64 research outputs found

    A SOCIO-TECHNICAL PERPECTIVE ON THE DESIGN OF IT ARCHITECTURE: THE LOWLAND LENS

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    The paper aims at developing a more comprehensive design theory for designing effective IT architectures based on organizational design principles. It builds on the sociotechnical systems design theory (STS-D) for the design of work, workplaces and organizations as developed in the Lowlands (The Netherlands and Belgium). Traditional sociotechnical approaches study the effects of the technical system on the social system and tries to jointly optimize both systems by end-users’ participation. The Lowlands STS-D approach focuses on creating organizational conditions for developing humane and productive organizations. Organizations are considered as social systems. Technical systems need to support the effective functioning of work and control of work within that social system. Therefore, the division of labour is central in the Lowlands STS-D approach. It is articulated in designing the execution tasks (production structure) and control tasks (control structure). Furthermore, it claims that the design of IT architecture follows after organizational design of the production and control structure. This boils down to the design of provisioning of information needed at workplaces and between workplaces. To understand the Lowlands approach for designing IT architecture, called archipelago, we will first in-depth explain its organizational design principles and sequence, and its application for designing IT architecture, that is becoming ever more feasible with new technologies Furthermore, with this paper we attempt to bridge the different languages used by organizational and IT designers as they should jointly work on the same outcome: humane and productive organizations

    Genome sequence of the necrotrophic plant pathogen Pythium ultimum reveals original pathogenicity mechanisms and effector repertoire

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    Background: Pythium ultimum (P. ultimum) is a ubiquitous oomycete plant pathogen responsible for a variety of diseases on a broad range of crop and ornamental species. Results: The P. ultimum genome (42.8 Mb) encodes 15,290 genes and has extensive sequence similarity and synteny with related Phytophthora species, including the potato blight pathogen Phytophthora infestans. Whole transcriptome sequencing revealed expression of 86% of genes, with detectable differential expression of suites of genes under abiotic stress and in the presence of a host. The predicted proteome includes a large repertoire of proteins involved in plant pathogen interactions although surprisingly, the P. ultimum genome does not encode any classical RXLR effectors and relatively few Crinkler genes in comparison to related phytopathogenic oomycetes. A lower number of enzymes involved in carbohydrate metabolism were present compared to Phytophthora species, with the notable absence of cutinases, suggesting a significant difference in virulence mechanisms between P. ultimum and more host specific oomycete species. Although we observed a high degree of orthology with Phytophthora genomes, there were novel features of the P. ultimum proteome including an expansion of genes involved in proteolysis and genes unique to Pythium. We identified a small gene family of cadherins, proteins involved in cell adhesion, the first report in a genome outside the metazoans. Conclusions: Access to the P. ultimum genome has revealed not only core pathogenic mechanisms within the oomycetes but also lineage specific genes associated with the alternative virulence and lifestyles found within the pythiaceous lineages compared to the Peronosporaceae

    Human Antigen-Specific Regulatory T Cells Generated by T Cell Receptor Gene Transfer

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    Therapies directed at augmenting regulatory T cell (Treg) activities in vivo as a systemic treatment for autoimmune disorders and transplantation may be associated with significant off-target effects, including a generalized immunosuppression that may compromise beneficial immune responses to infections and cancer cells. Adoptive cellular therapies using purified expanded Tregs represents an attractive alternative to systemic treatments, with results from animal studies noting increased therapeutic potency of antigen-specific Tregs over polyclonal populations. However, current methodologies are limited in terms of the capacity to isolate and expand a sufficient quantity of endogenous antigen-specific Tregs for therapeutic intervention. Moreover, FOXP3+ Tregs fall largely within the CD4+ T cell subset and are thus routinely MHC class II-specific, whereas class I-specific Tregs may function optimally in vivo by facilitating direct tissue recognition.To overcome these limitations, we have developed a novel means for generating large numbers of antigen-specific Tregs involving lentiviral T cell receptor (TCR) gene transfer into in vitro expanded polyclonal natural Treg populations. Tregs redirected with a high-avidity class I-specific TCR were capable of recognizing the melanoma antigen tyrosinase in the context of HLA-A*0201 and could be further enriched during the expansion process by antigen-specific reactivation with peptide loaded artificial antigen presenting cells. These in vitro expanded Tregs continued to express FOXP3 and functional TCRs, and maintained the capacity to suppress conventional T cell responses directed against tyrosinase, as well as bystander T cell responses. Using this methodology in a model tumor system, murine Tregs designed to express the tyrosinase TCR effectively blocked antigen-specific effector T cell (Teff) activity as determined by tumor cell growth and luciferase reporter-based imaging.These results support the feasibility of class I-restricted TCR transfer as a promising strategy to redirect the functional properties of Tregs and provide for a more efficacious adoptive cell therapy

    Buffer management to solve bed-blocking in the Netherlands, 2000-2010. Cooperation from an integrated care chain perspective as a key success factor for managing patient flows.

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    <p><strong>Introduction</strong>: Bed-blocking problems in hospitals reflect how difficult and complex it is to move patients smoothly through the chain of care. In the Netherlands, during the first decade of the 21<sup>st</sup> century, some hospitals attempted to tackle this problem by using an Intermediate Care Department (ICD) as a buffer for bed-blockers. However, research has shown that ICDs do not sufficiently solve the bed-blocking problem and that bed-blocking is often caused by a lack of buffer management.</p><p><strong>Tool:</strong> Buffer management (BM) is a tool that endeavors to balance patient flow in the hospital to nursing home chain of care. </p><p><strong>Results</strong>: Additional research has indicated that the absence of BM is not the result of providers' thinking that BM is unnecessary, unethical or impossible because of unpredictable patient flows. Instead, BM is hampered by a lack of cooperation between care providers.</p><p><strong>Conclusion</strong>: Although stakeholders recognize that cooperation is imperative, they often fail to take the actions necessary to realize cooperation. Our assumption is that this lack of willingness and ability to cooperate is the result of several impeding conditions as well as stakeholders' perceptions of these conditions and the persistence of their current routines, principles and beliefs (RPBs).</p><p><strong>Discussion</strong>: We recommend simultaneously working on improving the conditions and changing stakeholders' perceptions and RPBs.</p
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