Evidence of recombination in putative ancient asexuals.

Ancient asexuals have been considered to be a contradiction of the basic tenets of evolutionary theory. Barred from rearranging genetic variation by recombination, their reduced number of gene arrangements is thought to hamper their response to changing environments. For the same reason, it should be difficult for them to avoid the build-up of deleterious mutations. Several groups of taxonomically diverse organisms are thought to be ancient asexuals, although clear evidence for or against the existence of recombination events is scarce. Several methods have recently been developed for predicting recombination events by analyzing aligned sequences of a given region of DNA that all originate from one species. The methods are based on phylogenetic, substitution, and compatibility analyses. Here we present the results of analyses of sequence data from different loci studied in several groups of evolutionarily distant species that are considered to be ancient asexuals, using seven different types of analysis. The groups of organisms were the arbuscular mycorrhizal fungi (Glomales), Darwinula stevensoni (Darwinuloidea crustacean ostracods) and the bdelloid rotifers (Bdelloidea), which are thought to have been asexual for the last 400, 25-100, and 35-40 Myr, respectively. The seven different analytical methods evaluated the evolutionary relationships among haplotypes, and these methods had previously been shown to be reliable for predicting the occurrence of recombination events. Despite the different degree of genetic variation among the different groups of organisms, at least some evidence for recombination was found in all species groups. In particular, predictions of recombination events in the arbuscular mycorrhizal fungi were frequent. Predictions of recombination were also found for sequence data that have previously been used to infer the absence of recombination in bdelloid rotifers. Although our results have to be taken with some caution because they could signal very ancient recombination events or possibly other genetic variation of nonrecombinant origin, they suggest that some cryptic recombination events may exist in these organisms.

Virtaviivainen LEAN-liiketoiminta

Työn tarkoituksena oli löytää ratkaisu omasta kokemuksesta nousseeseen tarpeeseen, kuinka LEAN-toimintaa tulisi ylläpitää ja organisoida yrityksessä. Samalla halusin ymmärtää, kuinka paljon suomalaisissa yrityksissä LEAN-toiminnasta ja sen johtamisesta tiedetään. Ensiksi kävin lävitse LEAN-teoriaa ja hukkia. Menetelmiä olen käsitellyt lähinnä siitä näkökulmasta, mitä niistä Abloy Oy:ssä voisi parhaiten käyttää yrityksen virtaviivaistamiseen. Työn empiirisessä osassa selvitetään haastattelututkimuksella ongelmakenttään liittyviä kysymyksiä. Merkittäväksi havainnoksi nousi se, että haastateltavat eivät nähneet LEAN-toimintaa erityisen hyvin johdetuksi alueeksi suomalaisissa yrityksissä. Haastatellut olivat sen sijaan melko yksimielisiä siitä, kuinka LEAN-toiminta tulisi organisoida yrityksessä, ja että sen tulisi raportoida korkealle yrityksen hierarkiassa. Tämän työn tulokset auttavat yrityksen LEAN-johtamistyötä. Selkeästi käy ilmi, että LEAN-johtajakoulutusta pitäisi organisoida. Abloy Oy:n johto on tullut tietoiseksi LEAN-toiminnan mahdollisuuksista ja merkityksestä monin tavoin. Ei riitä, että LEAN-työskentelyvain aloitetaan, se täytyy myös organisoida. Yrityksen korkeimman johdon on sitouduttava virtaviivaistamistyöhön. Tässä työssä annetut suositukset organisaation peruspiirteistä voivat edesauttaa yritysjohtoa LEAN-työskentelyn aloittamisessa.

