Combining RT-PCR-seq and RNA-seq to catalog all genic elements encoded in the human genome.

Within the ENCODE Consortium, GENCODE aimed to accurately annotate all protein-coding genes, pseudogenes, and noncoding transcribed loci in the human genome through manual curation and computational methods. Annotated transcript structures were assessed, and less well-supported loci were systematically, experimentally validated. Predicted exon-exon junctions were evaluated by RT-PCR amplification followed by highly multiplexed sequencing readout, a method we called RT-PCR-seq. Seventy-nine percent of all assessed junctions are confirmed by this evaluation procedure, demonstrating the high quality of the GENCODE gene set. RT-PCR-seq was also efficient to screen gene models predicted using the Human Body Map (HBM) RNA-seq data. We validated 73% of these predictions, thus confirming 1168 novel genes, mostly noncoding, which will further complement the GENCODE annotation. Our novel experimental validation pipeline is extremely sensitive, far more than unbiased transcriptome profiling through RNA sequencing, which is becoming the norm. For example, exon-exon junctions unique to GENCODE annotated transcripts are five times more likely to be corroborated with our targeted approach than with extensive large human transcriptome profiling. Data sets such as the HBM and ENCODE RNA-seq data fail sampling of low-expressed transcripts. Our RT-PCR-seq targeted approach also has the advantage of identifying novel exons of known genes, as we discovered unannotated exons in ~11% of assessed introns. We thus estimate that at least 18% of known loci have yet-unannotated exons. Our work demonstrates that the cataloging of all of the genic elements encoded in the human genome will necessitate a coordinated effort between unbiased and targeted approaches, like RNA-seq and RT-PCR-seq.

Disseny i implementació d'una aplicació per a dispositius mòbils per identificar elements geològics en el terreny

En aquests treball es presenta el procés de disseny i desenvolupament d'una aplicació per a dispositius mòbils que permet millorar la localització i identificació de les zones d'allaus. L'aplicació anomenada IdAllau, té les següents funcions principals: emmagatzematge, geolocalització, fotografia, representació cartografica, realitat augmentada i recerca per proximitat. La aplicació s'ha desenvolupat amb Android i llibreries i API's de codi lliure (Osmdroid i Appunta); amb els avantatges i inconvenients que comporta treballar-hi. El resultat final és una aplicació que permetrà als tècnics identificar les zones d'allaus en el camp utilitzant principalment la realitat augmentada i la geolocalització amb cartografia temàtica

Use of Remote Sensing for Collection of Data Elements for Linear Referencing Systems, 2001

This report evaluates the use of remotely sensed images in implementing the Iowa DOT LRS that is currently in the stages of system architecture. The Iowa Department of Transportation is investing a significant amount of time and resources into creation of a linear referencing system (LRS). A significant portion of the effort in implementing the system will be creation of a datum, which includes geographically locating anchor points and then measuring anchor section distances between those anchor points. Currently, system architecture and evaluation of different data collection methods to establish the LRS datum is being performed for the DOT by an outside consulting team.

Presentació: Elements per a la comprensió crítica de la reforma de l'ensenyament secundari

La reforma de l'ensenyament secundari ha estat i és encara un tema polèmic, controvertit. En sentir crítiques referents a l'estat actual de l'ensenyament secundari per part de professionals procedents de sectors deis diferents estaments educatius, tant si aquestes crítiques són favorables a la reforma com si no ho són, és fàcil percebre un ambient general de preocupació. Davant d'aquest ambient, cal pensar que alguna cosa no deu acabar d'anar bé perquè s'hagi creat un clima de descontent tan generalitzat.

