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1.
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
2.
Lorena Rodríguez-López Myriam Rincón-Fontán Xanel Vecino Ana B. Moldes Jose M. Cruz 《Journal of surfactants and detergents》2020,23(1):79-90
Over the last few years, the global biosurfactant market has raised due to the increasing awareness among consumers, for the use of biological or bio-based products. Because of their composition, it can be speculated that these are more biocompatible and more biodegradable than their chemical homologous. However, at the moment, no studies exist in the literature about the biodegradability of biosurfactants. In this work, a biosurfactant contained in a crude extract, obtained from a corn wet-milling industry stream that ferments spontaneously in the presence of lactic acid bacteria, was subjected to a biodegradation study, without addition of external microbial biomass, under different conditions of temperature (5–45 °C), biodegradation time (15–55 days), and pH (5–7). For that, a Box–Behnken factorial design was applied, which allowed to predict the percentage of biodegradation for the biosurfactant contained in the crude extract, between the range of the independent variables selected in the study, obtaining biodegradation values between 3 and 80%. The percentage of biodegradation for the biosurfactant was calculated based on the increase in the surface tension of samples of the crude extract. Furthermore, it was also possible to predict the variation in t1/2 for the biosurfactant (time to achieve the 50% of biodegradation) under different conditions. 相似文献
3.
Jean-Louis Havet Myriam Billiau-Loreau Catherine Porte Alain Delacroix 《Journal of Automated Methods and Management in Chemistry》2002,24(4):111-119
Chemometric tools were used to generate the modelling of solvent e inverted exclamation markects on the N-alkylation of an isocyanuric acid salt. The method proceeded from a central composite design applied on the Carlson solvent classification using principal components analysis. The selectivity of the reaction was studied from the production of different substituted isocyanuric derivatives. Response graphs were obtained for each compound and used to devise a strategy for solvent selection. The prediction models were validated and used to search for the best selectivity for the reaction system. The solvent most often selected as the best for the reaction is the N,N-dimethylformamide. 相似文献
4.
A pattern is a model or a template used to summarize and describe the behavior (or the trend) of data having generally some recurrent events. Patterns have received a considerable attention in recent years and were widely studied in the data mining field. Various pattern mining approaches have been proposed and used for different applications such as network monitoring, moving object tracking, financial or medical data analysis, scientific data processing, etc. In these different contexts, discovered patterns were useful to detect anomalies, to predict data behavior (or trend) or, more generally, to simplify data processing or to improve system performance. However, to the best of our knowledge, patterns have never been used in the context of Web archiving. Web archiving is the process of continuously collecting and preserving portions of the World Wide Web for future generations. In this paper, we show how patterns of page changes can be useful tools to efficiently archive Websites. We first define our pattern model that describes the importance of page changes. Then, we present the strategy used to (i) extract the temporal evolution of page changes, (ii) discover patterns, to (iii) exploit them to improve Web archives. The archive of French public TV channels France Télévisions is chosen as a case study to validate our approach. Our experimental evaluation based on real Web pages shows the utility of patterns to improve archive quality and to optimize indexing or storing. 相似文献
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J. C. Coyne and V. E. Whiffen (1995) reviewed research on personality vulnerability to depression, focusing on S. J. Blatt's (1974, 1990) concepts of dependency and self-criticism and A. T. Beck's (1983) concepts of sociotropy and autonomy. The authors discuss 6 issues raised in that review: (a) the typological or dimensional nature of vulnerability, (b) the theoretical implications of "mixed" vulnerability, (c) the relations of vulnerability to Neuroticism. (d) the potential confounding of vulnerability with concurrent depression, (e) the potential confounding of vulnerability with social context, and (f) the differentiation of dependency from relatedness. The authors conclude that Blatt's and Beck's concepts are continuous, nearly orthogonal dimensions that can be identified and measured independently from Neuroticism, depression, and social context. (PsycINFO Database Record (c) 2010 APA, all rights reserved) 相似文献
8.
