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31.
D.R. Santos‐Peñate C.M. Campos‐Rodríguez J.A. Moreno‐Pérez 《International Transactions in Operational Research》2019,26(1):340-363
The ‐centroid problem or leader–follower problem is generalized considering different customer choice rules where a customer may use facilities belonging to different firms, if the difference in travel distance (or time) is small enough. Assuming essential goods, some particular customer choice rules are analyzed. Linear programming formulations for the generalized ‐medianoid and ‐centroid problems are presented and an exact solution approach is applied. Some computational examples are included. 相似文献
32.
Myriam Gonzlez María Ovejero-Snchez Alba Vicente-Blzquez Raquel lvarez Ana B. Herrero Manuel Medarde Rogelio Gonzlez-Sarmiento Rafael Pelez 《International journal of molecular sciences》2021,22(4)
Pan-Gyn cancers entail 1 in 5 cancer cases worldwide, breast cancer being the most commonly diagnosed and responsible for most cancer deaths in women. The high incidence and mortality of these malignancies, together with the handicaps of taxanes—first-line treatments—turn the development of alternative therapeutics into an urgency. Taxanes exhibit low water solubility that require formulations that involve side effects. These drugs are often associated with dose-limiting toxicities and with the appearance of multi-drug resistance (MDR). Here, we propose targeting tubulin with compounds directed to the colchicine site, as their smaller size offer pharmacokinetic advantages and make them less prone to MDR efflux. We have prepared 52 new Microtubule Destabilizing Sulfonamides (MDS) that mostly avoid MDR-mediated resistance and with improved aqueous solubility. The most potent compounds, N-methyl-N-(3,4,5-trimethoxyphenyl-4-methylaminobenzenesulfonamide 38, N-methyl-N-(3,4,5-trimethoxyphenyl-4-methoxy-3-aminobenzenesulfonamide 42, and N-benzyl-N-(3,4,5-trimethoxyphenyl-4-methoxy-3-aminobenzenesulfonamide 45 show nanomolar antiproliferative potencies against ovarian, breast, and cervix carcinoma cells, similar or even better than paclitaxel. Compounds behave as tubulin-binding agents, causing an evident disruption of the microtubule network, in vitro Tubulin Polymerization Inhibition (TPI), and mitotic catastrophe followed by apoptosis. Our results suggest that these novel MDS may be promising alternatives to taxane-based chemotherapy in chemoresistant Pan-Gyn cancers. 相似文献
33.
Andrés Aguirre Matías Cabruja Rodolfo Cabrera Florencia Eberhardt Salvador Peirú Hugo G. Menzella Rodolfo M. Rasia 《Journal of the American Oil Chemists' Society》2015,92(1):47-53
Steryl glucosides (SG) are common contaminants in biodiesel that form precipitates, which form and cause problems due to fouling during transport and storage. Therefore, their quantification is necessary to assess the quality of this fuel. The methods currently available for SG analysis require expensive instrumentation, need a previous concentration step by solid‐phase extraction (SPE) or are of limited use for the quantitative assessment. We developed an enzymatic method for SG quantification in biodiesel samples based on the hydrolysis of the glucoside catalyzed by a broadly specific beta glucosidase and the subsequent determination of the glucose released by the reaction. The method is non‐expensive, sensitive and was adapted to 96‐well format fluorescence plate reader, making it useful for the parallel assay of multiple samples. The enzymatic assay presented here represent a valuable tool for both quality control and the development of improved biodiesel production and purification procedures. 相似文献
34.
Electrochemical impedance spectroscopy (EIS), anodic polarization and scanning electron microscopy techniques were used to investigate the damage mechanism in the transpassive potential region of AISI ... 相似文献
35.
36.
Anna Potocki Mathilde Chailleux Manuel Gimenes Jean Pylouster 《Journal of Computer Assisted Learning》2021,37(5):1324-1335
Many studies have demonstrated the crucial role of vocabulary in predicting reading performance in general. More recent work has indicated that one particular facet of vocabulary (its depth) is more closely related to language comprehension, especially inferential comprehension. On this basis, we developed a training application to specifically improve vocabulary depth. The objective of this study was to test the effectiveness of a mobile application designed to improve vocabulary depth. The effectiveness of this training was examined on 3rd and 4th grade children's vocabulary (breadth and depth), decoding and comprehension performances. A randomized waiting-list control paradigm was used in which an experimental group first received the intervention during the first 4 weeks (between pretest and post-test1), thereafter, a waiting control group received the training for the next 4 weeks (between postest1 and posttest2). Results showed that the developed application led to significant improvements in terms of vocabulary depth performance, as well as a significant transfer effect to reading comprehension. However, we did not observe such a beneficial effect on either vocabulary breadth or written word identification. These results are discussed in terms of the links between vocabulary depth and comprehension, and the opportunities the app presents for remedying language comprehension deficits in children. 相似文献
37.
