•Finite element model updating (FEMU) problem is formulated and further implemented as a game theory problem.•Three different game models (non-cooperative, cooperative and evolutionary) have been ...considered to cope with FEMU problem.•The performance (accuracy and simulation time) of the different game models has been compared when they are implemented to perform the FEMU of a laboratory footbridge.•Direct determination of the optimal solution for the FEMU problem reducing the simulation time (it is not necessary either to compute the Pareto front or to solve the subsequent decision-making problem) without compromising the accuracy of the solution.
Finite element modelling is performed to numerically predict the behaviour of civil engineering structures. Due to the different assumptions adopted during the modelling phase, this initial model does not always reflect adequately the actual structural behaviour. In this context, the results of experimental structural dynamic properties can be used to improve initial numerical model via the implementation of the so-called finite element model updating method. After this process, the updated model better reflects the actual structural behaviour. Due to its simplicity, for practical engineering applications, the updating process is usually performed considering the maximum likelihood method. According to this approach, the updating problem may be formulated as the combination of two sub-problems: (i) a bi-objective optimization sub-problem; and (ii) a decision-making sub-problem. The bi-objective function is usually defined in terms of the residuals between the experimental and numerical modal properties. As optimization method, nature-inspired computational algorithms have been usually considered due to their high efficiency to cope with non-linear optimization problems. Despite this extensive use, this method presents two main limitations: (i) the high simulation time required to compute the Pareto optimal front; and (ii) the necessity of solving a subsequent decision making problem (the selection of the best solution among the different elements of the Pareto front). In order to overcome these limitations, in this paper game theory has been adopted as computational tool to improve the performance of the updating process. For this purpose, the updating problem has been re-formulated as a game theory problem considering three different game models: (i) non-cooperative; (ii) cooperative; and (iii) evolutionary. Finally, the performance of proposal has been assessed when it is implemented for the model updating of a laboratory footbridge. As result of this study, game theory has been shown up as efficient tool to improve the performance of the updating process under the maximum likelihood method since it allows a direct estimation of the solution reducing the simulation time without compromising the accuracy of the result.
In vibration serviceability checks of footbridges, a force induced by a single person walking is usually modelled as a harmonic force having a frequency that matches one of the footbridge natural ...frequencies. This approach assumes that, among the infinite number of harmonics a walking force is composed of, only a single harmonic is important for a vibration serviceability check. Another usual assumption is that the footbridge can be modelled as an SDOF system, implying that only vibration in a single mode is of interest. In addition, due to the deterministic nature of this approach, it cannot take into account inter- and intra-subject variabilities in the walking force that are now well documented in the literature. To account for these variabilities, a novel probabilistic approach to carry out a vibration serviceability check is developed in this paper. Factors such as the probability distribution of walking frequencies, step lengths and amplitude of walking force for its five lowest harmonics and subharmonics are taken into account. Using walking force time histories measured on a treadmill, the frequency content of the force was investigated, resulting in the formulation of a multi-harmonic force model. This model can be used to estimate the multi-mode response in footbridges. This was verified successfully on an as-built catenary footbridge structure. Although only the vibration response of footbridges was analysed in this paper, the force model proposed has the potential to be implemented in the estimation of floor vibration as well, where multi-mode response occurs more frequently. The model is easily programmable and as such could present a powerful tool for estimating efficiently the probability of various levels of vibration response due to single person walking. Therefore, the proposed probability-based methodology has the potential to revolutionise the philosophy of the current codes of practice dealing with vibration serviceability of structures under human-induced vibration.
