Inhibition of FAK prevents blister formation in the neonatal mouse model of pemphigus vulgaris

Pemphigus vulgaris (PV) is an autoimmune blistering skin disease characterized by suprabasal acantholysis and by autoantibodies against desmoglein 3 localized on desmosomes. In addition, caspases also seem to participate in this blistering disease. Focal adhesion kinase (FAK) is a non-receptor tyrosine kinase involved in cytoskeleton remodelling and formation and disassembly of cell adhesion structures. We have previously demonstrated that HER (human epidermal growth factor receptor related) isoforms, Src (Rous sarcoma) and mammalian target of rapamycin (mTOR), three molecules implicated in signalling processes, take part in suprabasal acantholysis and apoptosis induced by PV-IgG in a mouse model. Our aim was to investigate whether upregulation of FAK is implicated in the development of PV lesions. Herein, using a mouse model, PV-IgG administration showed an increased level of FAK phosphorylated on 397 and 925 tyrosine residues in the basal layer of epidermis. When mice were pretreated with a FAK inhibitor (FI), the acantholysis of the basal layer of epidermis was absent. More interestingly, we observed that phosphorylated FAK (Y397/925) decreased when HER isoforms, Src, mTOR and pan-caspases inhibitors were employed before PV-IgG administration. In addition, pretreatment with the FI before PV-IgG injection prevented the changes in both Bax and Bcl-2 expression and caspase-9 and caspase-3 activities induced by PV-IgG. Finally, FI reduced the expression of phosphorylated Src and mTOR in the basal cells of epidermis. In conclusion, our data reveal a novel role of phosphorylated FAK (Y397/925) in PV development involving HER isoforms, Src and mTOR kinase

Physico-mechanical properties, durability and treatability of Pinus uncinata from the Pyrenees

Pinus uncinata is a native pine from the mountain zones of Spain and of the centre and west of the Alps. Since centuries, it has been known that this species presents an excellent structural competence and his heartwood is perceived as highly durable. Nevertheless, its properties have not been studied in depth. The timber characterized comes from the French and the Spanish Pyrenees. The study analyses the mechanical and the physical properties of the clear wood, as well as the durability and the treatability. All the tests were done according the European standards. Pinus uncinata is soft, lightweight and not as stiff as the native pines of southern Europe. The natural durability was evaluated and the mountain pine was classified as non-durable. The sapwood wood is treatable while the heartwood is little or non-treatable. (Résumé d'auteur

A methodological and conceptual review of inter organizational information systems integration

The proliferation of applications to support cross-enterprise processes has left companies nursing a collection of systems. The integration of such systems, within and across the organizational boundaries, remains a top issue of researchers and practitioners’ agendas. Although integration has long been treated as a key variable in the IS field, the construct has received little conceptual scrutiny. In this essay we argue that the concept of IOIS integration (cross-enterprise integration of information systems) is still ambiguous and lacks an understanding on its nature. Thus we explore prior literature that has attempted to conceptualize IOIS integration. We examine dimensions that concern both the methodology used (epistemology, theoretical perspective, research approach, duration of the study, conceptual model and unit of analysis), and the construct (scope, layer of integration and conceptualization of the ICT artefact). Sixty-one articles are reviewed. We present the results and discuss different dimensions of the construct (definition, antecedents, consequences and measures). The purpose of this literature survey is to shed some light on the IOIS integration construct as well as to uncover areas for future research

The Dynamics of Architecture-Governance Configurations: An Assemblage Theory Approach

Research on digital infrastructures and platforms studies large-scale systems that are characterized by constant evolution, loosely defined boundaries, and growing complexity. This research demonstrates that evolution is driven by tensions (between stability and change), which are in turn determined by the systems’ architecture and governance structures. This paper argues that architecture and governance are intrinsically related and conceptualizes them as a unified entity that we call an architecture-governance (A-G) configuration. We focus on the dynamics of A-G configurations—i.e., how architecture and governance interact and, in combination, shape the evolution of digital infrastructures, while, at the same time, change as emergent outcomes of the evolution of infrastructures. Toward this end, this paper applies assemblage theory as a lens for conducting a longitudinal study on an electronic prescription infrastructure. We identify three overall A-G configurations corresponding to different phases of the evolution of the infrastructure. This paper makes three contributions. First, we theorize the A-G configuration as an intertwined intermediate-scale entity that represents the form of the infrastructure and simultaneously constitutes an assemblage in its own right. Second, we demonstrate how an A-G configuration and its infrastructure coevolved through a series of interacting stabilization and destabilization processes operating within and across levels. Finally, we argue that tensions driving the evolution of infrastructures are also dynamic and that, accordingly, the focus of study should be on the processes of stabilization and destabilization rather than on stability and change themselves