Minerais, métaux, isotopes : recherches archéométriques sur les mines de plomb et d'argent en Valais, Suisse

RESUME Les nombreuses mines de plomb et d'argent du Valais témoignent d'une activité minière importante par le passé, sans toutefois dévoiler ni l'importance des minéralisations, ni l'ancienneté de l'exploitation. La présente recherche a pour but de comprendre pourquoi les grandes mines sont concentrées dans une région, et de déterminer la chronologie de leur exploitation. L'originalité de ce travail réside dans son interdisciplinarité, plus précisément dans l'application des méthodes minéralogiques pour résoudre une problématique historique. Afin d'évaluer les ressources minières en plomb et en argent du Valais, 57 mines et indices ont été repérés et échantillonnés. Les signatures isotopiques du Pb (74 analyses) et les compositions chimiques élémentaires (45 analyses) ont été déterminées. Les plus grandes exploitations se situent dans la nappe de Siviez-Mischabel, au Sud d'une ligne Vallée du Rhône / Val de Bagnes ainsi que dans le Lötschental. Elles sont liées, d'après leur signature isotopique de plomb, à des minéralisations d'âge calédonien (408 à 387 Ma) ou tardi-hercynien (333 à 286 Ma). À ces périodes, l'ancien continent est très lourd et subit une subsidence thermique. Des premières fractures d'extrême importance se forment. Comme il s'agit d'accidents tectoniques majeurs, des gisements de grande extension peuvent se former dans ce contexte. D'autres minéralisations se situent dans les domaines helvétiques (Massif des Aiguilles Rouges, Massif du Mont Blanc et couverture sédimentaire), couvrant une région au Nord de la Vallée du Rhône et du Val d'Entremont. D'âge post-hercynien à tardi-alpin (notons qu'il n'y a pas de minéralisations d'âge tertiaire), elles sont pour la plupart liées à des intrusions granitiques, sources de plomb juvénile. Les mines situées dans ces unités tectoniques sont nettement moins étendues que celles de la nappe de Siviez-Mischabel, ce qui permet de penser que les minéralisations correspondantes le sont également. Les périodes d'exploitation des mines peuvent être déterminées par quatre approches différentes l'archéologie minière, la lecture des textes historiques, l'étude des déchets métallurgiques et la comparaison de la signature isotopique du plomb, que l'on mesure dans un objet archéologique bien daté (monnaie, bijoux etc.), avec celles des minerais. Cette dernière méthode a été appliquée et développée dans le cadre de la présente recherche. Pour ce faire, 221 échantillons d'objet en plomb ou en argent datés entre l'Âge du Fer et le Moyen Age ont été analysés par la méthode des isotopes de plomb et comparés à environ 1800 signatures isotopiques de minerais des gisements les plus importants en Suisse et en Europe. Avant l'époque romaine et jusqu'au 1 er siècle de cette époque, le plomb provient principalement des mines de la péninsule ibérique alors en pleine activité. Un apport des mines d'Europe tempérée, notamment des Vosges, reste à confirmer. A partir du 1" siècle de notre ère, le plomb a principalement été importé en Suisse occidentale de grands centres de productions situées en Allemagne du Nord (région d'Eifel). Les mines de plomb valaisannes, notamment celles de Siviez, débutent leur exploitation en même temps, principalement pour couvrir les besoins locaux, mais également pour l'exportation jusque dans l'arc lémanique et, dans une moindre importance, au-delà. À partir du 4ème siècle, le besoin en plomb a été couvert par un apport des mines locales et par la refonte d'objets anciens. Ce changement d'approvisionnement est probablement lié aux tensions créées par les invasions germaniques durant la seconde moitié du 3' siècle ; le marché suisse n'est dès lors plus approvisionné par le nord, c'est-à-dire par la vallée du Rhin. Quant à l'argent, l'exploitation de ce métal est attestée à partir de la fin du La Tène, peu après l'apparition de ce métal dans la région valaisanne. L'échantillonnage ne couvrant pas l'époque romaine, rien n'est connu pour cette période. A partir du 5" siècle, une exploitation d'argent est de nouveau attestée. Cependant, l'exploitation d'argent des mines locales ne gagne en importance qu'à partir du Moyen Âge avec les frappes monétaires, notamment les frappes carolingiennes et épiscopales valaisannes. Les sources d'argent sont différentes selon leur utilisation : à part quelques exceptions notamment vers la fin du La Tène et au tardo-antique, les