Differential miRNA and IncRNA expression in embryonic stem cells lacking the Notch1 receptor

Embryonic stem (ES) cells-derived cardiomyocytes represent an attractive source of cells in cell replacement therapies for heart disease. However, controlled cardiogenic differentiation of ES cells requires a complete understanding of the complex molecular mechanisms regulating the differentiation process. We have previously shown that differentiation of ES cells into cardiomyocytes is favored by inactivation of the Notch 1 receptor pathway. In the present study, we therefore compared two ES cell lines, one with normal Notchl expression and one carrying deleted Notchl receptor alleles (Notchl-deleted ES cells) in order to identify genes responsible for the increased propensity of Notchl-deleted ES cells to produce cardiomyocytes. Using RNA-sequencing, we found approximately 300 coding and noncoding transcripts, which are differently expressed in undifferentiated Notchl-deleted ES cells. Since accumulating evidences indicate that long noncoding RNAs (IncRNAs) play important roles in ES cell pluripotency and differentiation, we focused our analysis on modulated IncRNAs. In particular, two IncRNAs, named here lnc 1230 and lnc 1335, are highly induced in the absence of Notchl receptor expression. These represent therefore prime candidates that could favor cardiogenic commitment in undifferentiated ES cells. Indeed, we demonstrate that forced expression of these two IncRNAs in wild-type ES cells result in a significant increase of the number of cardiac progenitor cells and cardiomyocytes in the differentiated progeny of these ES cells. Furthermore, we also identify several microRNAs that are differentially modulated in absence of Notchl expression. Among these are miR-142-5p and miR- 381-3p. Interestingly, both lncl230 and lncl335 are targets of these two microRNAs. Altogether, these data suggest that Notchl-dependent noncoding gene networks, implicating microRNAs and IncRNAs, control embryonic stem cell commitment into the mesodermal and cardiac lineages already at the undifferentiated state. - Les cardiomyocytes issus cellules souches embryonnaires sont une source très prometteuse pour les thérapies cellulaire de remplacement dans le cadre des maladies cardiaques. Cependant, l'utilisation de telles cellules requiert une compréhension poussée des mécanismes moléculaire régulant la différenciation. Nous avons par le passé démontré que la différenciation des cellules souches embryonnaires en cardiomyocytes est favorisée par l'inactivation de la voie d'activation intracellulaire dépendante du récepteur Notch 1. Nous avons donc comparé deux lignées de cellules souches embryonnaires, une présentant une voie d'activation Notchl normale et une chez laquelle les allèles codant pour le récepteur Notchl avaient été invalidés, de façon à identifier les gènes impliqués dans la capacité augmentée des cellules déficientes à produire des cardiomyocytes. En utilisant du séquençage d'ARN à haut débit, nous avons trouvé environ 300 gènes différemment exprimés dans les cellules déficientes pour Notchl. Par ailleurs, des évidences de plus en plus nombreuses suggèrent qu'une nouvelle classe de molécules appelée « long noncoding RNAs » joue un rôle prépondérant dans la maintenance de l'état non différencié et de la capacité de différenciation des cellules souches embryonnaires. Nous avons trouvé que plusieurs « long noncoding RNAs » étaient modulés en l'absence de Notchl, et en particulier deux molécules que nous avons appelées lncl230 et lncl335. Ces derniers représentent des candidats potentiels devant permettre de favoriser la production de cardiomyocytes. Nous avons en effet démontré que la surexpression de ces deux candidats dans des cellules souches embryonnaires résultait en une surproduction de cardiomyocytes. De plus, nous avons également identifié plusieurs microRNAs dont l'expression était modulée dans les cellules souches embryonnaires déficientes dans la voie Notchl. De façon intéressante, parmi ces microRNAs, le miR-142-5p et le miR-381-3p sont capables de cibler lncl230 and lncl335. Dans l'ensemble, ces résultats indiquent donc que des réseaux d'interaction dépendant de la voie d'activation Notch 1 et impliquant des ARNs non codant existent dans les cellules souches embryonnaires pour réguler leur différenciation en différent types cellulaires spécifiques.

Cytoskeletal and DNA structure abnormalities result from bypass of requirement for the cdc10 start gene in the fission yeast Schizosaccharomyces pombe.

The cdc10 gene of the fission yeast S. pombe is required for traverse of the start control in late G1 and commitment to the mitotic cell cycle. To increase our understanding of the events which occur at start, a pseudoreversion analysis was undertaken to identify genes whose products may interact with cdc10 or bypass the requirement for it. A single gene, sct1+ (suppressor of cdc ten), has been identified, mutation of which suppresses all conditional alleles and a null allele of cdc10. Bypass of the requirement for cdc10+ function by sct1-1 mutations leads to pleiotropic defects, including microtubule, microfilament and nuclear structural abnormalities. Our data suggest that sct1 encodes a protein that is dependent upon cdc10+ either for its normal function or expression, or is a component of a checkpoint that monitors execution of p85cdc10 function.

