The systematic profiling of false identity documents: method validation and performance evaluation using seizures known to originate from common and different sources

False identity documents constitute a potential powerful source of forensic intelligence because they are essential elements of transnational crime and provide cover for organized crime. In previous work, a systematic profiling method using false documents' visual features has been built within a forensic intelligence model. In the current study, the comparison process and metrics lying at the heart of this profiling method are described and evaluated. This evaluation takes advantage of 347 false identity documents of four different types seized in two countries whose sources were known to be common or different (following police investigations and dismantling of counterfeit factories). Intra-source and inter-sources variations were evaluated through the computation of more than 7500 similarity scores. The profiling method could thus be validated and its performance assessed using two complementary approaches to measuring type I and type II error rates: a binary classification and the computation of likelihood ratios. Very low error rates were measured across the four document types, demonstrating the validity and robustness of the method to link documents to a common source or to differentiate them. These results pave the way for an operational implementation of a systematic profiling process integrated in a developed forensic intelligence model.

Variants : The Journal of the European Society for Textual Scholarship

This volume is the 10th issue of Variants . In keeping with the mission of the European Society for Textual Scholarship, the articles are richly interdisciplinary and transnational. They bring to bear a wide range of topics and disciplines on the field of textual scholarship: historical linguistics, digital scholarly editing, classical philology, Dutch, English, Finnish and Swedish Literature, publishing traditions in Japan, book history, cultural history and folklore. The questions that are explored - what texts are worth editing? what is the nature of the relationship between text, work, document and book? what is a critical digital edition? - all return to fundamental issues that have been at the heart of the editorial discipline for decades. With refreshing insight they assess the increasingly hybrid nature of the theoretical considerations and practical methodologies employed by textual scholars, while reasserting the relevance and need for producing scholarly editions, whether in print or digital, and continuing advanced research in bibliographical codes, textual transmissions, genetic dossiers, the fluidity of texts and other such subjects that connect textual scholarship with broader investigations into our nations' literary culture and written heritage.

PPARβ/δ activation blocks lipid-induced inflammatory pathways in mouse heart and human cardiac cells.

Owing to its high fat content, the classical Western diet has a range of adverse effects on the heart, including enhanced inflammation, hypertrophy, and contractile dysfunction. Proinflammatory factors secreted by cardiac cells, which are under the transcriptional control of nuclear factor-κB (NF-κB), may contribute to heart failure and dilated cardiomyopathy. The underlying mechanisms are complex, since they are linked to systemic metabolic abnormalities and changes in cardiomyocyte phenotype. Peroxisome proliferator-activated receptors (PPARs) are transcription factors that regulate metabolism and are capable of limiting myocardial inflammation and hypertrophy via inhibition of NF-κB. Since PPARβ/δ is the most prevalent PPAR isoform in the heart, we analyzed the effects of the PPARβ/δ agonist GW501516 on inflammatory parameters. A high-fat diet induced the expression of tumor necrosis factor-α, monocyte chemoattractant protein-1, and interleukin-6, and enhanced the activity of NF-κB in the heart of mice. GW501516 abrogated this enhanced proinflammatory profile. Similar results were obtained when human cardiac AC16 cells exposed to palmitate were coincubated with GW501516. PPARβ/δ activation by GW501516 enhanced the physical interaction between PPARβ/δ and p65, which suggests that this mechanism may also interfere NF-κB transactivation capacity in the heart. GW501516-induced PPARβ/δ activation can attenuate the inflammatory response induced in human cardiac AC16 cells exposed to the saturated fatty acid palmitate and in mice fed a high-fat diet. This is relevant, especially taking into account that PPARβ/δ has been postulated as a potential target in the treatment of obesity and the insulin resistance state.

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.

