1,922 research outputs found

    SIMULATION AND MODELLING OF RAID 0 SYSTEM PERFORMANCE

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    RAID systems are fundamental components of modern storage infrastructures. It is therefore important to model their performance effectively. This paper describes a simulation model which predicts the cumulative distribution function of I/O request response time in a RAID 0 system consisting of homogeneous zoned disk drives. The model is constructed in a bottom-up manner, starting by abstracting a single disk drive as an M/G/1 queue. This is then extended to model a RAID 0 system using a split-merge queueing network. Simulation results of I/O request response time for RAID 0 systems with various numbers of disks are computed and compared against device measurements

    Motivated proteins: a web application for studying small three-dimensional protein motifs

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    <b>BACKGROUND:</b> Small loop-shaped motifs are common constituents of the three-dimensional structure of proteins. Typically they comprise between three and seven amino acid residues, and are defined by a combination of dihedral angles and hydrogen bonding partners. The most abundant of these are alphabeta-motifs, asx-motifs, asx-turns, beta-bulges, beta-bulge loops, beta-turns, nests, niches, Schellmann loops, ST-motifs, ST-staples and ST-turns.We have constructed a database of such motifs from a range of high-quality protein structures and built a web application as a visual interface to this. <b>DESCRIPTION:</b> The web application, Motivated Proteins, provides access to these 12 motifs (with 48 sub-categories) in a database of over 400 representative proteins. Queries can be made for specific categories or sub-categories of motif, motifs in the vicinity of ligands, motifs which include part of an enzyme active site, overlapping motifs, or motifs which include a particular amino acid sequence. Individual proteins can be specified, or, where appropriate, motifs for all proteins listed. The results of queries are presented in textual form as an (X)HTML table, and may be saved as parsable plain text or XML. Motifs can be viewed and manipulated either individually or in the context of the protein in the Jmol applet structural viewer. Cartoons of the motifs imposed on a linear representation of protein secondary structure are also provided. Summary information for the motifs is available, as are histograms of amino acid distribution, and graphs of dihedral angles at individual positions in the motifs. <b>CONCLUSION:</b> Motivated Proteins is a publicly and freely accessible web application that enables protein scientists to study small three-dimensional motifs without requiring knowledge of either Structured Query Language or the underlying database schem

    Insufficient activity of MAPK pathway is a key monitor of Kidney-Yang Deficiency Syndrome.

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    OBJECTIVE: To explore the genetic characteristics and molecular regulator of Kidney-Yang Deficiency Syndrome (KDS). DESIGN: A typical KDS family was collected using a questionnaire of cold feeling and a 40-item scoring table of KDS based on Traditional Chinese Medicine (TCM), by single-blind method repeated annually over three years. Their transcriptomes were assayed by microarray and validated by RT-PCR and ELISA. Simultaneously, 10 healthy volunteers were recruited as controls and the same protocols were performed. RESULTS: This typical KDS family has 35 members, of whom 11 were evaluated as having severe KDS and 6 as having common KDS. Results of the cDNA microarray revealed that there were 420 genes/expressed sequence tags differentially expressed in KDS transcriptomes, indicating a global functional impairment in the mass-energy-information carrying network of KDS patients, involving energy metabolism, signal transduction, development, cell cycle, and immunity. Pathway analysis by gene set enrichment assay (GSEA) and other tools demonstrated that mitogenic activated protein kinase (MAPK) is among the most insufficiently activated pathways, while the oxidative phosphorylation and glycolysis/gluconeogenesis pathways, the two main pathways relevant to ATP synthesis, were among the most excessively activated pathways in KDS patients. Results of RT-PCR and ELISA confirmed the status of insufficient activity of the MAPK pathway. CONCLUSION: KDS patients undergo overall attenuated functions in the mass-energy-information carrying network. The marked low level of energy output in KDS may be primarily attributed to the insufficient activity of the MAPK pathway, which may be a key monitor for the abnormal energy metabolism and other impaired activities in KDS.published_or_final_versio

    Expression and Function of Macrophage Migration Inhibitory Factor (MIF) in Melioidosis

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    Melioidosis is a severe tropical infection caused by the bacterium Burkholderia pseudomallei. B. pseudomallei is the major cause of community-acquired septicemia in northeast Thailand with a mortality rate in severe cases of around 40% Little is known, however, about the mechanisms of the host defense to B. pseudomallei infection. Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine that has emerged as an important mediator of the host defense in severe bacterial infections. In this article, we studied the expression and function of MIF both in patients with melioidosis and in mice during experimental melioidosis. We found that MIF concentrations were elevated in patients with melioidosis. Furthermore, high MIF concentrations are associated with poor outcome in patients with melioidosis. Also, in mice with experimentally induced melioidosis, we observed an upregulation of MIF concentrations. Furthermore, mice with melioidosis that were treated with a MIF blocking treatment showed lower bacterial counts in their lungs during infection. In conclusion, MIF seems to impair host defense mechanisms during melioidosis

