Enantioseparation and ecotoxicity evaluation of ibrutinib by Electrokinetic Chromatography using single and dual systems

In this work, two chiral methods enabling the separation of ibrutinib enantiomers were developed by Electrokinetic Chromatography. A cyclodextrin (CD) or a mixture of the CD and a chiral ionic liquid (CIL) was used as chiral selector. Using the single CD system, seven neutral and six anionic CDs were tested in a formate buffer at pH 3.0 working in positive and negative polarity, respectively. The use of sulfated-?-CD (S-?-CD) and negative polarity originated the best results considering analysis time and enantioresolution. The optimization of the experimental conditions allowed obtaining the separation of ibrutinib enantiomers in an analysis time of 4.2 min with an enantioresolution value of 1.5. The effect of the addition of fifteen CILs on the enantioresolution was evaluated showing that both analysis time and enantioresolution were generally increased. A mixture of S-?-CD and [TMA][L-Lys] was selected which provided the separation of ibrutinib enantiomers in 8.1 min with an enantioresolution value of 3.3 under the same experimental conditions as in the case of using the single CD system. The enantiomeric impurity (S-ibrutinib) was the first-migrating isomer when using the single CD and the combined CD/CIL systems, as corresponds to the most desirable situation. Both chiral methods allowed the detection of the enantiomeric impurity up to a 0.1 % as established by the International Council on Harmonization. After establishing the analytical characteristics of both chiral methodologies developed, they were applied to the enantiomeric determination of ibrutinib in a pharmaceutical formulation for hospital use marketed as pure enantiomer (R-ibrutinib) and to evaluate the stability and ecotoxicity of racemic ibrutinib and R-ibrutinib on Daphnia magna. The developed methodologies enabled, for the first time, the rapid chiral quantitation of ibrutinib in abiotic and biotic matrices

Development of an in-capillary derivatization method by CE for the determination of chiral amino acids in dietary supplements and wines

A fast in-capillary derivatization method by CE with 6-aminoquinolyl-N-hydroxysuccinimidyl\ud carbamate was developed for the first time for the determination of\ud amino acid enantiomers (arginine, lysine, and ornithine) in dietary supplements and\ud wines. Because of the initial current problems due to the formation of precipitates into\ud the capillary during the derivatization reaction, a washing step with an organic solvent as\ud DMSO between injections was necessary. Different approaches were also investigated to\ud enhance the sensitivity of detection. A derivatization procedure, where plugs of ACN,\ud derivatizing agent (10mM 6-aminoquinolyl-N-hydroxysuccinimidyl carbamate), and\ud sample in borate (1:1 v/v) were injected in tandem (2, 3, and 6 s, respectively, at 50 mbar),\ud was selected because it enabled to obtain the most sensitive and reproducible results.\ud Appropriate analytical characteristics (linearity, LOD and LOQ, precision, absence of\ud matrix interferences, and accuracy) were obtained for this method. Finally, the optimized\ud method was successfully applied to the determination of the enantiomers of arginine,\ud lysine, and ornithine in food samples of different complexities (dietary supplements and\ud wines).The authors thank the Ministry of Education and Science (Spain) and the Comunidad Autónoma de Madrid (Spain) for research projects CTQ2006-03849/BQU and S-0505/AGR- 0312, respectively. Carmen Garcı´a-Ruiz thanks the Ministry of Science and Technology (Spain) for the Ramon y Cajal program (RYC-2003-001). A.B.M.-G. thanks the University of Alcala for her pre-doctoral contract

aZIBO Shape Descriptor for Monitoring Tool Wear in Milling

El objetivo de este trabajo es estimar eficientemente el desgaste del mecanizado de metales y mejorar las operaciones de sustitución de la herramienta. El procesamiento de imágenes y la clasificación se utilizan para automatizar la toma de decisiones sobre el tiempo adecuado para el reemplazo dela herramienta. Específicamente, el descriptor de forma aZIBO (momentos absolutos de Zernike con orientación de contorno invariable) se ha utilizado para caracterizar el desgaste de la plaquita y garantizar su uso óptimo. Se ha creado un conjunto de datos compuesto por 577 regiones con diferentes niveles de desgaste. Se han llevado a cabo dos procesos de clasificación diferentes: el primero con tres clases diferentes (desgaste bajo, medio y alto -L, M y H, respectivamente) y el segundo con sólo dos clases: Low (L) y High (H). La clasificación se llevó a cabo utilizando por un lado kNN con cinco distancias diferentes y cinco valores de k y, por otra parte, una máquina de vectores de soporte (SVM). El rendimiento de aZIBO se ha comparado con descriptores de forma clásicos como los momentos de Hu y Flusser. Los supera, obteniendo tasas de éxito de hasta el 91,33% para la clasificación L-H y 90,12% para la clasificación L-M-H