Tasasähkön hyödyntämismahdollisuudet sähkönjakelussa

Tässä työssä on tutkittu tasasähkönsiirron tuomia mahdollisuuksia sähkönjakelussa, kun pienjännitedirektiivin pienjännitemäärittelyn soveltamista laajennetaan koskemaan vaihtojännitteen lisäksi myös tasajännitettä. Aiemmin tasasähköjärjestelmiä on käytetty ainoastaan sähköistymisen alkuaikoina 1900-luvun alussa. Viime vuosikymmeninä on sähkönjakelussa käytetty pelkästään vaihtosähköverkkoja, koska tehoelektronisten laitteiden korkea hintataso ja tekniset ominaisuudet ovat mahdollistaneet tasasähkön käytön vain suurjännitteellä. Suomalaisten sähkönkäyttö on lisääntynyt muutamalla prosenttiyksiköllä vuosittain ja kasvun taantumista ei ole odotettavissa lähiaikoina. Samaan aikaan yhteiskunta muuttuu jatkuvasti yhä riippuvaisemmaksi sähköstä ja odotukset toteutuvasta sähkönlaadusta ovat jatkuvasti korkeammat. Sähkönlaadun näkökulmasta ilmasto on tuonut aiempia suurempia haasteita sähkön toimitusvarmuudelle, kun myrskyjen aiheuttamat tuhot ovat olleet yhä entisiä suurempia. Toimitusvarmuuden parantamiseksi ovat muutamat vuosikymmenen alun rajut myrskyt johtaneet pohdintaan tulevien haasteiden hoitamiseksi ja edelleen uuden 3-portaiseen 20/1/0,4 kV vaihtosähköjärjestelmän kehittämiseen. Tasasähkönsiirron avulla halutaan tuoda käyttöön niitä hyötyjä, joita järjestelmän vaihdolla on saavutettavissa. Täysimääräisellä tasajännitteen hyödyntämisellä voidaan saavuttaa mm. aiempaa edullisempia investointivaihtoehtoja,parempi sähkönlaatu, parempi hajautetun tuotannon liitettävyys verkkoon ja erilaisten asiakaskohtaisten laitteiden helppo integroitavuus osaksi jakelujärjestelmää. Tämän työn puitteissa on pohdittu sekä teknisiä ratkaisuja että järjestelmän teknistaloudellista käyttöaluetta. Lisäksi on pyritty hahmottamaan eri tekijöiden vaikutuksia sähkönjakeluun.

Tukki- ja parruoptimoinnintoimivuuden kehittäminen

Diplomityön tutkimusfunktio käsittelee toimeksiantajan, Stora Enso Timber Oy Ltd Kotkan sahan, sahalinjan optimointikokonaisuuden relevanttia ongelmakenttää. Tutkimuksen alussa profiloivan sahalinjan tukinpyörityksen, pelkan sivuttaissiirron tai sivulautaoptimoinnin toimivuudesta ei ollut varmuutta. Työn painopistealue on sivulautaoptimointi, jonka toimivuus tutkimuksen alussa on hyvin kyseenalaista tuotantoajossa. Työn tavoitteet kiteytyvät paremman raaka-aineen käyttösuhteen saavuttamiselle, jolloin pitkän aikajänteen kannattavuus on realistisempaa saavuttaa. Kotkan sahalinjan optimointijärjestelmässä on kokonaisuudessaan saavutettu tuotantoajoon hyväksyttävä taso. Tukinpyörityksen tarkkuudessa saavutettiin asetettu tavoite, eli 90 % pyöritystuloksista menee virheikkunaan ± 10° , sekä virheen keskiarvon itseisarvo jasen ympärillä olevan hajonnan summa on maksimissaan 10° . Pelkan sivuttaissiirto todettiin tutkimuksessa sekundääriseksi optimointijärjestelmäksi. Ohjaus perustuu tukkimittarin mittaamaan dataan, jolloin tukinpyörityksen hajonta aiheuttaa epätarkkuutta pelkan suuntauksessa. Pelkan sivuttaisiirron käyttäminen vaatii lisämittauksia, jolloin voidaan varmistua pelkan suuntauksen optimoinnin toimivuudesta. Sivulautaoptimoinnin toimivuuden kehittämisessä saavutettiin se taso, missä todellista kehitystyötä voidaan tehdä. Koeajoissa ja optimointiohjelman tarkastamisessa havaittiin periaatteellisia virheitä, jotka korjattiin. Toimivan sivulautaoptimoinnin myötä on mahdollista hallita paremmin tuotannonohjaus, jolloin tuotanto voidaan etenkin sivulautojen osalta kohdentaa paremmin vastaamaan kysyntää sekä asete-erän hyvää käyttösuhdetta. Raaka-aineen käyttösuhde on parantunut. Yksittäisten asetevertailujen sekä esimerkkilaskelmien perusteella tuottopotentiaali tukinpyörityksen ja sivulautaoptimoinnin osalta on 0,6...1,5 MEUR Välillinen tuottopotentiaali on suurempi, koska tuotantoprosessi sahauksen osalta on erittäin joustava markkinoiden tarpeen muutoksille. Sahalinjalla on mahdollista tuottaa helposti laajalla tukkisumalla laajaa tuotematriisia, jossa sivulautaoptimoinnilla on avainrooli. Tuotannonsuunnittelufunktiota tulee kehittää vastaamaan mahdollisuuksiin,joita sivulautaoptimointi tarjoaa. Tuotematriisi ja sitä vastaavat asetteet lankeavalla tukkisumalla tulee rakentaa uudestaan niiltä osin, joihin sivulautaoptimointi antaa variaatiomahdollisuuksia.

