Preemptive treatment approach to cytomegalovirus (CMV) infection in solid organ transplant patients: relationship between compliance with the guidelines and prevention of CMV morbidity.

Cytomegalovirus (CMV) remains a major cause of morbidity in solid organ transplant patients. In order to reduce CMV morbidity, we designed a program of routine virological monitoring that included throat and urine CMV shell vial culture, along with peripheral blood leukocyte (PBL) shell vial quantitative culture for 12 weeks post-transplantation, as well as 8 weeks after treatment for acute rejection. The program also included preemptive ganciclovir treatment for those patients with the highest risk of developing CMV disease, i.e., with either high-level viremia (>10 infectious units [IU]/106 PBL) or low-level viremia (<10 IU/106 PBL) and either D+/R- CMV serostatus or treatment for graft rejection. During 1995-96, 90 solid organ transplant recipients (39 kidneys, 28 livers, and 23 hearts) were followed up. A total of 60 CMV infection episodes occurred in 45 patients. Seventeen episodes were symptomatic. Of 26 episodes managed according to the program, only 4 presented with CMV disease and none died. No patient treated preemptively for asymptomatic infection developed disease. In contrast, among 21 episodes managed in non-compliance with the program (i.e., the monitoring was not performed or preemptive treatment was not initiated despite a high risk of developing CMV disease), 12 episodes turned into symptomatic infection (P=0.0048 compared to patients treated preemptively), and 2 deaths possibly related to CMV were recorded. This difference could not be explained by an increased proportion of D+/R- patients or an increased incidence of rejection among patients with episodes treated in non-compliance with the program. Our data identify compliance with guidelines as an important factor in effectively reducing CMV morbidity through preemptive treatment, and suggest that the complexity of the preemptive approach may represent an important obstacle to the successful prevention of CMV morbidity by this approach in the regular healthcare setting.

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.

Engaging students in an e-learning experience : how to manage information resources through wikis and web blogs

The purpose of this paper is to describe the collaboration between librarians and scholars, from a virtual university, in order to facilitate collaborative learning on how to manage information resources. The personal information behaviour of e-learning students when managing information resources for academic, professional and daily life purposes was studied from 24 semi-structured face-to-face interviews. The results of the content analysis of the interview' transcriptions, highlighted that in the workplace and daily life contexts, competent information behaviour is always linked to a proactive attitude, that is to say, that participants seek for information without some extrinsic reward or avoiding punishment. In the academic context, it was observed a low level of information literacy and it seems to be related with a prevalent uninvolved attitude.

PAX5 activates the transcription of the human telomerase reverse transcriptase gene in B cells.

Telomerase is an RNA-dependent DNA polymerase that synthesizes telomeric DNA. Its activity is not detectable in most somatic cells but it is reactivated during tumorigenesis. In most cancers, the combination of hTERT hypermethylation and hypomethylation of a short promoter region is permissive for low-level hTERT transcription. Activated and malignant lymphocytes express high telomerase activity, through a mechanism that seems methylation-independent. The aim of this study was to determine which mechanism is involved in the enhanced expression of hTERT in lymphoid cells. Our data confirm that in B cells, some T cell lymphomas and non-neoplastic lymph nodes, the hTERT promoter is unmethylated. Binding sites for the B cell-specific transcription factor PAX5 were identified downstream of the ATG translational start site through EMSA and ChIP experiments. ChIP assays indicated that the transcriptional activation of hTERT by PAX5 does not involve repression of CTCF binding. In a B cell lymphoma cell line, siRNA-induced knockdown of PAX5 expression repressed hTERT transcription. Moreover, ectopic expression of PAX5 in a telomerase-negative normal fibroblast cell line was found to be sufficient to activate hTERT expression. These data show that activation of hTERT in telomerase-positive B cells is due to a methylation-independent mechanism in which PAX5 plays an important role.

Isolation and in vitro chondrogenic potential of human foetal spine cells.