Aryl Hydrocarbon Receptor (AHR) ligands, upon binding, induce distinct gene expression profiles orchestrated by the AHR, leading to a spectrum of pro- or anti-inflammatory effects. In this study, we ...designed, synthesized and evaluated three indole-containing potential AHR ligands (FluoAHRL: AGT-4, AGT-5 and AGT-6). All synthesized compounds were shown to emit fluorescence in the near-infrared. Their AHR agonist activity was first predicted using in silico docking studies, and then confirmed using AHR luciferase reporter cell lines. FluoAHRLs were tested in vitro using mouse peritoneal macrophages and T lymphocytes to assess their immunomodulatory properties. We then focused on AGT-5, as it illustrated the predominant anti-inflammatory effects. Notably, AGT-5 demonstrated the ability to foster anti-inflammatory regulatory T cells (Treg) while suppressing pro-inflammatory T helper (Th)17 cells in vitro. AGT-5 actively induced Treg differentiation from naïve CD4+ cells, and promoted Treg proliferation, cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) expression and interleukin-10 (IL-10) production. The increase in IL-10 correlated with an upregulation of Signal Transducer and Activator of Transcription 3 (STAT3) expression. Importantly, the Treg-inducing effect of AGT-5 was also observed in human tonsil cells in vitro. AGT-5 showed no toxicity when applied to zebrafish embryos and was therefore considered safe for animal studies. Following oral administration to C57BL/6 mice, AGT-5 significantly upregulated Treg while downregulating pro-inflammatory Th1 cells in the mesenteric lymph nodes. Due to its fluorescent properties, AGT-5 could be visualized both in vitro (during uptake by macrophages) and ex vivo (within the lamina propria of the small intestine). These findings make AGT-5 a promising candidate for further exploration in the treatment of inflammatory and autoimmune diseases.
This study aimed to compare the biological properties of newly synthesized cements based on calcium phosphate with a commercially used cement, mineral trioxide aggregate (MTA). Strontium (Sr)-, ...Copper (Cu)-, and Zinc (Zn)-doped hydroxyapatite (miHAp) powder was obtained through hydrothermal synthesis and characterized by scanning electron microscopy (SEM), X-ray diffraction (XRD), and energy dispersive X-ray spectrometry (EDX). Calcium phosphate cement (CPC) was produced by mixing miHAp powder with a 20 wt.% citric acid solution, followed by the assessment of its compressive strength, setting time, and in vitro bioactivity. Acetylsalicylic acid (ASA) was added to the CPC, resulting in CPCA. Biological tests were conducted on CPC, CPCA, and MTA. The biocompatibility of the cement extracts was evaluated in vitro using human dental pulp stem cells (hDPSCs) and in vivo using a zebrafish model. Antibiofilm and antimicrobial effect (quantified by CFUs/mL) were assessed against Streptococcus mutans and Lactobacillus rhamnosus. None of the tested materials showed toxicity, while CPCA even increased hDPSCs proliferation. CPCA showed a better safety profile than MTA and CPC, and no toxic or immunomodulatory effects on the zebrafish model. CPCA exhibited similar antibiofilm effects against S. mutans and L. rhamnosus to MTA.
Over 80 hands-on recipes to improve your skills in project management, team management, process improvement, and Redmine administration About This Book * Efficiently install and customize Redmine for ...your own infrastructure, whether that be Microsoft or open source * Manage multiple projects with multiple teams across the globe in a standardized and effective way * Customize Redmine to fit your organisation's specific and unique needs Who This Book Is For This book is for those who working in management or administrator positions who are already using Redmine or are willing to start using it for project management, tracking, collaboration, or process management. Additionally, individual developers or teams can benefit from recipes related to code repositories, bug tracking, and software project management. What You Will Learn * Make Redmine run on Microsoft SQL Server with IIS * Enjoy the benefits of updating the code on a real-time basis and maintaining consistency * Manage multiple projects and teams simultaneously * Leverage Redmine features to enhance team's performance * Use Redmine for SCRUM and Agile methodologies * Deploy Redmine for Service Desk * Customize the user experience by manually tracking the ongoing projects * Extend Redmine through various plugins In Detail In a variety of online project management tools, Redmine markets itself as offering flexibility. Choosing the right management tool can mean the difference between the success and failure of a project. Flexible project management tools bend themselves to fit your needs, whether that's communication regarding a simple project, or collaboration, or more complex project methodology such as SCRUM, or an issue-code relationship, or the need of different methodology for your project. Whether you are project manager or system administrator, this book provides valuable recipes to get the best possible performance out of your team, organization, infrastructure, and Redmine itself. Through a series of carefully crafted recipes covering the nitty-gritty of Redmine, you'll be guided through the installation of Redmine, as well as how to fine-tune and customize your Redmine installation. Finally, we walk you through integrating Redmine with other softwares and databases like Tortoise SVN and Visual Studio and troubleshooting Redmine. Style and approach This book follows a step-by-step recipe-based approach. Detailed prerequisites make each recipe easy to follow and apply in practice in any kind of live environment.
