kognitiiviseen psykologiaan. Kateuden tutkimus on monialaistunut ja vilkastunut viime vuosikymmenen aikana. Sosiaali−psykologia, sosiologia, kulttuuriantropologia ja tunnefilosofia ovat kiinnostuneet ymmärtämään tätä kompleksista negatiivista tunnetta paremmin. Kulttuurissamme kateus toimii universaalisesti yhteydessä muihin rinnakkaistunteisiin, kuten moraaliseen paheksuntaan tai sitä lievempään närkästymiseen. Kateus ei ole perustunne, mutta sille on löydettävissä prototyypillisiä piirteitä, joskin kateus ei helposti antaudu propositionaaliseen tai kognitiiviseen arvostelmasisältöön yksin mentaalisen analyysin välityksellä (Solomon 1976). Siitä pitää huolen kateuden affektuaalnen instrumentaalisuus (feeling) ja kognitiivisen komponentiaalisen tulkinnan vaikeus kateellisen väistellessä oman itsetunnon inferiorisuuden tai omaa toimintavalmiutta heikentävien ilkeämielisten motiiviensa alaisuudessa. Kateelliselle ei ns. perisyntinä riitä, että kadehditulta olisi saatu pois haluttu myönteinen ominaisuus, kohde−esine tai asema, vaan lähietäisyydellä toimivasta kadehditusta pitäisi päästä kokonaan eroon (ns. venäläinen kateus). Siksi kateus approksimoi naapureita, ystäviä, kollegoita tai myös toisen ihmisen aviopuolisoa, mutta usein arkiyhteydessä käsitteellisesti väärinymmärrettynä, koska jälkimmäisessä on kyse kolmepaikkaisesta mustasukkaisuuden tunteesta. Kaksipaikkaisena tunteena (kateellinen & kadehdittu) ja sen vastatunteenaan usein mainittu kiittämättömyys saavat aikaan sen, että kateellinen on myös taipuvainen aggressiivisuuteen ja vihaisuuteen, mutta kun asiaa tarkastelee tarkemmin taustalta paljastuu itsepetoksen elementtejä. Kateellinen hyödyntää itsepetoksen paradoksia eli kahden vastakkaisen uskomuksen (Kateellinen, koska P & Kateellinen, koska ~P) samanaikaista voimassaoloa tilanteessa, jossa omat teot ovat suuntautuneet intentionaalisesti muualle kuin kadehditun komparatiiivisesti parempana näyttäytyvien arvostuserojen kuromiseksi tilanteen tasavertaistamiseksi kiinni. Kateellinen voi olla deliberatiivisen ahne ja nopea epäreilussa reaktiossaan kadehdittua kohtaan. Näin uppiniskainen kateustunne voi tulla eriäväksi havaitun arvioivan arvostelman kanssa. Kateustunne olisi näin määritelmällisesti intensiivistä puutetta (toistuvissa) epätasa−arvoisissa ja irrationalisoituneissa ihmiskohtaamisissa. Tutkimus esitteli kateustunteen adekvaattisena käsitteenä ja toi havaintoja kognitiivisen tunneteorian riittämättömyydestä kateustunteen tutkimukselle. Kiinnostavaa oli, että poliittisessa yhteiskuntafilosofiasta löytyi myös Rawlsin psykologisten erityistaipumuksien ja erityisesti kateuden yhteiskuntapoliittista kritiikkiä. Tunneteoreettisesti kateustunne on kognitiivista perustunnetta holistisempi, intensiivisempi ja intentionaalisempi sekä lisäksi affektuaalisesti motivoiva, joka mahdollistaa myös inhimillisen toiminnan kehittymisen, mutta myös kadehtijan tuhoamisen. Itsepetos sen sijaan tekee kateudesta haavoittuvan ja myös narsismia ruokkivan tunnetilan, jossa kateellinen toimii hedonistisesti ei−kognitiivisen irrationaalisen tietämyksen (envious feeling proper) varassa ja kieltää tunteen konsekventionaaliset usein negatiiviset seuraukset itselleen ja lähiympäristölleen.