bijoux et objets de cultes ont été souvent créés à partir d'argent refondu, contrairement aux monnaies pour lesquelles l'argent provient des mines locales. On note un approvisionnement différent de ce métal pour les objets, notamment les monnaies, selon leur lieu de fabrication : on peut clairement distinguer les objets valaisans de ceux du Plateau Suisse. SUMMARY The many lead and silver mines of the Valais testify of an important mining activity in the past, without however revealing neither the importance of the mineralizations, nor the era of the exploitation. The purpose of this research is to understand why the large mines are concentrated in one region, and to determine the history of their exploitation. The uniqueness of this work lies in its interdisciplinarity, more precisely in the application of mineralogical methods to solve historical problems. In order to evaluate the lead and silver mining resources of the Valais region, 57 mines and ore deposits were located and sampled. The isotope signatures of Pb (74 analyses) and the compositions of the chemical elements (45 analyses) were determined. The largest activities are in the Siviez-Mischabel area, located in the South of the boundary formed by the Rhone, Bagnes and Lotschental valleys. According to their lead isotope signatures, they are linked to mineralizations of the Caledonian (408 to 387 my) or tardi-Hercynian (333 to 286 my) orogenies. In those times, the old continent was very heavy and underwent a thermal subsidence. First fractures of great significance were formed. Through these major tectonic events, large extended ore deposits can be formed. Other mineralizations are found in the helvetic regions situated north of the Rhone and the Entremont valley (the Aiguilles Rouges basement, Mount Blanc basement and the covering sediment). Because they are from post-hercynien to tardi-alpine age (there are no mineralizations of tertiary age), they are mainly linked to granite intrusions, the sources of juvenile lead. The mines found in these tectonic units are significantly less extensive than those of the Siviez-Mischabel area, leading to the assumption that the respective mineralizations extend accordingly. The history of exploitation of the mines can be determined by four different sources: mining archaeology, historical texts, metallurgical waste, and the comparison of the isotope signature of the lead from accurately dated archaeological objects (currency, jewels etc), with those of the ores. This last approach was applied and developed within the framework of this research. The lead isotope signatures of 221 lead or silver objects from the Iron Age to the Middle Age were compared with approximately 1800 samples of ore of the most important ore deposits in Switzerland and Europe. Before the Roman time up to the 1st century, lead comes mainly from the mines of the Iberian Peninsula then in full activity. A contribution of the mines of Central Europe, in particular of the Vosges, remains to be confirmed. From the 1st century on, lead was mainly imported into Western Switzerland from Northern Germany (Eiffel region). The lead mines in the Valais region, in particular those of Siviez, begin their exploitation at the same time, mainly to meet the local needs, but also for export to the lemanic basin and of lesser importance, beyond. As from the 4th century, the need of lead was met by the production from local mines and the recycling of old objects. This change of supply is probably related to the tensions created by the Germanic invasions during second half of the 3rd century; as a consequence, the Swiss market is not supplied any more by the north, i.e. the Rhine valley. Silver production is confirmed starting from the end of La Tene, shortly after the appearance of this metal in the Valais region. Since no objects of Roman origin were analyzed, nothing is known for this period. From the 5th century on, silver production is again confirmed. However, significant silver production from local mines starts only in the Middle Age with the coinage, in particular Carolingian and Episcopal minting from the Valais region. The sources of silver differ according to their use: besides some exceptions in particular towards the end of La Tene and the tardi-Roman, the jewels and objects of worships were often created from recycled silver, contrary to the coins the silver for which comes from the local mines. A different source of silver is observed according to