    MyD88 Dependent Signaling Contributes to Protective Host Defense against Burkholderia pseudomallei

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    Background: Toll-like receptors (TLRs) have a central role in the recognition of pathogens and the initiation of the innate immune response. Myeloid differentiation primary-response gene 88 (MyD88) and TIR-domain-containing adaptor protein inducing IFNb (TRIF) are regarded as the key signaling adaptor proteins for TLRs. Melioidosis, which is endemic in SE-Asia, is a severe infection caused by the gram-negative bacterium Burkholderia pseudomallei. We here aimed to characterize the role of MyD88 and TRIF in host defense against melioidosis. Methodology and Principal Findings: First, we found that MyD88, but not TRIF, deficient whole blood leukocytes released less TNFa upon stimulation with B. pseudomallei compared to wild-type (WT) cells. Thereafter we inoculated MyD88 knockout (KO), TRIF mutant and WT mice intranasally with B. pseudomallei and found that MyD88 KO, but not TRIF mutant mice demonstrated a strongly accelerated lethality, which was accompanied by significantly increased bacterial loads in lungs, liver and blood, and grossly enhanced liver damage compared to WT mice. The decreased bacterial clearance capacity of MyD88 KO mice was accompanied by a markedly reduced early pulmonary neutrophil recruitment and a diminished activation of neutrophils after infection with B. pseudomallei. MyD88 KO leukocytes displayed an unaltered capacity to phagocytose and kill B. pseudomallei in vitro. Conclusions: MyD88 dependent signaling, but not TRIF dependent signaling, contributes to a protective host respons

    A systematic review of the evidence for single stage and two stage revision of infected knee replacement

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    BACKGROUND: Periprosthetic infection about the knee is a devastating complication that may affect between 1% and 5% of knee replacement. With over 79 000 knee replacements being implanted each year in the UK, periprosthetic infection (PJI) is set to become an important burden of disease and cost to the healthcare economy. One of the important controversies in treatment of PJI is whether a single stage revision operation is superior to a two-stage procedure. This study sought to systematically evaluate the published evidence to determine which technique had lowest reinfection rates. METHODS: A systematic review of the literature was undertaken using the MEDLINE and EMBASE databases with the aim to identify existing studies that present the outcomes of each surgical technique. Reinfection rate was the primary outcome measure. Studies of specific subsets of patients such as resistant organisms were excluded. RESULTS: 63 studies were identified that met the inclusion criteria. The majority of which (58) were reports of two-stage revision. Reinfection rated varied between 0% and 41% in two-stage studies, and 0% and 11% in single stage studies. No clinical trials were identified and the majority of studies were observational studies. CONCLUSIONS: Evidence for both one-stage and two-stage revision is largely of low quality. The evidence basis for two-stage revision is significantly larger, and further work into direct comparison between the two techniques should be undertaken as a priority

    Blockade of insulin-like growth factors increases efficacy of paclitaxel in metastatic breast cancer.

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    Breast cancer remains the leading cause of cancer death in women owing to metastasis and the development of resistance to established therapies. Macrophages are the most abundant immune cells in the breast tumor microenvironment and can both inhibit and support cancer progression. Thus, gaining a better understanding of how macrophages support cancer could lead to the development of more effective therapies. In this study, we find that breast cancer-associated macrophages express high levels of insulin-like growth factors 1 and 2 (IGFs) and are the main source of IGFs within both primary and metastatic tumors. In total, 75% of breast cancer patients show activation of insulin/IGF-1 receptor signaling and this correlates with increased macrophage infiltration and advanced tumor stage. In patients with invasive breast cancer, activation of Insulin/IGF-1 receptors increased to 87%. Blocking IGF in combination with paclitaxel, a chemotherapeutic agent commonly used to treat breast cancer, showed a significant reduction in tumor cell proliferation and lung metastasis in pre-clinical breast cancer models compared to paclitaxel monotherapy. Our findings provide the rationale for further developing the combination of paclitaxel with IGF blockers for the treatment of invasive breast cancer, and Insulin/IGF1R activation and IGF+ stroma cells as potential biomarker candidates for further evaluation

