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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.
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
3.
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
4.
5.
Dr. Manuel Nieto-Domínguez Dr. Pablo I. Nikel 《Chembiochem : a European journal of chemical biology》2020,21(18):2551-2571
The diversity of life relies on a handful of chemical elements (carbon, oxygen, hydrogen, nitrogen, sulfur and phosphorus) as part of essential building blocks; some other atoms are needed to a lesser extent, but most of the remaining elements are excluded from biology. This circumstance limits the scope of biochemical reactions in extant metabolism – yet it offers a phenomenal playground for synthetic biology. Xenobiology aims to bring novel bricks to life that could be exploited for (xeno)metabolite synthesis. In particular, the assembly of novel pathways engineered to handle nonbiological elements (neometabolism) will broaden chemical space beyond the reach of natural evolution. In this review, xeno-elements that could be blended into nature's biosynthetic portfolio are discussed together with their physicochemical properties and tools and strategies to incorporate them into biochemistry. We argue that current bioproduction methods can be revolutionized by bridging xenobiology and neometabolism for the synthesis of new-to-nature molecules, such as organohalides. 相似文献
6.
Enrique Alexandre Antonio Pena Manuel Sobreira 《IEEE transactions on information technology in biomedicine》2006,10(4):809-811
This paper discusses the convenience of using two-dimensional (2-D) coding techniques for the compression of electrocardiogram (ECG) signals. These signals present a very clear periodicity that can be exploited by the use of a 2-D time/frequency transform to decorrelate it as much as possible. A brief theoretical approach is given to justify the use of this technique, and a comparison is made between a 2-D and a one-dimensional (1-D) uniform quantization scenarios. The influence of the error as well as the frame size on the estimation of the fundamental period is studied. 相似文献
7.
F Abadía-Molina R Calvente R Carmona R Luján F Abadía-Fenoll 《Canadian Metallurgical Quarterly》1993,8(2):297-304
In this study chick embryo optic cups at HH stage 13 of development were analyzed under normal conditions and after inoculation with colchicine for 1, 2, 4, and 8 h. Several changes were seen after these periods of treatment: 1) modifications of the structure, with thicker regions in the cup and a general decrease in the total volume according to the duration of exposure to the drug (about 4 times less than normal, 5,035 x 10(3) microns 3 vs 1,334 x 10(3) microns 3 after 8 h of treatment); 2) enlargement of the ventricular cavity and its closure, due to failure of approximation of retinal and pigmentary layers; 3) failure of lens development, with delay and impairment of pit formation and deformation of all structures; lens volume was less than normal (about 4 times less, 2,148 x 10(3) microns 3 vs 658 x 10(3) microns 3 after 8 h of treatment); 4) a general segregation of the cells making up the structure, principally in the more active proliferating zones. The local alterations found are described. 相似文献
8.
Studied how 26 senior managers and 47 senior professional technical staff (recently repatriated) of 4 US owned multinational organizations viewed their international posting, specifically with respect to career path satisfaction. Results of satisfaction scales indicate that many Ss felt under-prepared for their international assignment. It is suggested that a comprehensive international employee development program should assess, provide feedback, and coach individuals on career path, culture shock and adjustment, and performance issues prior, during, and on return from the expatriate assignment. Results suggest that opportunities exist for individual and organizational intervention. (PsycINFO Database Record (c) 2010 APA, all rights reserved) 相似文献
9.
The thermal and mechanical properties and the morphologies of blends of poly(propylene) (PP) and an ethylene–(vinyl alcohol) copolymer (EVOH) and of blends of PP/EVOH/ethylene–(methacrylic acid)–Zn2+ ionomer were studied to establish the influence of the ionomer addition on the compatibilization of PP/EVOH blends and on their properties. The oxygen transmission rate (O2TR) values of the blends were measured as well. PP and EVOH are initially incompatible as was determined by tensile tests and scanning electronic microscopy. Addition of the ionomer Zn2+ led to good compatibility and mechanical behaviour was improved in all blends. The mechanical properties on extruded films were studied for 90/10 and 80/20 w/w PP/EVOH blends compatibilized with 10 % of ionomer Zn2+. These experiments have shown that the tensile properties are better than in the injection‐moulded samples. The stretching during the extrusion improved the compatibility of the blends, diminishing the size of EVOH domains and enhancing their distribution in the PP matrix. As was to be expected, the EVOH improved the oxygen permeation of the films, even in compatibilized blends. Copyright © 2004 Society of Chemical Industry 相似文献
10.
Atmospheric corrosion of reference metals in Antarctic sites 总被引:1,自引:0,他引:1
Manuel Morcillo Beln Chico Daniel de la Fuente Elisabete Almeida Günter Joseph Susana Rivero Blanca Rosales 《Cold Regions Science and Technology》2004,40(3):165-178
This paper presents the results obtained at three Antarctic test sites participating in the “Ibero-American Map of Atmospheric Corrosiveness” (MICAT), a project on atmospheric corrosion carried out during the period 1988–1994 at some 70 sites distributed across 12 countries of the Latin-American region, Spain and Portugal. The three Antarctic sites are located near the coastline.The singular climatic characteristics of Antarctic regions are related with the purity of the air, the absence of rainfall and the formation of ice on the metallic surface during an important part of the exposure time. However, electrochemical activity is possible below ice layers. This situation affects the structure and morphology of corrosion product films and the resulting corrosion rates of metallic surfaces. 相似文献