The political ecology of weeds : a scalar approach to landscape transformations

How do plants that move and spread across landscapes become branded as weeds and thereby objects of contention and control? We outline a political ecology approach that builds on a Lefebvrian understanding of the production of space, identifying three scalar moments that make plants into 'weeds' in different spatial contexts and landscapes. The three moments are: the operational scale, which relates to empirical phenomena in nature and society; the observational scale, which defines formal concepts of these phenomena and their implicit or explicit 'biopower' across institutional and spatial categories; and the interpretive scale, which is communicated through stories and actions expressing human feelings or concerns regarding the phenomena and processes of socio-spatial change. Together, these three scalar moments interact to produce a political ecology of landscape transformation, where biophysical and socio-cultural processes of daily life encounter formal categories and modes of control as well as emotive and normative expectations in shaping landscapes. Using three exemplar 'weeds' - acacia, lantana and ambrosia - our political ecology approach to landscape transformations shows that weeds do not act alone and that invasives are not inherently bad organisms. Humans and weeds go together; plants take advantage of spaces and opportunities that we create. Human desires for preserving certain social values in landscapes in contradiction to actual transformations is often at the heart of definitions of and conflicts over weeds or invasives.

Geografia associativa e imperialismo svizzero. Il caso di Ginevra (1858-1914)

ASSOCIATIVE GEOGRAPHY AND SWISS IMPERIALISM. THE EXAMPLE OF GENEVA (1858-1914) − This article is about geographical society of Geneva and its involvement in the 19th century colonial imperialism. Through this society, Swiss bourgeoisie takes part in the exploration and colonization of the world. Is this participation a sign of Swiss imperialism? This issue will be at the heart of this study.

De la Tartarie à l'Asie centrale : le coeur d'un continent dans l'histoire des idées entre la cartographie et la géopolitique

Résumé: Relevant du domaine des représentations, cette thèse porte sur la reconstitution du processus relatif à l'invention des notions liées au «coeur du continent » asiatique, distinguant deux phases: avant et après l'apparition de la dénomination Asie centrale. Partant de l'idée que dans le processus de création de cet objet d'investigation deux actes restent primordiaux - le découpage d'un continuum géographique et culturel et la nomination des parties extraites cette étude cherche à reconstituer selon quels critères et en fonction de quelles justifications et de quels arguments, il a été possible de parvenir, via des mots, à créer les notions centre-asiatiques, afin de faire valoir des «choses» en les représentant verbalement ou graphiquement comme réelles. Cette optique invite, dans une perspective d'histoire des sciences, à travers des images changeantes, à interroger l'Asie centrale en tant qu'objet d'étude, tel qu'il a été historiquement inventé, construit et représenté par les voyageurs et les scientifiques, sans négliger l'analyse du processus politique qui a réussi à insérer des lignes-frontières dans cet espace. Cette investigation aidera à mieux comprendre le sens épistémologique des expressions relatives à l'Asie centrale, souvent imprégnées d'une vision eurocentriste, lors de la progression des connaissances sur la région, en faisant revivre des courants de pensées multiples afin de pouvoir saisir la logique du développement des idées et comprendre quel rôle ces limites centre-asiatiques inventées, qui ne sont que la codification temporelle de certaines données, jouent dans les investigations scientifiques. Abstract: This dissertation proposes a reconstitution of the process of construction of the concepts relating to the Asia's «Heart of the Continent». It is divided into two parts: I: before the invention of the Central. Asia concept, from Antiquity until nineteenth century; II: the notion after this event. The study is mainly devoted to an epistemologic analysis of the arguments used during the delineation and the designation of this space

Jésus historique: une quête de l'inaccessible étoile? Bilan de la "troisième quête"

La «troisième Quête» du Jésus historique relance le débat sur des acquis de la recherche. Bien qu'il s'agisse d'une nébuleuse de positions dissemblables plutôt que d'un courant homogène, cette constellation de chercheurs remet en cause le consensus antérieur. Son nouveau paradigme peut être saisi sur cinq points : 1) Les sources documentaires sur Jésus sont étendues et leur exploitation modifiée. 2) On relève un puissant retour à la judaïté du Nazaréen. 3) Le coeur de l'agir de Jésus n'est plus nécessairement une position millénariste, mais une conviction sapientiale. 4) L'histoire sociale met en valeur la réaction du messianisme populaire contre une politique d'acculturation gréco-romaine en Palestine. 5) Une christologie implicite redevient pensable au niveau de Jésus lui-même. The third Quest for the historical Jesus has re-opened the debate concerning research findings. Although this consists of a nebulous set of dissimilar positions rather than a homogenous trend, five previous points of consensus are being challenged by the constellation of researchers. The new paradigm may be summarised in five points: 1) The documentary sources on Jesus are spread out and their use is thereby modified. 2) A notable return to the Jewishness of Jesus of Nazareth. 3) The heart of Jesus' action is no longer seen as a millenarist position, but more as a conviction informed by Wisdom. 4) Social history emphasises the reaction of popular messianism confronting Greek-Roman political acculturation. 5) An implicit Christology becomes possible once more at the level of Jesus Himself.