Kulu- ja verotehokkuus rahastojen rahastoissa

Tutkimuksen tavoitteena on tutkia kulu- ja verotehokkuutta rahastojen rahastoissa. Tutkimus ontoteutettu yhteistyössä Sampo Rahastoyhtiö Oy:n kanssa. Tutkimuksessa verrataan, miten rahastojen rahastot ovat menestyneet suhteessa yksittäisen sijoittajan itse rakentamaan portfolioon. Tutkimuksessa on käytetty mallirahastona Sampo Kompassi 50 Kasvu -rahastoa. Alkuperäisen rahaston ympärille on rakennettu kuusi Kompassi 50 -rahastoa jäljittelevää rahastoportfoliota. Rahastoportfoliot on rakennettu joko merkitsemällä suoraan yksittäisiä rahastoja tai hyödyntämällä sijoitusvakuutusta. Tutkimus perustuu Sampo Rahastoyhtiö Oy:n tilastoihin kahden vuoden ajanjaksolta. Tutkimustulosten perusteella vertaillaan eri sijoitusvaihtoehtojentuottoja, palkkioita, veroja, riskejä sekä tuotto-riskisuhdetta. Tutkielma jakautuu teoreettiseen ja empiiriseen osaan. Teoriaosuuden tarkoituksena on johdattaa lukija sijoitusrahastojen maailmaan. Samassa osiossa syvennytään lisäksi tutkimuksen kannalta oleellisiin tekijöihin: tuottoon ja riskiin,palkkioihin sekä verotukseen. Tutkielman empiirisessä osassa selvitetään vastausta tutkimusongelmaan matemaattisia laskelmia hyväksikäyttäen. Kyseisestä aiheesta ei ole aiempia empiirisiä tutkimuksia.

Arabidopsis Basic Helix-Loop-Helix Transcription Factors MYC2, MYC3, and MYC4 Regulate Glucosinolate Biosynthesis, Insect Performance, and Feeding Behavior.

Arabidopsis thaliana plants fend off insect attack by constitutive and inducible production of toxic metabolites, such as glucosinolates (GSs). A triple mutant lacking MYC2, MYC3, and MYC4, three basic helix-loop-helix transcription factors that are known to additively control jasmonate-related defense responses, was shown to have a highly reduced expression of GS biosynthesis genes. The myc2 myc3 myc4 (myc234) triple mutant was almost completely devoid of GS and was extremely susceptible to the generalist herbivore Spodoptera littoralis. On the contrary, the specialist Pieris brassicae was unaffected by the presence of GS and preferred to feed on wild-type plants. In addition, lack of GS in myc234 drastically modified S. littoralis feeding behavior. Surprisingly, the expression of MYB factors known to regulate GS biosynthesis genes was not altered in myc234, suggesting that MYC2/MYC3/MYC4 are necessary for direct transcriptional activation of GS biosynthesis genes. To support this, chromatin immunoprecipitation analysis showed that MYC2 binds directly to the promoter of several GS biosynthesis genes in vivo. Furthermore, yeast two-hybrid and pull-down experiments indicated that MYC2/MYC3/MYC4 interact directly with GS-related MYBs. This specific MYC-MYB interaction plays a crucial role in the regulation of defense secondary metabolite production and underlines the importance of GS in shaping plant interactions with adapted and nonadapted herbivores.

