A possibilistic framework for constraint-based metabolic flux analysis

<p>Abstract</p> <p>Background</p> <p>Constraint-based models allow the calculation of the metabolic flux states that can be exhibited by cells, standing out as a powerful analytical tool, but they do not determine which of these are likely to be existing under given circumstances. Typical methods to perform these predictions are (a) flux balance analysis, which is based on the assumption that cell behaviour is optimal, and (b) metabolic flux analysis, which combines the model with experimental measurements.</p> <p>Results</p> <p>Herein we discuss a possibilistic framework to perform metabolic flux estimations using a constraint-based model and a set of measurements. The methodology is able to handle inconsistencies, by considering sensors errors and model imprecision, to provide rich and reliable flux estimations. The methodology can be cast as linear programming problems, able to handle thousands of variables with efficiency, so it is suitable to deal with large-scale networks. Moreover, the possibilistic estimation does not attempt necessarily to predict the actual fluxes with precision, but rather to exploit the available data – even if those are scarce – to distinguish possible from impossible flux states in a gradual way.</p> <p>Conclusion</p> <p>We introduce a possibilistic framework for the estimation of metabolic fluxes, which is shown to be flexible, reliable, usable in scenarios lacking data and computationally efficient.</p

Dynamic estimations of metabolic fluxes with constraint-based models and possibility theory

Living cells can be modelled by successively imposing known constraints that limit their behaviour, such as mass balances, thermodynamic laws or enzyme capacities. The resulting constraint-based models enclose all the functional states that the modelled cells may exhibit. Then, predictions can be obtained from the models in two main ways: adding experimental data to determine the state of cells at given conditions (MFA) or invoking an assumption of evolved optimal behaviour (FBA). Both MFA and FBA predictions are typically performed at steady state. However, it is easy to take extracellular dynamics into account. This work explores the benefits of using possibility theory to get these dynamic predictions. It will be shown that the possibilistic methods (a) provide rich estimates for time-varying fluxes and metabolite concentrations, (b) account for uncertainty and data scarcity, and (c) give predictions relaxing the optimality assumption of FBA. On the other hand, these methods could serve as basis for monitoring and fault detection systems in industrial bioprocesses.This research has been partially supported by the Spanish Government MINECO (1st and 3rd authors are grateful to grant CICYT DPI2011-28112-C04-01, and A. Sala is grateful to grant DPI2011-27845-C02-01).Llaneras Estrada, F.; Sala, A.; Picó Marco, JA. (2012). Dynamic estimations of metabolic fluxes with constraint-based models and possibility theory. Journal of Process Control. 22(10):1946-1955. https://doi.org/10.1016/j.jprocont.2012.09.00119461955221