Bill Robert Fleck Martin Troya Javier Mayerhofer Tanja Wimmer Manuel 《Software and Systems Modeling》2019,18(2):1017-1046
Software and Systems Modeling - Many model transformation scenarios require flexible execution strategies as they should produce models with the highest possible quality. At the same time,... 相似文献
38.
Dr. Emilianne M. Limbrick Audrey E. Yñigez-Gutierrez Callie C. Dulin Dagmara K. Derewacz Dr. Jeffrey M. Spraggins Dr. Kathryn M. McCulloch Prof. T. M. Iverson Prof. Brian O. Bachmann 《Chembiochem : a European journal of chemical biology》2020,21(23):3349-3358
Everninomicins are orthoester oligosaccharide antibiotics with potent activity against multidrug-resistant bacterial pathogens. Everninomicins act by disrupting ribosomal assembly in a distinct region in comparison to clinically prescribed drugs. We employed microporous intergeneric conjugation with Escherichia coli to manipulate Micromonospora for targeted gene-replacement studies of multiple putative methyltransferases across the octasaccharide scaffold of everninomicin effecting the A1, C, F, and H rings. Analyses of gene-replacement and genetic complementation mutants established the mutability of the everninomicin scaffold through the generation of 12 previously unreported analogues and, together with previous results, permitted assignment of the ten methyltransferases required for everninomicin biosynthesis. The in vitro activity of A1- and H-ring-modifying methyltransferases demonstrated the ability to catalyze late-stage modification of the scaffold on an A1-ring phenol and H-ring C-4’ hydroxy moiety. Together these results establish the potential of the everninomicin scaffold for modification through mutagenesis and in vitro modification of advanced biosynthetic intermediates. 相似文献
39.
Jasmin Kuhn Philipp M. Klein Nader Al Danaf Joel Z. Nordin Sren Reinhard Dominik M. Loy Miriam Hhn Samir El Andaloussi Don C. Lamb Ernst Wagner Yoshitsugu Aoki Taavi Lehto Ulrich Lchelt 《Advanced functional materials》2019,29(48)
Phosphorodiamidate morpholino oligomers (PMOs) are oligonucleotide analogs that can be used for therapeutic modulation of pre‐mRNA splicing. Similar to other classes of nucleic acid‐based therapeutics, PMOs require delivery systems for efficient transport to the intracellular target sites. Here, artificial peptides based on the oligo(ethylenamino) acid succinyl‐tetraethylenpentamine (Stp), hydrophobic modifications, and an azide group are presented, which are used for strain‐promoted azide‐alkyne cycloaddition conjugation with splice‐switching PMOs. By systematically varying the lead structure and formulation, it is determined that the type of contained fatty acid and supramolecular assembly have a critical impact on the delivery efficacy. A compound containing linolenic acid with three cis double bonds exhibits the highest splice‐switching activity and significantly increases functional protein expression in pLuc/705 reporter cells in vitro and after local administration in vivo. Structural and mechanistic studies reveal that the lipopeptide PMO conjugates form nanoparticles, which accelerate cellular uptake and that the content of unsaturated fatty acids enhances endosomal escape. In an in vitro Duchenne muscular dystrophy exon skipping model using H2K‐mdx52 dystrophic skeletal myotubes, the highly potent PMO conjugates mediate significant splice‐switching at very low nanomolar concentrations. The presented aminoethylene‐lipopeptides are thus a promising platform for the generation of PMO‐therapeutics with a favorable activity/toxicity profile. 相似文献
40.
Medel Manuel L. Zulueta Donala Janreddy Shang-Cheng Hung 《Israel journal of chemistry》2015,55(3-4):347-359
In recent years, there has been rapid expansion of glycan synthesis, fueled by the recognition that the structural complexity of sugars translates to a myriad of biological functions. Such chemical syntheses involve many challenges, mostly due to the regio- and stereochemical aspects of glycosidic bond formation. One-pot strategies were developed to assist in attaining faster and more economical access to the glycan constructs. In this front, achievements in protecting group manipulation, glycosylation, and combinations of these have been reported. Protecting group manipulations in one pot take advantage of the reaction compatibility of commonly used transformations, many of which occur in high regioselectivity. Sequential glycosylations, on the other hand, rely on leaving group orthogonalities and reactivity tuning, as well as the preactivation technique. Altogether, these approaches offer attractive means to the much needed glycan structures and, consequently, help usher in advances in glycoscience. 相似文献