MIG-juotto väsymiskestävyyden parantamismenetelmänä

Tässä tutkimuksessa esitellään MIG-juoton periaatteet ja tarkastellaan menetelmää siitä näkökulmasta, että menetelmä voisi toimia yhtenä varteenotettavana hitsattujen liitosten väsymiskestävyyden parantamismenetelmänä. Muiden parantamismenetelmien laajaa kirjoa esitellään lyhyesti. MIG-juoton soveltuvuutta parantamismenetelmäksi tutkittiin väsytyskokein. Kokeiden avulla määritettiin pelkästään MIG-juotetun liitoksen väsymiskestävyys erilaisissa tapauksissa. Lisäksi määritettiin väsymiskestävyys tapauksessa, jossa perinteisen MAG-pienahitsin rajaviivalle MIG-juotetiin ylimääräinen palko. Jälkimmäisessä tapauksessa menetelmä toimii väsymiskestävyyden parantamismenetelmänä. Väsytyskokeita tehtiin kaikkiaan 63 kpl.Kaikkiaan erilaisia väsytyskoesarjoja oli kymmenen, joista kuusi oli 8-10 koekappaletta käsittäviä varsinaisia tutkittavia tapauksia ja neljä pieniä, vain kaksi tai kolme koesauvaa käsittäviä pilottikoesarjoja. Koetuloksia verrattiin IIW:n(International Institute of Welding) suunnitteluohjeisiin ja suosituksiin. MIG-juotettujen liitosten väsymiskestävyys oli yleisesti ottaen hyvä. Päittäisliitosoli vähintään yhtä hyvä kuin tavanomaisesti hitsattu. Voimaa kantavassa taivutustapauksessa saatiin 110 % parempi väsymislujuus verrattuna IIW:n suunnitteluohjeeseen. Voimaa kantamattomissa poikittaisissa kiinnitysliitoksissa puolestaan saavutettiin paikallisia nimellisiä jännityksiä käyttäen 70-80 %:n parannus suunnitteluohjeeseen nähden. Pelkästään MIG-juotetun liitoksen ja 'parannetun' liitoksen väsymislujuudet olivat tässä tapauksessa likimain yhtä suuret. MIG-juottoa käytetään vaihtoehtoisena liittämismenetelmänä jo joissakin teollisissa sovelluksissa. Tämän tutkimuksen koetulokset antavat selviä viitteitä siitä, että menetelmä voisi toimia yhtenä varteenotettavana väsymiskestävyyden parantamiskeinona uusille tai korjatuille rakenteille. Vaaditaan kuitenkin vielä lisätutkimuksia, jotta menetelmää voisi soveltaa luottavaisin mielin tuotantokäytössä väsymiskestävyyden parantamismenetelmänä.

Introducing Basic Systematic Requirements Engineering Practices in Small Organizations with an Easy to Adopt Method

Requirements-relatedissues have been found the third most important risk factor in software projects and as the biggest reason for software project failures. This is not a surprise since; requirements engineering (RE) practices have been reported deficient inmore than 75% of all; enterprises. A problem analysis on small and low maturitysoftware organizations revealed two; central reasons for not starting process improvement efforts: lack of resources and uncertainty; about process improvementeffort paybacks.; In the constructive part of the study a basic RE method, BaRE, was developed to provide an; easy to adopt way to introduce basic systematic RE practices in small and low maturity; organizations. Based on diffusion of innovations literature, thirteen desirable characteristics; were identified for the solution and the method was implemented in five key components:; requirements document template, requirements development practices, requirements; management practices, tool support for requirements management, and training.; The empirical evaluation of the BaRE method was conducted in three industrial case studies. In; this evaluation, two companies established a completely new RE infrastructure following the; suggested practices while the third company conducted continued requirements document; template development based on the provided template and used it extensively in practice. The; real benefits of the adoption of the method were visible in the companies in four to six months; from the start of the evaluation project, and the two small companies in the project completed; their improvement efforts with an input equal to about one person month. The collected dataon; the case studies indicates that the companies implemented new practices with little adaptations; and little effort. Thus it can be concluded that the constructed BaRE method is indeed easy to; adopt and it can help introduce basic systematic RE practices in small organizations.