Occupation as a protective factor in mild cognitive impairment

EditorialN

Cosmetotecnia de los dentífricos.Relevancia del comportamiento reológico

RESUMEN: Cosmetotecnia de los dentífricos. Relevancia del comportamiento reológico. Códigos UNESCO: 220499 (reología). 220402 (dispersiones). Los dentífricos se consideran productos semisólidos diseñados para limpiar los dientes y proporcionar un aliento fresco y agradable. Estos productos son una combinación de abrasivos (p.e. hydrated silica), humectantes, agua, surfactantes, agente anticaries (p.e. flúor), espesantes (p.e. cellulose gum, xanthan gum and carrageenan) y aromas, entre otros. Además, deben ser fácilmente extruibles del envase (“squeezing out”), mantener la suficiente rigidez (“stand up”) sobre el cepillo y tener un sabor aceptable para el consumidor. La elaboración de los mismos, supone procesos complejos a nivel industrial y la literatura científica publicada sobre su composición, fabricación y/o controles de producto acabado, así como la referente al estudio de parámetros reológicos, resulta escasa. Con objeto de profundizar en la cosmetotecnia de los dentífricos se ha elaborado la presente Tesis Doctoral, en la que se han realizado tres tipos de estudios: Primero, se ha procedido a la caracterización de los principales indicadores físicos (densidad, pH y viscosidad), químicos (conservantes y flúor) y microbiológicos que garantizan la estabilidad de los dentífricos (pastas, geles y 2 en 1) fabricados por Korott®. Los valores de densidad y pH, presentaron valores similares en todas las categorías, mientras que la viscosidad mostró diferencias. Las concentraciones de los diferentes conservantes y el ingrediente activo flúor, se mantuvieron estables con el tiempo. Asimismo, los dentífricos cumplieron con los límites microbiológicos establecidos y en ningún caso se detectó la presencia de microorganismos patógenos. A continuación, se ha profundizado en el comportamiento reológico de los dentífricos de Korott®, comparándolo con diferentes marcas de referencia (Colgate®, Sensodyne®, Binaca®, etc.) del sector de la Higiene Oral. Los productos Korott® presentaron un comportamiento altamente pseudoplástico y viscoelástico, con una estructuración de tipo gel débil. Las pastas y gel de Korott® mostraron un comportamiento reológico intermedio respecto a las marcas de referencia, mientras que los 2 en 1 mostraron una menor pseudoplasticidad. Como consecuencia del diferente comportamiento pseudoplástico, las diferencias observadas en la consistencia visual sobre el cepillo “stand up” se reducen con las altas velocidades de cepillado. Por otro lado, las pastas y geles presentan valores de esfuerzo umbral, “squeezing out”, superiores a los 2 en 1. Finalmente, se han elaborado varias mezclas, de complejidad creciente, para estudiar la influencia de los principales ingredientes que modifican el comportamiento reológico de los dentífricos. Se observó que la concentración de CMC modifica el comportamiento newtoniano de la mezcla sorbitol/agua, dando lugar a mezclas pseudoplásticas. La adición del PEG-12 apenas modifica las propiedades reológicas pero incrementa la viscosidad inicial de las mezclas (sorbitol/agua y CMC). La incorporación de un 10% de sílice abrasiva al medio acuoso con sorbitol, CMC y PEG no afecta apreciablemente el comportamiento de flujo, mientras que la misma cantidad de sílice espesante incrementa considerablemente su pseudoplasticidad y viscosidad inicial. La combinación de sílice espesante/abrasiva da lugar a valores de viscosidad similares a la del producto acabado. Por todo ello sería razonable concluir que este estudio ha permitido determinar la influencia del tipo de sílice espesante y/o abrasiva, hidrocoloide y humectantes sobre la microestructura del producto acabado.Dentifrices are considered to be semi-solid products which are designed to clean the teeth and provide a fresh and pleasant breath. These products are a mix of abrasives (e.g. hydrated silica), humectants, water, surfactants, agents for preventing tooth decay (e.g. fluoride), thickeners (e.g. cellulose gum, xanthan gum and carrageenans) and flavor, among others. Furthermore, it should be easily extrudable from the package (“squeezing out”), keep enough tightness (“stand up”) over the toothbrush and have an acceptable flavor for the consumer. The dentrifices manufacturing implies complex industrial procedures, and the scientific literature about their composition, manufacturing or quality control, and rheological properties is very limited. The main objective of this PhD thesis was to improve the knowledge about cosmetotecnica of the dentifrices. In order to achieve this goal, three different studies have been carried out: First, characterisation of different dentifrices categories (“pastes”, “gels” and “liquid dentifrice” o “2 en 1”) of Korott manufactured products has been performed. The main physical (density, pH, viscosity), chemical (preservatives and fluoride) and microbiological indicators which guarantee stability have been analysed. The values of density and pH presented similar values in all categories, whereas the viscosity showed significant differences. The concentrations of the different preservatives and the active ingredient fluoride remained stable over time. Likewise, the dentifrices fulfilled with the microbiological limits established and in any case the presence of pathogenic microorganism were detected. Following, a rheological study (flow and viscoelastic behavior) of Korott® dentifrices was carried out in order not only to characterize them but also to compare them with some reference brands at Oral Care sector (Colgate®, Sensodyne®, Binaca®, etc.) . The Korott® products presented a highly shear thinning and viscoelastic behaviour, with a typical weak gel-like structure. The Korott® pastes and gels showed an intermediate rheological behavior, while the 2 in 1 had a lower shear thinning behavior than the reference brands. As a consequence of the different shear thinning behavior, the differences observed in visual consistency over the toothbrush (“stand up”) are reduced for brushing shear rates. On the other hand, the pastes and gels present greater yield stress values (“squeezing out”) than the ones corresponding to 2 in 1 dentifrices. Finally, in order to study the influence of the main rheological modifiers, some mixtures of increasing complexity have been studied. Presence of CMC modifies the Newtonian behavior of sorbitol/water mixtures, developing shear thinning systems. The addition of PEG-12 hardly modifies the rheological properties but increases the initial viscosity of the mixtures (sorbitol/water and CMC). The addition of a 10% of abrasive silica to the aqueous medium with sorbitol, CMC and PEG, does not significantly affect the flow behavior, whereas the same quantity of thickening silica increases initial viscosity and shear thinning characteristics. The combination of thicknening and abrasive silica produces systems with similar viscosity to the final product