Remodelage des canaux potassiques dépendants de l'ATP lors de l'hypertrophie et de l'insuffisance cardiaque

RESUME :Introduction. Les maladies cardiovasculaires représentent la première cause de mortalité dans les pays développés et l'insuffisance cardiaque (IC) est la plus fréquente. Suite à un infarctus, le coeur des patients subit un remodelage ventriculaire pouvant évoluer vers un état d'IC. L'IC se définit comme un état dans lequel le coeur n'est plus capable d'approvisionner suffisamment les organes et cet état s'accompagne souvent de troubles du rythme cardiaque. Le remodelage ventriculaire touche de nombreux gènes codant à la fois pour les voies métaboliques et pour des canaux ioniques favorisant ainsi l'apparition des arythmies responsables de la mort subite des patients atteints d'IC. Comprendre ce passage entre remodelage et IC est crucial afin de pouvoir un jour prévenir l'IC et les complications médicales qui l'accompagnent. Nous nous sommes intéressés aux canaux potassiques dépendants de l'ATP (KATP) car ces canaux ont la capacité de coupler le métabolisme de la cellule à son activité électrique. En effet, les canaux KATP s'ouvrent quand la charge énergétique (rapport ATP/ ADP) de la cellule chute. Dans les cardiomyocytes, l'ouverture des KATP induit une hyperpolarisation de la membrane cellulaire ce qui diminue indirectement la surcharge calcique et de ce fait préserve la cellule. Les canaux KATp sont formés de 4 sous-unités Kir6.x (Kir6.1 ou Kir6.2) formant le pore du canal associées à 4 sous-unités régulatrices SUR. Les propriétés électrophysiologiques ainsi que la sensibilité pharmacologique des canaux KATP dépendent de leur composition et seuls les canaux KATP formés par la sous-unité Kirô.l sont activés par le diazoxyde.Méthodes et résultats. Nous avons d'abord montré dans un modèle in vivo d'IC chez le rat adulte que les sous-unités Kir6.1 et SUR sont surexprimées dans ces conditions pathologiques. Par ailleurs, les cardiomyocytes issus des coeurs infarcis deviennent sensibles au diazoxyde reflétant la surexpression de Kir6.1. Les potentiels d'action qui sont prolongés dans l'IC et qui sont à l'origine d'arythmies majeures sont normalisés par l'ouverture des canaux KATp induite par le diazoxyde. Ainsi, l'ouverture pharmacologique des canaux KATp contribuerait à la cardio-protection. Dans une seconde partie, nous avons déterminé quels étaient les facteurs de transcription responsables de ce changement d'expression des sous-unités formant les KATP. Dans notre modèle, nous avons pu montrer que la surexpression de Kirô.l est due aux facteurs de transcription Fox03 et FoxF2 qui est aussi responsable de la surexpression des sous-unités SUR. Dans la dernière partie de ce travail, nous avons mis au point un modèle d'IC in vitro en cultivant les cardiomyocytes de rats adultes en présence d'angiotensine II (Angll) ou de TNFa. Ce modèle expérimental nous a non seulement permis de mettre en relation l'importance de L'AnglI et du TNFa sur le remodelage des canaux KATP mais aussi de développer un modèle in vitro présentant les mêmes caractéristiques que le modèle in vivo concernant le remodelage des KATP lors de l'IC. Ce dernier modèle expérimental ouvre des perspectives afin de mieux caractériser les voies de signalisation impliquées dans le remodelage des canaux KATp lors de l'IC.Conclusion. Les canaux KATp subissent un remodelage lors de l'IC et les résultats obtenus montrent le potentiel cardio-protecteur de ces canaux.ABSTRACT :Background and aim. Cardiovascular disease is the leading cause of death in developed countries and heart failure (HF) is the most common. Following myocardial infarction, the heart of the patient undergoes ventricular remodeling which may evolve toward a state of HF. HF is defined as a state in which heart is unable to supply enough blood to organs and this state is often accompanied by cardiac arrhythmias. Ventricular remodeling involves many genes coding for both metabolic enzymes and ion channels. Changes in ion channel expression can promote arrhythmias responsible for sudden death in patients with HF. A better understanding of the transition between remodeling and HF is crucial in order to prevent the complications associated to HF We were interested in ATP-dependent potassium channels (KATp) because they couple cell metabolism to electrical activity of the cell. Indeed, KATP channels open when the energy charge (ratio of ATP / ADP) of the cell collapses. In cardiomyocytes, the opening of KATP channels induces hyper- polanzation of the cell membrane which reduces calcium overload and thereby protects the cell. KATp channels are composed by 4 Kir6.x subumts (Kir6.1 or Kir6.2) forming the pore channel associated with 4 regulatory subunits SUR. The electrophysiological properties as well as pharmacological sensitivity of KATp channels depend on their composition and only KATP channels formed by Kir6.1 subunit are activated by diazoxide.Methods and results. Firstly, using an in vivo model of HF in adult rats, we showed that Kir6.1 and SUR subunits are overexpressed in HF. In addition, cardiomyocytes from post-infarction hearts became sensitive to diazoxide reflecting the overexpression of the Kir6.1 subunit. The opening of KATP by diazoxide tended to reduce the action potential duration (APD) which is extended in HF. This increase in APD is known to be a major source of arrhythmias during HF. Therefore, the opening of KATP channels by diazoxide would be cardio-protective. Secondly, we wanted to determine which transcription factors were responsible for this KATP remodeling. In our model of HF, we showed that overexpression of Kir6.1 is due to the transcription factors Fox03 and FOXF2 which is also responsible for SUR subunits overexpression. Thirdly, we developed an in vitro model of HF by cultivation of adult rat cardiomyocytes in the presence of angiotensin II (Angll) or TNFa. This model is very interesting not only because it underlines the importance of Angll and TNFa in KATp remodeling but also because this in vitro model presents the same KATP remodeling as the in vivo model of HF. These findings show that our in vitro model of HF opens up many possibilities to investigate more precisely the signaling pathways involved in remodeling of the KATP channels in HF.Conclusion. KATP channels undergo remodeling during HF and our results show the cardio¬protective potential of KATP channels in this disease.