Mehiläisten (Apis mellifera) kukkavierailut mansikalla (Fragaria x ananassa) ja vadelmalla (Rubus idaeus) sekä kukkavierailuihin vaikuttavat tekijät

Hyönteispölytys lisää monien ristipölytteisten viljelykasvien siemensatoa sekä parantaa sadon laatua. Marjakasveilla, kuten mansikalla ja vadelmalla marjojen koko suurenee sekä niiden laatu paranee onnistuneen pölytyksen seurauksena. Aiempien havaintojen mukaan mansikan kukat eivät pääsääntöisesti houkuttele mehiläisiä, kun taas vadelma on yksi mehiläisten pääsatokasveista. Tutkimuksen tarkoituksena oli selvittää, miten tehokkaasti mehiläiset vierailevat mansikalla sekä vadelmalla, keskittyen kukkakohtaisiin käynteihin tuntia kohti. Mehiläisiä voidaan käyttää Gliocladium catenulatum-vektoreina torjuttaessa mansikan ja vadelman harmaahometta (Botrytis cinerea). Kukkavierailujen perusteella arvioidaan, onko vektorilevitys riittävän tehokas torjumaan harmaahometta ja miten hyvin mehiläisiä voidaan käyttää pölytyspalveluihin, etenkin mansikalla. Havainnot kerättiin kuudelta eri tilalta Sisä-Savosta kesällä 2007. Kukkavierailuja laskettiin mansikan ja vadelman kukinnan aikana erilaisissa sääolosuhteissa, eri kellonaikoina ja eri etäisyyksillä mehiläispesistä. Kukat valittiin satunnaisesti, ja valintaperusteena oli kukan avonaisuus. Tarkkailuaika riippui mehiläisten lentoaktiivisuudesta. Mansikan koko havaintojakson keskiarvoksi tuli 1,75 käyntiä kukkaa kohti tunnissa. Vadelmalla vastaava luku oli 4,27, joten keskiarvojen perusteella vadelma oli houkuttelevampi kuin mansikka. Kasvukauden vaiheella ei ollut eroja vierailuihin kummallakaan kasvilla, mutta vuorokaudenajan suhteen vierailuja oli enemmän aamupäivällä kuin iltapäivällä. Lämpötila korreloi positiivisesti vierailutiheyden kanssa kummallakin kasvilla. Sääolosuhteet rajoittivat havaintojen keräämistä ja kesä oli erittäin sateinen. Mehiläiset vierailivat kukissa riittävästi haastavissakin sääolosuhteissa niin, että harmaahometorjunta onnistui. Vektorilevitystä suunnitellessa, etenkin mansikalla, tulee ottaa huomioon pesien sijoittelu sekä riittävä lukumäärä. Pesien ravinnontarpeen tulee olla suuri, jotta mehiläiset keräisivät ravintoa kukista mahdollisimman tehokkaasti. Pesiin voidaan lisätä tarvittaessa avosikiöitä tai poistaa siitepölyvarastoja ravinnonkeruuaktiivisuuden lisäämiseksi. Lisätutkimusta tarvitaan pesien sijoittelun, kilpailevien kasvien sekä mansikkalajikkeiden houkuttelevuuden vaikutuksesta vierailutiheyteen. Suomalaisten mansikkalajikkeiden meden sekä siitepölyneritystä olisi myös hyvä selvittää.

Two levels of MCT1 and CD147 expression in the equine red blood cells and muscle

Monocarboxylate transporters (MCTs), especially the isoforms MCT1 - MCT4, cotransport lactate and protons across the cell membranes. They are thus essential for pH regulation and homeostasis in glycolytic cells such as red blood cells (RBCs), and skeletal muscle cells during intense exercise. In 70% of the Standardbred horses the lactate transport activity (TA) in RBCs is high and transport is mediated mainly by MCTs. In the rest 30% of the Standardbreds MCT mediated transport route is not active and the TA is low. MCTs need an ancillary protein for their proper localization and functioning in the plasma membrane. The ancillary protein for MCT1 and MCT4 is a member of immunoglobulin superfamily, CD147. Here we determined the expression of MCT isoforms and CD147 in equine RBCs and gluteal muscle. We sequenced the cDNA of horse MCT1 and CD147 to achieve horse-specific antibodies and to reveal sequence variations that may affect the TA of RBCs. The amount of MCT1 and CD147 mRNA in muscle were also studied. ---- In all, 73 horses representing different breeds were used. Blood samples were drawn from the jugular vein and muscle samples were taken either from gluteal muscle using biopsy needle or during castration from expendable cremaster muscle. The TA of RBCs was studied using radiolabeled lactate and the amount of MCT isoforms and CD147 in the plasma membranes using Western blotting. The level of mRNA in muscle cells was determined using qPCR. Isoforms MCT1 and MCT2 were found in the RBCs and isoforms MCT1 and MCT4 in the muscle cells of horses. The TA of RBCs was dependent on the expression of CD147 and MCT1 in the plasma membrane. Sequence variations were found in the cDNA of both MCT1 and CD147, but they did not explain the inactivity of MCT1 mediated transport route. The single nucleotide polymorphism (SNP) Met125Val in CD147 that existed parallel with an SNP in 3´-untranslated region explained, however, attenuation in CD147 expression in Standardbreds. A single mutation Ile51Val also decreased the expression of CD147 in one Warmblood. The MCT1 and CD147 mRNA concentrations in the gluteal muscle were higher in horses with higher MCT1 and CD147 expression in RBCs and lower in horses with minor expression of CD147 and MCT1. This suggests that the bimodal distribution of TA is due to differences in transcriptional regulation that is functioning in parallel in MCT1 and CD147 gene.