Design and Synthesis of N-Doped Carbons as Efficient Metal-Free Catalysts in the Hydrogenation of 1-Chloro-4-Nitrobenzene

Metal-free catalysts based on nitrogen-doped porous carbons were designed and synthesized from mixtures of melamine as nitrogen and carbon sources and calcium citrate as carbon source and porogen system. Considering the physicochemical and textural properties of the prepared carbons, a melamine/citrate ratio of 2:1 was selected to study the effect of the pyrolysis temperature. It was observed that a minimum pyrolysis temperature of 750 ◦C is required to obtain a carbonaceous structure. However, although there is a decrease in the nitrogen amount at higher pyrolysis temperatures, a gradual development of the porosity is produced from 750 ◦C to 850 ◦C. Above that temperature, a deterioration of the carbon porous structure is produced. All the prepared carbon materials, with no need for a further activation treatment, were active in the hydrogenation reaction of 1-chloro-4-nitrobenzene. A full degree of conversion was reached with the most active catalysts obtained from 2:1 melamine/citrate mixtures pyrolyzed at 850 ◦C and 900 ◦C, which exhibited a suitable compromise between the N-doping level and developed mesoporosity that facilitates the access of the reactants to the catalytic sites. What is more, all the materials showed 100% selectivity for the hydrogenation of the nitro group to form the corresponding chloro-aniline.Financial support from the Ministry of Science and Innovation (Spain, PID2019-108453GB-C21) and Generalitat Valenciana (Spain, CIPROM/2021/022) is gratefully acknowledged

N-Doped Activated Carbons from Polypyrrole – Effect of Steam Activation Conditions

Polypyrrole (PPy) has been prepared by oxidative polymerization of pyrrole and used as a raw material for the preparation of N-doped activated carbons. Thus, PPy has been pyrolyzed at 900 °C and then activated with steam under different activation conditions (time and temperature). This has allowed for the preparation of activated carbons with different porosity development and nitrogen content, as well as distinctive distribution of nitrogen species. It has been observed that the presence of nitrogen functionalities favors water adsorption at low relative pressures but, at relative pressures higher than 0.5 it is determined by the porosity development.Financial support from Ministerio de Ciencia e Innovación (Spain, Project PID2019-108453GB-C21) is gratefully acknowledged. Open access funding enabled and organized by Projekt DEAL

Doped activated carbons obtained from nitrogen and sulfur-containing polymers as metal-free catalysts for application in nitroarenes hydrogenation

Activated carbons doped with nitrogen and/or sulfur have been obtained by pyrolysis followed of steam activation of a sulfur containing polymer (polythiophene) and two nitrogen-containing polymers (polyaniline and polypyrrole). These polymers were synthesized by oxidative chemical polymerization in aqueous media of their corresponding monomers. The influence of the steam activation on the textural properties and surface chemistry of the carbons has been evaluated and their catalytic activity has been determined in the hydrogenation reaction of 1-chloro-4-nitrobenzene. The degree of conversion in the reaction depends on the development of adequate porosity in the activated carbon (which is determined by the activation conditions) together with the presence of heteroatoms that act as active catalytic sites, with S showing considerably greater effectiveness than N. A compromise between an acceptable level of doping with sulfur and an adequate porosity is necessary, which has been achieved in a carbon obtained from polythiophene pyrolyzed at 900 °C and steam activated at 800 °C for 4 h, with a specific surface area of 742 m2/g and S content of 1.71 at%.Financial support from Spain Ministry of Science and Innovation (PID2019-108453GB-C21) is gratefully acknowledged