Tapping the innovation potential of corporate engagement with stakeholders

Summary This dissertation explores how stakeholder dialogue influences corporate processes, and speculates about the potential of this phenomenon - particularly with actors, like non-governmental organizations (NGOs) and other representatives of civil society, which have received growing attention against a backdrop of increasing globalisation and which have often been cast in an adversarial light by firms - as a source of teaming and a spark for innovation in the firm. The study is set within the context of the introduction of genetically-modified organisms (GMOs) in Europe. Its significance lies in the fact that scientific developments and new technologies are being generated at an unprecedented rate in an era where civil society is becoming more informed, more reflexive, and more active in facilitating or blocking such new developments, which could have the potential to trigger widespread changes in economies, attitudes, and lifestyles, and address global problems like poverty, hunger, climate change, and environmental degradation. In the 1990s, companies using biotechnology to develop and offer novel products began to experience increasing pressure from civil society to disclose information about the risks associated with the use of biotechnology and GMOs, in particular. Although no harmful effects for humans or the environment have been factually demonstrated even to date (2008), this technology remains highly-contested and its introduction in Europe catalysed major companies to invest significant financial and human resources in stakeholder dialogue. A relatively new phenomenon at the time, with little theoretical backing, dialogue was seen to reflect a move towards greater engagement with stakeholders, commonly defined as those "individuals or groups with which. business interacts who have a 'stake', or vested interest in the firm" (Carroll, 1993:22) with whom firms are seen to be inextricably embedded (Andriof & Waddock, 2002). Regarding the organisation of this dissertation, Chapter 1 (Introduction) describes the context of the study, elaborates its significance for academics and business practitioners as an empirical work embedded in a sector at the heart of the debate on corporate social responsibility (CSR). Chapter 2 (Literature Review) traces the roots and evolution of CSR, drawing on Stakeholder Theory, Institutional Theory, Resource Dependence Theory, and Organisational Learning to establish what has already been developed in the literature regarding the stakeholder concept, motivations for engagement with stakeholders, the corporate response to external constituencies, and outcomes for the firm in terms of organisational learning and change. I used this review of the literature to guide my inquiry and to develop the key constructs through which I viewed the empirical data that was gathered. In this respect, concepts related to how the firm views itself (as a victim, follower, leader), how stakeholders are viewed (as a source of pressure and/or threat; as an asset: current and future), corporate responses (in the form of buffering, bridging, boundary redefinition), and types of organisational teaming (single-loop, double-loop, triple-loop) and change (first order, second order, third order) were particularly important in building the key constructs of the conceptual model that emerged from the analysis of the data. Chapter 3 (Methodology) describes the methodology that was used to conduct the study, affirms the appropriateness of the case study method in addressing the research question, and describes the procedures for collecting and analysing the data. Data collection took place in two phases -extending from August 1999 to October 2000, and from May to December 2001, which functioned as `snapshots' in time of the three companies under study. The data was systematically analysed and coded using ATLAS/ti, a qualitative data analysis tool, which enabled me to sort, organise, and reduce the data into a manageable form. Chapter 4 (Data Analysis) contains the three cases that were developed (anonymised as Pioneer, Helvetica, and Viking). Each case is presented in its entirety (constituting a `within case' analysis), followed by a 'cross-case' analysis, backed up by extensive verbatim evidence. Chapter 5 presents the research findings, outlines the study's limitations, describes managerial implications, and offers suggestions for where more research could elaborate the conceptual model developed through this study, as well as suggestions for additional research in areas where managerial implications were outlined. References and Appendices are included at the end. This dissertation results in the construction and description of a conceptual model, grounded in the empirical data and tied to existing literature, which portrays a set of elements and relationships deemed important for understanding the impact of stakeholder engagement for firms in terms of organisational learning and change. This model suggests that corporate perceptions about the nature of stakeholder influence the perceived value of stakeholder contributions. When stakeholders are primarily viewed as a source of pressure or threat, firms tend to adopt a reactive/defensive posture in an effort to manage stakeholders and protect the firm from sources of outside pressure -behaviour consistent with Resource Dependence Theory, which suggests that firms try to get control over extemal threats by focussing on the relevant stakeholders on whom they depend for critical resources, and try to reverse the control potentially exerted by extemal constituencies by trying to influence and manipulate these valuable stakeholders. In situations where stakeholders are viewed as a current strategic asset, firms tend to adopt a proactive/offensive posture in an effort to tap stakeholder contributions and connect the organisation to its environment - behaviour consistent with Institutional Theory, which suggests that firms try to ensure the continuing license to operate by internalising external expectations. In instances where stakeholders are viewed as a source of future value, firms tend to adopt an interactive/innovative posture in an effort to reduce or widen the embedded system and bring stakeholders into systems of innovation and feedback -behaviour consistent with the literature on Organisational Learning, which suggests that firms can learn how to optimize their performance as they develop systems and structures that are more adaptable and responsive to change The conceptual model moreover suggests that the perceived value of stakeholder contribution drives corporate aims for engagement, which can be usefully categorised as dialogue intentions spanning a continuum running from low-level to high-level to very-high level. This study suggests that activities aimed at disarming critical stakeholders (`manipulation') providing guidance and correcting misinformation (`education'), being transparent about corporate activities and policies (`information'), alleviating stakeholder concerns (`placation'), and accessing stakeholder opinion ('consultation') represent low-level dialogue intentions and are experienced by stakeholders as asymmetrical, persuasive, compliance-gaining activities that are not in line with `true' dialogue. This study also finds evidence that activities aimed at redistributing power ('partnership'), involving stakeholders in internal corporate processes (`participation'), and demonstrating corporate responsibility (`stewardship') reflect high-level dialogue intentions. This study additionally finds evidence that building and sustaining high-quality, trusted relationships which can meaningfully influence organisational policies incline a firm towards the type of interactive, proactive processes that underpin the development of sustainable corporate strategies. Dialogue intentions are related to type of corporate response: low-level intentions can lead to buffering strategies; high-level intentions can underpin bridging strategies; very high-level intentions can incline a firm towards boundary redefinition. The nature of corporate response (which encapsulates a firm's posture towards stakeholders, demonstrated by the level of dialogue intention and the firm's strategy for dealing with stakeholders) favours the type of learning and change experienced by the organisation. This study indicates that buffering strategies, where the firm attempts to protect itself against external influences and cant' out its existing strategy, typically lead to single-loop learning, whereby the firm teams how to perform better within its existing paradigm and at most, improves the performance of the established system - an outcome associated with first-order change. Bridging responses, where the firm adapts organisational activities to meet external expectations, typically leads a firm to acquire new behavioural capacities characteristic of double-loop learning, whereby insights and understanding are uncovered that are fundamentally different from existing knowledge and where stakeholders are brought into problem-solving conversations that enable them to influence corporate decision-making to address shortcomings in the system - an outcome associated with second-order change. Boundary redefinition suggests that the firm engages in triple-loop learning, where the firm changes relations with stakeholders in profound ways, considers problems from a whole-system perspective, examining the deep structures that sustain the system, producing innovation to address chronic problems and develop new opportunities - an outcome associated with third-order change. This study supports earlier theoretical and empirical studies {e.g. Weick's (1979, 1985) work on self-enactment; Maitlis & Lawrence's (2007) and Maitlis' (2005) work and Weick et al's (2005) work on sensegiving and sensemaking in organisations; Brickson's (2005, 2007) and Scott & Lane's (2000) work on organisational identity orientation}, which indicate that corporate self-perception is a key underlying factor driving the dynamics of organisational teaming and change. Such theorizing has important implications for managerial practice; namely, that a company which perceives itself as a 'victim' may be highly inclined to view stakeholders as a source of negative influence, and would therefore be potentially unable to benefit from the positive influence of engagement. Such a selfperception can blind the firm from seeing stakeholders in a more positive, contributing light, which suggests that such firms may not be inclined to embrace external sources of innovation and teaming, as they are focussed on protecting the firm against disturbing environmental influences (through buffering), and remain more likely to perform better within an existing paradigm (single-loop teaming). By contrast, a company that perceives itself as a 'leader' may be highly inclined to view stakeholders as a source of positive influence. On the downside, such a firm might have difficulty distinguishing when stakeholder contributions are less pertinent as it is deliberately more open to elements in operating environment (including stakeholders) as potential sources of learning and change, as the firm is oriented towards creating space for fundamental change (through boundary redefinition), opening issues to entirely new ways of thinking and addressing issues from whole-system perspective. A significant implication of this study is that potentially only those companies who see themselves as a leader are ultimately able to tap the innovation potential of stakeholder dialogue.