the location of coin manufacture: Objects originating from the Valais region are clearly distinguished from those from the Plateau Suisse. ZUSAMMENFASSUNG Die grosse Zahl von Blei- und Silberminen im Wallis ist Zeugnis einer bedeutenden Bergbautätigkeit, es fehlen aber Hinweise über ihren Umfang und den Zeitraum ihrer Ausbeutung. Die vorliegende Arbeit sucht zu ergründen, warum grosse Minen sich in einer eng begrenzten Region häufen und in welchem Zeitraum sie genutzt wurden. Die Besonderheit der Studie liegt in ihrer Interdisziplinarität, genauer in der Anwendung von mineralogischen Methoden zur Beantwortung historischer Fragestellungen. Zur Beurteilung der Lagerstätten wurden von 57 Minen und Aufschlüssen Proben entnommen oder Nachweise erbracht und mittels 74 Isotopen-Analysen von Blei und 45 chemischen Gesamtanalysen ausgewertet. Die wichtigsten Vorkommen liegen in der Siviez- Mischabel- Decke südlich der Linie Rhonetal- Val de Bagnes, sowie im Lötschental. Die Bleiisotopen- Alter weisen ihre Entstehung der kaledonischen (408 - 387 Mio. J.) oder der spät- herzynischen (333 - 286 Mio. J.) Gebirgsbildungsphase zu. In dieser Periode ist die kompakte Landmasse sehr schwer und erfairt eine thermische Absenkung. Es bilden sich tektonische Brüche von kontinentaler Ausdehnung. Die grossen tektonischen Bewegungen ermöglichen die Bildung von ausgedehnten Lagerstätten. Andere Vorkommen finden sich im Bereich der Helvetischen Alpen (Aiguilles Rouges Massiv, Mont-Blanc-Massiv und Sediment-Decken) im Gebiet nördlich des Rhonetales bis zum Val d'Entremont. Altersmässig sind sie der nach-hercynischen bis zur spät-alpidischen Orogenese zuzuweisen (auffällig ist das Fehlen von Vorkommen im Tertiär) und haben sich meist in der Folge von Granit- Intrusion, dem Ursprung von primärem Blei ausgebildet. Die Bergwerke in diesem Bereich sind deutlich weniger ausgedehnt als jene in der Siviez-Mischabel-Decke und entsprechen wahrscheinlich dem geringen Umfang der zugehörigen Vorkommen. Die Nutzungsperioden der Minen können mit vier verschiedenen Methoden bestimmt werden: Minenarchäologie, Historische Quellen, Auswertung von metallischen Abfällen (Schlacken) und Vergleich der Bleiisotopen-Zusammensetzung von Erzen mit jener von zeitlich gut datierbaren archäologischen Gegenständen (Münzen, Schmuckstücke). Die letztere Methode wurde im Rahmen der vorliegenden Forschungsarbeit entwickelt und angewendet. Zu diesem Zweck wurden an 221 Proben von Blei- oder Silberobjekten, die in die Periode zwischen Eisenzeit und Mittelalter eingestuft werden können, Bleiisotopen- Analysen durchgeführt und mit ca. 1800 Proben aus den wichtigsten Lagerstätten der Schweiz und Europas verglichen. Vor der Römerzeit und bis ins 1. Jahrh. stammt das Blei vornehmlich aus den in jener Zeit in voller Ausbeutung begriffenen Minen der Iberischen Halbinsel. Der Beitrag von Mitteleuropa, besonders der Vogesen, muss noch bestätigt werden. Ab dem 1. Jahrh. nach Chr. wurde die Westschweiz hauptschlich mit Blei aus den grossen Produktionszentren Norddeutschlands, vorwiegend der Eifel, versorgt. In dieser Periode setzt die Ausbeutung der Bleiminen des Wallis, besonders von Siviez, ein. Sie dienen der Deckung des örtlichen Bedarfs aber auch der Ausfuhr in das Gebiet des Genfersees und in einem bescheidenen Rahmen sogar darüber hinaus. Ab dem 4. Jahrhundert wurden vermehrt alte Objekte eingeschmolzen. Dieser Wechsel der Versorgungsquellen war vermutlich eine Folge der Wölkerwanderung in der zweiten Hälfte des 3. Jahrhunderts. Ab diesem Zeitpunkt war Helvetien der Zugang zu den Versorgungsquellen des Nordens, besonders des Rheinlandes, verwehrt. Der Abbau von Silber ist ab dem Ende des La Tène nachgewiesen, nur wenig nach dem Auftreten dieses Metalls im Wallis. Über die Römerzeit können wegen dem Fehlen entsprechender Proben keine Aussagen gemacht werden. Eine erneute Abbauperiode ist ab dem 5. Jahrhundert nachgewiesen. Die Produktion der örtlichen Minen erreicht aber erst im Mittelalter eine gewisse Bedeutung mit der Prägung von Mnzen durch die Karolinger und die Walliser Bischöfe. Die Herkunft des Silbers ist abhängig von dessen Verwendung. Mit wenigen Ausnahmen in der Zeit des La Tène und der späteren Römerzeit wurde für Kunst- und Kult- Gegenstände rezykliertes Silber verwendet, für Münzprägungen neues Silber aus den örtlichen Minen. Von Einfluss auf die Herkunft war auch der Produktionsstandort: Die Objekte aus dem Wallis unterscheiden sich deutlich von jenen des Mittellandes.