Sample Entropy Analysis of Noisy Atrial Electrograms during Atrial Fibrillation

[EN] Most cardiac arrhythmias can be classified as atrial flutter, focal atrial tachycardia, or atrial fibrillation. They have been usually treated using drugs, but catheter ablation has proven more effective. This is an invasive method devised to destroy the heart tissue that disturbs correct heart rhythm. In order to accurately localise the focus of this disturbance, the acquisition and processing of atrial electrograms form the usual mapping technique. They can be single potentials, double potentials, or complex fractionated atrial electrogram (CFAE) potentials, and last ones are the most effective targets for ablation. The electrophysiological substrate is then localised by a suitable signal processing method. Sample Entropy is a statistic scarcely applied to electrograms but can arguably become a powerful tool to analyse these time series, supported by its results in other similar biomedical applications. However, the lack of an analysis of its dependence on the perturbations usually found in electrogram data, such as missing samples or spikes, is even more marked. This paper applied SampEn to the segmentation between non-CFAE and CFAE records and assessed its class segmentation power loss at different levels of these perturbations. The results confirmed that SampEn was able to significantly distinguish between non-CFAE and CFAE records, even under very unfavourable conditions, such as 50% of missing data or 10% of spikes.This research was supported by Research Center for Informatics (no. CZ.02.1.01/0.0/0.0/16-019/0000765).Cirugeda Roldan, EM.; Molina Picó, A.; Novák, D.; Cuesta Frau, D.; Kremen, V. (2018). Sample Entropy Analysis of Noisy Atrial Electrograms during Atrial Fibrillation. Computational and Mathematical Methods in Medicine. https://doi.org/10.1155/2018/1874651SAhmed, S., Claughton, A., & Gould, P. A. (2015). Atrial Flutter — Diagnosis, Management and Treatment. Abnormal Heart Rhythms. doi:10.5772/60700Kirchhof, P., & Calkins, H. (2016). Catheter ablation in patients with persistent atrial fibrillation. European Heart Journal, 38(1), 20-26. doi:10.1093/eurheartj/ehw260Nademanee, K., Lockwood, E., Oketani, N., & Gidney, B. (2010). Catheter ablation of atrial fibrillation guided by complex fractionated atrial electrogram mapping of atrial fibrillation substrate. Journal of Cardiology, 55(1), 1-12. doi:10.1016/j.jjcc.2009.11.002NG, J., & GOLDBERGER, J. J. (2007). Understanding and Interpreting Dominant Frequency Analysis of AF Electrograms. Journal of Cardiovascular Electrophysiology, 18(6), 680-685. doi:10.1111/j.1540-8167.2007.00832.xKottkamp, H., & Hindricks, G. (2007). Complex fractionated atrial electrograms in atrial fibrillation: A promising target for ablation, but why, when, and how? Heart Rhythm, 4(8), 1021-1023. doi:10.1016/j.hrthm.2007.05.011Křemen, V., Lhotská, L., Macaš, M., Čihák, R., Vančura, V., Kautzner, J., & Wichterle, D. (2008). A new approach to automated assessment of fractionation of endocardial electrograms during atrial fibrillation. Physiological Measurement, 29(12), 1371-1381. doi:10.1088/0967-3334/29/12/002Nademanee, K., McKenzie, J., Kosar, E., Schwab, M., Sunsaneewitayakul, B., Vasavakul, T., … Ngarmukos, T. (2004). A new approach for catheter ablation of atrial fibrillation: mapping of the electrophysiologic substrate. Journal of the American College of Cardiology, 43(11), 2044-2053. doi:10.1016/j.jacc.2003.12.054Scherr, D., Dalal, D., Cheema, A., Cheng, A., Henrikson, C. A., Spragg, D., … Dong, J. (2007). Automated detection and characterization of complex fractionated atrial electrograms in human left atrium during atrial fibrillation. Heart Rhythm, 4(8), 1013-1020. doi:10.1016/j.hrthm.2007.04.021Almeida, T. P., Chu, G. S., Salinet, J. L., Vanheusden, F. J., Li, X., Tuan, J. H., … Schlindwein, F. S. (2016). Minimizing discordances in automated classification of fractionated electrograms in human persistent atrial fibrillation. Medical & Biological Engineering & Computing, 54(11), 1695-1706. doi:10.1007/s11517-016-1456-2Molina-Picó, A., Cuesta-Frau, D., Aboy, M., Crespo, C., Miró-Martínez, P., & Oltra-Crespo, S. (2011). Comparative