Soil diffuse degassing and thermal energy fluxes from the southern Lakki plain, Nisyros (Greece)

Two diffuse soil CO2 flux surveys from the southern Lakki plain show that CO2 is mainly released from the hydrothermal explosion craters. The correspondence between high CO2 fluxes and elevated soil temperatures suggests that a flux of hot hydrothermal fluids ascends towards the surface. Steam mostly condenses near the surface and the heat given off is conductively transferred to the atmosphere through the soil, accompanied by a large CO2 flux. Tt was calculated, that 68 t d(-1) of hydrothermal CO2 are released through the total surveyed area of similar to1.3 km(2) Admitting that a steam flux of 2200 t d(-1) accompanies this CO2 flux, the thermal energy released through steam condensation amounts to 58 MW.

Mechanisms of garnet growth in eclogites of the Zermatt-Saas Fee unit, Western Alps

THESIS ABSTRACT Garnets are one of the key metamorphic minerals used to study peak metamorphic conditions or crystallization ages. Equilibrium is typically assumed between the garnet and the matrix. This thesis attempts to understand garnet growth in the Zermatt-Saas Fee (ZSF) eclogites, and discusses consequences for Sm/Nd and Lu/Hf dating and the equilibrium assumption. All studied garnets from the ZSF eclogites are strongly zoned in Mn, Fe, Mg, and Ca. Methods based on chemical zoning patterns and on 3D spatial statistics indicate different growth mechanisms depending on the sample studied. Garnets from the Pfulwe area are grown in a system where surface kinetics likely dominated over intergranular diffusion kinetics. Garnets fram two other localities, Nuarsax and Lago di Cignana, seem to have grown in a system where intergranular diffusion kinetics were dominating over surface kinetics, at least during initial growth. Garnets reveal strong prograde REE+Y zoning. They contain narrow central peaks for Lu + Yb + Tm ± Er and at least one additional small peak towards the rim. The REE Sm + Eu + Gd + Tb ± Dy are depleted in the cores but show one prominent peak close to the rim. It is shown that these patterns cam be explained using a transient matrix diffusion model where REE uptake is limited by diffusion in the matrix surrounding the porphyroblast. The secondary peaks in the garnet profiles are interpreted to reflect thermally activated diffusion due to a temperature increase during prograde metamorphism. The model predicts anomalously low 176Lu/177Hf and 147Sm/144Nd ratios in garnets where growth rates are fast compared to diffusion of the REE, which decreases garnet isochron precisions. The sharp Lu zoning was further used to constrain maximum Lu volume diffusion rates in garnet. The modeled minimum pre-exponential diffusion coefficient which fits the measured central peak is in the order of Do = 5.7* 106 m2/s, taking an activation energy of 270 kJ/mol. The latter was chosen in agreement with experimentally determined values. This can be used to estimate a minimum closure temperature of around 630°C for the ZSF zone. Zoning of REE was combined with published Lu/Hf and Sm/Nd age information to redefine the prograde crystallization interval for Lago di Cignana UHP eclogites. Modeling revealed that a prograde growth interval in the order of 25 m.y. is needed to produce the measured spread in ages. RÉSUMÉ Le grenat est un minéral métamorphique clé pour déterminer les conditions du pic de métamorphisme ainsi que l'âge de cristallisation. L'équilibre entre le grenat et la matrice est requis. Cette étude a pour but de comprendre la croissance du grenat dans les éclogites de la zone de Zermatt-Saas Fee (ZSF) et d'examiner quelques conséquences sur les datations Sm/Nd et Lu/Hf. Tous les grenats des éclogites de ZSF étudiés sont fortement zonés en Mn, Fe, Mg et partiellement en Ca. Les différentes méthodes basées sur le modèle de zonation chimique ainsi que sur les statistiques de répartition spatiale en 3D indiquent un mécanisme de croissance différent en fonction de la localité d'échantillonnage. Les grenats provenant de la zone de Pfulwe ont probablement crû dans un système principalement dominé par la cinétique de surface au détriment de 1a cinétique de diffusion intergranulaire. Les grenats provenant de deux autres localités, Nuarsax et Lago di Cignana, semblent avoir cristallisé dans un système dominé par la diffusion intergranulaire, au moins durant les premiers stades de croissance. Les grenats montrent une forte zonation