112 research outputs found

    Understanding lean implementation: Perspectives and approaches of an American construction organisation

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    Lean, its principles and implementation rationale are characteristically interpreted as a means to reduce waste and increase productivity. Representation of the approach is typically supported by deductive perspectives. Deductive representations of the decision rationale underpinning lean implementation in construction organisations is cause for concern; particularly in understanding culturally the principles guiding lean implementation and the impact on management, contractual relationships and the organisational environment. A qualitative methodological and inductive approach encompassing face-to-face and focus group interviews has been used to explore lean rationale, implementation and practice within a singular in-depth case study. The analysis of the case has identified two further emerging lean perspectives and approaches of lean implementation that assist in addressing cultural neglect within lean theory. The first is the implementation of lean as means to establish efficient, effective and meaningful industry and contracting relationships. The second is the implementation of lean as a means to improve internal organisational and managerial practice. The study highlights the importance and need to understand the lean implementation process within construction organisations culturally rather than a process of tool implementation versus cultural change

    Swift trust and commitment: the missing links for humanitarian supply chain coordination?

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    Coordination among actors in a humanitarian relief supply chain decides whether a relief operation can be or successful or not. In humanitarian supply chains, due to the urgency and importance of the situation combined with scarce resources, actors have to coordinate and trust each other in order to achieve joint goals. This paper investigated empirically the role of swift trust as mediating variable for achieving supply chain coordination. Based on commitment-trust theory we explore enablers of swift-trust and how swift trust translates into coordination through commitment. Based on a path analytic model we test data from the National Disaster Management Authority of India. Our study is the first testing commitment-trust theory (CTT) in the humanitarian context, highlighting the importance of swift trust and commitment for much thought after coordination. Furthermore, the study shows that information sharing and behavioral uncertainty reduction act as enablers for swift trust. The study findings offer practical guidance and suggest that swift trust is a missing link for the success of humanitarian supply chains

    FLI1 Induces Plaque Psoriasis and Its Inhibition Attenuates Disease Progression

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    Maoting Hu,1,2 Kunlin Yu,1,2 Chunlin Wang,1,2 Wuling Liu,1,2 Anling Hu,1,2 Yi Kuang,1,2 Babu Gajendran,3 Eldad Zacksenhaus,4 Giulio Sartori,5 Francesco Bertoni,5,6 Xiao Xiao,1,2 Yaacov Ben-David1,2 1State Key Laboratory of Discovery and Utilization of Functional Components in Traditional Chinese Medicine, Guizhou Medical University, Guiyang, 550014, People’s Republic of China; 2The Natural Products Research Center of Guizhou Province, Guiyang, Guizhou, People’s Republic of China; 3School of Pharmaceutical Sciences, Guizhou Medical University, Guiyang, Guizhou Province, 550025, People’s Republic of China; 4Division of Advanced Diagnostics, Toronto General Research Institute, University Health Network, Toronto, Ontario, Canada; 5Institute of Oncology Research, Faculty of Biomedical Sciences, USI, Bellinzona, Switzerland; 6Oncology Institute of Southern Switzerland, Ente Ospedaliero Cantonale, Bellinzona, SwitzerlandCorrespondence: Yaacov Ben-David; Xiao Xiao, Email [email protected]; [email protected] Psoriasis: Plaque psoriasis is an inflammatory skin disorder affecting nearly 2% of the world population. Despite recent advances in psoriasis treatment, there is still a need for more effective therapies. The ETS transcription factor FLI1 plays critical roles in hematopoiesis, angiogenesis, immunity, and cancer. Emerging evidence suggests that FLI1 is intricately involved in inflammatory processes underlying psoriasis pathogenesis.Methods: RNAseq and bioinformatic analysis were used to identify the correlation between FLI1 levels and the expression of inflammatory genes associated with psoriasis. Over-expression of FLI1 in skin cells determined FLI1’s role in inducing transcription of psoriasis-related inflammatory genes, including IL6, IL1A, IL1B, IL23, and TNFα. Inhibitors such as chelerythrine (CLT) were tested for their suppressive effects on these genes. Mouse models of plaque psoriasis were employed to assess the therapeutic potential of CLT and tacrolimus (TAC).Results: Over-expression of FLI1 in skin cells upregulated 24 psoriasis-associated genes, which were identified through RNAseq. Inhibitors of FLI1, such as CLT, suppressed these inflammatory genes in skin cells. In mouse models of plaque psoriasis induced by imiquimod (IMQ) or phorbol ester (TPA), treatment with the anti-FLI1 inhibitor CLT, administered either peritoneally or topically, significantly downregulated inflammatory genes and alleviated psoriasis symptoms. Similarly, TAC, a common immunosuppressive agent, effectively attenuated IMQ-induced psoriasis by acting as a potent anti-FLI1 compound.Conclusion: These findings demonstrate that FLI1 plays a central role in psoriasis development and highlight it as a potential therapeutic target for this skin disorder. Keywords: psoriasis, FLI1, protein kinase C, inflammation markers, inhibitors, chelerythrin

    The Comprehensive Phytopathogen Genomics Resource: a web-based resource for data-mining plant pathogen genomes