Coping with Technology: A Study on Economic Methodology and Strategic Management of Technology

There is a broad consensus among economists that technologicalchange has been a major contributor to the productivity growth and, hence, to the growth of the material welfare in western industrialized countries at least over the last century. Paradoxically, this issue has not been the focal point of theoretical economics. At the same time, we have witnessed the rise of the importance of technological issues at the strategic management level of business firms. Interestingly, the research has not accurately responded to this challenge either. The tension between the overwhelming empirical evidence of the importance of technology and its relative omission in the research offers a challenging target for a methodological endeavor. This study deals with the question of how different theories cope with technology and explain technological change. The focusis at the firm level and the analysis concentrates on metatheoretical issues, except for the last two chapters, which examine the problems of strategic management of technology. Here the aim is to build a new evolutionary-based theoreticalframework to analyze innovation processes at the firm level. The study consistsof ten chapters. Chapter 1 poses the research problem and contrasts the two basic approaches, neoclassical and evolutionary, to be analyzed. Chapter 2 introduces the methodological framework which is based on the methodology of isolation. Methodological and ontoogical commitments of the rival approaches are revealed and basic questions concerning their ways of theorizing are elaborated. Chapters 3-6 deal with the so-called substantive isolative criteria. The aim is to examine how different approaches cope with such critical issues as inherent uncertainty and complexity of innovative activities (cognitive isolations, chapter 3), theboundedness of rationality of innovating agents (behavioral isolations, chapter4), the multidimensional nature of technology (chapter 5), and governance costsrelated to technology (chapter 6). Chapters 7 and 8 put all these things together and look at the explanatory structures used by the neoclassical and evolutionary approaches in the light of substantive isolations. The last two cpahters of the study utilize the methodological framework and tools to appraise different economics-based candidates in the context of strategic management of technology. The aim is to analyze how different approaches answer the fundamental question: How can firms gain competitive advantages through innovations and how can the rents appropriated from successful innovations be sustained? The last chapter introduces a new evolutionary-based technology management framework. Also the largely omitted issues of entrepreneurship are examined.

Database Rights in Safe European Home: The Path to More Rigorous Protection of Information