Cell therapy for nucleus pulposus (NP) regeneration is an attractive treatment for early disc degeneration as shown by studies using autologous NP cells or stem cells. Another potential source of cells is foetal cells. We investigated the feasibility of isolating foetal cells from human foetal spine tissues and assessed their chondrogenic potential in alginate bead cultures. Histology and immunohistochemistry of foetal tissues showed that the structure and the matrix composition (aggrecan, type I and II collagen) of foetal intervertebral disc (IVD) were similar to adult IVD. Isolated foetal cells were cultured in monolayer in basic media supplemented with 10% Fetal Bovine Serum (FBS) and from each foetal tissue donation, a cell bank of foetal spine cells at passage 2 was established and was composed of around 2000 vials of 5 million cells. Gene expression and immunohistochemistry of foetal spine cells cultured in alginate beads during 28 days showed that cells were able to produce aggrecan and type II collagen and very low level of type I and type X collagen, indicating chondrogenic differentiation. However variability in matrix synthesis was observed between donors. In conclusion, foetal cells could be isolated from human foetal spine tissues and since these cells showed chondrogenic potential, they could be a potential cell source for IVD regeneration.

Determining, Balancing and Controlling of Pitch and White Pitch at Stora Enso Kabel Production Line 4

Työn ensimmäisenä tarkoituksena oli kartoittaa kiinteä-neste ja neste-neste uuttomenetelmillä pihkan ja valkopihkan määrä Stora Enso Kabelin tuotantolinja 4:llä. Työn kannalta oli myöstärkeää saada selvyys saostumien koostumuksesta. Lopullinen päämäärä oli automatisoida fiksatiivin annostelu uuden, jatkuvatoimisen märänpäänanalysaattorin avulla. Mäntyosuuden kasvattaminen hiokemassassa lisää hydrofobisten partikkeleiden lukumäärää, minkä uskotaan lisäävän saostumariskiä. Työtä varten kehitetty neste-neste uuttomenetelmä, jota ei ole liiemmin paperiteollisuudessa käytetty, voi olla hyvä menetelmä lipofiilisten komponenttien määrän arviointiin tietyssä määrässä massa- tai prosessivesinäytettä. Virtaussytometri-menetelmän avulla tutkittiin pihka- tai valkopihkapartikkeleiden määrää ja kokojakaumaa eri prosessinäytteissä. Virtaussytometri-menetelmällä mitattujen valkopihkapartikkeleiden lukumäärän ja päällystetyn hylyn saostimen suodoksen sameuden välille löytyiselvä korrelaatio. Fiksatiivimäärän vaikutusta päällystetyn hylyn saostimen suodoksen sameuteen tutkittiin koeajojaksolla, jossa fiksatiivin annostelua säädettiin käsin. Käytetyt annosmäärät eivät riittäneet sameuden pitämiseen tasaisena matalalla tasolla.

Kuorimon automaatiojärjestelmän optimointi

Työn tavoitteena oli pienentää kuorinnassa syntyviä puuhäviöitä ja parantaa linjan käytettävyyttä nykyaikaisella puunkuorimolla. Tavoitteet toteutettiin automaatiojärjestelmään tehdyillä muutoksilla. Rumpukuorintaprosessi on säilynyt pitkään samanlaisena. Viime vuosina on markkinoille tullut uusia älykkäitä mittalaitteita ja optimointiin kykeneviä säätöjärjestelmiä. Uudenlaisella automaatiotekniikalla on mahdollista mitata kuorintatulosta ja kuorinnassa syntyneitä puuhäviöitä reaaliaikaisesti. Laaduntarkkailun lisäksi tietoja hyödynnetään kuorintaprosessin automaattisessa ohjauksessa. Optimaalisen kuorintatuloksen saavuttaminen edellyttää virheetöntä automaation toimintaa ja tarkkaa viritystä säädöiltä. Työssä perehdyttiin kuorimon perusautomaatioon ja ylemmän tason säädön toimintaan. Prosessinohjauksessa havaitut ongelmakohdat korjattiin. Lopputuloksena saatiin vakiokuorintatehon malli, joka pienentää puuhäviöitä ja parantaa linjaston käytettävyyttä. Saaduilla tuloksilla on merkittävä taloudellinen arvo, ja menetelmät ovat hyödynnettävissä myös toisilla rumpukuorimoilla.

