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1.
Profiling engineered data with robust mining methods continues attracting attention in knowledge engineering systems. The purpose of this article is to propose a simple technique that deals with non-linear multi-factorial multi-characteristic screening suitable for knowledge discovery studies. The method is designed to proactively seek and quantify significant information content in engineered mini-datasets. This is achieved by deploying replicated fractional-factorial sampling schemes. Compiled multi-response data are converted to a single master-response effectuated by a series of distribution-free transformations and multi-compressed data fusions. The resulting amalgamated master response is deciphered by non-linear multi-factorial stealth stochastics intended for saturated schemes. The stealth properties of our method target processing datasets which might be overwhelmed by a lack of knowledge about the nature of reference distributions at play. Stealth features are triggered to overcome restrictions regarding the data normality conformance, the effect sparsity assumption and the inherent collapse of the ‘unexplainable error’ connotation in saturated arrays. The technique is showcased by profiling four ordinary controlling factors that influence webpage content performance by collecting data from a commercial browser monitoring service on a large scale web host. The examined effects are: (1) the number of Cascading Style Sheets files, (2) the number of JavaScript files, (3) the number of Image files, and (4) the Domain Name System Aliasing. The webpage performance level was screened against three popular characteristics: (1) the time to first visual, (2) the total loading time, and (3) the customer satisfaction. Our robust multi-response data mining technique is elucidated for a ten-replicate run study dictated by an L9(34) orthogonal array scheme where any uncontrolled noise embedded contribution has not been necessarily excluded. 相似文献
2.
Henry Dring David Kreutzer Christoph Ritter Andreas Hilgeroth 《Molecules (Basel, Switzerland)》2021,26(1)
Despite the development of targeted therapies in cancer, the problem of multidrug resistance (MDR) is still unsolved. Most patients with metastatic cancer die from MDR. Transmembrane efflux pumps as the main cause of MDR have been addressed by developed inhibitors, but early inhibitors of the most prominent and longest known efflux pump P-glycoprotein (P-gp) were disappointing. Those inhibitors have been used without knowledge about the expression of P-gp by the treated tumor. Therefore the use of inhibitors of transmembrane efflux pumps in clinical settings is reconsidered as a promising strategy in the case of the respective efflux pump expression. We discovered novel symmetric inhibitors of the symmetric efflux pump MRP4 encoded by the ABCC4 gene. MRP4 is involved in many kinds of cancer with resistance to anticancer drugs. All compounds showed better activities than the best known MRP4 inhibitor MK571 in an MRP4-overexpressing cell line assay, and the activities could be related to the various substitution patterns of aromatic residues within the symmetric molecular framework. One of the best compounds was demonstrated to overcome the MRP4-mediated resistance in the cell line model to restore the anticancer drug sensitivity as a proof of concept. 相似文献
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Eco‐friendly ionic liquid assisted capillary electrophoresis and α‐acid glycoprotein‐assisted liquid chromatography for simultaneous determination of anticancer drugs in human fluids
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Deia Abd El‐Hady Hassan M. Albishri Rajesh Rengarajan 《Biomedical chromatography : BMC》2015,29(6):925-934
In the current work, two eco‐friendly analytical methods based on capillary electrophoresis (CE) and reversed phase liquid chromatography (RPLC) were developed for simultaneous determination of the most commonly used anticancer drugs for Hodgkin's disease: methotrexate (MTX), vinblastine, chlorambucil and dacarbazine. A background electrolyte (BGE) of 12.5 mmol/L phosphate buffer at pH 7.4 and 0.1 µmol/L 1‐butyl‐3‐methyl imidazolium bromide (BMImBr) ionic liquid (IL) was used for CE measurements at 250 nm detection wavelength, 20 kV applied voltage and 25 °C. The rinsing protocol was significantly improved to reduce the adsorption of IL on the interior surface of capillary. Moreover, RPLC method was developed on α‐1‐acid glycoprotein (AGP) column. Mobile phase was 10 mmol/L phosphate buffer at pH 6.0 (100% v/v) and flow rate at 0.1 mL/min. As AGP is a chiral column, it was successfully separated l ‐MTX from its enantiomer impurity d ‐MTX. Good linearity of quantitative analysis was achieved with coefficients of determinations (r2) >0.995. The stability of drugs measurements was investigated with adequate recoveries up to 24 h storage time under ambient temperature. The limits of detection were <50 and 90 ng/mL by CE and RPLC, respectively. The using of short‐chain IL as an additive in BGE achieved 600‐fold sensitivity enhancement compared with conventional Capillary Zone Electrophoresis (CZE). Therefore, for the first time, the proposed methods were successfully applied to determine simultaneously the analytes in human plasma and urine samples at clinically relevant concentrations with fast and simple pretreatments. Developed IL‐assisted CE and RPLC methods were also applied to measure MTX levels in patients’ samples over time. Copyright © 2014 John Wiley & Sons, Ltd. 相似文献
4.