1. Introduction "The one that has compiled ... a database, the collection, securing the validity or presentation of which has required an essential investment, has the sole right to control the content over the whole work or over either a qualitatively or quantitatively substantial part of the work both by means of reproduction and by making them available to the public", Finnish Copyright Act, section 49.1 These are the laconic words that implemented the much-awaited and hotly debated European Community Directive on the legal protection of databases,2 the EDD, into Finnish Copyright legislation in 1998. Now in the year 2005, after more than half a decade of the domestic implementation it is yet uncertain as to the proper meaning and construction of the convoluted qualitative criteria the current legislation employs as a prerequisite for the database protection both in Finland and within the European Union. Further, this opaque Pan-European instrument has the potential of bringing about a number of far-reaching economic and cultural ramifications, which have remained largely uncharted or unobserved. Thus the task of understanding this particular and currently peculiarly European new intellectual property regime is twofold: first, to understand the mechanics and functioning of the EDD and second, to realise the potential and risks inherent in the new legislation in economic, cultural and societal dimensions. 2. Subject-matter of the study: basic issues The first part of the task mentioned above is straightforward: questions such as what is meant by the key concepts triggering the functioning of the EDD such as presentation of independent information, what constitutes an essential investment in acquiring data and when the reproduction of a given database reaches either qualitatively or quantitatively the threshold of substantiality before the right-holder of a database can avail himself of the remedies provided by the statutory framework remain unclear and call for a careful analysis. As for second task, it is already obvious that the practical importance of the legal protection providedby the database right is in the rapid increase. The accelerating transformationof information into digital form is an existing fact, not merely a reflection of a shape of things to come in the future. To take a simple example, the digitisation of a map, traditionally in paper format and protected by copyright, can provide the consumer a markedly easier and faster access to the wanted material and the price can be, depending on the current state of the marketplace, cheaper than that of the traditional form or even free by means of public lending libraries providing access to the information online. This also renders it possible for authors and publishers to make available and sell their products to markedly larger, international markets while the production and distribution costs can be kept at minimum due to the new electronic production, marketing and distributionmechanisms to mention a few. The troublesome side is for authors and publishers the vastly enhanced potential for illegal copying by electronic means, producing numerous virtually identical copies at speed. The fear of illegal copying canlead to stark technical protection that in turn can dampen down the demand for information goods and services and furthermore, efficiently hamper the right of access to the materials available lawfully in electronic form and thus weaken the possibility of access to information, education and the cultural heritage of anation or nations, a condition precedent for a functioning democracy. 3. Particular issues in Digital Economy and Information Networks All what is said above applies a fortiori to the databases. As a result of the ubiquity of the Internet and the pending breakthrough of Mobile Internet, peer-to-peer Networks, Localand Wide Local Area Networks, a rapidly increasing amount of information not protected by traditional copyright, such as various lists, catalogues and tables,3previously protected partially by the old section 49 of the Finnish Copyright act are available free or for consideration in the Internet, and by the same token importantly, numerous databases are collected in order to enable the marketing, tendering and selling products and services in above mentioned networks. Databases and the information embedded therein constitutes a pivotal element in virtually any commercial operation including product and service development, scientific research and education. A poignant but not instantaneously an obvious example of this is a database consisting of physical coordinates of a certain selected group of customers for marketing purposes through cellular phones, laptops and several handheld or vehicle-based devices connected online. These practical needs call for answer to a plethora of questions already outlined above: Has thecollection and securing the validity of this information required an essential input? What qualifies as a quantitatively or qualitatively significant investment? According to the Directive, the database comprises works, information and other independent materials, which are arranged in systematic or methodical way andare individually accessible by electronic or other means. Under what circumstances then, are the materials regarded as arranged in systematic or methodical way? Only when the protected elements of a database are established, the question concerning the scope of protection becomes acute. In digital context, the traditional notions of reproduction and making available to the public of digital materials seem to fit ill or lead into interpretations that are at variance with analogous domain as regards the lawful and illegal uses of information. This may well interfere with or rework the way in which the commercial and other operators have to establish themselves and function in the existing value networks of information products and services. 4. International sphere After the expiry of the implementation period for the European Community Directive on legal protection of databases, the goals of the Directive must have been consolidated into the domestic legislations of the current twenty-five Member States within the European Union. On one hand, these fundamental questions readily imply that the problemsrelated to correct construction of the Directive underlying the domestic legislation transpire the national boundaries. On the other hand, the disputes arisingon account of the implementation and interpretation of the Directive on the European level attract significance domestically. Consequently, the guidelines on correct interpretation of the Directive importing the practical, business-oriented solutions may well have application on European level. This underlines the exigency for a thorough analysis on the implications of the meaning and potential scope of Database protection in Finland and the European Union. This position hasto be contrasted with the larger, international sphere, which in early 2005 does differ markedly from European Union stance, directly having a negative effect on international trade particularly in digital content. A particular case in point is the USA, a database producer primus inter pares, not at least yet having aSui Generis database regime or its kin, while both the political and academic discourse on the matter abounds. 5. The objectives of the study The above mentioned background with its several open issues calls for the detailed study of thefollowing questions: -What is a database-at-law and when is a database protected by intellectual property rights, particularly by the European database regime?What is the international situation? -How is a database protected and what is its relation with other intellectual property regimes, particularly in the Digital context? -The opportunities and threats provided by current protection to creators, users and the society as a whole, including the commercial and cultural implications? -The difficult question on relation of the Database protection and protection of factual information as such. 6. Dsiposition The Study, in purporting to analyse and cast light on the questions above, is divided into three mainparts. The first part has the purpose of introducing the political and rationalbackground and subsequent legislative evolution path of the European database protection, reflected against the international backdrop on the issue. An introduction to databases, originally a vehicle of modern computing and information andcommunication technology, is also incorporated. The second part sets out the chosen and existing two-tier model of the database protection, reviewing both itscopyright and Sui Generis right facets in detail together with the emergent application of the machinery in real-life societal and particularly commercial context. Furthermore, a general outline of copyright, relevant in context of copyright databases is provided. For purposes of further comparison, a chapter on the precursor of Sui Generi, database right, the Nordic catalogue rule also ensues. The third and final part analyses the positive and negative impact of the database protection system and attempts to scrutinize the implications further in the future with some caveats and tentative recommendations, in particular as regards the convoluted issue concerning the IPR protection of information per se, a new tenet in the domain of copyright and related rights.