study of approximate entropy and sample entropy robustness to spikes. Artificial Intelligence in Medicine, 53(2), 97-106. doi:10.1016/j.artmed.2011.06.007Cuesta–Frau, D., Miró–Martínez, P., Jordán Núñez, J., Oltra–Crespo, S., & Molina Picó, A. (2017). Noisy EEG signals classification based on entropy metrics. Performance assessment using first and second generation statistics. Computers in Biology and Medicine, 87, 141-151. doi:10.1016/j.compbiomed.2017.05.028Demont-Guignard, S., Benquet, P., Gerber, U., & Wendling, F. (2009). Analysis of Intracerebral EEG Recordings of Epileptic Spikes: Insights From a Neural Network Model. IEEE Transactions on Biomedical Engineering, 56(12), 2782-2795. doi:10.1109/tbme.2009.2028015Molina–Picó, A., Cuesta–Frau, D., Miró–Martínez, P., Oltra–Crespo, S., & Aboy, M. (2013). Influence of QRS complex detection errors on entropy algorithms. Application to heart rate variability discrimination. Computer Methods and Programs in Biomedicine, 110(1), 2-11. doi:10.1016/j.cmpb.2012.10.014Ganesan, P., Cherry, E. M., Pertsov, A. M., & Ghoraani, B. (2015). Characterization of Electrograms from Multipolar Diagnostic Catheters during Atrial Fibrillation. BioMed Research International, 2015, 1-9. doi:10.1155/2015/272954Lake, D. E., Richman, J. S., Griffin, M. P., & Moorman, J. R. (2002). Sample entropy analysis of neonatal heart rate variability. American Journal of Physiology-Regulatory, Integrative and Comparative Physiology, 283(3), R789-R797. doi:10.1152/ajpregu.00069.2002Kim, K. K., Baek, H. J., Lim, Y. G., & Park, K. S. (2012). Effect of missing RR-interval data on nonlinear heart rate variability analysis. Computer Methods and Programs in Biomedicine, 106(3), 210-218. doi:10.1016/j.cmpb.2010.11.011Richman, J. S., & Moorman, J. R. (2000). Physiological time-series analysis using approximate entropy and sample entropy. American Journal of Physiology-Heart and Circulatory Physiology, 278(6), H2039-H2049. doi:10.1152/ajpheart.2000.278.6.h2039Cirugeda–Roldán, E., Novak, D., Kremen, V., Cuesta–Frau, D., Keller, M., Luik, A., & Srutova, M. (2015). Characterization of Complex Fractionated Atrial Electrograms by Sample Entropy: An International Multi-Center Study. Entropy, 17(12), 7493-7509. doi:10.3390/e17117493PORTER, M., SPEAR, W., AKAR, J. G., HELMS, R., BRYSIEWICZ, N., SANTUCCI, P., & WILBER, D. J. (2008). Prospective Study of Atrial Fibrillation Termination During Ablation Guided by Automated Detection of Fractionated Electrograms. Journal of Cardiovascular Electrophysiology, 19(6), 613-620. doi:10.1111/j.1540-8167.2008.01189.xKonings, K. T., Kirchhof, C. J., Smeets, J. R., Wellens, H. J., Penn, O. C., & Allessie, M. A. (1994). High-density mapping of electrically induced atrial fibrillation in humans. Circulation, 89(4), 1665-1680. doi:10.1161/01.cir.89.4.1665Fay, M. P., & Proschan, M. A. (2010). Wilcoxon-Mann-Whitney or t-test? On assumptions for hypothesis tests and multiple interpretations of decision rules. Statistics Surveys, 4(0), 1-39. doi:10.1214/09-ss051Richman, J. S. (2007). Sample Entropy Statistics and Testing for Order in Complex Physiological Signals. Communications in Statistics - Theory and Methods, 36(5), 1005-1019. doi:10.1080/03610920601036481Pincus, S. M., Gladstone, I. M., & Ehrenkranz, R. A. (1991). A regularity statistic for medical data analysis. Journal of Clinical Monitoring, 7(4), 335-345. doi:10.1007/bf01619355Alcaraz, R., & Rieta, J. J. (2009). Non-invasive organization variation assessment in the onset and termination of paroxysmal atrial fibrillation. Computer Methods and Programs in Biomedicine, 93(2), 148-154. doi:10.1016/j.cmpb.2008.09.001Alcaraz, R., Abásolo, D., Hornero, R., & Rieta, J. J. (2010). Optimal parameters study for sample entropy-based atrial fibrillation organization analysis. Computer Methods and Programs in Biomedicine, 99(1), 124-132. doi:10.1016/j.cmpb.2010.02.009Costa, M., Goldberger, A. L., & Peng, C.-K. (2002). Multiscale Entropy Analysis of Complex Physiologic Time Series. Physical Review Letters, 89(6). doi:10.1103/physrevlett.89.06810