La revascularisation transmyocardique au laser--un risque potentiel en condition aiguë [Laser transmyocardial revascularization--a potential risk in an acute situation?]

Morphological and functional effects of transmyocardial laser revascularization (TMLR) are analyzed in an acute setting on a porcine model. Ten channels were drilled in the left lateral wall of the heart of 15 pigs (mean weight, 73 +/- 4 kg) with a Holmium-YAG laser (wavelength: 2.1 mu, probe diameter: 1.75 mm). Echocardiographic control was performed before the TMLR procedure as well as 5 min and 30 min thereafter. Echocardiographic parameters were recorded in short-axis at the level of the laser channels, and included left ventricular ejection fraction, fractional shortening and segmental wall motility of the channels' area (scale 0-3: 0 = normal, 1 = hypokinesia, 2 = akinesia, 3 = dyskinesia). After sacrifice the lased region was sliced perpendicularly to the channels for histological and morphometrical analysis. Five minutes after the drilling of the channels, all the echocardiographic index worsened significantly in comparison with baseline values (p < 0.01). All recovered after 30 min and showed no difference with baseline values. Cross-section of the channel lesions measured 8.8 +/- 2.4 mm2 which is more than three times that of the probe (p < 0.01). In acute conditions, the lesions due to the TMLR probe are significantly larger than the probe itself and cause a transient drop of the segmental wall motility on a healthy myocardium. These results suggest that TMLR should be used cautiously in the clinical setting for patients with an impaired ventricular function.