Functional analysis of cis- and trans-acting elements of the Candida albicans CDR2 promoter with a novel promoter reporter system.

Azole resistance in Candida albicans can be mediated by the upregulation of the ATP binding cassette transporter genes CDR1 and CDR2. Both genes are regulated by a cis-acting element called the drug-responsive element (DRE), with the consensus sequence 5'-CGGAWATCGGATATTTTTTT-3', and the transcription factor Tac1p. In order to analyze in detail the DRE sequence necessary for the regulation of CDR1 and CDR2 and properties of TAC1 alleles, a one-hybrid system was designed. This system is based on a P((CDR2))-HIS3 reporter system in which complementation of histidine auxotrophy can be monitored by activation of the reporter system by CDR2-inducing drugs such as estradiol. Our results show that most of the modifications within the DRE, but especially at the level of CGG triplets, strongly reduce CDR2 expression. The CDR2 DRE was replaced by putative DREs deduced from promoters of coregulated genes (CDR1, RTA3, and IFU5). Surprisingly, even if Tac1p was able to bind these putative DREs, as shown by chromatin immunoprecipitation, those from RTA3 and IFU5 did not functionally replace the CDR2 DRE. The one-hybrid system was also used for the identification of gain-of-function (GOF) mutations either in TAC1 alleles from clinical C. albicans isolates or inserted in TAC1 wild-type alleles by random mutagenesis. In all, 17 different GOF mutations were identified at 13 distinct positions. Five of them (G980E, N972D, A736V, T225A, and N977D) have already been described in clinical isolates, and four others (G980W, A736T, N972S, and N972I) occurred at already-described positions, thus suggesting that GOF mutations can occur in a limited number of positions in Tac1p. In conclusion, the one-hybrid system developed here is rapid and powerful and can be used for characterization of cis- and trans-acting elements in C. albicans.

La problemàtica psicopedagògica a secundària : alguns elements de particular incidència actual

Aquest article presenta una breu anàlisi de la situació actual de l’Educació Secundària, centrada en vuit punts: els continguts curriculars, els mètodes d’ensenyament-aprenentatge, la motivació de l’alumnat, la motivació del professorat, l’avaluació, la tutoria de grup, la tutoria individual i les relacions escola-família. Com a pistes de futur assenyala cinc aspectes: els espais de trobada escola-família, concretar els valors i conviccions de pares i mestres, l’actuació dels equips interdisciplinaris, la valoració multidimensional del progrés dels alumnes i el rellançament de la tutoria.