Linking landscape- and population ecology for large population management modelling: the case of Ibex (capra ibex) in Switzerland

La biologie de la conservation est communément associée à la protection de petites populations menacées d?extinction. Pourtant, il peut également être nécessaire de soumettre à gestion des populations surabondantes ou susceptibles d?une trop grande expansion, dans le but de prévenir les effets néfastes de la surpopulation. Du fait des différences tant quantitatives que qualitatives entre protection des petites populations et contrôle des grandes, il est nécessaire de disposer de modèles et de méthodes distinctes. L?objectif de ce travail a été de développer des modèles prédictifs de la dynamique des grandes populations, ainsi que des logiciels permettant de calculer les paramètres de ces modèles et de tester des scénarios de gestion. Le cas du Bouquetin des Alpes (Capra ibex ibex) - en forte expansion en Suisse depuis sa réintroduction au début du XXème siècle - servit d?exemple. Cette tâche fut accomplie en trois étapes : En premier lieu, un modèle de dynamique locale, spécifique au Bouquetin, fut développé : le modèle sous-jacent - structuré en classes d?âge et de sexe - est basé sur une matrice de Leslie à laquelle ont été ajoutées la densité-dépendance, la stochasticité environnementale et la chasse de régulation. Ce modèle fut implémenté dans un logiciel d?aide à la gestion - nommé SIM-Ibex - permettant la maintenance de données de recensements, l?estimation automatisée des paramètres, ainsi que l?ajustement et la simulation de stratégies de régulation. Mais la dynamique d?une population est influencée non seulement par des facteurs démographiques, mais aussi par la dispersion et la colonisation de nouveaux espaces. Il est donc nécessaire de pouvoir modéliser tant la qualité de l?habitat que les obstacles à la dispersion. Une collection de logiciels - nommée Biomapper - fut donc développée. Son module central est basé sur l?Analyse Factorielle de la Niche Ecologique (ENFA) dont le principe est de calculer des facteurs de marginalité et de spécialisation de la niche écologique à partir de prédicteurs environnementaux et de données d?observation de l?espèce. Tous les modules de Biomapper sont liés aux Systèmes d?Information Géographiques (SIG) ; ils couvrent toutes les opérations d?importation des données, préparation des prédicteurs, ENFA et calcul de la carte de qualité d?habitat, validation et traitement des résultats ; un module permet également de cartographier les barrières et les corridors de dispersion. Le domaine d?application de l?ENFA fut exploré par le biais d?une distribution d?espèce virtuelle. La comparaison à une méthode couramment utilisée pour construire des cartes de qualité d?habitat, le Modèle Linéaire Généralisé (GLM), montra qu?elle était particulièrement adaptée pour les espèces cryptiques ou en cours d?expansion. Les informations sur la démographie et le paysage furent finalement fusionnées en un modèle global. Une approche basée sur un automate cellulaire fut choisie, tant pour satisfaire aux contraintes du réalisme de la modélisation du paysage qu?à celles imposées par les grandes populations : la zone d?étude est modélisée par un pavage de cellules hexagonales, chacune caractérisée par des propriétés - une capacité de soutien et six taux d?imperméabilité quantifiant les échanges entre cellules adjacentes - et une variable, la densité de la population. Cette dernière varie en fonction de la reproduction et de la survie locale, ainsi que de la dispersion, sous l?influence de la densité-dépendance et de la stochasticité. Un logiciel - nommé HexaSpace - fut développé pour accomplir deux fonctions : 1° Calibrer l?automate sur la base de modèles de dynamique (par ex. calculés par SIM-Ibex) et d?une carte de qualité d?habitat (par ex. calculée par Biomapper). 2° Faire tourner des simulations. Il permet d?étudier l?expansion d?une espèce envahisseuse dans un paysage complexe composé de zones de qualité diverses et comportant des obstacles à la dispersion. Ce modèle fut appliqué à l?histoire de la réintroduction du Bouquetin dans les Alpes bernoises (Suisse). SIM-Ibex est actuellement utilisé par les gestionnaires de la faune et par les inspecteurs du gouvernement pour préparer et contrôler les plans de tir. Biomapper a été appliqué à plusieurs espèces (tant végétales qu?animales) à travers le Monde. De même, même si HexaSpace fut initialement conçu pour des espèces animales terrestres, il pourrait aisément être étndu à la propagation de plantes ou à la dispersion d?animaux volants. Ces logiciels étant conçus pour, à partir de données brutes, construire un modèle réaliste complexe, et du fait qu?ils sont dotés d?une interface d?utilisation intuitive, ils sont susceptibles de nombreuses applications en biologie de la conservation. En outre, ces approches peuvent également s?appliquer à des questions théoriques dans les domaines de l?