The serine protease, DegP exhibits proteolytic and chaperone activities, essential for cellular protein quality control and normal cell development in eukaryotes. The P. falciparum DegP is essential for the parasite survival and required to combat the oscillating thermal stress conditions during the infection, protein quality checks and protein homeostasis in the extra-cytoplasmic compartments, thereby establishing it as a potential target for drug development against malaria. Previous studies have shown that diisopropyl fluorophosphate (DFP) and the peptide SPMFKGV inhibit E. coli DegP protease activity. To identify novel potential inhibitors specific to PfDegP allosteric and the catalytic binding sites, we performed a high throughput in silico screening using Malaria Box, Pathogen Box, Maybridge library, ChEMBL library and the library of FDA approved compounds. The screening helped identify five best binders that showed high affinity to PfDegP allosteric (T0873, T2823, T2801, , CD00811) and the catalytic binding site (T0078L, T1524, T2328, BTB11534 and 552691). Further, molecular dynamics simulation analysis revealed RJC02337, BTB11534 as the best hits forming a stable complex. WaterMap and electrostatic complementarity were used to evaluate the novel bio-isosteric chemotypes of RJC02337, that led to the identification of 231 chemotypes that exhibited better binding affinity. Further analysis of the top 5 chemotypes, based on better binding affinity, revealed that the addition of electron donors like nitrogen and sulphur to the side chains of butanoate group are more favoured than the backbone of butanoate group. In a nutshell, the present study helps identify novel, potent and Plasmodium specific inhibitors, using high throughput in silico screening and bio-isosteric replacement, which may be experimentally validated. RJC02337相似文献
5.
NMR screening techniques in drug discovery and drug design 总被引:7,自引:0,他引:7
Brian J. Stockman Claudio Dalvit 《Progress in Nuclear Magnetic Resonance Spectroscopy》2002,41(3-4):187-231
6.
The drawbacks of our earlier report of preparing fuel cell catalyst arrays by borohydride reduction of inkjet prepared arrays of metal salts are discussed along with the need for inclusion of state-of-the-art metrics in all array screening. An alternative method for screening of hydrogen/air cathode catalysts, direct methanol fuel cell (DMFC) anode catalysts, and catalyst loading studies is provided. State-of-the-art Johnson Matthey catalysts were used in control experiments to demonstrate the utility of the array fuel cell for high throughput screening of fuel cell catalysts in the 3-4 mg/cm2 range. This report lays out hard learned rules for high throughput screening and demonstrates that the array fuel cell can be used for very precise screening of libraries of membrane electrode assembly (MEA) components without the pitfalls discussed in the introduction. 相似文献
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The use of high-throughput techniques allowed the rapid identification of new catalysts for the enantioselective reduction of imines using polymethylhydrosiloxane (PMHS) as a reducing agent. By a simple modification of the chiral ligand structure that came out of the screening, the enantioselectivity of the reduction was increased from 40% ee to 60% ee. 相似文献
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