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    The Comprehensive Phytopathogen Genomics Resource (CPGR) provides a web-based portal for plant pathologists and diagnosticians to view the genome and trancriptome sequence status of 806 bacterial, fungal, oomycete, nematode, viral and viroid plant pathogens. Tools are available to search and analyze annotated genome sequences of 74 bacterial, fungal and oomycete pathogens. Oomycete and fungal genomes are obtained directly from GenBank, whereas bacterial genome sequences are downloaded from the A Systematic Annotation Package (ASAP) database that provides curation of genomes using comparative approaches. Curated lists of bacterial genes relevant to pathogenicity and avirulence are also provided. The Plant Pathogen Transcript Assemblies Database provides annotated assemblies of the transcribed regions of 82 eukaryotic genomes from publicly available single pass Expressed Sequence Tags. Data-mining tools are provided along with tools to create candidate diagnostic markers, an emerging use for genomic sequence data in plant pathology. The Plant Pathogen Ribosomal DNA (rDNA) database is a resource for pathogens that lack genome or transcriptome data sets and contains 131 755 rDNA sequences from GenBank for 17 613 species identified as plant pathogens and related genera

    Innovative Capability of Building Information Modeling in Construction Design

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    The construction industry has long been urged to innovate, but innovation has been elusive because of the inherent social and organizational complexity of construction. Therefore, developing insight into the practice of innovating is needed to better understand and perform innovation in construction. Focusing on the practice of innovating requires exploring the enabling capability of solutions for practitioners to establish novel ways of doing things for improvement, referred to as ‘innovative capability.’ Building information modeling (BIM) has been promoted as an enabler of innovation in construction design because of its data management capabilities and the opportunities for interdisciplinary work based on them. Nevertheless, previous work presents divergent results exploring what BIM technologies can do for people and what people can actually do in BIM-enabled design practices, which presents confusion about the innovative capability of BIM. This paper aims to establish the basis of this confusion as a necessary step in developing more realistic ways of assessing and exploiting this capability. A conceptual continuum is proposed based on the functionalist/technology-centered and nonfunctionalist/human-centered perspectives on BIM to consider divergent arguments about its innovative capability; this continuum is used to analyze empirical findings from BIM-enabled design practices. The analyses suggest that individuals use BIM but are confused about its innovative capability because they adopt different views of BIM depending on their job and perspective. Given this, innovation is held back by the unexpressed differences between the views of BIM adopted by various practitioners who have to work together. It is argued that recognizing these differences, and working toward their reconciliation, is the way forward in establishing and exploiting the innovative capability of BIM

    Transcriptome of Aphanomyces euteiches: New Oomycete Putative Pathogenicity Factors and Metabolic Pathways

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    Aphanomyces euteiches is an oomycete pathogen that causes seedling blight and root rot of legumes, such as alfalfa and pea. The genus Aphanomyces is phylogenically distinct from well-studied oomycetes such as Phytophthora sp., and contains species pathogenic on plants and aquatic animals. To provide the first foray into gene diversity of A. euteiches, two cDNA libraries were constructed using mRNA extracted from mycelium grown in an artificial liquid medium or in contact to plant roots. A unigene set of 7,977 sequences was obtained from 18,864 high-quality expressed sequenced tags (ESTs) and characterized for potential functions. Comparisons with oomycete proteomes revealed major differences between the gene content of A. euteiches and those of Phytophthora species, leading to the identification of biosynthetic pathways absent in Phytophthora, of new putative pathogenicity genes and of expansion of gene families encoding extracellular proteins, notably different classes of proteases. Among the genes specific of A. euteiches are members of a new family of extracellular proteins putatively involved in adhesion, containing up to four protein domains similar to fungal cellulose binding domains. Comparison of A. euteiches sequences with proteomes of fully sequenced eukaryotic pathogens, including fungi, apicomplexa and trypanosomatids, allowed the identification of A. euteiches genes with close orthologs in these microorganisms but absent in other oomycetes sequenced so far, notably transporters and non-ribosomal peptide synthetases, and suggests the presence of a defense mechanism against oxidative stress which was initially characterized in the pathogenic trypanosomatids

    LRRK2 Biology from structure to dysfunction: research progresses, but the themes remain the same

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    Since the discovery of leucine-rich repeat kinase 2 (LRRK2) as a protein that is likely central to the aetiology of Parkinson's disease, a considerable amount of work has gone into uncovering its basic cellular function. This effort has led to the implication of LRRK2 in a bewildering range of cell biological processes and pathways, and probable roles in a number of seemingly unrelated medical conditions. In this review we summarise current knowledge of the basic biochemistry and cellular function of LRRK2. Topics covered include the identification of phosphorylation substrates of LRRK2 kinase activity, in particular Rab proteins, and advances in understanding the activation of LRRK2 kinase activity via dimerisation and association with membranes, especially via interaction with Rab29. We also discuss biochemical studies that shed light on the complex LRRK2 GTPase activity, evidence of roles for LRRK2 in a range of cell signalling pathways that are likely cell type specific, and studies linking LRRK2 to the cell biology of organelles. The latter includes the involvement of LRRK2 in autophagy, endocytosis, and processes at the trans-Golgi network, the endoplasmic reticulum and also key microtubule-based cellular structures. We further propose a mechanism linking LRRK2 dimerisation, GTPase function and membrane recruitment with LRRK2 kinase activation by Rab29. Together these data paint a picture of a research field that in many ways is moving forward with great momentum, but in other ways has not changed fundamentally. Many key advances have been made, but very often they seem to lead back to the same places

    P-dist Based Regularized Twin Support Vector Machine on Imbalanced Binary Dataset

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