Alternative News Sources as 'Collaboratory' Journalism. A case study of Helsingin Sanomat and its relation with the Youth Voice Editorial Board

The new paradigm of connectedness and empowerment brought by the interactivity feature of the Web 2.0 has been challenging the traditional centralized performance of mainstream media. The corporation has been able to survive the strong winds by transforming itself into a global multimedia business network embedded in the network society. By establishing networks, e.g. networks of production and distribution, the global multimedia business network has been able to sight potential solutions by opening the doors to innovation in a decentralized and flexible manner. Under this emerging context of re-organization, traditional practices like sourcing need to be re- explained and that is precisely what this thesis attempts to tackle. Based on ICT and on the network society, the study seeks to explain within the Finnish context the particular case of Helsingin Sanomat (HS) and its relations with the youth news agency, Youth Voice Editorial Board (NÄT). In that sense, the study can be regarded as an explanatory embedded single case study, where HS is the principal unit of analysis and NÄT its embedded unit of analysis. The thesis was able to reach explanations through interrelated steps. First, it determined the role of ICT in HS’s sourcing practices. Then it mapped an overview of the HS’s sourcing relations and provided a context in which NÄT was located. And finally, it established conceptualized institutional relational data between HS and NÄT for their posterior measurement through social network analysis. The data set was collected via qualitative interviews addressed to online and offline editors of HS as well as interviews addressed to NÄT’s personnel. The study concluded that ICT’s interactivity and User Generated Content (UGC) are not sourcing tools as such but mechanism used by HS for getting ideas that could turn into potential news stories. However, when it comes to visual communication, some exemptions were found. The lack of official sources amidst the immediacy leads HS to rely on ICT’s interaction and UGC. More than meets the eye, ICT’s input into the sourcing practice may be more noticeable if the interaction and UGC is well organized and coordinated into proper and innovative networks of alternative content collaboration. Currently, HS performs this sourcing practice via two projects that differ, precisely, by the mode they are coordinated. The first project found, Omakaupunki, is coordinated internally by Sanoma Group’s owned media houses HS, Vartti and Metro. The second project found is coordinated externally. The external alternative sourcing network, as it was labeled, consists of three actors, namely HS, NÄT (professionals in charge) and the youth. This network is a balanced and complete triad in which the actors connect themselves in relations of feedback, recognition, creativity and filtering. However, as innovation is approached very reluctantly, this content collaboration is a laboratory of experiments; a ‘COLLABORATORY’.

Nikotiinireseptoreiden kautta vaikuttavat lääkeaineet nikotiiniriippuvuuden ja neurologisten sairauksien hoidossa