Apart from cytotoxicity, inhibitors of the COX-2 enzyme have demonstrated additional effects important for cancer treatment (such as radiosensitization of tumor cells and cell antimigratory effects); ...however, the relationship between the inhibition of other inflammation-related enzyme 5-LOX inhibitors and anticancer activity is still not well understood. In our study, the cytotoxicity of thirteen COX-2 and 5-LOX inhibitors previously presented by our group (1–13) was tested on three cancer cell lines (HCT 116, HT-29 and BxPC-3) and one healthy cell line (MRC-5). Compounds 3, 5, 6 and 7 showed moderate cytotoxicity, but good selectivity towards cancer cell lines. IC50 values were in the range of 22.99–51.66 µM (HCT 116 cell line), 8.63–41.20 µM (BxPC-3 cell line) and 24.78–81.60 µM (HT-29 cell line; compound 7 > 100 µM). In comparison to tested, commercially available COX-2 and 5-LOX inhibitors, both cytotoxicity and selectivity were increased. The addition of compounds 6 and 7 to irradiation treatment showed the most significant decrease in cell proliferation of the HT-29 cell line (p < 0.001). The antimigratory potential of the best dual COX-2 and 5-LOX inhibitors (compounds 1, 2, 3 and 5) was tested by a wound-healing assay using the SW620 cell line. Compounds 1 and 3 were singled out as compounds with the most potent effect (relative wound closure was 3.20% (24 h), 5,08% (48 h) for compound 1 and 3.86% (24 h), 7.68% (48 h) for compound 3). Considering all these results, compound 3 stood out as the compound with the most optimal biological activity, with the best dual COX-2 and 5-LOX inhibitory activity, good selectivity towards tested cancer cell lines, significant cell antimigratory potential and a lack of toxic effects at therapeutic doses.
The research into modeling walking-induced dynamic loading and its effects on footbridge structures and people using them has been intensified in the past decade after some high profile vibration ...serviceability failures. In particular, the crowd induced loading, characterized by spatially restricted movement of pedestrians, has kept attracting attention of researchers. However, it is the normal spatially unrestricted pedestrian traffic, and its vertical dynamic loading component, that is the most relevant for vibration serviceability checks for most footbridges. Despite the existence of numerous design procedures concerned with this loading, the current confidence in its modeling is low due to lack of verification of the models on as-built structures. This is the motivation behind reviewing the existing design procedures for modeling normal pedestrian traffic in this paper and evaluating their performance against the experimental data acquired on two as-built footbridges. Additionally, the use of Monte Carlo simulations is also investigated. Possible factors that cause discrepancies between measured and calculated vibration responses, including possibility of existence of pedestrian-structure dynamic interaction, are discussed.
We describe the preparation, dynamic, assembly characteristics of vase‐shaped basket 13− along with its ability to form an inclusion complex with anticancer drug mitoxantrone in abiotic and biotic ...systems. This novel cavitand has a deep nonpolar pocket consisting of three naphthalimide sides fused to a bicyclic platform at the bottom while carrying polar glycines at the top. The results of 1H Nuclear Magnetic Resonance (NMR), 1H NMR Chemical Exchange Saturation Transfer (CEST), Calorimetry, Hybrid Replica Exchange Molecular Dynamics (REMD), and Microcrystal Electron Diffraction (MicroED) measurements are in line with 1 forming dimer 126−, to be in equilibrium with monomers 1(R)3− (relaxed) and 1(S)3− (squeezed). Through simultaneous line‐shape analysis of 1H NMR data, kinetic and thermodynamic parameters characterizing these equilibria were quantified. Basket 1(R)3− includes anticancer drug mitoxantrone (MTO2+) in its pocket to give stable binary complex MTO⊂1− (Kd=2.1 μM) that can be precipitated in vitro with UV light or pH as stimuli. Both in vitro and in vivo studies showed that the basket is nontoxic, while at a higher proportion with respect to MTO it reduced its cytotoxicity in vitro. With well‐characterized internal dynamics and dimerization, the ability to include mitoxantrone, and biocompatibility, the stage is set to develop sequestering agents from deep‐cavity baskets.