écologie des populations et du paysage.<br/><br/>Conservation biology is commonly associated to small and endangered population protection. Nevertheless, large or potentially large populations may also need human management to prevent negative effects of overpopulation. As there are both qualitative and quantitative differences between small population protection and large population controlling, distinct methods and models are needed. The aim of this work was to develop theoretical models to predict large population dynamics, as well as computer tools to assess the parameters of these models and to test management scenarios. The alpine Ibex (Capra ibex ibex) - which experienced a spectacular increase since its reintroduction in Switzerland at the beginning of the 20th century - was used as paradigm species. This task was achieved in three steps: A local population dynamics model was first developed specifically for Ibex: the underlying age- and sex-structured model is based on a Leslie matrix approach with addition of density-dependence, environmental stochasticity and culling. This model was implemented into a management-support software - named SIM-Ibex - allowing census data maintenance, parameter automated assessment and culling strategies tuning and simulating. However population dynamics is driven not only by demographic factors, but also by dispersal and colonisation of new areas. Habitat suitability and obstacles modelling had therefore to be addressed. Thus, a software package - named Biomapper - was developed. Its central module is based on the Ecological Niche Factor Analysis (ENFA) whose principle is to compute niche marginality and specialisation factors from a set of environmental predictors and species presence data. All Biomapper modules are linked to Geographic Information Systems (GIS); they cover all operations of data importation, predictor preparation, ENFA and habitat suitability map computation, results validation and further processing; a module also allows mapping of dispersal barriers and corridors. ENFA application domain was then explored by means of a simulated species distribution. It was compared to a common habitat suitability assessing method, the Generalised Linear Model (GLM), and was proven better suited for spreading or cryptic species. Demography and landscape informations were finally merged into a global model. To cope with landscape realism and technical constraints of large population modelling, a cellular automaton approach was chosen: the study area is modelled by a lattice of hexagonal cells, each one characterised by a few fixed properties - a carrying capacity and six impermeability rates quantifying exchanges between adjacent cells - and one variable, population density. The later varies according to local reproduction/survival and dispersal dynamics, modified by density-dependence and stochasticity. A software - named HexaSpace - was developed, which achieves two functions: 1° Calibrating the automaton on the base of local population dynamics models (e.g., computed by SIM-Ibex) and a habitat suitability map (e.g. computed by Biomapper). 2° Running simulations. It allows studying the spreading of an invading species across a complex landscape made of variously suitable areas and dispersal barriers. This model was applied to the history of Ibex reintroduction in Bernese Alps (Switzerland). SIM-Ibex is now used by governmental wildlife managers to prepare and verify culling plans. Biomapper has been applied to several species (both plants and animals) all around the World. In the same way, whilst HexaSpace was originally designed for terrestrial animal species, it could be easily extended to model plant propagation or flying animals dispersal. As these softwares were designed to proceed from low-level data to build a complex realistic model and as they benefit from an intuitive user-interface, they may have many conservation applications. Moreover, theoretical questions in the fields of population and landscape ecology might also be addressed by these approaches.