Neuronaaliset nikotiinireseptorit liittyvät tupakkariippuvuuden lisäksi moniin neurologisiin sairauksiin, kuten Alzheimerin tautiin, skitsofreniaan, masennukseen ja tarkkaavaisuus- ja ylivilkkaushäiriöön. Nikotiinireseptorien stimulaation on tutkimuksissa havaittu parantavan kognitiota. Useat lääkeyritykset tutkivat nikotiinireseptoriagonisteja ja -antagonisteja eri neurologisten sairauksien hoidossa. Ongelmana nikotiinireseptori-agonisteja käytettäessä on reseptorissa tapahtuva desensitisaatio. Tällöin reseptori sulkeutuu, eikä aktivoidu vaikka agonistia olisi tarjolla tai sitoutuneena reseptoriin. Varsinkin alfa7-reseptori desensitoituu hyvin nopeasti agonistialtistuksen seurauksena. Reseptorien desensitoituminen voi kliinisessä käytössä aiheuttaa lääkeaineen tehon menetyksen. Perinteisen agonistin sitoutumiskohdan lisäksi nikotiinireseptorissa sijaitsee myös muita sitoutumiskohtia, joita kutsutaan allosteerisiksi sitoutumispaikoiksi. Tutkimuksissa on havaittu, että eräät allosteerisesti sitoutuvat aineet, kuten PNU-120596, voivat vahvistaa agonistin aikaansaamaa vastetta ja/tai estää reseptorin desensitoitumista. Näitä aineita kutsutaan positiivisiksi allosteerisiksi modulaattoreiksi ja niiden ajatellaan olevan vaihtoehto desensitoitumisen aiheuttamaan tehon menetyksen ongelmaan. Nikotiinireseptorien positiivisten allosteeristen modulaattorien tarkkaa vaikutusta ja sitoutumiskohtaa reseptoriin ei vielä tarkkaan tiedetä. Tutkimuksen aiheena oli karakterisoida positiivisten allosteeristen modulaattoreiden vaikutuksia alfa7-nikotiinireseptoriin. Tutkimuksessa tarkoituksena oli käyttää hyväksi laboratoriossa aiemmin tehtyä havaintoa, jonka mukaan alfa7-nikotiinireseptorin transmembraaniosan aminohappoon tehdyn mutaation L247T seurauksena positiiviset allosteeriset modulaattorit muuttuvat agonisteiksi. Haluttiin selvittää, kuinka agonistin sitoutumiskohtaan kohdennettua mutageneesiä käyttäen tehty mutaatio W149M tai W149F vaikuttavat PNU-120596:n kykyyn toimia agonistina alfa7L247T reseptoriin. Asetyylikoliini toimi konventionaalisen agonistin mallina tutkimuksessa. Tutkimuksen toinen tavoite oli tehdä mutaatio M253Lalfa7-reseptorin transmembraaniosaan. Mutaation on todettu estävän allosteeristen potentiaattoreiden kykyä voimistaa agonistin aikaansaamaa vastetta. Tarkoitus oli tutkia millaisia vaikutuksia M253L-mutaatiolla on allosteerisen potentiaattorin kykyyn toimia agonistina L247T-mutaation sisältävään reseptoriin. Mutatoidun reseptorin mRNA mikroinjektoitiin oosyyttiin ja elektrofysiologian avulla tutkittiin ilmennettyjen reseptorien toimintaa käyttäen kahden elektrodin jännitelukitus -menetelmää. Kaikki suunnitellut mutaatiot saatiin tehtyä onnistuneesti alfa7- ja alfa7L247T-reseptoreihin. Ortosteerisen sitoutumiskohdan mutaatio villin tyypin Į7-reseptorissa vaikutti hyvin voimakkaasti joko asetyylikoliinin sitoutumiseen reseptoriin tai reseptorin toimintaan, sillä asetyylikoliinilla ei reseptorista saatu mitattua vasteita. Myöskään PNU-120596 yksinään ei saanut aikaan vasteita alfa7W149M-reseptorissa. Kaksoismutatoidussa alfa7W149M/L247T-reseptorissa puolestaan havaittiin, että asetyylikoliinin annos-vaste -kuvaaja siirtyi huomattavasti enemmän oikealle kuin PNU-120596:n, kun verrattiin annos-vaste –kuvaajia alfa7L247T ja alfa7W149M/L247T–reseptoreiden välillä. Transmembraaniosan mutaatio M253L ei vaikuttanut PNU-120596:n kykyyn toimia agonistina alfa7L247T-reseptoriin, eikä sillä ollut vaikutusta asetyylikoliinin annosvaste-kuvaajiin. Tutkimus tukee aiempia havaintoja siitä, että positiivisten allosteeristen modulaattoreiden sitoutumiskohta nikotiinireseptorissa sijaitsisi transmembraaniosassa. M253L-mutaation osalta tulokset ovat hieman ristiriidassa aiempien tulosten kanssa. L247T-mutaatio vaikuttaa hyvin voimakkaasti nikotiinireseptorin toimintaan sekä sijaitsee aminohapon M253 läheisyydessä. On mahdollista, että se peittää M253L-mutaation vaikutuksen. Toisaalta voi olla, että M253 on aminohappo, joka vaikuttaa vain reseptorivasteiden voimistumiseen eikä allosteeristen potentiaattoreiden sitoutumiseen.