Deep‐cavity baskets are novel, accessible, modular, and biocompatible hosts. With intriguing conformational dynamics, assembly characteristics and great capacity to bind anticancer drug mitoxantrone, deep‐cavity baskets hold promise for developing antidotes as a countermeasure against a broad range of aromatic toxicants in complex biological systems.
Wild Meripilus giganteus Karst belongs to the order Polyporales, in which some members are known to possess a wide range of pharmacological properties. M. giganteus showed to be rich in carbohydrates ...(74.49 g/100 g) and proteins (15.94 g/100 g), presenting low fat content (1.51 g/100 g). Chemical composition was determined by using chromatographic techniques. Also, various bioactive compounds were detected including all four tocopherol isoforms with δ- and γ-tocopherols being predominant (123.35 and 77.80 μg/100 g, respectively); five organic acids (oxalic, malic, quinic, citric and fumaric acids) with predominant malic acid (3.17 g/100 g); and three phenolic acids and related compounds (p-hydroxybenzoic, p-coumaric and cinnamic acids; 1010, 2420 and 340 μg/100 g, respectively). M. giganteus methanolic extract exhibited antioxidant activity tested by five different assays with the strongest potential in TBARS assay (EC50 0.31 mg/mL); and antimicrobial activities (MIC/MBC 0.0125–5 mg/mL; MIC/MFC 0.025–0.4 mg/mL). Furthermore, treatment of cervical carcinoma cell line (HeLa) led to reduction in cell's viability in MTT assay (IC50 0.41 mg/mL after 48 h), induced process of apoptosis and inhibited cell's migration in vitro. The analysed extract was not toxic for zebrafish embryos (at 0.5 mg/mL), indicating its biosafety and potential application as a dietary supplement in chemoprevention.
•M. giganteus showed to be rich in carbohydrates and proteins, with low fat content.•Tocopherols, five organic acids and three phenolic acids were identified.•M. giganteus extract exhibited antioxidant and antimicrobial activity.•M. giganteus extract reduced cancer cells viability and induced apoptosis.•M. giganteus extract inhibited migration of cancer cells in vitro.
Monitoring natural human gait in real-life environments is essential in many applications, including quantification of disease progression, monitoring the effects of treatment, and monitoring ...alteration of performance biomarkers in professional sports. Nevertheless, developing reliable and practical techniques and technologies necessary for continuous real-life monitoring of gait is still an open challenge. A systematic review of English-language articles from scientific databases including Scopus, ScienceDirect, Pubmed, IEEE Xplore, EBSCO and MEDLINE were carried out to analyse the 'accuracy' and 'practicality' of the current techniques and technologies for quantitative measurement of the tri-axial walking ground reactions outside the laboratory environment, and to highlight their strengths and shortcomings. In total, 679 relevant abstracts were identified, 54 full-text papers were included in the paper and the quantitative results of 17 papers were used for meta-analysis and comparison. Three classes of methods were reviewed: (1) methods based on measured kinematic data; (2) methods based on measured plantar pressure; and (3) methods based on direct measurement of ground reactions. It was found that all three classes of methods have competitive accuracy levels with methods based on direct measurement of the ground reactions showing highest accuracy while being least practical for long-term real-life measurement. On the other hand, methods that estimate ground reactions using measured body kinematics show highest practicality of the three classes of methods reviewed. Among the most prominent technical and technological challenges are: (1) reducing the size and price of tri-axial load-cells; (2) improving the accuracy of orientation measurement using IMUs; (3) minimizing the number and optimizing the location of required IMUs for kinematic measurement; (4) increasing the durability of pressure insole sensors, and (5) enhancing the robustness and versatility of the ground reactions estimation methods to include pathological gaits and natural variability of gait in real-life physical environment.
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