prograde en Terres Rares (REE) ainsi qu'en Y. Les profils présentent au coeur un pic étroit en Lu + Yb+ Tm ± Er et au moins un petit pic supplémentaire vers le bord. Les coeurs des grenats sont appauvris en Sm + Eu + Gd + Tb ± Dy, mais les bords sont marqués par un pic important de ces REE. Ces profils s'expliquent par un modèle de diffusion matricielle dans lequel l'apport en REE est limité par la diffusion dans la matrice environnant les porphyroblastes. Les pics secondaires en bordure de grain reflètent la diffusion activée par l'augmentation de la température lors du métamorphisme prograde. Ce modèle prédit des rapports 176Lu/177Hf et 147Sm/144Nd anormalement bas lorsque les taux de croissance sont plus rapides que la diffusion des REE, ce qui diminue la précision des isochrones impliquant le grenat. La zonation nette en Lu a permis de contraindre le maximum de diffusion volumique par une approche numérique. Le coefficient de diffusion minimum modélisé en adéquation avec les pics mesurés est de l'ordre de Do = 5.7*10-6 m2/s, en prenant une énergie d'activation ~270 kJ/mol déterminée expérimentalement. Ainsi, la température de clôture minimale est estimée aux alentours de 630°C pour la zone ZSF. Des nouvelles données de zonation de REE sont combinées aux âges obtenus avec les rapports Lu/Hf et Sm/Nd qui redéfissent l'intervalle de cristallisation prograde pour les éclogites UHP de Lago di Cignana. La modélisation permet d'attribuer au minimum un intervalle de croissance prograde de 25 Ma afin d'obtenir les âges préalablement mesurés. RESUME GRAND PUBLIC L'un des principaux buts du pétrologue .métamorphique est d'extraire des roches les informations sur l'évolution temporelle, thermique et barométrique qu'elles ont subi au cours de la formation d'une chaîne de montagne. Le grenat est l'un des minéraux clés dans une grande variété de roches métamorphiques. Il a fait l'objet de nombreuses études dans des terrains d'origines variées ou lors d'études expérimentales afin de comprendre ses domaines de stabilité, ses réactions et sa coexistence avec d'autres minéraux. Cela fait du grenat l'un des minéraux les plus attractifs pour la datation des roches. Cependant, lorsqu'on l'utilise pour la datation et/ou pour la géothermobarométrie, on suppose toujours que le grenat croît en équilibre avec les phases coexistantes de la matrice. Pourtant, la croissance d'un minéral est en général liée au processus de déséquilibre. Cette étude a pour but de comprendre comment croît le grenat dans les éclogites de Zermatt - Saas Fee et donc d'évaluer le degré de déséquilibre. Il s'agit aussi d'expliquer les différences d'âges obtenues grâce aux grenats dans les différentes localités de l'unité de Zermatt-Saas Fee. La principale question posée lors de l'étude des mécanismes de croissance du grenat est: Parmi les processus en jeu lors de la croissance du grenat (dissolution des anciens minéraux, transport des éléments vers le nouveau grenat, précipitation d'une nouvelle couche en surface du minéral), lequel est le plus lent et ainsi détermine le degré de déséquilibre? En effet, les grenats d'une des localités (Pfulwe) indiquent que le phénomène d'adhérence en surface est le plus lent, contrairement aux grenats des autres localités (Lago di Cignana, Nuarsax) dans lesquels ce sont les processus de transport qui sont les plus lents. Cela montre que les processus dominants sont variables, même dans des roches similaires de la même unité tectonique. Ceci implique que les processus doivent être déterminés individuellement pour chaque roche afin d'évaluer le degré de déséquilibre du grenat dans la roche. Tous les grenats analysés présentent au coeur une forte concentration de Terres Rares: Lu + Yb + Tm ± Er qui décroît vers le bord du grain. Inversement, les Terres Rares Sm + Eu + Gd + Tb ± Dy sont appauvries au coeur et se concentrent en bordure du grain. La modélisation révèle que ces profils sont-dus à des cinétiques lentes de transport des Terres Rares. De plus, les modèles prédisent des concentrations basses en éléments radiogéniques pères dans certaines roches, ce qui influence fortement sur la précision des âges obtenus par la méthode d'isochrone. Ceci signifie que les roches les plus adaptées pour les datations ne doivent contenir ni beaucoup de grenat ni de très gros cristaux, car dans ce cas, la compétition des éléments entre les cristaux limite à de faibles concentrations la quantité d'éléments pères dans chaque cristal.