Campylobacter jejuni and C. coli in Finnish poultry production

Campylobacter, mainly Campylobacter jejuni and C. coli, are worldwide recognized as a major cause of bacterial food-borne gastroenteritis. Epidemiological studies have shown handling or eating of poultry to be significant risk factors for human infections. Campylobacter contamination can occur at all stages of a poultry meat production cycle. The aim of this thesis was to study the occurrence and diversity of Campylobacter in broiler and turkey production in Finland. In summer 1999, 2.9 % of slaughtered broiler flocks were Campylobacter-positive. From the isolated strains 94 % were C. jejuni and 6% were C. coli. During years 2005-2006 one turkey parent flock, the hatchery, six different commercial turkey farms and different stages of the slaughterhouse were monitored during one and the half year. No Campylobacter were detected in either of the samples from the turkey parent flock or from the hatchery using the culture method. Instead PCR detected DNA of Campylobacter from the turkey parent flock and samples from the hatchery. Six out of 12 commercial turkey flocks were found negative at the farm level but only two of those were negative at slaughter. Campylobacter-positive samples within the flock at slaughter were detected between 0% and 94% with evisceration and chilling water being the most critical stages for contamination. All of Campylobacter isolates were shown to be C. jejuni. Campylobacter-positive turkey flocks were colonized by a limited number of Campylobacter genotypes both at the farm and slaughter level. In conclusion, in our first study in 1999 a low prevalence of Campylobacter in Finnish broiler flocks was detected and it has remained at a low level during the study period until the present. In the turkey meat production, we found that flocks which were negative at the farm became contaminated with Campylobacter at the slaughter process. These results suggest that proper and efficient cleaning and disinfection of slaughter and processing premises are needed to avoid cross-contamination. Prevention of colonization at the farm by a high level of biosecurity control and hygiene may be one of the most efficient ways to reduce the amount of Campylobacter-positive poultry meat in Finland. With a persistent low level of Campylobacter-positive flocks, it could be speculated that the use of logistic slaughtering, according to Campylobacter status at farm, might have be advantageous in reducing Campylobacter contamination of retail poultry products. However, the significance of the domestic poultry meat for human campylobacteriosis in Finland should be evaluated.

Noncommutative Quantum Field Theory : Problem of Time and Some Applications

In this thesis the current status and some open problems of noncommutative quantum field theory are reviewed. The introduction aims to put these theories in their proper context as a part of the larger program to model the properties of quantized space-time. Throughout the thesis, special focus is put on the role of noncommutative time and how its nonlocal nature presents us with problems. Applications in scalar field theories as well as in gauge field theories are presented. The infinite nonlocality of space-time introduced by the noncommutative coordinate operators leads to interesting structure and new physics. High energy and low energy scales are mixed, causality and unitarity are threatened and in gauge theory the tools for model building are drastically reduced. As a case study in noncommutative gauge theory, the Dirac quantization condition of magnetic monopoles is examined with the conclusion that, at least in perturbation theory, it cannot be fulfilled in noncommutative space.

Heating values of mature trees.

The effective heating values of the above and below ground biomass components of mature Scots pine (Pinus sylvestris), Norway spruce (Picea abies), downy birch (Betula pubescens), silver birch (Betula pendula), grey alder (Alnus incana), black alder (Alnus glutinosa) and trembling aspen (Populus tremula) were studied. Each sample tree was divided into wood, bark and foliage components. Bomb calorimetry was used to determine the calorimetric heating values. The species is a significant factor in the heating value of individual tree components. The heating value of the wood proper is highest in conifers. Broad-leaved species have a higher heating value of bark than conifers. The species factor diminishes when the weighted heating value of crown, whole stems or stump-root-system are considered. The crown material has a higher heating value per unit weight in comparison with fuelwood from small-sized stems or wholetrees. The additional advantages of coniferous crown material are that it is a non-industrial biomass resource and is readily available. The variability of both the chemical composition and the heating value is small in any given tree component of any species. However, lignin, carbohydrate and extractive content were found to vary from one part of the tree to another and to correlate with the heating value.