Implication of DNA methylation, CTCF and BORIS factors in the transcriptional regulation of the human telomerase catalytic subunit hTERT

RESUME La télomérase confère une durée de vie illimitée et est réactivée dans la plupart des cellules tumorales. Sa sous-unité catalytique hTERT est définie comme le facteur limitant pour son activation. De l'identification de facteurs liant la région régulatrice d'hTERT, au rôle de la méthylation de l'ADN et de la modification des histones, de nombreux modèles de régulation ont été suggérés. Cependant, aucun de ces modèles n'a pu expliquer l'inactivation de la télomérase dans la plupart des cellules somatiques et sa réactivation dans la majorité des cellules tumorales. De plus, les observations contradictoires entre le faible niveau d'expression d'ARN messager d'hTERT dans les cellules télomérase-positives et la très forte activité transcriptionnelle du promoteur d'hTERT en transfection restent incomprises. Dans cette étude, nous avons montré que la région proximale du gène hTERT (exon 1 et 2) était impliquée dans la répression de l'activité de son promoteur. Nous avons identifié le facteur CTCF comme étant un inhibiteur du promoteur d'hTERT, en se liant au niveau de son premier exon. La méthylation de l'exon 1 du gène hTERT, couramment observée dans les tumeurs mais pas dans les cellules normales, empêcherait la liaison de CTCF. L'étude du profil de méthylation du promoteur d'hTERT indique qu'une partie du promoteur reste déméthylée et qu'elle semble suffisante pour permettre une faible activité transcriptionnelle du gène hTERT. Ainsi, la méthylation particulière des régions régulatrices d'hTERT inhibe la liaison de CTCF tout en permettant une faible transcription du gène. Cependant, dans certaines cellules tumorales, le promoteur et la région proximale du gène hTERT ne sont pas méthylés. Dans les lignées cellulaires tumorales de tesitcules et d'ovaires, l'inhibition de CTCF est contrée par son paralogue BORIS, qui se lie aussi au niveau de l'exon 1 d'hTERT, mais permet ainsi l'activation du promoteur. L'étude de l'expression du gène BORIS montre qu'il est exclusivement exprimé dans les tissus normaux de testicules et d'ovaires jeunes, ainsi qu'à différents niveaux dans la plupart des tumeurs. Sa transcription est sous le contrôle de deux promoteurs. Le promoteur proximal est régulé par méthylation et un transcrit alternatif majoritaire, délété de l'exon 6, est trouvé lorsque ce promoteur est actif. Tous ces résultats conduisent à un modèle de régulation du gène hTERT qui tient compte du profil épigénétique du gène et qui permet d'expliquer le faible taux de transcription observé in vivo. De plus, l'expression de BORIS dans les cancers et son implication dans l'activation du gène hTERT pourrait permettre de comprendre les phénomènes de dérégulation épigénétique et d'immortalisation qui ont lieu durant la tumorigenèse. SUMMARY Telomerase confers an unlimited lifespan, and is reactivated in most tumor cells. The catalytic subunit of telomerase, hTERT, is defined as the limiting factor for telomerase activity. Between activators and repressors that bind to the hTERT 5' regulatory region, and the role of CpG methylation and histone acetylation, an abundance of regulatory models have been suggested. None of these models can explain the silence of telomerase in most somatic cells and its reactivation in tumor cells. Moreover, the contradictory observations of the low level of hTERT mRNA in telomerase-positive cells and the high transcriptional activity of the hTERT promoter in transfection experiments remain unresolved. In this study, we demonstrated that the proximal exonic region of the hTERT gene (exon 1 and 2) is involved in the inhibition of its promoter. We identified the protein CTCF as the inhibitor of the hTERT promoter, through its binding to the first exon. The methylation of the first exon region, which is often observed in cancer cells but not in noimal cells, represses CTCF binding. Study of hTERT promoter methylation shows a partial demethylation sufficient to activate the transcription of the hTERT gene. Therefore, we demonstrated that the particular methylation profile of the hTERT regulatory sequences inhibits the binding of CTCF, while it allows a low transcription of the gene. Nevertheless, in some tumor cells, the promoter and the proximal exonic region of hTERT are unmethylated. In testicular and ovarian cancer cell lines, CTCF inhibition is counteracted by its BORIS paralogue that also binds the hTERT first exon but allows the promoter activation. The study of BORIS gene regulation showed that this factor is exclusively expressed in normal tissue of testis and ovary of young woman, as well as in almost all tumors with different levels. Two promoters were found to induce its transcription. The proximal promoter was regulated by methylation. Moreover, a major alternative transcript, deleted of the exon 6, is detected when this promoter is active. All these results lead to a model for hTERT regulation that takes into account the epigenetic profile of the gene and provides an explanation for the low transcriptional level observed in vivo. BORIS expression in cancers and its implication in hTERT activation might also permit the understanding of epigenetic deregulation and immortalization phenomena that occur during tumorigenesis.