Argumentation and education. Theoretical foundations and practices

During the last decade, argumentation has attracted growing attention as a means to elicit processes (linguistic, logical, dialogical, psychological, etc.) that can sustain or provoke reasoning and learning. Constituting an important dimension of daily life and of professional activities, argumentation plays a special role in democracies and is at the heart of philosophical reasoning and scientific inquiry. Argumentation, as such, requires specific intellectual and social skills. Hence, argumentation will have an increasing importance in education, both because it is a critical competence that has to be learned, and because argumentation can be used to foster learning in philosophy, history, sciences and in many other domains. Argumentation and Education answers these and other questions by providing both theoretical backgrounds, in psychology, education and theory of argumentation, and concrete examples of experiments and results in school contexts in a range of domains. It reports on existing innovative practices in education settings at various levels.

Angiotensin II-induced cardiac hypertrophy is associated with different mitogen-activated protein kinase activation in normotensive and hypertensive mice.

OBJECTIVE: In addition to its haemodynamic effects, angiotensin II (AngII) is thought to contribute to the development of cardiac hypertrophy via its growth factor properties. The activation of mitogen-activated protein kinases (MAPK) is crucial for stimulating cardiac growth. Therefore, the present study aimed to determine whether the trophic effects of AngII and the AngII-induced haemodynamic load were associated with specific cardiac MAPK pathways during the development of hypertrophy. Methods The activation of the extracellular-signal-regulated kinase (ERK), the c-jun N-terminal kinase (JNK) and the p38 kinase was followed in the heart of normotensive and hypertensive transgenic mice with AngII-mediated cardiac hypertrophy. Secondly, we used physiological models of AngII-dependent and AngII-independent renovascular hypertension to study the activation of cardiac MAPK pathways during the development of hypertrophy. RESULTS: In normotensive transgenic animals with AngII-induced cardiac hypertrophy, p38 activation is associated with the development of hypertrophy while ERK and JNK are modestly stimulated. In hypertensive transgenic mice, further activation of ERK and JNK is observed. Moreover, in the AngII-independent model of renovascular hypertension and cardiac hypertrophy, p38 is not activated while ERK and JNK are strongly stimulated. In contrast, in the AngII-dependent model, all three kinases are stimulated. CONCLUSIONS: These data suggest that p38 activation is preferentially associated with the direct effects of AngII on cardiac cells, whereas stimulation of ERK and JNK occurs in association with AngII-induced mechanical stress.

AMP-activated protein kinase mediates glucocorticoid-induced metabolic changes: a novel mechanism in Cushing's syndrome.

Chronic exposure to glucocorticoid hormones, resulting from either drug treatment or Cushing's syndrome, results in insulin resistance, central obesity, and symptoms similar to the metabolic syndrome. We hypothesized that the major metabolic effects of corticosteroids are mediated by changes in the key metabolic enzyme adenosine monophosphate-activated protein kinase (AMPK) activity. Activation of AMPK is known to stimulate appetite in the hypothalamus and stimulate catabolic processes in the periphery. We assessed AMPK activity and the expression of several metabolic enzymes in the hypothalamus, liver, adipose tissue, and heart of a rat glucocorticoid-excess model as well as in in vitro studies using primary human adipose and primary rat hypothalamic cell cultures, and a human hepatoma cell line treated with dexamethasone and metformin. Glucocorticoid treatment inhibited AMPK activity in rat adipose tissue and heart, while stimulating it in the liver and hypothalamus. Similar data were observed in vitro in the primary adipose and hypothalamic cells and in the liver cell line. Metformin, a known AMPK regulator, prevented the corticosteroid-induced effects on AMPK in human adipocytes and rat hypothalamic neurons. Our data suggest that glucocorticoid-induced changes in AMPK constitute a novel mechanism that could explain the increase in appetite, the deposition of lipids in visceral adipose and hepatic tissue, as well as the cardiac changes that are all characteristic of glucocorticoid excess. Our data suggest that metformin treatment could be effective in preventing the metabolic complications of chronic glucocorticoid excess.