Campylobacter jejuni and C.coli in Finnish poultry production

Campylobacter, mainly Campylobacter jejuni and C. coli, are worldwide recognized as a major cause of bacterial food-borne gastroenteritis (World Health Organization 2010). Epidemiological studies have shown handling or eating of poultry to be significant risk factors for human infections. Campylobacter contamination can occur at all stages of a poultry meat production cycle. In summer 1999, every broiler flock from all three major Finnish poultry slaughterhouses was studied during a five month period. Caecal samples were taken in the slaughterhouses from five birds per flock. A total of 1 132 broiler flocks were tested and 33 (2.9%) of those were Campylobacter-positive. Thirty-one isolates were identified as C. jejuni and two isolates were C. coli. The isolates were serotyped for heat-stable antigens (HS) and genotyped by pulsed-field gel electrophoresis (PFGE). The most common serotypes found were HS 6,7, 12 and 4-complex. Using a combination of SmaI and KpnI patterns, 18 different PFGE types were identified. Thirty-five Finnish C. jejuni strains with five SmaI/SacII PFGE types selected among human and chicken isolates from 1997 and 1998 were used for comparison of their PFGE patterns, amplified fragment length polymorphism (AFLP) patterns, HaeIII ribotypes, and HS serotypes. The discriminatory power of PFGE, AFLP and ribotyping with HaeIII were shown to be at the same level for this selected set of strains, and these methods assigned the strains into the same groups. The PFGE and AFLP patterns within a genotype were highly similar, indicating genetic relatedness. An HS serotype was distributed among different genotypes, and different serotypes were identified within one genotype. From one turkey parent flock, the hatchery, six different commercial turkey farms (together 12 flocks) and from 11 stages at the slaughterhouse a total of 456 samples were collected during one and the half year. For the detection of Campylobacter both conventional culture and a PCR method were used. No Campylobacter were detected in either of the samples from the turkey parent flock or from the hatchery samples using the culture method. Instead PCR detected DNA of Campylobacter in five faecal samples from the turkey parent flock and in one fluff and an eggshell sample. Six out of 12 commercial turkey flocks were found negative at the farm level but only two of those were negative at slaughter. Campylobacter-positive samples within the flock at slaughter were detected between 0% and 94%, with evisceration and chilling water being the most critical stages for contamination. All of a total of 121 Campylobacter isolates were shown to be C. jejuni using a multiplex PCR assay. PFGE analysis of all isolates with KpnI restriction enzyme resulted in 11 PFGE types (I-XI) and flaA-SVR typing yielded nine flaA-SVR alleles. Three Campylobacter-positive turkey flocks were colonized by a limited number of Campylobacter genotypes both at the farm and slaughter level.In conclusion, in our first study in 1999 a low prevalence of Campylobacter in Finnish broiler flocks was detected and it has remained at a low level during the study period until the present. In the turkey meat production, we found that flocks which were negative at the farm became contaminated with Campylobacter at the slaughter process. These results suggest that proper and efficient cleaning and disinfection of slaughter and processing premises are needed to avoid cross-contamination. Prevention of colonization at the farm by a high level of biosecurity control and hygiene may be one of the most efficient ways to reduce the amount of Campylobacter-positive poultry meat in Finland. In Finland, with a persistent low level of Campylobacter-positive flocks, it could be speculated that the use of logistic slaughtering, according to Campylobacter status at farm, might have be advantageous in reducing Campylobacter contamination of retail poultry products. However, the significance of the domestic poultry meat for human campylobacteriosis in Finland should be evaluated.

Accurate mass-based analysis in human sport doping control : Application of liquid chromatography - time-of-flight mass spectrometry

Human sport doping control analysis is a complex and challenging task for anti-doping laboratories. The List of Prohibited Substances and Methods, updated annually by World Anti-Doping Agency (WADA), consists of hundreds of chemically and pharmacologically different low and high molecular weight compounds. This poses a considerable challenge for laboratories to analyze for them all in a limited amount of time from a limited sample aliquot. The continuous expansion of the Prohibited List obliges laboratories to keep their analytical methods updated and to research new available methodologies. In this thesis, an accurate mass-based analysis employing liquid chromatography - time-of-flight mass spectrometry (LC-TOFMS) was developed and validated to improve the power of doping control analysis. New analytical methods were developed utilizing the high mass accuracy and high information content obtained by TOFMS to generate comprehensive and generic screening procedures. The suitability of LC-TOFMS for comprehensive screening was demonstrated for the first time in the field with mass accuracies better than 1 mDa. Further attention was given to generic sample preparation, an essential part of screening analysis, to rationalize the whole work flow and minimize the need for several separate sample preparation methods. Utilizing both positive and negative ionization allowed the detection of almost 200 prohibited substances. Automatic data processing produced a Microsoft Excel based report highlighting the entries fulfilling the criteria of the reverse data base search (retention time (RT), mass accuracy, isotope match). The quantitative performance of LC-TOFMS was demonstrated with morphine, codeine and their intact glucuronide conjugates. After a straightforward sample preparation the compounds were analyzed directly without the need for hydrolysis, solvent transfer, evaporation or reconstitution. The hydrophilic interaction technique (HILIC) provided good chromatographic separation, which was critical for the morphine glucuronide isomers. A wide linear range (50-5000 ng/ml) with good precision (RSD<10%) and accuracy (±10%) was obtained, showing comparable or better performance to other methods used. In-source collision-induced dissociation (ISCID) allowed confirmation analysis with three diagnostic ions with a median mass accuracy of 1.08 mDa and repeatable ion ratios fulfilling WADA s identification criteria. The suitability of LC-TOFMS for screening of high molecular weight doping agents was demonstrated with plasma volume expanders (PVE), namely dextran and hydroxyethylstarch (HES). Specificity of the assay was improved, since interfering matrix compounds were removed by size exclusion chromatography (SEC). ISCID produced three characteristic ions with an excellent mean mass accuracy of 0.82 mDa at physiological concentration levels. In summary, by combining TOFMS with a proper sample preparation and chromatographic separation, the technique can be utilized extensively in doping control laboratories for comprehensive screening of chemically different low and high molecular weight compounds, for quantification of threshold substances and even for confirmation. LC-TOFMS rationalized the work flow in doping control laboratories by simplifying the screening scheme, expediting reporting and minimizing the analysis costs. Therefore LC-TOFMS can be exploited widely in doping control, and the need for several separate analysis techniques is reduced.

