160 research outputs found

    Designing an information system for updating land records in Bangladesh: action design ethnographic research (ADER)

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    Open Access. This article is distributed under the terms of the Creative Commons Attribution License which permits any use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited.This article has been made available through the Brunel Open Access Publishing Fund.Information Systems (IS) has developed through adapting, generating and applying diverse methodologies, methods, and techniques from reference disciplines. Further, Action Design Research (ADR) has recently developed as a broad research method that focuses on designing and redesigning IT and IS in organizational contexts. This paper reflects on applying ADR in a complex organizational context in a developing country. It shows that ADR requires additional lens for designing IS in such a complex organizational context. Through conducting ADR, it is seen that an ethnographic framework has potential complementarities for understanding complex contexts thereby enhancing the ADR processes. This paper argues that conducting ADR with an ethnographic approach enhances design of IS and organizational contexts. Finally, this paper aims presents a broader methodological framework, Action Design Ethnographic Research (ADER), for designing artefacts as well as IS. This is illustrated through the case of a land records updating service in Bangladesh

    Mutations in protocadherin 15 and cadherin 23 affect tip links and mechanotransduction in mammalian sensory hair cells

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    Immunocytochemical studies have shown that protocadherin-15 (PCDH15) and cadherin-23 (CDH23) are associated with tip links, structures thought to gate the mechanotransducer channels of hair cells in the sensory epithelia of the inner ear. The present report describes functional and structural analyses of hair cells from Pcdh15av3J (av3J), Pcdh15av6J (av6J) and Cdh23v2J (v2J) mice. The av3J and v2J mice carry point mutations that are predicted to introduce premature stop codons in the transcripts for Pcdh15 and Cdh23, respectively, and av6J mice have an in-frame deletion predicted to remove most of the 9th cadherin ectodomain from PCDH15. Severe disruption of hair-bundle morphology is observed throughout the early-postnatal cochlea in av3J/av3J and v2J/v2J mice. In contrast, only mild-to-moderate bundle disruption is evident in the av6J/av6J mice. Hair cells from av3J/av3J mice are unaffected by aminoglycosides and fail to load with [3H]-gentamicin or FM1-43, compounds that permeate the hair cell's mechanotransducer channels. In contrast, hair cells from av6J/av6J mice load with both FM1-43 and [3H]-gentamicin, and are aminoglycoside sensitive. Transducer currents can be recorded from hair cells of all three mutants but are reduced in amplitude in all mutants and have abnormal directional sensitivity in the av3J/av3J and v2J/v2J mutants. Scanning electron microscopy of early postnatal cochlear hair cells reveals tip-link like links in av6J/av6J mice, substantially reduced numbers of links in the av3J/av3J mice and virtually none in the v2J/v2J mice. Analysis of mature vestibular hair bundles reveals an absence of tip links in the av3J/av3J and v2J/v2J mice and a reduction in av6J/av6J mice. These results therefore provide genetic evidence consistent with PCDH15 and CDH23 being part of the tip-link complex and necessary for normal mechanotransduction

    A conceptual model for action and design research

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    Organizational research has a pattern of special characteristics which make a clear distinction from other research paradigms. When using these approaches – based on Action and Design – the Interpretivist, Constructivist, and Participatory perspectives dominate. They have already proven to have strong foundations, which turn these paradigmatic approaches into effective ways for getting knowledge, doing things, and promoting change within organizational settings. It combines the traditional scientific, engineering, and organization development approaches, depicting how an organization can, simultaneously, solve multidimensional problems and produce actionable knowledge, effective change and useful artifacts. It has been developed using a Design Science Research approach, tested in a major organizational change program (Henriques, 2015; Henriques & ONeill, 2014), and successfully used to teach research methods essentials to Master and DBA students.info:eu-repo/semantics/publishedVersio

    Arterivirus Nsp1 Modulates the Accumulation of Minus-Strand Templates to Control the Relative Abundance of Viral mRNAs

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    The gene expression of plus-strand RNA viruses with a polycistronic genome depends on translation and replication of the genomic mRNA, as well as synthesis of subgenomic (sg) mRNAs. Arteriviruses and coronaviruses, distantly related members of the nidovirus order, employ a unique mechanism of discontinuous minus-strand RNA synthesis to generate subgenome-length templates for the synthesis of a nested set of sg mRNAs. Non-structural protein 1 (nsp1) of the arterivirus equine arteritis virus (EAV), a multifunctional regulator of viral RNA synthesis and virion biogenesis, was previously implicated in controlling the balance between genome replication and sg mRNA synthesis. Here, we employed reverse and forward genetics to gain insight into the multiple regulatory roles of nsp1. Our analysis revealed that the relative abundance of viral mRNAs is tightly controlled by an intricate network of interactions involving all nsp1 subdomains. Distinct nsp1 mutations affected the quantitative balance among viral mRNA species, and our data implicate nsp1 in controlling the accumulation of full-length and subgenome-length minus-strand templates for viral mRNA synthesis. The moderate differential changes in viral mRNA abundance of nsp1 mutants resulted in similarly altered viral protein levels, but progeny virus yields were greatly reduced. Pseudorevertant analysis provided compelling genetic evidence that balanced EAV mRNA accumulation is critical for efficient virus production. This first report on protein-mediated, mRNA-specific control of nidovirus RNA synthesis reveals the existence of an integral control mechanism to fine-tune replication, sg mRNA synthesis, and virus production, and establishes a major role for nsp1 in coordinating the arterivirus replicative cycle