Elements diagnòstics en medicina interna. Una experiència d'ensenyament no presencial

La docencia no presencial permite ahorro de tiempo y de desplazamientos para los alumnos, de manera que contribuye a disminuir el coste de la docencia.

The Caribbean-North America-Cocos Triple Junction and the dynamics of the Polochic-Motagua fault systems: Pull-up and zipper models

The Polochic-Motagua fault systems (PMFS) are part of the sinistral transform boundary between the North American and Caribbean plates. To the west, these systems interact with the subduction zone of the Cocos plate, forming a subduction-subduction-transform triple junction. The North American plate moves westward relative to the Caribbean plate. This movement does not affect the geometry of the subducted Cocos plate, which implies that deformation is accommodated entirely in the two overriding plates. Structural data, fault kinematic analysis, and geomorphic observations provide new elements that help to understand the late Cenozoic evolution of this triple junction. In the Miocene, extension and shortening occurred south and north of the Motagua fault, respectively. This strain regime migrated northward to the Polochic fault after the late Miocene. This shift is interpreted as a ``pull-up'' of North American blocks into the Caribbean realm. To the west, the PMFS interact with a trench-parallel fault zone that links the Tonala fault to the Jalpatagua fault. These faults bound a fore-arc sliver that is shared by the two overriding plates. We propose that the dextral Jalpatagua fault merges with the sinistral PMFS, leaving behind a suturing structure, the Tonala fault. This tectonic ``zipper'' allows the migration of the triple junction. As a result, the fore-arc sliver comes into contact with the North American plate and helps to maintain a linear subduction zone along the trailing edge of the Caribbean plate. All these processes currently make the triple junction increasingly diffuse as it propagates eastward and inland within both overriding plates.

Epigenetic regulatory elements associate with specific histone modifications to prevent silencing of telomeric genes.

In eukaryotic cells, transgene expression levels may be limited by an unfavourable chromatin structure at the integration site. Epigenetic regulators are DNA sequences which may protect transgenes from such position effect. We evaluated different epigenetic regulators for their ability to protect transgene expression at telomeres, which are commonly associated to low or inconsistent expression because of their repressive chromatin environment. Although to variable extents, matrix attachment regions (MARs), ubiquitous chromatin opening element (UCOE) and the chicken cHS4 insulator acted as barrier elements, protecting a telomeric-distal transgene from silencing. MARs also increased the probability of silent gene reactivation in time-course experiments. Additionally, all MARs improved the level of expression in non-silenced cells, unlike other elements. MARs were associated to histone marks usually linked to actively expressed genes, especially acetylation of histone H3 and H4, suggesting that they may prevent the spread of silencing chromatin by imposing acetylation marks on nearby nucleosomes. Alternatively, an UCOE was found to act by preventing deposition of repressive chromatin marks. We conclude that epigenetic DNA elements used to enhance and stabilize transgene expression all have specific epigenetic signature that might be at the basis of their mode of action.

Vessel centerline tracking and boundary sgementation in coronary MRA with minimal manual interaction.

Magnetic resonance angiography (MRA) provides a noninvasive means to detect the presence, location and severity of atherosclerosis throughout the vascular system. In such studies, and especially those in the coronary arteries, the vessel luminal area is typically measured at multiple cross-sectional locations along the course of the artery. The advent of fast volumetric imaging techniques covering proximal to mid segments of coronary arteries necessitates automatic analysis tools requiring minimal manual interactions to robustly measure cross-sectional area along the three-dimensional track of the arteries in under-sampled and non-isotropic datasets. In this work, we present a modular approach based on level set methods to track the vessel centerline, segment the vessel boundaries, and measure transversal area using two user-selected endpoints in each coronary of interest. Arterial area and vessel length are measured using our method and compared to the standard Soap-Bubble reformatting and analysis tool in in-vivo non-contrast enhanced coronary MRA images.

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.