Mechanism-based inhibition of CYP2C8 by gemfibrozil in humans : characterisation of time and dose relationships

Drug-drug interactions may cause serious, even fatal clinical consequences. Therefore, it is important to examine the interaction potential of new chemical entities early in drug development. Mechanism-based inhibition is a pharmacokinetic interaction type, which causes irreversible loss of enzyme activity and can therefore lead to unusually profound and long-lasting consequences. The in vitro in vivo extrapolation (IVIVE) of drug-drug interactions caused by mechanism-based inhibition is challenging. Consequently, many of these interactions have remained unrecognised for many years. The concomitant use of the fibrate-class lipid-lowering agent gemfibrozil increases the concentrations of some drugs and their effects markedly. Even fatal cases of rhabdomyolysis occurred in patients administering gemfibrozil and cerivastatin concomitantly. One of the main mechanisms behind this effect is the mechanism-based inhibition of the cytochrome P450 (CYP) 2C8 enzyme by a glucuronide metabolite of gemfibrozil leading to increased cerivastatin concentrations. Although the clinical use of gemfibrozil has clearly decreased during recent years, gemfibrozil is still needed in some special cases. To enable safe use of gemfibrozil concomitantly with other drugs, information concerning the time and dose relationships of CYP2C8 inhibition by gemfibrozil should be known. This work was carried out as four in vivo clinical drug-drug interaction studies to examine the time and dose relationships of the mechanism-based inhibitory effect of gemfibrozil on CYP2C8. The oral antidiabetic drug repaglinide was used as a probe drug for measuring CYP2C8 activity in healthy volunteers. In this work, mechanism-based inhibition of the CYP2C8 enzyme by gemfibrozil was found to occur rapidly in humans. The inhibitory effect developed to its maximum already when repaglinide was given 1-3 h after gemfibrozil intake. In addition, the inhibition was shown to abate slowly. A full recovery of CYP2C8 activity, as measured by repaglinide metabolism, was achieved 96 h after cessation of gemfibrozil treatment. The dose-dependency of the mechanism-based inhibition of CYP2C8 by gemfibrozil was shown for the first time in this work. CYP2C8 activity was halved by a single 30 mg dose of gemfibrozil or by twice daily administration of less than 30 mg of gemfibrozil. Furthermore, CYP2C8 activity was decreased over 90% by a single dose of 900 mg gemfibrozil or twice daily dosing of approximately 100 mg gemfibrozil. In addition, with the application of physiological models to the data obtained in the dose-dependency studies, the major role of mechanism-based inhibition of CYP2C8 in the interaction between gemfibrozil and repaglinide was confirmed. The results of this work enhance the proper use of gemfibrozil and the safety of patients. The information related to time-dependency of CYP2C8 inhibition by gemfibrozil may also give new insights in order to improve the IVIVE of the drug-drug interactions of new chemical entities. The information obtained by this work may be utilised also in the design of clinical drug-drug interaction studies in the future.

Lean Thinking in Software Development : Impacts of Kanban on Projects

The history of software development in a somewhat systematical way has been performed for half a century. Despite this time period, serious failures in software development projects still occur. The pertinent mission of software project management is to continuously achieve more and more successful projects. The application of agile software methods and more recently the integration of Lean practices contribute to this trend of continuous improvement in the software industry. One such area warranting proper empirical evidence is the operational efficiency of projects. In the field of software development, Kanban as a process management method has gained momentum recently, mostly due to its linkages to Lean thinking. However, only a few empirical studies investigate the impacts of Kanban on projects in that particular area. The aim of this doctoral thesis is to improve the understanding of how Kanban impacts on software projects. The research is carried out in the area of Lean thinking, which contains a variety of concepts including Kanban. This article-type thesis conducts a set of case studies expanded with the research strategy of quasi-controlled experiment. The data-gathering techniques of interviews, questionnaires, and different types of observations are used to study the case projects, and thereby to understand the impacts of Kanban on software development projects. The research papers of the thesis are refereed, international journal and conference publications. The results highlight new findings regarding the application of Kanban in the software context. The key findings of the thesis suggest that Kanban is applicable to software development. Despite its several benefits reported in this thesis, the empirical evidence implies that Kanban is not all-encompassing but requires additional practices to keep development projects performing appropriately. Implications for research are given, as well. In addition to these findings, the thesis contributes in the area of plan-driven software development by suggesting implications both for research and practitioners. As a conclusion, Kanban can benefit software development projects but additional practices would increase its potential for the projects.

