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1.
Johan Revstedt 《国际流体数值方法杂志》2004,45(7):775-795
The flow around spherical, solid objects is considered. The boundary conditions on the solid boundaries have been applied by replacing the boundary with a surface force distribution on the surface, such that the required boundary conditions are satisfied. The velocity on the boundary is determined by extrapolation from the flow field. The source terms are determined iteratively, as part of the solution. They are then averaged and are smoothed out to nearby computational grid points. A multi‐grid scheme has been used to enhance the computational efficiency of the solution of the force equations. The method has been evaluated for flow around both moving and stationary spherical objects at very low and intermediate Reynolds numbers. The results shows a second order accuracy of the method both at creeping flow and at Re=100. The multi‐grid scheme is shown to enhance the convergence rate up to a factor 10 as compared to single grid approach. Copyright © 2004 John Wiley & Sons, Ltd. 相似文献
2.
J.-L. Hainaut V. Englebert J. Henrard J.-M. Hick D. Roland 《Applied Categorical Structures》1996,3(1-2):9-45
This paper analyzes the requirements that CASE tools should meet for effective database reverse engineering (DBRE), and proposes
a general architecture for data-centered applications reverse engineering CASE environments. First, the paper describes a
generic DBMS-independent DBRE methodology, then it analyzes the main characteristics of DBRE activities in order to collect
a set of desirable requirements. Finally, it describes DB-MAIN, an operational CASE tool developed according to these requirements.
The main features of this tool that are described in this paper are its unique generic specification model, its repository,
its transformation toolkit, its user interface, the text processors, the assistants, the methodological control and its functional
extensibility. Finally, the paper describes five real-world projects in which the methodology and the CASE tool were applied.
This is a heavily revised and extended version of “Requirements for Information System Reverse Engineering Support” by J.-L.
Hainaut, V. Englebert, J. Henrard, J.-M. Hick, D. Roland, which first appeared in the Proceedings of the Second Working Conference
on Reverse Engineering, IEEE Computer Society Press, pp. 136–145, July 1995. This paper presents some results of the DB-MAIN
project. This project is partially supported by the Région Wallonne, the European Union, and by a consortium comprising ACEC-OSI (Be), ARIANE-II (Be), Banque UCL (Lux), BBL (Be), Centre de recherche public H.
Tudor (Lux), CGER (Be), Cockerill-Sambre (Be), CONCIS (Fr), D'Ieteren (Be), DIGITAL, EDF (Fr), EPFL (CH), Groupe S (Be), IBM,
OBLOG Software (Port), ORIGIN (Be), Ville de Namur (Be), Winterthur (Be), 3 Suisses (Be). The DB-Process subproject is supported
by the Communauté Fran?aise de Belgique. 相似文献
3.
This paper presents the development and laboratory evaluation of a PM10/2.5/1.0 trichotomous sampling inlet that consists of two main parts: a previously designed PM10 size‐selective inlet part and a PM2.5/1.0 two‐stage virtual impactor, which was newly fabricated and attached serially to the PM10 size selective inlet part. Particles are collected in three locations through the trichotomous sampling inlet to provide for not only particle concentration measurements of PM10, PM2.5 and PM1.0, but also those of PM2.5–10 and PM1.0–2.5. 相似文献
4.
介绍了虚拟技术在实验教学改革中的作用与意义,探讨了电子信息系统实验教学改革的新思路与实现措施,并总结了实验教学改革的初步成果. 相似文献
5.
Mariyana Atanasova Ivan Dimitrov Stefan Ivanov Borislav Georgiev Strahil Berkov Dimitrina Zheleva-Dimitrova Irini Doytchinova 《Molecules (Basel, Switzerland)》2022,27(10)
Acetylcholinesterase (AChE) is one of the classical targets in the treatment of Alzheimer’s disease (AD). Inhibition of AChE slows down the hydrolysis of acetycholine and increases choline levels, improving the cognitive function. The achieved success of plant-based natural drugs acting as AChE inhibitors, such as galantamine (GAL) from Galanthus genus and huperzine A from Huperzia serrate (approved drug in China), in the treatment of AD, and the fact that natural compounds (NCs) are considered as safer and less toxic compared to synthetic drugs, led us to screen the available NCs (almost 150,000) in the ZINC12 database for AChE inhibitory activity. The compounds were screened virtually by molecular docking, filtered for suitable ADME properties, and 32 ligands from 23 structural groups were selected. The stability of the complexes was estimated via 1 μs molecular dynamics simulation. Ten compounds formed stable complexes with the enzyme and had a vendor and a reasonable price per mg. They were tested for AChE inhibitory and antioxidant activity. Five compounds showed weak AChE inhibition and three of them exhibited high antioxidant activity. 相似文献
6.