    Requirements for an Intelligent Maintenance System for Industry 4.0

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    comprobación paso "titulo publicación " - Service Oriented, Holonic and Multi-agent Manufacturing Systems for Industry of the Future[EN] Recent advances in the development of technological devices and software for Industry 4.0 have pushed a change in the maintenance management systems and processes. Nowadays, in order to maintain a company competitive, a computerised management system is required to help in its maintenance tasks. This paper presents an analysis of the complexities and requirements for maintenance of Industry 4.0. It focuses on intelligent systems that can help to improve the intelligent management of maintenance. Finally, it presents a summary of lessons learned specified as guidelines for the design of such intelligent systems that can be applied horizontally to any company in the Industry.This work is supported by the FEDER/Ministry of Science, Innovation and Universities - State Research Agency RTC-2017-6401-7Garcia, E.; Araujo, A.; Palanca Cámara, J.; Giret Boggino, AS.; Julian Inglada, VJ.; Botti, V. (2019). Requirements for an Intelligent Maintenance System for Industry 4.0. Springer. 340-351. https://doi.org/10.1007/978-3-030-27477-1_26S340351CEN, European Committee for Standardization: EN 13306:2017. Maintenance Terminology. European Standard (2017)Chen, B., Wan, J., Shu, L., Li, P., Mukherjee, M., Yin, B.: Smart factory of Industry 4.0: key technologies, application case, and challenges. IEEE Access 6, 6505–6519 (2018). https://doi.org/10.1109/access.2017.2783682Crespo Marquez, A., Gupta, J.N.: Contemporary maintenance management: process, framework and supporting pillars. Omega 34(3), 313–326 (2006). https://doi.org/10.1016/j.omega.2004.11.003Ferreira, L.L., Albano, M., Silva, J., Martinho, D., Marreiros, G., di Orio, G., Malo, P., Ferreira, H.: A pilot for proactive maintenance in Industry 4.0. In: 2017 IEEE 13th International Workshop on Factory Communication Systems (WFCS). IEEE (2017). https://doi.org/10.1109/wfcs.2017.7991952Goh, K., Tjahjono, B., Baines, T., Subramaniam, S.: A review of research in manufacturing prognostics. In: 2006 IEEE International Conference on Industrial Informatics, Singapore, pp. 417–422. IEEE (2006). https://doi.org/10.1109/INDIN.2006.275836Hashemian, H.M., Bean, W.C.: State-of-the-art predictive maintenance techniques. IEEE Trans. Instrum. Meas. 60(10), 3480–3492 (2011). https://doi.org/10.1109/TIM.2009.2036347Lee, W.J., Wu, H., Yun, H., Kim, H., Jun, M.B., Sutheralnd, J.W.: Predictive maintenance of machine tool systems using artificial intelligence techniques applied to machine condition data. Procedia CIRP 80, 506–511 (2019)Lu, B., Durocher, D., Stemper, P.: Predictive maintenance techniques. IEEE Ind. Appl. Mag. 15(6), 52–60 (2009). https://doi.org/10.1109/MIAS.2009.934444Mrugalska, B., Wyrwicka, M.K.: Towards lean production in Industry 4.0. Procedia Eng. 182, 466–473 (2017). https://doi.org/10.1016/j.proeng.2017.03.135O’Donoghue, C., Prendergast, J.: Implementation and benefits of introducing a computerised maintenance management system into a textile manufacturing company. J. Mater. Process. Technol. 153, 226–232 (2004)Paolanti, M., Romeo, L., Felicetti, A., Mancini, A., Frontoni, E., Loncarski, J.: Machine learning approach for predictive maintenance in Industry 4.0. In: 2018 14th IEEE/ASME International Conference on Mechatronic and Embedded Systems and Applications (MESA). IEEE (2018). https://doi.org/10.1109/mesa.2018.8449150Patil, R.B., Mhamane, D.A., Kothavale, P.B., Kothavale, B.: Fault tree analysis: a case study from machine tool industry. Available at SSRN 3382241 (2018)Potes Ruiz, P.A., Kamsu-Foguem, B., Noyes, D.: Knowledge reuse integrating the collaboration from experts in industrial maintenance management. Knowl. Based Syst. 50, 171–186 (2013). https://doi.org/10.1016/j.knosys.2013.06.005Razmi-Farooji, A., Kropsu-Vehkaperä, H., Härkönen, J., Haapasalo, H.: Advantages and potential challenges of data management in e-maintenance. J. Qual. Maint. Eng. (2019)Rüßmann, M., Lorenz, M., Gerbert, P., Waldner, M., Justus, J., Harnisch, M.: Industry 4.0: the future of productivity and growth in manufacturing industries. Boston Consult. Group 9(1), 54–89 (2015)Wan, J., Tang, S., Li, D., Wang, S., Liu, C., Abbas, H., Vasilakos, A.V.: A manufacturing big data solution for active preventive maintenance. IEEE Trans. Ind. Inform. 13(4), 2039–2047 (2017). https://doi.org/10.1109/tii.2017.267050
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