The roles of nitrification and nitrate reduction pathways in nitrogen cycling of Baltic Sea

The Baltic Sea is one of the largest brackish water bodies in the world. Primary production in the Baltic Sea is limited by nitrogen (N) availability with the exception of river outlets and the northernmost phosphorus limited basin. The excess human induced N load from the drainage basin has caused severe eutrophication of the sea. The excess N loads can be mitigated by microbe mediated natural N removal processes that are found in the oxic-anoxic interfaces in sediments and water column redoxclines. Such interfaces allow the close coupling between the oxic nitrification process, and anoxic denitrification and anaerobic ammonium oxidation (anammox) processes that lead to the formation of molecular nitrogen gas. These processes are governed by various environmental parameters. The effects of these parameters on N processes were investigated in the northern Baltic Sea sediments. During summer months when the sediment organic content is at its highest, nitrification and denitrification reach their maximum rates. However, nitrification had no excess potential, which was probably because of high competition for molecular oxygen (O2) between heterotrophic and nitrification microbes. Subsequently, the limited nitrate (NO3-) availability inhibited denitrification. In fall, winter and spring, nitrification was limited by ammonium availability and denitrification limited by the availability of organic carbon and occasionally by NO3-. Anaerobic ammonium oxidation (anammox) was not an important N removal process in the northern Baltic Sea. Modeling studies suggest that when hypoxia expands in the Baltic Sea, N removal intensifies. However, the results of this study suggest the opposite because bottom water hypoxia (O2< 2 ml l-1) decreased the denitrification rates in sediments. Moreover, N was recycled by the dissimilatory nitrate reduction to ammonium (DNRA) process instead of being removed from the water ecosystem. High N removal potentials were found in the anoxic water column in the deep basins of the Baltic Proper. However, the N removal in the water column appeared to be limited by low substrate availability, because the water at the depths at which the substrate producing nitrification process occurred, rarely mix with the water at the depths at which N removal processes were found. Overall, the natural N removal capacity of the northern Baltic Sea decreased compared to values measured in mid 1990s and early 2000. The reason for this appears to be increasing hypoxia.

The function and regulation of the U11-48K protein in U12-dependent splicing

The removal of noncoding sequences, or introns, from the eukaryotic messenger RNA precursors is catalyzed by a ribonucleoprotein complex known as the spliceosome. In most eukaryotes, two distinct classes of introns exist, each removed by a specific type of spliceosome. The major, U2-type introns account for over 99 % of all introns, and are almost ubiquitous. The minor, U12-type introns are found in most but not all eukaryotes, and reside in conserved locations in a specific set of genes. Due to their slow excision rates, the U12-type introns are expected to be involved in the regulation of the genes containing them by inhibiting the maturation of the messenger RNAs. However, little information is currently available on how the activity of the U12-dependent spliceosome itself is regulated. The levels of many known splicing factors are regulated through unproductive alternative splicing events, which lead to inclusion of premature STOP codons, targeting the transcripts for destruction by the nonsense-mediated decay pathway. These alternative splice sites are typically found in highly conserved sequence elements, which also contain binding sites for factors regulating the activation of the splice sites. Often, the activation is achieved by binding of products of the gene in question, resulting in negative feedback loops. In this study, I show that U11-48K, a protein factor specific to the minor spliceosome, specifically recognizes the U12-type 5' splice site sequence, and is essential for proper function of the minor spliceosome. Furthermore, the expression of U11-48K is regulated through a feedback mechanism, which functions through conserved sequence elements that activate alternative splicing and nonsense-mediated decay. This mechanism is conserved from plants to animals, highlighting both the importance and early origin of this mechanism in regulating splicing factors. I also show that the feedback regulation of U11-48K is counteracted by a component of the major spliceosome, the U1 small nuclear ribonucleoprotein particle, as well as members of the hnRNP F/H protein family. These results thus suggest that the feedback mechanism is finely tuned by multiple factors to achieve precise control of the activity of the U12-dependent spliceosome.