375 research outputs found

    Rhizostoma optimization algorithm and its application in different real-world optimization problems

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    In last decade, numerous meta-heuristic algorithms have been proposed for dealing the complexity and difficulty of numerical optimization problems in the realworld which is growing continuously recently, but only a few algorithms have caught researchers’ attention. In this study, a new swarm-based meta-heuristic algorithm called Rhizostoma optimization algorithm (ROA) is proposed for solving the optimization problems based on simulating the social movement of Rhizostoma octopus (barrel jellyfish) in the ocean. ROA is intended to mitigate the two optimization problems of trapping in local optima and slow convergence. ROA is proposed with three different movement strategies (simulated annealing (SA), fast simulated annealing (FSA), and Levy walk (LW)) and tested with 23 standard mathematical benchmark functions, two classical engineering problems, and various real-world datasets including three widely used datasets to predict the students’ performance. Comparing the ROA algorithm with the latest meta-heuristic optimization algorithms and a recent published research proves that ROA is a very competitive algorithm with a high ability in optimization performance with respect to local optima avoidance, the speed of convergence and the exploration/exploitation balance rate, as it is effectively applicable for performing optimization tasks

    Integrin α2β1 Expression Regulates Matrix Metalloproteinase-1-Dependent Bronchial Epithelial Repair in Pulmonary Tuberculosis.

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    Pulmonary tuberculosis (TB) is caused by inhalation of Mycobacterium tuberculosis, which damages the bronchial epithelial barrier to establish local infection. Matrix metalloproteinase-1 plays a crucial role in the immunopathology of TB, causing breakdown of type I collagen and cavitation, but this collagenase is also potentially involved in bronchial epithelial repair. We hypothesized that the extracellular matrix (ECM) modulates M. tuberculosis-driven matrix metalloproteinase-1 expression by human bronchial epithelial cells (HBECs), regulating respiratory epithelial cell migration and repair. Medium from monocytes stimulated with M. tuberculosis induced collagenase activity in bronchial epithelial cells, which was reduced by ~87% when cells were cultured on a type I collagen matrix. Matrix metalloproteinase-1 had a focal localization, which is consistent with cell migration, and overall secretion decreased by 32% on type I collagen. There were no associated changes in the specific tissue inhibitors of metalloproteinases. Decreased matrix metalloproteinase-1 secretion was due to ligand-binding to the α2β1 integrin and was dependent on the actin cytoskeleton. In lung biopsies, samples from patients with pulmonary TB, integrin α2β1 is highly expressed on the bronchial epithelium. Areas of lung with disrupted collagen matrix showed an increase in matrix metalloproteinases-1 expression compared with areas where collagen was comparable to control lung. Type I collagen matrix increased respiratory epithelial cell migration in a wound-healing assay, and this too was matrix metalloproteinase-dependent, since it was blocked by the matrix metalloproteinase inhibitor GM6001. In summary, we report a novel mechanism by which α2β1-mediated signals from the ECM modulate matrix metalloproteinase-1 secretion by HBECs, regulating their migration and epithelial repair in TB

    Fluid Flows of Mixed Regimes in Porous Media

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    In porous media, there are three known regimes of fluid flows, namely, pre-Darcy, Darcy and post-Darcy. Because of their different natures, these are usually treated separately in literature. To study complex flows when all three regimes may be present in different portions of a same domain, we use a single equation of motion to unify them. Several scenarios and models are then considered for slightly compressible fluids. A nonlinear parabolic equation for the pressure is derived, which is degenerate when the pressure gradient is either small or large. We estimate the pressure and its gradient for all time in terms of initial and boundary data. We also obtain their particular bounds for large time which depend on the asymptotic behavior of the boundary data but not on the initial one. Moreover, the continuous dependence of the solutions on initial and boundary data, and the structural stability for the equation are established.Comment: 33 page

    Efficacy of combined phenotypic methods for methicillin-resistant Staphylococcus aureus detection and antibiotic susceptibility

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    Background: The main aim of our study is to demonstrate comparative evaluation of oxacillin disc diffusion (ODD), oxacillin screen agar (OSA), CHROM agar (CA) with cefoxitin disc diffusion (CDD) method for the detection of methicillin-resistant Staphylococcus aureus obtained from various clinical samples.Methods: This prospective study was conducted to detect Methicillin resistance among staphylococcus aureus by four phenotypic methods isolated from various clinical samples received in the Department of microbiology MMIMSR, Mullana.Results: The data was statistically analyzed, compiled in form of tables, graphs, percentage and test of significance will also be done wherever necessary (using Microsoft Excel, 2008 version) CDD+ODD+OSA+CA proved to be 100% followed by ODD+OSA+CA and CDD+OSA+CA 82.07% and CDD+ODD+OSA 80.1%.Conclusions: Combined phenotypic methods are better in evaluating and studying MRSA infections in hospitals as compared to tests done in isolation for proper diagnosis and timely treatment of infections