Une européanisation des politiques de conciliation de la vie familiale et professionnelle? : les cas de l'Italie et de la France

Les différents pays membres de l'UE connaissent des politiques dites de « conciliation de la vie professionnelle et familiale » qui correspondent à un ensemble de dispositifs hétéroclites, plus ou moins complexes, mais rarement cohérents. Alliant des objectifs tels que la hausse de la natalité, la protection des mères et des enfants, l'égalité entre femmes et hommes, la lutte contre la pauvreté des enfants et des familles monoparentales et l'activation des femmes, ces politiques sont fortement ancrées dans des traditions nationales de politiques familiales, d'emploi et fiscales. Ces politiques portent en elles l'héritage et les tensions de l'histoire d'un pays. Au moment où un nouvel acteur international, l'Union européenne, intervient de manière de plus en plus explicite dans le débat et dans la définition de ces politiques, la présente étude tend à analyser l'influence exercées par les référentiels européens en matière de politiques de conciliation sur les discours et politiques nationales de l'Italie et de la France. A partir d'une analyse cognitive du processus d'européanisation, nous montrons que les référentiels développés au sein de l'UE, par leur caractère abstrait et flou, n'ont eu jusqu'ici qu'une faible influence sur les discours et politiques en Italie et en France. Croisant une perspective néo-institutionnaliste historique et discursive, notre recherche a été construite autour de deux axes de réflexion. Premièrement, il a été question d'analyser, d'une part, l'évolution du discours tenu par les différentes instances européennes (notamment de la Commission européenne, le Conseil européen et le Fonds Social européen) et, d'autre part, questionner comment un consensus a pu émerger entre des pays et des acteurs qui ont des traditions extrêmement différentes en matière de politique sociale, de politique familiale et de convention de genre. Deuxièmement, il a été question d'analyser si et comment un cadre de référence conçu au niveau communautaire a pu influencer les discours et politiques au niveau national. - The reconciliation of work and family life policies forms, in the EU's member States, a plurality of politics, more or less complex, but rarely coherent. Combining different objectives such as fertility increase, mothers and children protection, equality between men and women, fight against children and lone-parent families poverty and women activation, these policies are part of the national traditions of family, employment and tax policy and bear the heritage and the tensions of the country history. At a moment when a new global player, the European Union, interferes increasingly explicitly in the debate and the definition of reconciling work and family life policies, the question at the heart of this thesis was to define what kind of influence the référentiels of European discourses have on reconciliation policies since the late 1990s, in the Italian and French discourses and policies. Starting from a cognitive analysis of the Europeanization process, we show that the référentiels developed within the EU, by their abstract and vague nature, have had little influence in Italy and France. Crossing an historical and a discursive neo-institutionalist perspective, our research was based on two axes of reasoning. First, we have analysed, on the one hand, the evolution of various European institutions' discoursed (including the European Commission, the European Council and the European Social Fund) and, on the other hand, we have questioned how a consensus has emerged between countries and actors who have very different traditions in social policy, family policy and gender conventions. Secondly, we have observed if and how a framework developed at Community level, as a kind of ideal to strive for, has influenced discourses and policies at the national level.

Calcineurin blockade prevents cardiac mitogen-activated protein kinase activation and hypertrophy in renovascular hypertension.

Chronic stimulation of the renin-angiotensin system induces an elevation of blood pressure and the development of cardiac hypertrophy via the actions of its effector, angiotensin II. In cardiomyocytes, mitogen-activated protein kinases as well as protein kinase C isoforms have been shown to be important in the transduction of trophic signals. The Ca(2+)/calmodulin-dependent phosphatase calcineurin has also been suggested to play a role in cardiac growth. In the present report, we investigate possible cross-talks between calcineurin, protein kinase C, and mitogen-activated protein kinase pathways in controlling angiotensin II-induced hypertrophy. Angiotensin II-stimulated cardiomyocytes and mice with angiotensin II-dependent renovascular hypertension were treated with the calcineurin inhibitor cyclosporin A. Calcineurin, protein kinase C, and mitogen-activated protein kinase activations were determined. We show that cyclosporin A blocks angiotensin II-induced mitogen-activated protein kinase activation in cultured primary cardiomyocytes and in the heart of hypertensive mice. Cyclosporin A also inhibits specific protein kinase C isoforms. In vivo, cyclosporin A prevents the development of cardiac hypertrophy, and this effect appears to be independent of hemodynamic changes. These data suggest cross-talks between the calcineurin pathway, the protein kinase C, and the mitogen-activated protein kinase signaling cascades in transducing angiotensin II-mediated stimuli in cardiomyocytes and could provide the basis for an integrated model of cardiac hypertrophy.