New Chemotypes for the Inhibition of (p)ppGpp Synthesis in the Quest for New Antimicrobial Compounds
Crescenzo Coppa Luca Sorrentino Monica Civera Marco Minneci Francesca Vasile Sara Sattin 《Molecules (Basel, Switzerland)》2022,27(10)
Antimicrobial resistance (AMR) poses a serious threat to our society from both the medical and economic point of view, while the antibiotic discovery pipeline has been dwindling over the last decades. Targeting non-essential bacterial pathways, such as those leading to antibiotic persistence, a bacterial bet-hedging strategy, will lead to new molecular entities displaying low selective pressure, thereby reducing the insurgence of AMR. Here, we describe a way to target (p)ppGpp (guanosine tetra- or penta-phosphate) signaling, a non-essential pathway involved in the formation of persisters, with a structure-based approach. A superfamily of enzymes called RSH (RelA/SpoT Homolog) regulates the intracellular levels of this alarmone. We virtually screened several fragment libraries against the (p)ppGpp synthetase domain of our RSH chosen model RelSeq, selected three main chemotypes, and measured their interaction with RelSeq by thermal shift assay and STD-NMR. Most of the tested fragments are selective for the synthetase domain, allowing us to select the aminobenzoic acid scaffold as a hit for lead development. 相似文献
7.
Yahya S. Alqahtani Sunil S. More Keerthana R. Ibrahim Ahmed Shaikh Anusha K. J. Veena S. More Francois N. Niyonzima Uday M. Muddapur Aejaz A. Khan 《Molecules (Basel, Switzerland)》2022,27(13)
Enzymes that degrade pectin are called pectinases. Pectinases of microbial origin are used in juice clarification as the process is cost-effective. This study screened a pectinase-producing bacterium isolated from soil and identified as Bacillus subtilis 15A B-92 based on the 16S rRNA molecular technique. The purified pectinase from the isolate showed 99.6 U/mg specific activity and 11.6-fold purity. The molecular weight of the purified bacterial pectinase was 14.41 ± 1 kD. Optimum pectinase activity was found at pH 4.5 and 50 °C, and the enzyme was 100% stable for 3.5 h in these conditions. No enzymatic inhibition or activation effect was seen with Fe2+, Ca2+, or Mg2+. However, a slight inhibition was seen with Cu2+, Mn2+, and Zn2+. Tween 20 and 80 slightly inhibited the pectinase, whereas iodoacetic acid (IAA), ethylenediaminetetraacetate (EDTA), urea, and sodium dodecyl sulfate (SDS) showed potent inhibition. The bacterial pectinase degraded citrus pectin (100%); however, it was inactive in the presence of galactose. With citrus pectin as the substrate, the Km and Vmax were calculated as 1.72 mg/mL and 1609 U/g, respectively. The high affinity of pectinase for its substrate makes the process cost-effective when utilized in food industries. The obtained pectinase was able to clarify orange and apple juices, justifying its application in the food industry. 相似文献
8.
9.
Salvatore Galati Stefano Sainas Marta Giorgis Donatella Boschi Marco L. Lolli Gabriella Ortore Giulio Poli Tiziano Tuccinardi 《Molecules (Basel, Switzerland)》2022,27(12)
Human dihydroorotate dehydrogenase (hDHODH) is an enzyme belonging to a flavin mononucleotide (FMN)-dependent family involved in de novo pyrimidine biosynthesis, a key biological pathway for highly proliferating cancer cells and pathogens. In fact, hDHODH proved to be a promising therapeutic target for the treatment of acute myelogenous leukemia, multiple myeloma, and viral and bacterial infections; therefore, the identification of novel hDHODH ligands represents a hot topic in medicinal chemistry. In this work, we reported a virtual screening study for the identification of new promising hDHODH inhibitors. A pharmacophore-based approach combined with a consensus docking analysis and molecular dynamics simulations was applied to screen a large database of commercial compounds. The whole virtual screening protocol allowed for the identification of a novel compound that is endowed with promising inhibitory activity against hDHODH and is structurally different from known ligands. These results validated the reliability of the in silico workflow and provided a valuable starting point for hit-to-lead and future lead optimization studies aimed at the development of new potent hDHODH inhibitors. 相似文献
10.
Natlia Aniceto Vanda Marques Joana D. Amaral Patrícia A. Serra Rui Moreira Cecília M. P. Rodrigues Rita C. Guedes 《Molecules (Basel, Switzerland)》2022,27(15)
Necroptosis has emerged as an exciting target in oncological, inflammatory, neurodegenerative, and autoimmune diseases, in addition to acute ischemic injuries. It is known to play a role in innate immune response, as well as in antiviral cellular response. Here we devised a concerted in silico and experimental framework to identify novel RIPK1 inhibitors, a key necroptosis factor. We propose the first in silico model for the prediction of new RIPK1 inhibitor scaffolds by combining docking and machine learning methodologies. Through the data analysis of patterns in docking results, we derived two rules, where rule #1 consisted of a four-residue signature filter, and rule #2 consisted of a six-residue similarity filter based on docking calculations. These were used in consensus with a machine learning QSAR model from data collated from ChEMBL, the literature, in patents, and from PubChem data. The models allowed for good prediction of actives of >90, 92, and 96.4% precision, respectively. As a proof-of-concept, we selected 50 compounds from the ChemBridge database, using a consensus of both molecular docking and machine learning methods, and tested them in a phenotypic necroptosis assay and a biochemical RIPK1 inhibition assay. A total of 7 of the 47 tested compounds demonstrated around 20–25% inhibition of RIPK1’s kinase activity but, more importantly, these compounds were discovered to occupy new areas of chemical space. Although no strong actives were found, they could be candidates for further optimization, particularly because they have new scaffolds. In conclusion, this screening method may prove valuable for future screening efforts as it allows for the exploration of new areas of the chemical space in a very fast and inexpensive manner, therefore providing efficient starting points amenable to further hit-optimization campaigns. 相似文献