Control biológico de Panonychus ulmi (Koch) mediante ácaros fitoseidos en plantaciones de control integrado de manzano en Cataluña

Se ha aplicado el Control Integrado de Plagas en unas 40 parcelas comerciales de manzano de Girona y de Lleida desde 1991 a 1993 con el objetivo de controlar biológicamente la araña roja (P. ulmi) mediante ácaros Phytoseiidae. Así mismo, se ha evaluado la estrategia de control de esta plaga, se han evaluado los factores principales que pueden influir en el éxito del control biológico y se ha diseñado una estrategia de defensa sencilla. En la mayoría de los casos, el control biológico se ha debido a la acción de Amblyseius andersoni o a la acción combinada de A. andersoni y A. californicus. A. andersoni impide el desarrollo de poblaciones elevadas de araña roja y la aparición de daños por decoloración. En las parcelas de Girona se ha producido la sustitución paulatina de A. californicus por A. andersoni. Los factores determinantes del éxito del control biológico fueron el nivel de actividad de P. ulmi y la presencia de A. andersoni, lo que plantea nuevas cuestiones relativas a cómo se puede favorecer la implantación de esta especie en parcelas comerciales. Finalmente, se propone una estrategia de defensa sencilla, basada en la época de aparición de la plaga y de los fitoseidos y en la relación que se establece entre ambas poblaciones durante el ciclo vegetativo.

Hapettavan BIMODES-mikrobientorjuntamenetelmän vaikutukset paperikoneella

The aim of this study was to examine the effects of oxidising BIMODES microbiological control program on three paper machine process. The chemicals used in BIMODES program are sodium hypochlorite (NaOCl) and bromo-chloro-di-methyl-hydantoin (BCDMH). The literary part of this study discusses the microbiological problems in paper making industry, describes functional mechanisms of oxidants and also introduces the BIMODES- program. In the experimental part the aim was to examine the effects of BIMODES in three different paper machines. The purpose was to find out the effects and changes in wet end chemistry, bacterial counts, in the other additives and also in the sheet defects and holes. The study also examines what are the most important measurements to control BIMODES dosing. In addition the optimal dosing level for each machine was tried to find out. It was found that there is a clear correlation between the total chlorine level and bacterial counts. Changes in the BIMODES dosing level can be measured by redox potential, but the correlation is very poor. BIMODES program doesn’t have straight influence to pH values, but if dosage level is too low the bacterial activity can affect degreasing in the pH value. In this study couldn’t find any consequential effects for the other additives by using BIMODES. In addition the optimal dosing levels were found and by following correct halogen levels it is possible to decrease bacterial levels for very low level.

Disseny de circuit de proves de traçabilitat amb rfid

ITENE és un institut tecnològic de recerca situat a Paterna (València). Té una plantapilot especialitzada en logística on les empreses que ho vulguin (mitjançant convenis,en règim de lloguer, etc.), poden utilitzar les instal•lacions (magatzem intel•ligent,aplicacions RFID, etc.), per provar els seus productes i simular processos de logística itraçabilitat.En aquesta planta s'ha detectat la necessitat de poder provar nous productes cometiquetes, detectors i processadors equipats amb tecnologia RFID (Identificació perRadiofreqüència). Aquesta tecnologia consisteix en passar informació que conté unaetiqueta “intel•ligent” cap a un terminal (PC) mitjançant uns detectors que, perproximitat, poden llegir la informació. Per exemple, quan un camió ple de mercaderiesprèviament etiquetades, passa per un pòrtic amb detectors RFID, es genera unainformació que passa directament a un terminal. Al moment es pot saber què porta elcamió, quantitat, color, mides, etc. Si això es combina amb un ERP, es pot descomptarde l'estoc en temps real. De fet s'utilitza per moltes aplicacions logística, control deprocessos de fabricació, traçabilitat de productes, etc.Per aquest motiu, ITENE, mitjançant el contacte de AIFOS SOLUTIONS S.L (empresaespecialitzada en RFID) ha encarregat un sistema de transportadors de banda per provarnoves solucions.L'objecte del present projecte consisteix en el disseny i automatització d'un sistema de 4cintes transportadores 2 elevadors per tal de fer un circuit tancat per moure caixes en un“bucle” de forma automàtica. L'objectiu és “llençar” caixes plenes de productes (etiquetats amb RFID) mitjançant untransportador equipat amb un pòrtic que té instal•lats diversos detectors de radiofreqüència,i poder-ne provar la correcta detecció a diferents velocitats. Un “buffer” s'encarrega desubministrar les caixes d'una en una que, un cop acabat el circuit, tornen al lloc d'on hansortit. Per donar un producte per bo, es realitzen tests de diverses hores i se n'obté unaestadística de lectures bones/dolentes. Si la ràtio és la desitjada es dóna per bo elproducte.Per aconseguir un disseny correcte s'ha utilitzat diferents eines CAD per dimensionar elsistema de transportadors i els seus elements. Tota l'aplicació està realitzada en 3Dmitjançant el software AutoCAD 3D. L'abast d'aquest projecte inclourà la solució mecànica i pneumàtica del sistema, aixícom el seu muntatge i tot el referent a les normes de seguretat per tal que el sistemacompleixi la normativa referida a la seguretat de màquines