In vivo Structural Imaging of the Cerebellum, the Contribution of Ultra-High Fields.

This review covers some of the contributions to date from cerebellar imaging studies performed at ultra-high magnetic fields. A short overview of the general advantages and drawbacks of the use of such high field systems for imaging is given. One of the biggest advantages of imaging at high magnetic fields is the improved spatial resolution, achievable thanks to the increased available signal-to-noise ratio. This high spatial resolution better matches the dimensions of the cerebellar substructures, allowing a better definition of such structures in the images. The implications of the use of high field systems is discussed for several imaging sequences and image contrast mechanisms. This review covers studies which were performed in vivo in both rodents and humans, with a special focus on studies that were directed towards the observation of the different cerebellar layers.

The parties' voices in a therapeutic interview

Drawing on a dialogical approach inspired by Bakhtin, we start from the assumptionthat a concrete discussion is an intermingling between dialogue in praesentia and dialogue inabsentia, and we refer to the notion of 'enunciative positioning' to account for the variousrelations that a speaker may express towards the voices that he or she invokes. Our data arebased on a first therapeutic interview between a therapist, a mother and a child in a counselingcenter for children and adolescents. We identify the various voices invoked in this interviewand show that three levels of discursive process were involved: (a) the speakers invokedabsent speakers; (b) at the same time they developed their own discourse on the basis of theirinterlocutors' discourse which (c) itself drew on absent speakers or voices. We highlight thevarious discursive processes through which the speakers integrate their own voice into absentvoices, or integrate a distant voice so that it loses its property of being a distant (andborrowed) voice. As a theoretical and methodological contribution to dialogism, our resultsshow that absent voices and their specific intermingling with hic et nunc exchanges were amajor resource for therapeutic changes.

Software SMEs asStrategic Partners in the Partner Programs of Large International Companies

Tutkielman tavoitteena oli tutkia pienten- ja keskisuurten (PK) ohjelmistoyritysten kansainvälisiä kumppanuuksia. Päätavoitteena oli löytää keinoja kuinka PK-ohjelmistoyritykset voisivat tulla strategisiksi kumppaneksi suurten kansainvälisten yritysten kumppanuusohjelmissa. Lisäksi tutkielmassa oli tavoitteena selvittää kuinka kumppaneiden välistä sitoutumista voitaisiin vahvistaa, jotta PK-ohjelmistoyritykset voisivat saavuttaa todellista lisäarvoa ja kansainvälistä kasvua kumppanuusohjelmien kautta. Tutkielma jakaantuu teoreettiseen ja empiiriseen osaan. Teoreettinen osa keskittyy tarkastelemaan korkean teknologian markkinointia ohjelmistoalalla sekä kansainvälisiä kumppanuuksia. Suurten yritystenkumppanuusohjelmia ei ole tutkittu suomalaisten PK-ohjelmistoyritysten näkökulmasta, minkä vuoksi empiirinen tutkimus on perusteltua. Empiirinen tutkimus toteutettiin laadullisena case-tutkimuksena ja tutkimusmenetelmänä käytettiin puolistrukturoitua haastattelua. Tutkimustulokset osoittavat, että strategisen kumppanin aseman saavuttaminen on pitkä ja haastava matka PK-yrityksille. Suurten kansainvälisten yritysten kumppanuusohjelmat ovat useimmiten monimutkaisia ja todellisen lisäarvon saavuttaminen kumppanuusohjelman kautta vaatii paljon resursseja PK-yrityksiltä. Jotta PK-yritykset voisivat saavuttaa ja säilyttää strategisen kumppanin aseman kumppanuusohjelmassa, vaatii se aktiivista ja päivittäistä vuorovaikutusta kumppaneiden kesken. Erityisesti tiiviit henkilösuhteet oikeiden avainhenkilöiden kanssa ovat välttämättömyys. Läheiset kontaktit mahdollistavat sen, että PK-yritykset voivat ainakin osittain ohittaa kumppanuusohjelman byrokratian, mikä lisää luottamusta ja sitoutumista kumppanuussuhteessa sekä edistää kansainvälistä kasvua ja menestystä liiketoiminnassa.