Comunicación, sentido y vida cotidiana

La pregunta por la vida cotidiana, su estructura, su funcionamiento, no es una novedad en el ámbito de las ciencias sociales. Se han ocupado de esta problemática pensadores de la talla de Heller, Habermas, Goffman, Freiré, Wolf, por citar sólo algunos. Diferentes enfoques, teorías y preocupaciones han derivado en un vasto campo de estudio que observa y rescata lo que era considerado como "materiales secundarios", indagando cómo los pequeñísimos actos cotidianos realzan temas muy importantes (Wolf, 1979). En el campo de la comunicación cobran fuerza en cantidad y calidad, a partir de 1980 (Fuentes, 1991) los estudios que abordan diferentes aspectos de la cotidianidad para indagar por ejemplo, en un cambio de perspectiva, no ya lo que los medios hacen a la gente, sino lo que la gente hace con y a partir de los medios, haciendo aparecer en primer plano al actor de la comunicación.ITESO, A.C

Involvement of nitric oxide in the mitochondrial action of efavirenz: a differential effect on neurons and glial cells

The anti-human immunodeficiency virus (HIV) drug efavirenz (EFV) alters mitochondrial function in cultured neurons and glial cells. Nitric oxide (NO) is a mediator of mitochondrial dysfunction associated with HIV central nervous system symptoms. We show that EFV promotes inducible nitric oxide synthase (iNOS) expression in cultured glial cells and generated NO undermines their mitochondrial function, as inhibition of NOS partially reverses this effect. EFV inhibits mitochondrial Complex I in both neurons and glia; however, when the latter cells are treated for longer periods, other mitochondrial complexes are also affected in accordance with the increased NO production. These findings shed light on the mechanisms responsible for the frequent EFV-associated neurotoxicity

Design of a TCM System Based on Vibration Signal for Metal Turning Processe

Este artículo presenta un estudio sobre la identificación del estado de desgaste de la herramienta de corte mediante el análisis de señales de vibración en operaciones de torneado en seco de acero. Al analizar la evolución del valor RMS y los espectros de frecuencia FFT de la señal, se ha desarrollado un sistema de monitoreo de condición de herramienta en línea. El propósito principal es determinar el instante desde el cual la condición de la herramienta se considera inaceptable, lo que afecta la calidad del proceso de mecanizado. Después del análisis que se llevó a cabo el, la conclusión principal es que tanto el RMS como los rangos de amplitud de frecuencia de ciertas bandas de espectro, están relacionados con el desgaste de la herramienta

Stereoselective separation of sulfoxaflor by electrokinetic chromatography and applications to stability and ecotoxicological studies

An Electrokinetic Chromatography method was developed for the stereoselective analysis of sulfoxaflor, a novel sulfoximine agrochemical with two chiral centers. A screening with fourteen negatively charged CDs was performed and Succinyl-?-CD (Succ-?-CD) was selected. A 15 mM concentration of this CD in a 100 mM borate buffer (pH 9.0), using an applied voltage of 20 kV and a temperature of 15 ?C made possible the baseline separation of the four stereoisomers of sulfoxaflor in 13.8 min. The evaluation of the linearity, accuracy, precision, LODs and LOQs of the method developed showed its performance to be applied to the analysis of commercial agrochemical formulations, the evaluation of the stability of sulfoxaflor stereoisomers under biotic and abiotic conditions, and to predict, for the first time, sulfoxaflor toxicity (using real concentrations instead of nominal concentrations), on two non-target aquatic organisms, the freshwater plant, Spirodela polyrhiza, and the marine bacterium, Vibrio fischer

Enantiomeric separation of panthenol by Capillary Electrophoresis. Analysis of commercial formulations and toxicity evaluation on non-target organisms