Architectural Constraints on the Bootstrapping of a Personal Health Record

During the last decade we have seen a proliferation of electronic personal health record systems (PHRs) aiming to change the way people manage and receive healthcare. However, many of these initiatives have failed to take-off. We inquire into such unsatisfactory outcomes by drawing upon the perspective proposed in the information infrastructure (II) literature. This literature views the value of PHRs as dependent on the number of actors using them. This poses a challenge for designers (referred to as ‘bootstrapping’): how to persuade users to adopt a PHR when the user base is still small. To address the bootstrap- ping challenge, II literature suggests starting with a simple solution that creates immediate user value and enables users to enroll gradually. This paper seeks to explore how PHR architecture can hinder PHR bootstrapping through a longitudinal case study on the implementation of an integrated PHR. Our case analysis identifies four architectural constraints: poor data quality; coordination across heterogeneity; privacy and control; and re-configurability. This paper concludes by discussing the implications of the findings for the literature on personal and electronic health records and on the design of information infrastructures

Tackling the Problem of Transferability in IS Qualitative Research

Despite the diverse calls for transferability in IS research, most IS qualitative research studies still pay little attention to the potential applicability of their results in other social contexts (settings). We argue that one way to support the assessment of transferability is to characterize the deep features of the research setting. The two main premises of this paper are that although in IS qualitative research knowledge about results is context-bound, (1) the settings in which IS phenomena occur may have common features and characteristics, and therefore, the settings may be commensurable, and (2) the transferability of research results from one setting to another depends on the fittingness between the features and characteristics of the settings. In this article, we draw on the constituents of structure proposed by Giddens to suggest these common features and develop a framework of four pure ‘structural configurations’. We demonstrate proof of concept concerning the feasibility of this framework by classifying the research settings of a sample of papers. We consider this framework may be a first approximation to typifying the setting in which IS phenomena occur, and therefore, a way to support the transferability of IS qualitative research by delineating the applicability of its results

SEGMENTATION INFORMS THE GAMIFICATION OF SUSTAINABLE FOOD CONSUMPTION

Food systems activities produce around 30% of global anthropogenic greenhouse gas (GHG) emissions and are responsible for numerous environmental issues which could ultimately harm our ability to grow food reliably. One way to reduce the food system’s impacts is to transition to a more sustainable diet composed of low impact foods. The objective of this study is to identify consumers demonstrating an intention to consume sustainably produced foods, and to identify their characteristics to inform the design of targeted gamified interventions that would promote sustainable food purchasing. A survey incorporating variables from the theory of planned behaviour (e.g. attitude), socio-demographic information (e.g. age), gamification profiling variables (e.g. player typology), as well as preferred mobile applications, was developed in this study and distributed via a market survey company. Statistical analysis in the form of hierarchical clustering was used to segment and identify target markets, while contingency analysis assessed the most effective means of promoting sustainable diets. A total of four hundred and ninety surveys were distributed and three hundred and seventy-six of them were validated because they agreed to participate, were not detected as potential AI powered responses, and their responses from the theory of planned behaviour were completed. Linear regression was used to assess the significance of all variables on the intent to consume a sustainable diet. Cluster analysis identified 3 potential target segments, and contingency analysis was used to detect their unique features. Two consumer segments were identified as having high potential as a target market. Individuals in this market intended to consume a sustainable diet but lacked follow through. Strong evidence towards the effectiveness of gamification of interventions was not observed due to low and medium frequency in gaming behaviours for the two target segments. Interventions distributed through mobile applications would be most effective if they were delivered through social media and included game design elements associated with Philanthropist and Free Spirit user types. The survey was confined to Ontario, therefore it may not be generalizable to other regions. Nevertheless, this study is unique in its assessment of the profiles of consumers with high intention to purchase sustainably sourced foods through a combination of the theory of planned behaviour, socio-demographic factors, gamification player types and game behaviours, as well as preferred mobile application usage