Light-mediated polarization of the PIN3 auxin transporter for the phototropic response in Arabidopsis.

Phototropism is an adaptation response, through which plants grow towards the light. It involves light perception and asymmetric distribution of the plant hormone auxin. Here we identify a crucial part of the mechanism for phototropism, revealing how light perception initiates auxin redistribution that leads to directional growth. We show that light polarizes the cellular localization of the auxin efflux carrier PIN3 in hypocotyl endodermis cells, resulting in changes in auxin distribution and differential growth. In the dark, high expression and activity of the PINOID (PID) kinase correlates with apolar targeting of PIN3 to all cell sides. Following illumination, light represses PINOID transcription and PIN3 is polarized specifically to the inner cell sides by GNOM ARF GTPase GEF (guanine nucleotide exchange factor)-dependent trafficking. Thus, differential trafficking at the shaded and illuminated hypocotyl side aligns PIN3 polarity with the light direction, and presumably redirects auxin flow towards the shaded side, where auxin promotes growth, causing hypocotyls to bend towards the light. Our results imply that PID phosphorylation-dependent recruitment of PIN proteins into distinct trafficking pathways is a mechanism to polarize auxin fluxes in response to different environmental and endogenous cues.

Neurophysiologic and proteomic investigations of experience-dependent plasticity in the somatosensory cortex of the adult mouse following chronic whisker stimulation

