2,433 research outputs found

    Developing a Tailored RBS Linking to BIM for Risk Management of Bridge Projects

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    Purpose – The purpose of this paper is to address the current theoretical gap in integrating knowledge and experience into Building Information Model (BIM) for risk management of bridge projects by developing a tailored Risk Breakdown Structure (RBS) and formalising an active link between the resulting RBS and BIM. Design/methodology/approach – A three-step approach is used in this study to develop a tailored RBS for bridge projects and a conceptual model for the linkage between the RBS and BIM. First, the integrated bridge information model is in concept separated into four levels of contents (LOCs) and six technical systems based on analysis of the Industry Foundation Classes specification, a critical review of previous studies and authors’ project experience. The second step develops a knowledge-based risk database through an extensive collection of risk data, a process of data mining, and further assessment and translation of data. A critical analysis is conducted in the last step to determine on which level the different risks should be allocated to bridge projects and to propose a conceptual model for linking the tailored RBS to the four LOCs and six technical systems of BIM. Findings – The findings suggest that the traditional method and BIM can be merged as an integrated solution for risk management by establishing the linkage between RBS and BIM. This solution can take advantage of both the traditional method and BIM for managing risks. On the one hand, RBS enables risk information to be stored in a formal structure, used and communicated effectively. On the other hand, some features of BIM such as 3D visualisation and 4D construction scheduling can facilitate the risk identification, analysis, and communication at an early project stage. Research limitations/implications – A limitation is that RBS is a qualitative technique and only plays a limited role in quantitative risk analysis. As a result, when implementing this proposed method, further techniques may be needed for assisting quantitative risk analysis, evaluation, and treatment. Another limitation is that the proposed method has not yet been implemented for validation in practice. Hence, recommendations for future research are to: improve the quantitative risk analysis and treatment capabilities of this proposed solution; develop computer tools to support the solution; integrate the linkage into a traditional workflow; and test this solution in some small and large projects for validation. Practical implications – Through linking risk information to BIM, project participants could check and review the linked information for identifying potential risks and seeking possible mitigation measures, when project information is being transferred between different people or forwarded to the next phase. Originality/value – This study contributes to the theoretical development for aligning traditional methods and BIM for risk management, by introducing a new conceptual model for linking RBS to BIM

    Medicated Janus fibers fabricated using a Teflon-coated side-by-side spinneret.

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    A family of medicated Janus fibers that provides highly tunable biphasic drug release was fabricated using a side-by-side electrospinning process employing a Teflon-coated parallel spinneret. The coated spinneret facilitated the formation of a Janus Taylor cone and in turn high quality integrated Janus structures, which could not be reliably obtained without the Teflon coating. The fibers prepared had one side consisting of polyvinylpyrrolidone (PVP) K60 and ketoprofen, and the other of ethyl cellulose (EC) and ketoprofen. To modulate and tune drug release, PVP K10 was doped into the EC side in some cases. The fibers were linear and had flat morphologies with an indent in the center. They provide biphasic drug release, with the PVP K60 side dissolving very rapidly to deliver a loading dose of the active ingredient, and the EC side resulting in sustained release of the remaining ketoprofen. The addition of PVP K10 to the EC side was able to accelerate the second stage of release; variation in the dopant amount permitted the release rate and extent this phase to be precisely tuned. These results offer the potential to rationally design systems with highly controllable drug release profiles, which can complement natural biological rhythms and deliver maximum therapeutic effects

    Design of Electronic Nose Detection System for Apple Quality Grading Based on Computational Fluid Dynamics Simulation and K-Nearest Neighbor Support Vector Machine

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    Apples are one of the most widely planted fruits in the world, with an extremely high annual production. Several issues should be addressed to avoid the damaging of samples during the quality grading process of apples (e.g., the long detection period and the inability to detect the internal quality of apples). In this study, an electronic nose (e-nose) detection system for apple quality grading based on the K-nearest neighbor support vector machine (KNN-SVM) was designed, and the nasal cavity structure of the e-nose was optimized by computational fluid dynamics (CFD) simulation. A KNN-SVM classifier was also proposed to overcome the shortcomings of the traditional SVMs. The performance of the developed device was experimentally verified in the following steps. The apples were divided into three groups according to their external and internal quality. The e-nose data were pre-processed before features extraction, and then Principal Component Analysis (PCA) and Linear Discriminant Analysis (LDA) were used to reduce the dimension of the datasets. The recognition accuracy of the PCA–KNN-SVM classifier was 96.45%, and the LDA–KNN-SVM classifier achieved 97.78%. Compared with other commonly used classifiers, (traditional KNN, SVM, Decision Tree, and Random Forest), KNN-SVM is more efficient in terms of training time and accuracy of classification. Generally, the apple grading system can be used to evaluate the quality of apples during storage

    Celecoxib exerts protective effects in the vascular endothelium via COX-2-independent activation of AMPK-CREB-Nrf2 signalling