    Nitrogenase MoFe-Protein at 1.16 Å Resolution: A Central Ligand in the FeMo-Cofactor

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    A high-resolution crystallographic analysis of the nitrogenase MoFe-protein reveals a previously unrecognized ligand coordinated to six iron atoms in the center of the catalytically essential FeMo-cofactor. The electron density for this ligand is masked in structures with resolutions lower than 1.55 angstroms, owing to Fourier series termination ripples from the surrounding iron and sulfur atoms in the cofactor. The central atom completes an approximate tetrahedral coordination for the six iron atoms, instead of the trigonal coordination proposed on the basis of lower resolution structures. The crystallographic refinement at 1.16 angstrom resolution is consistent with this newly detected component being a light element, most plausibly nitrogen. The presence of a nitrogen atom in the cofactor would have important implications for the mechanism of dinitrogen reduction by nitrogenase

    Repurposing proteins for new bioinorganic functions

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    Inspired by the remarkable sophistication and complexity of natural metalloproteins, the field of protein design and engineering has traditionally sought to understand and recapitulate the design principles that underlie the interplay between metals and protein scaffolds. Yet, some recent efforts in the field demonstrate that it is possible to create new metalloproteins with structural, functional and physico-chemical properties that transcend evolutionary boundaries. This essay aims to highlight some of these efforts and draw attention to the ever-expanding scope of bioinorganic chemistry and its new connections to synthetic biology, biotechnology, supramolecular chemistry and materials engineering

    Evidence for involvement of non‐classical pathways in the protection from UV‐induced DNA damage by vitamin D‐related compounds

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    The vitamin D hormone, 1,25dihydroxyvitamin D3 (1,25(OH)2D3), and related compounds derived from vitamin D3 or lumisterol as a result of metabolism via the enzyme CYP11A1, have been shown, when applied 24 hours before or immediately after UV irradiation, to protect human skin cells and skin from DNA damage due to UV exposure, by reducing both cyclobutane pyrimidine dimers (CPD) and oxidative damage in the form of 8‐oxo‐7,8‐dihydro‐2’‐ deoxyguanosine (8‐OHdG). We now report that knockdown of either the vitamin D receptor or the endoplasmic reticulum protein ERp57 by siRNA abolished the reductions in UV‐induced DNA damage with 20‐hydroxyvitamin D3 or 24‐hydroxylumisterol3, as previously shown for 1,25(OH)2D3. Treatment with 1,25(OH)2D3 reduced oxygen consumption rates in UV‐exposed and sham‐exposed human keratinocytes and reduced phosphorylation of CREB (cyclic AMP response binding element protein). Both these actions have been shown to inhibit skin carcinogenesis after chronic UV exposure, consistent with the anticarcinogenic activity of 1,25(OH)2D3. The requirement for a vitamin D receptor for the photoprotective actions of 1,25(OH)2D3 and of naturally occurring CYP11A1‐derived vitamin D related compounds may explain why mice lacking the vitamin D receptor in skin are more susceptible to UV‐induced skin cancers, whereas mice lacking the 1α‐hydroxylase and thus unable to make 1,25(OH)2D3 are not more susceptible. This article is protected by copyright. All rights reserved

    The toxicity of angiotensin converting enzyme inhibitors to larvae of the disease vectors Aedes aegypti and Anopheles gambiae

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    The control of mosquitoes is threatened by the appearance of insecticide resistance and therefore new control chemicals are urgently required. Here we show that inhibitors of mosquito peptidyl dipeptidase, a peptidase related to mammalian angiotensin-converting enzyme (ACE), are insecticidal to larvae of the mosquitoes, Aedes aegypti and Anopheles gambiae. ACE inhibitors (captopril, fosinopril and fosinoprilat) and two peptides (trypsin-modulating oostatic factor/TMOF and a bradykinin-potentiating peptide, BPP-12b) were all inhibitors of the larval ACE activity of both mosquitoes. Two inhibitors, captopril and fosinopril (a pro-drug ester of fosinoprilat), were tested for larvicidal activity. Within 24 h captopril had killed >90% of the early instars of both species with 3rd instars showing greater resistance. Mortality was also high within 24 h of exposure of 1st, 2nd and 3rd instars of An. gambiae to fosinopril. Fosinopril was also toxic to Ae. aegypti larvae, although the 1st instars appeared to be less susceptible to this pro-drug even after 72 h exposure. Homology models of the larval An. gambiae ACE proteins (AnoACE2 and AnoACE3) reveal structural differences compared to human ACE, suggesting that structure-based drug design offers a fruitful approach to the development of selective inhibitors of mosquito ACE enzymes as novel larvicides
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