A web ontologies framework for digital rights management

In order to improve the management of copyright in the Internet, known as Digital Rights Management, there is the need for a shared language for copyright representation. Current approaches are based on purely syntactic solutions, i.e. a grammar that defines a rights expression language. These languages are difficult to put into practise due to the lack of explicit semantics that facilitate its implementation. Moreover, they are simple from the legal point of view because they are intended just to model the usage licenses granted by content providers to end-users. Thus, they ignore the copyright framework that lies behind and the whole value chain from creators to end-users. Our proposal is to use a semantic approach based on semantic web ontologies. We detail the development of a copyright ontology in order to put this approach into practice. It models the copyright core concepts for creation, rights and the basic kinds of actions that operate on content. Altogether, it allows building a copyright framework for the complete value chain. The set of actions operating on content are our smaller building blocks in order to cope with the complexity of copyright value chains and statements and, at the same time, guarantee a high level of interoperability and evolvability. The resulting copyright modelling framework is flexible and complete enough to model many copyright scenarios, not just those related to the economic exploitation of content. The ontology also includes moral rights, so it is possible to model this kind of situations as it is shown in the included example model for a withdrawal scenario. Finally, the ontology design and the selection of tools result in a straightforward implementation. Description Logic reasoners are used for license checking and retrieval. Rights are modelled as classes of actions, action patterns are modelled also as classes and the same is done for concrete actions. Then, to check if some right or license grants an action is reduced to check for class subsumption, which is a direct functionality of these reasoners.

The membrane-permeable calmodulin inhibitors (W-7/W-13) bind to membranes changing the electrostatic surface potential. Dual effect of W-13 on EGFR activation

Membrane-permeable calmodulin inhibitors, such as the napthalenesulfonamide derivatives W-7/W-13, trifluoperazine, and calmidazolium, are used widely to investigate the role of calcium/calmodulin (Ca2+/CaM) in living cells. If two chemically different inhibitors (e.g. W-7 and trifluoperazine) produce similar effects, investigators often assume the effects are due to CaM inhibition. Zeta potential measurements, however, show that these amphipathic weak bases bind to phospholipid vesicles at the same concentrations as they inhibit Ca 2 /CaM; this suggests that they also bind to the inner leaflet of the plasma membrane, reducing its negative electrostatic surface potential. This change will cause electrostatically bound clusters of basic residues on peripheral (e.g. Src and K-Ras4B) and integral (e.g. epidermal growth factor receptor (EGFR)) proteins to translocate from the membrane to the cytoplasm. We measured inhibitor-mediated translocation of a simple basic peptide corresponding to the calmodulin-binding juxtamembrane region of the EGFR on model membranes; W-7/W-13 causes translocation of this peptide from membrane to solution, suggesting that caution must be exercised when interpreting the results obtained with these inhibitors in living cells. We present evidence that they exert dual effects on autophosphorylation of EGFR;W-13 inhibits epidermal growth factordependent EGFR autophosphorylation under different experimental conditions, but in the absence of epidermal growth factor, W-13 stimulates autophosphorylation of the receptor in four different cell types. Our interpretation is that the former effect is due toW-13inhibition of Ca 2 /CaM, but thelatter results could be due to binding of W-13 to the plasma membrane.