G.A. Oliveira Junior L.R. Schaeffer F. Schenkel F. Tiezzi C.F. Baes 《Journal of dairy science》2021,104(4):4404-4412
About 30% of producers use hormone protocols to synchronize ovulation and perform timed artificial insemination (AI) in Canada. Days from calving to first service (CTFS) and first service to conception (FSTC) become masked phenotypes leading to biased genetic evaluations of cows for these fertility traits. The objectives of this study were to (1) demonstrate and quantify the potential amount of bias in genetic evaluations, and (2) find a procedure that could remove the bias. Simulation was used for both objectives. The proposed solution was to identify cows that have been treated by hormone protocols, make their CTFS and FSTC missing, and perform a multiple trait analysis including traits that have high genetic correlations with CTFS and FSTC, and which are not affected by the hormone protocols themselves. A total of 12 scenarios (S1–S12) were tested, changing the percentage of herds and cows that were randomly selected to be under timed AI. Cows that were given hormone protocols had CTFS of 86 d and FSTC of 0, which were used in genetic evaluation. Four criteria were used to indirectly measure the presence of bias: (1) the correlation between true (TBV) and estimated (EBV) breeding values (accuracy); (2) the differences in the mean EBV of top 25, 50, and 75 sires; (3) changes in correlation between TBV and EBV rankings; and (4) the changes in mean EBV over the simulated generations. All criteria changed unfavorably and proportionally to the increased use of timed AI. The accuracy within each class of animals (cows, dams, or sires) decreased proportionally with increased use of timed AI, varying from 0.32 (S12) to 0.52 (S1) for bull EBV for CTFS. The average EBV of the top sires (best 25, 50, 75, or 100 sires) approached population average EBV values when increasing the number of treated animals. The sire rank correlation between EBV and TBV within simulated scenarios was smaller for scenarios with more synchronized animals, going from 0.38 (S12) to 0.67 (S1). The long-term use of hormonal synchronized cows clearly decreased the mean EBV over generations in the population for CTFS and FSTC. The inclusion of genetically correlated traits in a multiple trait model was effective in removing the bias due to the presence of hormonal synchronized cows. However, given the constraints within the simulation, it is important that further investigation with real data is conducted to determine the true effect of including timed AI records within genetic evaluations of fertility traits in dairy cattle. 相似文献
9.
Power-to-Substitute Natural Gas processes are investigated to offer solutions for renewable energy storing or transportation. In the present study, an original Power-to-SNG process combining high-temperature steam electrolysis and CO2 methanation is implemented and simulated. A reference process is firstly defined, including a specific modelling approach of the electrolysis and a methanation modelling including a kinetic law. The process also integrates a unit to clean the gas from residual CO2, H2 and H2O for gas network injection. Having set all the units, simulations are performed with ProsimPlus 3™ software for a reference case where the electrolyser and the methanation reactors are designed. The reference case allows to produce 67.5 Nm3/h of SNG with an electrical energy consumption of 14.4 kW h/Nm3. The produced SNG satisfies specifications required for network injection. From this reference process, two sensitivity analyses on electrolysis and methanation working points and on external parameters and constraints are considered. As a main result, we observe that the reference case maximises both process efficiency and SNG production when compared with other studied cases. 相似文献
10.
Amaury Delamarre Myriam Paire Jean‐Franois Guillemoles Laurent Lombez 《Progress in Photovoltaics: Research and Applications》2015,23(10):1305-1312
We investigate photoluminescence and electroluminescence (PL and EL) emission images from Cu(In,Ga)Se2‐based solar cells by means of a Hyperspectral Imager. Using the generalized Planck's law, maps of the effective quasi‐Fermi level splitting Δμeff in absolute values are obtained. A good agreement is found between the spatially averaged splitting in PL and the global open‐circuit voltage. However, from a local carrier transport discussion, we conclude that the equality does not hold locally. The spatial variations are rather attributed to local depth variations of the quasi‐Fermi level splitting due to material properties spatial fluctuations. By comparing PL and EL emissions, we discuss qualitatively the local effective lifetimes and collection efficiencies. Copyright © 2014 John Wiley & Sons, Ltd. 相似文献