    Scenario-Based Design Theorizing:The Case of a Digital Idea Screening Cockpit

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    As ever more companies encourage employees to innovate, a surplus of ideas has become reality in many organizations – often exceeding the available resources to execute them. Building on insights from a literature review and a 3-year collaboration with a banking software provider, the paper suggests a Digital Idea Screening Cockpit (DISC) to address this challenge. Following a design science research approach, it suggests a prescriptive design theory that provides practitioner-oriented guidance for implementing a DISC. The study shows that, in order to facilitate the assessment, selection, and tracking of ideas for different stakeholders, such a system needs to play a dual role: It needs to structure decision criteria and at the same be flexible to allow for creative expression. Moreover, the paper makes a case for scenario-based design theorizing by developing design knowledge via scenarios

    Harmonin-b, an actin-binding scaffold protein, is involved in the adaptation of mechanoelectrical transduction by sensory hair cells

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    We assessed the involvement of harmonin-b, a submembranous protein containing PDZ domains, in the mechanoelectrical transduction machinery of inner ear hair cells. Harmonin-b is located in the region of the upper insertion point of the tip link that joins adjacent stereocilia from different rows and that is believed to gate transducer channel(s) located in the region of the tip link's lower insertion point. In Ush1cdfcr-2J/dfcr-2J mutant mice defective for harmonin-b, step deflections of the hair bundle evoked transduction currents with altered speed and extent of adaptation. In utricular hair cells, hair bundle morphology and maximal transduction currents were similar to those observed in wild-type mice, but adaptation was faster and more complete. Cochlear outer hair cells displayed reduced maximal transduction currents, which may be the consequence of moderate structural anomalies of their hair bundles. Their adaptation was slower and displayed a variable extent. The latter was positively correlated with the magnitude of the maximal transduction current, but the cells that showed the largest currents could be either hyperadaptive or hypoadaptive. To interpret our observations, we used a theoretical description of mechanoelectrical transduction based on the gating spring theory and a motor model of adaptation. Simulations could account for the characteristics of transduction currents in wild-type and mutant hair cells, both vestibular and cochlear. They led us to conclude that harmonin-b operates as an intracellular link that limits adaptation and engages adaptation motors, a dual role consistent with the scaffolding property of the protein and its binding to both actin filaments and the tip link component cadherin-23

    Fostering teacher community development: A review of design principles and a case study of an innovative interdisciplinary team

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    To deal with recent reforms and the accompanying complexity of work in secondary education, ongoing collaboration between teachers has become more important. A community is seen as a promising learning environment to support and embed collaboration into the culture of the school. However, community theory for the design of teacher communities seems underdeveloped. Therefore, this study aims to formulate a set of design principles to foster the development of teacher communities in secondary education. The set of design principles is based on a review of literature, as well as on a best-practice case. The case study was used to validate design principles from the literature in the target context. The resulting design principles were based on context-intervention-mechanismoutcome logic that takes into account the context-dependency of interventions as well as the mechanisms that help with understanding of how interventions produce certain outcomes. Implications for practice relate to ownership and co-design of the arrangement. The set of design principles provides a practical basis for teachers and administrators aiming to facilitate community building in their school. Future research is recommended on testing the effectiveness of the arrangement in the target context by means of a multiple case study.NWO-pro

    Differentiation of normal and cancer cells induced by sulfhydryl reduction: biochemical and molecular mechanisms

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    We examined the morphological, biochemical and molecular outcome of a nonspecific sulfhydryl reduction in cells, obtained by supplementation of N-acetyl-L-cysteine (NAC) in a 0.1-10 mM concentration range. In human normal primary keratinocytes and in colon and ovary carcinoma cells we obtained evidences for: (i) a dose-dependent inhibition of proliferation without toxicity or apoptosis; (ii) a transition from a proliferative mesenchymal morphology to cell-specific differentiated structures; (iii) a noticeable increase in cell-cell and cell-substratum junctions; (iv) a relocation of the oncogenic beta-catenin at the cell-cell junctions; (v) inhibition of microtubules aggregation; (vi) upregulation of differentiation-related genes including p53, heat shock protein 27 gene, N-myc downstream-regulated gene 1, E-cadherin, and downregulation of cyclooxygenase-2; (vii) inhibition of c-Src tyrosine kinase. In conclusion, a thiol reduction devoid of toxicity as that operated by NAC apparently leads to terminal differentiation of normal and cancer cells through a pleiade of converging mechanisms, many of which are targets of the recently developed differentiation therapy
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