The first CE methodology enabling the enantiomeric separation of panthenol was developed in this work. Electrokinetic chromatography with cyclodextrins (CD-EKC) was the CE mode employed for this purpose. The effect of different experimental variables such as the nature and concentration of the cyclodextrin, the temperature and the separation voltage was investigated. The best enantiomeric separation was obtained with 25 mM (2-carboxyethyl)-?-CD (CE-?-CD) in 100 mM borate buffer (pH 9.0), with a separation voltage of 30 kV and a temperature of 30?C. Under these conditions, an enantiomeric resolution of 2.0 in an analysis time of 4.2 min was obtained, being the biologically active enantiomer D-panthenol (dexpanthenol) the second-migrating enantiomer. The analytical characteristics of the method were evaluated in terms of precision, accuracy, selectivity, linearity, LOD, and LOQ, showing a good performance for the quantitation of dexpanthenol in cosmetic and pharmaceutical formulations. The enantiomeric impurity (L-panthenol) could be detected at a 0.1 % level with respect to the majority enantiomer, allowing to accomplish the requirements of the ICH guidelines. The method was also successfully applied to study the stability of panthenol under abiotic and biotic conditions and its toxicity on non-target organisms (the aquatic plant Spirodela polyrhiza)

La gestión de la toma de riesgos como facilitador de la innovación en las organizaciones

The relationship between risk-taking and innovation in organizations has been analyzed from two distant perspectives. From a management approach, theories related to entrepreneurial orientation and leadership have provided a useful guideline to establish a direct and clear link between managers' risk-taking and innovation performance. From an employees' view, it has been pointer that an organizational climate favoring risk-taking is particularly effective to create and maintain innovative behaviors and outcomes among employees. However, few empirical studies have combined both perspectives to obtain a more general picture of the relationship between risk-taking and innovation performance. This paper aims to contribute to the relationship between managers' risk-taking propensity, risk-taking organizational climate and innovation performance. To do so, we develop and text a conceptual model where we analyze the relationships between the managers' propensity to take risks in the organization, the organizational climate and the innovation performance. We test our model on a sample of 182 companies. As expected, results indicate that a risk-taking climate and a higher managers' propensity to take risks play a significant role in determining the organizations' innovation performance.La relación entre la toma de riesgos y la innovación en la empresa ha sido analizada desde dos perspectivas de forma desconectada. Desde el punto de vista de gestión, las teorías relacionadas con la orientación emprendedora y el liderazgo han proporcionado una guía útil para establecer una relación directa y positiva entre la toma de riesgos de los directivos y la innovación. Desde una perspectiva del empleado, se ha señalado que un clima organizativo que promueva la toma de riesgos es particularmente efectivo para crear y mantener comportamientos innovadores entre los empleados. Sin embargo, existe poca evidencia empírica que combine ambas perspectivas para obtener una imagen global de la relación entre toma de riesgos y resultado innovador. Este trabajo pretende contribuir a la relación entre la propensión de los directivos hacia la toma de riesgos, el clima organizativo de toma de riesgos y la innovación. Con este objetivo, desarrollamos y testamos un modelo conceptual donde se analiza la relación entre la propensión hacia la toma de riesgos de los directivos, el clima organizativo y la innovación. Contrastamos las hipótesis sobre una muestra de 182 empresas. Tal como se esperaba, los resultados indican que el clima de toma de riesgos y la propensión de los directivos a tomar riesgos juegan un papel significativo en determinar el desempeño innovador

Enantiomeric separation of ornithine in complex mixtures of amino acids by EKC with off-line derivatization with 6-aminoquinolyl-N-hydroxysuccinimidyl carbamate

A new analytical methodology was developed by EKC enabling the fast enantiomeric separation of\ud Ornithine in complex mixtures of amino acids. A previous derivatization step with 6-aminoquinolyl-Nhydroxysuccinimidyl\ud carbamate (AQC) was achieved to enable the sensitive UV detection of amino acids\ud as well as to make possible their interaction with the CDs employed as chiral selectors. A dual CD system\ud containing an anionic and a neutral CD in phosphate buffer at acid pH showed a high resolving power\ud allowing the enantiomeric separation of 18 protein amino acids and Orn. The method was applied to the\ud analysis of fermented foods to investigate the extent of the presence of Orn enantiomers.Authors thank the Ministry of Education of Science (Spain) and\ud the Comunidad Autonoma de Madrid (Spain) for research projects CTQ2006-03849/BQU and S-0505/AGR-0312, respectively. Carmen Garcıa-Ruiz thanks the Ministry of Science and Technology (Spain) for the Ramon y Cajal program (RYC-2003-001). Ana Belen Martínez \ud Giron and Elena Domínguez-Vega thank the University of Alcala for their pre-doctoral grants