RESUME Les follicules des vibrisses des rongeurs sont représentés sous la forme d'une carte topographique dans le cortex à tonneaux. Lorsque un groupe de vibrisses est coupé pendant plusieurs jours chez un rongeur adulte, en laissant les autres vibrisses intactes, le champ réceptif des neurones du cortex à tonneaux est modifié, ce qui démontre que les cartes corticales sont plastiques. Dans notre étude, une expérience sensorielle a été induite chez une souris adulte se comportant librement en stimulant chroniquement une de ses vibrisses pendant 24h. Par une analyse des potentiels de champ locaux, nous démontrons que les caractéristiques spatiotemporelles du flux d'excitation évoqué par la vibrisse principale (VP) dans la colonne corticale correspondante à la vibrisse stimulée n'est pas altéré. Par contre, l'enregistrement des potentiels d'actions d'un total de 1041 neurones à travers le cortex à tonneaux révèlent plusieurs modifications de l'activité neuronale. L'activité spontanée ainsi que la réponse évoquée par la VP sont déprimées dans la colonne corticale stimulée (nombre moyen de potentiels d'action évoqués par la VP diminue de 25 % et 36% dans la couche IV et les couches II&III). La réponse des neurones à la vibrisse stimulée diminue également dans les colonnes corticales adjacentes, «non-stimulées». La dépression de l'activité spontanée et de la réponse à la VP est localisée à la colonne corticale stimulée. Dans le tonneau stimulé, la première partie de la réponse à la VP n'est pas affaiblie, démontrant que la dépression de la réponse n'est pas due à un phénomène de plasticité sous-corticale ou thalamocorticale. La stimulation chronique d'une vibrisse entraîne une augmentation du nombre de synapses GABAergiques dans la couche IV du tonneau correspondant (Knott et al, 2002). Dès lors, nos résultats suggèrent qu'une augmentation de l'inhibition dans le tonneau stimulé serait à l'origine de la diminution des potentiels d'action évoqués par la vibrisse stimulée et en conséquence de l'amplitude du flux d'excitation vers les couches II&III puis vers les colonnes corticales adjacentes. Toutes les réponses des neurones du tonneau stimulé ne sont pas déprimées. Les réponses des neurones à la vibrisse voisine caudale à VP diminuent dans la couche IV (42%) et dans les couches II&III (52%) mais pas les réponses aux 7 autres vibrisses voisines. Les entrées synaptiques en provenance de la vibrisse caudale pourraient avoir été spécifiquement déprimées en raison d'une décorrélation prolongée entre l'activité évoquée dans les chemins sensoriels relatifs à la vibrisse stimulée et à la vibrisse caudale, spécificité qui découlerait du fait que, parmi les vibrisses voisines à la VP, la vibrisse caudale génère les réponses les plus fortes dans la colonne corticale. Quatre jours après l'arrêt de la stimulation, l'activité neuronale n'est plus déprimée; au contraire, nous observons une potentiation des réponses à la VP dans la couche IV de la colonne corticale stimulée. De plus, nous montrons que l'expression des protéines GLT-1 et GLAST, deux transporteurs astrocytaires du glutamate, est augmentée de ~2.5 fois dans la colonne corticale stimulée, indiquant l'existence d'une «plasticité gliale» et suggérant que les cellules gliales participent activement à l'adaptation du cerveau à l'expérience. ABSTRACT In the barrel cortex, mystacial whisker follicles are represented in the form of a topographie map. The selective removal of a set of whiskers while sparing others for several days in an adult rodent alters receptive field of barrel cortex neurons, demonstrating experience-dependent plasticity of cortical maps. Here sensory experience was altered by chronic stimulation of a whisker for a 24h period in a freely behaving adult mouse. By means of an evoked local field potential analysis, we show that chronic stimulation does not alter the flow of excitation evoked by the principal whisker (PW) in the stimulated barrel column. However, the recording of neuronal firing from a total of 1041 single units throughout the barrel cortex reveals several changes in neuronal activity. Immediately after chronic stimulation, spontaneous activity as well as PW-responses are depressed in the stimulated barrel column (mean number of spikes per PW-deflection decreases by 25% and 36% in layer IV and layers II&III, respectively). Neuronal responses towards the chronically stimulated whisker are also significantly depressed in layers II&III of the adjacent "non-stimulated" barrel' columns. The depression of both spontaneous activity and PW-responses are restricted to the stimulated ban-el column. The earliest time epoch of the PW-response in the stimulated barrel is not depressed, demonstrating that the decrease of cortical responses is not due to subcortical or thalamocortical plasticity. The depression of PW-response in the stimulated barrel correlates with an increase in the number of GABAergic synapses in layer IV (Knott et al., 2002). Therefore, our results suggest that an increase in inhibition within the stimulated barrel may reduce its excitatory output and accordingly the flow of excitation towards layers and the subsequent horizontal spread into adjacent barrel columns. Not all responses of neurons in the stimulated barrel are depressed. Neuronal responses towards the caudal in-row whisker decrease by 42% in layer IV and 52% in layers MM but responses to the other 7 immediate surround whiskers (SWs) are not affected. The synaptic inputs from the SW that elicit the strongest responses in the stimulated barrel may have been specifically depressed following a prolonged period of diminished coherence between neuronal activity evoked in the pathways from the chronically stimulated whisker and from its surrounding in-row whisker. Four days after the cessation of the stimulation, depression of neuronal activity is no longer present; on the contrary, we observe a small but significant potentiation of PW-responses in layer IV of the stimulated barrel column. Moreover we show that the expression of astrocytic glutamate transporters GLT-1 and GLAST proteins were both upregulated by ~2.5 fold in the stimulated barrel column, which indicates that glial cells exhibit experience-dependent functional changes and could actively take part in the adaptation of the cerebral cortex to experience.

Quantitative developmental response to the length of exposure to long photoperiod in wheat and barley

The present study was designed to analyse the effect of the length of exposure to a long photoperiod imposed c. 3 weeks after sowing in spring wheat (cv. UQ189) and barley (cv. Arapiles) to (i) establish whether the response to the number of cycles of exposure is quantitative or qualitative, (ii) determine the existence of a commitment to particular stages well before the stage has been observable, and (iii) study the interrelationships between the effects on final leaf number and phyllochron when the stimulus is provided several days after seedling emergence. Both wheat and barley seemed to respond quantitatively to the number of long-day cycles they were exposed to. However, wheat showed a requirement of approximately 4 long-day cycles to be able to produce a significant response in time to heading. The barley cultivar used in the study was responsive to the minimum length of exposure. The response to extended photoperiod cycles during the stem elongation phase was due to the ‘ memory’ photoperiod effects being related, in the case of wheat, to the fact that the pre-terminal spikelet appearance phase saturated its photoperiod response well before that stage was reached. Therefore, the commitment to the terminal spikelet appearance in wheat may be reached well before this stage could be recognized. As the response in duration to heading exceeded that of the final leaf number, and the stem elongation phase responded to memory effects of photoperiod, the phyllochron of both cereals was responsive to the treatments accelerating the average phyllochron when exposed to longer periods of long days. The response in average phyllochron was due to a switch from bi-linear to linear models of leaf number v. time when the conditions were increasingly inductive, with the phyllochron of the initial (6–8) leaves being similar for all treatments (within each species), and from then on increased.

The multi-facets of sustainable nanotechnology : lessons from a nanosafety symposium

An international symposium for nanosafety was held recently at the Nanyang Technological University in Singapore. Topics relating to understanding nanomaterial properties, tools, and infrastructure required for predicting hazardous outcomes, measuring nanomaterial exposure levels, systems approach for risk assessment and public's perception of nanotechnology were covered. The need for a multidisciplinary approach, across both natural and social sciences, for developing sustainable nanotechnology solutions was heavily emphasized. This commentary highlights the major issues discussed and the commitment of the nanosafety research community in Singapore to contribute collectively to realise the vision of sustainable nanotechnology.