Noisy EEG signals classification based on entropy metrics. Performance assessment using first and second generation statistics

[EN] This paper evaluates the performance of first generation entropy metrics, featured by the well known and widely used Approximate Entropy (ApEn) and Sample Entropy (SampEn) metrics, and what can be considered an evolution from these, Fuzzy Entropy (FuzzyEn), in the Electroencephalogram (EEG) signal classification context. The study uses the commonest artifacts found in real EEGs, such as white noise, and muscular, cardiac, and ocular artifacts. Using two different sets of publicly available EEG records, and a realistic range of amplitudes for interfering artifacts, this work optimises and assesses the robustness of these metrics against artifacts in class segmentation terms probability. The results show that the qualitative behaviour of the two datasets is similar, with SampEn and FuzzyEn performing the best, and the noise and muscular artifacts are the most confounding factors. On the contrary, there is a wide variability as regards initialization parameters. The poor performance achieved by ApEn suggests that this metric should not be used in these contexts.Cuesta Frau, D.; Miró Martínez, P.; Jordán Núñez, J.; Oltra Crespo, S.; Molina Picó, A. (2017). Noisy EEG signals classification based on entropy metrics. Performance assessment using first and second generation statistics. Computers in Biology and Medicine. 87:141-151. doi:10.1016/j.compbiomed.2017.05.028S1411518

Effect of the Carbon Support and Conditions on the Carbothermal Synthesis of Cu-Molybdenum Carbide and Its Application on CO2 Hydrogenation to Methanol

The synthesis of methanol by carbon dioxide hydrogenation has been studied using copper-molybdenum carbides supported on high surface area graphite, reduced graphene oxide and carbon nanotubes. The synthesis conditions and the effect of the support were studied. The catalysts were prepared in situ using H2 or He at 600 °C or 700 °C. Both molybdenum carbide and oxycarbide were obtained. A support with less reactive carbon resulted in lower proportion of carbide obtained. The best results were achieved over a 5 wt.% Cu and 10 wt.% Mo on high surface area graphite that reached 96.3% selectivity to methanol.A.B. Dongil acknowledges financial support from Fundación General CSIC (Programa ComFuturo, Spain) and EU H2020-MSCA, GA. Nº 101008058. Financial support from the Spanish Agencia Estatal de Investigación (AEI) and EU (FEDER) (projects PID2020-119160RB-C21, PID2019-103453GB-C21, CTQ2017-89443-C3-1-R, and CTQ2017-89443-C3-3-R) is also acknowledged. The APC was funded by EU H2020-MSCA, GA. Nº 101008058