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    Although concern remains about the athero-thrombotic risk posed by cyclo-oxygenase (COX)-2-selective inhibitors, recent data implicates rofecoxib, while celecoxib appears equivalent to NSAIDs naproxen and ibuprofen. We investigated the hypothesis that celecoxib activates AMP kinase (AMPK) signalling to enhance vascular endothelial protection. In human arterial and venous endothelial cells (EC), and in contrast to ibuprofen and naproxen, celecoxib induced the protective protein heme oxygenase-1 (HO-1). Celecoxib derivative 2,5-dimethyl-celecoxib (DMC) which lacks COX-2 inhibition also upregulated HO-1, implicating a COX-2-independent mechanism. Celecoxib activated AMPKα(Thr172) and CREB-1(Ser133) phosphorylation leading to Nrf2 nuclear translocation. Importantly, these responses were not reproduced by ibuprofen or naproxen, while AMPKα silencing abrogated celecoxib-mediated CREB and Nrf2 activation. Moreover, celecoxib induced H-ferritin via the same pathway, and increased HO-1 and H-ferritin in the aortic endothelium of mice fed celecoxib (1000 ppm) or control chow. Functionally, celecoxib inhibited TNF-α-induced NF-κB p65(Ser536) phosphorylation by activating AMPK. This attenuated VCAM-1 upregulation via induction of HO-1, a response reproduced by DMC but not ibuprofen or naproxen. Similarly, celecoxib prevented IL-1β-mediated induction of IL-6. Celecoxib enhances vascular protection via AMPK-CREB-Nrf2 signalling, a mechanism which may mitigate cardiovascular risk in patients prescribed celecoxib. Understanding NSAID heterogeneity and COX-2-independent signalling will ultimately lead to safer anti-inflammatory drugs

    Phenoloxidase activity acts as a mosquito innate immune response against infection with semliki forest virus

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    Several components of the mosquito immune system including the RNA interference (RNAi), JAK/STAT, Toll and IMD pathways have previously been implicated in controlling arbovirus infections. In contrast, the role of the phenoloxidase (PO) cascade in mosquito antiviral immunity is unknown. Here we show that conditioned medium from the Aedes albopictus-derived U4.4 cell line contains a functional PO cascade, which is activated by the bacterium Escherichia coli and the arbovirus Semliki Forest virus (SFV) (Togaviridae; Alphavirus). Production of recombinant SFV expressing the PO cascade inhibitor Egf1.0 blocked PO activity in U4.4 cell- conditioned medium, which resulted in enhanced spread of SFV. Infection of adult female Aedes aegypti by feeding mosquitoes a bloodmeal containing Egf1.0-expressing SFV increased virus replication and mosquito mortality. Collectively, these results suggest the PO cascade of mosquitoes plays an important role in immune defence against arboviruses

    Clinical course, therapeutic responses and outcomes in relapsing MOG antibody-associated demyelination.

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    Abstract OBJECTIVE: We characterised the clinical course, treatment and outcomes in 59 patients with relapsing myelin oligodendrocyte glycoprotein (MOG) antibody-associated demyelination. METHODS: We evaluated clinical phenotypes, annualised relapse rates (ARR) prior and on immunotherapy and Expanded Disability Status Scale (EDSS), in 218 demyelinating episodes from 33 paediatric and 26 adult patients. RESULTS: The most common initial presentation in the cohort was optic neuritis (ON) in 54% (bilateral (BON) 32%, unilateral (UON) 22%), followed by acute disseminated encephalomyelitis (ADEM) (20%), which occurred exclusively in children. ON was the dominant phenotype (UON 35%, BON 19%) of all clinical episodes. 109/226 (48%) MRIs had no brain lesions. Patients were steroid responsive, but 70% of episodes treated with oral prednisone relapsed, particularly at doses <10\u2009mg daily or within 2 months of cessation. Immunotherapy, including maintenance prednisone (P=0.0004), intravenous immunoglobulin, rituximab and mycophenolate, all reduced median ARRs on-treatment. Treatment failure rates were lower in patients on maintenance steroids (5%) compared with non-steroidal maintenance immunotherapy (38%) (P=0.016). 58% of patients experienced residual disability (average follow-up 61 months, visual loss in 24%). Patients with ON were less likely to have sustained disability defined by a final EDSS of 652 (OR 0.15, P=0.032), while those who had any myelitis were more likely to have sustained residual deficits (OR 3.56, P=0.077). CONCLUSION: Relapsing MOG antibody-associated demyelination is strongly associated with ON across all age groups and ADEM in children. Patients are highly responsive to steroids, but vulnerable to relapse on steroid reduction and cessation

    Mitotic Spindle Orients Perpendicular to the Forces Imposed by Dynamic Shear

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    Orientation of the division axis can determine cell fate in the presence of morphogenetic gradients. Understanding how mitotic cells integrate directional cues is therefore an important question in embryogenesis. Here, we investigate the effect of dynamic shear forces on confined mitotic cells. We found that human epithelial cells (hTERT-RPE1) as well as MC3T3 osteoblasts align their mitotic spindle perpendicular to the external force. Spindle orientation appears to be a consequence of cell elongation along the zero-force direction in response to the dynamic shear. This process is a nonlinear response to the strain amplitude, requires actomyosin activity and correlates with redistribution of myosin II. Mechanosteered cells divide normally, suggesting that this mechanism is compatible with biological functions

    The Escherichia coli transcriptome mostly consists of independently regulated modules

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    Underlying cellular responses is a transcriptional regulatory network (TRN) that modulates gene expression. A useful description of the TRN would decompose the transcriptome into targeted effects of individual transcriptional regulators. Here, we apply unsupervised machine learning to a diverse compendium of over 250 high-quality Escherichia coli RNA-seq datasets to identify 92 statistically independent signals that modulate the expression of specific gene sets. We show that 61 of these transcriptomic signals represent the effects of currently characterized transcriptional regulators. Condition-specific activation of signals is validated by exposure of E. coli to new environmental conditions. The resulting decomposition of the transcriptome provides: a mechanistic, systems-level, network-based explanation of responses to environmental and genetic perturbations; a guide to gene and regulator function discovery; and a basis for characterizing transcriptomic differences in multiple strains. Taken together, our results show that signal summation describes the composition of a model prokaryotic transcriptome
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