Mitta-anturin mittauselektroniikan kehittäminen teräksen puutislepinnoituksen ohjaukseen

Työn tarkoituksena oli kehittää mittauselektroniikka puutislepinnoitusprosessin ohjaukseen. Mittauselektroniikalla on tarkoitus mitata pikoampeeriluokan virtoja mittaanturilta, jossa virtaa kuuma, noin 250 ºC asteinen kaasu. Mitta-anturin toiminta perustuu ioniliikkuvuusspektrometriaan. Työssä tutkitaan pikoampeeriluokan virtojen mittaamista sekä mittauskytkennöissä käytetyn virta-jännitemuuntimen ominaisuuksia ja mitoittamista. Työ tarkastelee myös T-kytkennän käyttöä vahvistimen takaisinkytkennässä. Jännitekertojakytkentöjä käsitellään teoreettisesti mitta-anturin biasjännitteiden luomiseksi vähäisellä piirilevypinta-alalla. Työssä suunniteltiin mittauselektroniikan esivahvistinprototyypit sekä mitta-anturin biasjännitekytkentä. Mitta-anturin kuumien olosuhteiden vuoksi on mittauselektroniikka siirrettävä etäämmäksi mitta-anturista. Prototyyppikytkennöillä sekä laboratoriomittauksilla selvitettiin mittauselektroniikan esivahvistimien siirtämiseen liittyviä ongelmia. Biasjännitekytkennän suunnittelussa pyrittiin kytkentä toteuttamaan mahdollisimman vähällä piirilevypinta-alalla. Mittauselektroniikka todettiin laboratoriomittausten perusteella toimivaksi puutislepinnoitusprosessissa suoritettavia koemittauksia varten.

Rehufosfaattitehtaan raaka-ainesyöttöjen säätöpiirien kehitys

Diplomityö tehtiin Kemira Chemicals Oy:n Kokkolan tehtaiden rehufosfaattitehtaalla. Työn tavoitteena oli uusien reseptiohjauksien suunnittelu ja käyttöönotto sekä tasaussäiliön pinnansäädön ja rakeistusrummun suhdesäädön suunnittelu. Käyttöhenkilöstön koulutus uuteen prosessinohjaukseen kuului myös osaksi diplomityötä. Uuden reseptiohjauksen avulla pyrittiin saamaan prosessin ohjaus havainnollisemmaksi ja ennustettavammaksi käyttäjille, yhdenmukaistamaan käyttäjien ajotapaa sekä suunnitella tuotereseptit vastaamaan paremmin todellista tuotantoa. Uusi reseptiohjaus mahdollistaa myös lajikekohtaisten parametrien käytön ja hyväksi havaittujen ajoreseptien tallennuksen. Tasaussäiliön pinnankorkeuden säädön tavoitteena on poistaa tuotantokatkokset, jotka johtuivat säiliön tyhjenemisestä tai täyttymisestä. Rakeistusrummun suhdesäädön tavoitteena on reaktoriliemen ja kuiva-ainesyöttöjen oikean suhteen säilyttäminen. Uuden reseptiohjauksen käyttöönoton jälkeen ajoreseptit ovat vastanneet todellista tuotantoa ja tuotantovauhti on jäänyt pysyvästi korkeammalle tasolle. Tasaussäiliön pinnansäätö toimii suunnitellulla tavalla ja on myös otettu käyttöön. Reaktoriliemen ja kuivasyöttöjen suhdesäätö on testattu käytännössä ja toimii halutulla tavalla. Suhdesäädön paremman toiminnan kannalta epätarkkoja toimilaitteita tulisi kuitenkin uusia.

RFID a les biblioteques.

Breu descripció del funcionament d"un sistema RFID, de les seves aplicacions en biblioteques, i dels problemes i limitacions que té.