Tobacco control policies in hospitals before and after the implementation of a national smoking ban in Catalonia, Spain

Background: Diverse projects and guidelines to assist hospitals towards the attainment of comprehensive smoke-free policies have been developed. In 2006, Spain government passed a new smoking ban that reinforce tobacco control policies and banned completely smoking in hospitals. This study assesses the progression of tobacco control policies in the Catalan Network of Smokefree Hospitals before and after a comprehensive national smoking ban. Methods: We used the Self-Audit Questionnaire of the European Network for Smoke-free Hospitals to score the compliance of 9 policy standards (global score = 102). We used two crosssectional surveys to evaluate tobacco control policies before (2005) and after the implementation of a national smoking ban (2007) in 32 hospitals of Catalonia, Spain. We compared the means of the overall score in 2005 and 2007 according to the type of hospital, the number of beds, the prevalence of tobacco consumption, and the number of years as a smoke-free hospital. Results: The mean of the implementation score of tobacco control policies was 52.4 (95% CI:45.4-59.5) in 2005 and 71.6 (95% CI: 67.0-76.2) in 2007 with an increase of 36.7% (p < 0.01). The hospitals with greater improvement were general hospitals (48% increase; p < 0.01), hospitals with > 300 beds (41.1% increase; p < 0.01), hospitals with employees' tobacco consumption prevalence 35-39% (72.2% increase; p < 0.05) and hospitals that had recently implemented smoke-free policies (74.2% increase; p < 0.01). Conclusion: The national smoking ban appears to increase tobacco control activities in hospitals combined with other non-bylaw initiatives such as the Smoke-free Hospital Network.

Tobacco control policies in hospitals before and after the implementation of a national smoking ban in Catalonia, Spain

Background: Diverse projects and guidelines to assist hospitals towards the attainment of comprehensive smoke-free policies have been developed. In 2006, Spain government passed a new smoking ban that reinforce tobacco control policies and banned completely smoking in hospitals. This study assesses the progression of tobacco control policies in the Catalan Network of Smokefree Hospitals before and after a comprehensive national smoking ban. Methods: We used the Self-Audit Questionnaire of the European Network for Smoke-free Hospitals to score the compliance of 9 policy standards (global score = 102). We used two crosssectional surveys to evaluate tobacco control policies before (2005) and after the implementation of a national smoking ban (2007) in 32 hospitals of Catalonia, Spain. We compared the means of the overall score in 2005 and 2007 according to the type of hospital, the number of beds, the prevalence of tobacco consumption, and the number of years as a smoke-free hospital. Results: The mean of the implementation score of tobacco control policies was 52.4 (95% CI:45.4-59.5) in 2005 and 71.6 (95% CI: 67.0-76.2) in 2007 with an increase of 36.7% (p < 0.01). The hospitals with greater improvement were general hospitals (48% increase; p < 0.01), hospitals with > 300 beds (41.1% increase; p < 0.01), hospitals with employees' tobacco consumption prevalence 35-39% (72.2% increase; p < 0.05) and hospitals that had recently implemented smoke-free policies (74.2% increase; p < 0.01). Conclusion: The national smoking ban appears to increase tobacco control activities in hospitals combined with other non-bylaw initiatives such as the Smoke-free Hospital Network.

Drumming in immersive virtual reality: the body shapes the way we play

It has been shown that it is possible to generate perceptual illusions of ownership in immersive virtual reality (IVR) over a virtual body seen from first person perspective, in other words over a body that visually substitutes the person's real body. This can occur even when the virtual body is quite different in appearance from the person's real body. However, investigation of the psychological, behavioral and attitudinal consequences of such body transformations remains an interesting problem with much to be discovered. Thirty six Caucasian people participated in a between-groups experiment where they played a West-African Djembe hand drum while immersed in IVR and with a virtual body that substituted their own. The virtual hand drum was registered with a physical drum. They were alongside a virtual character that played a drum in a supporting, accompanying role. In a baseline condition participants were represented only by plainly shaded white hands, so that they were able merely to play. In the experimental condition they were represented either by a casually dressed dark-skinned virtual body (Casual Dark-Skinned - CD) or by a formal suited light-skinned body (Formal Light-Skinned - FL). Although participants of both groups experienced a strong body ownership illusion towards the virtual body, only those with the CD representation showed significant increases in their movement patterns for drumming compared to the baseline condition and compared with those embodied in the FL body. Moreover, the stronger the illusion of body ownership in the CD condition, the greater this behavioral change. A path analysis showed that the observed behavioral changes were a function of the strength of the illusion of body ownership towards the virtual body and its perceived appropriateness for the drumming task. These results demonstrate that full body ownership illusions can lead to substantial behavioral and possibly cognitive changes depending on the appearance of the virtual body. This could be important for many applications such as learning, education, training, psychotherapy and rehabilitation using IVR.