Process Simulation and Optimization on Ionic Liquids.

Ionic liquids (ILs) are promising alternative compounds that enable the development of technologies based on their unique properties as solvents or catalysts. These technologies require integrated product and process designs to select ILs with optimal process performances at an industrial scale to promote cost-effective and sustainable technologies. The digital era and multiscale research methodologies have changed the paradigm from experiment-oriented to hybrid experimental-computational developments guided by process engineering. This Review summarizes the relevant contributions (>300 research papers) of process simulations to advance IL-based technology developments by guiding experimental research efforts and enhancing industrial transferability. Robust simulation methodologies, mostly based on predictive COSMO-SAC/RS and UNIFAC models in Aspen Plus software, were applied to analyze key IL applications: physical and chemical CO2 capture, CO2 conversion, gas separation, liquid-liquid extraction, extractive distillation, refrigeration cycles, and biorefinery. The contributions concern the IL selection criteria, operational unit design, equipment sizing, technoeconomic and environmental analyses, and process optimization to promote the competitiveness of the proposed IL-based technologies. Process simulation revealed that multiscale research strategies enable advancement in the technological development of IL applications by focusing research efforts to overcome the limitations and exploit the excellent properties of ILs.

Collective adaptability in a replication network of minimal nucleobase sequences.

A major challenge for understanding the origins of life is to explore how replication networks can engage in an evolutionary process. Herein, we shed light on this problem by implementing a network constituted by two different types of extremely simple biological components: the amino acid cysteine and the canonical nucleobases adenine and thymine, connected through amide bonds to the cysteine amino group and oxidation of its thiol into three possible disulfides. Supramolecular and kinetic analyses revealed that both self- and mutual interactions between such dinucleobase compounds drive their assembly and replication pathways. Those pathways involving sequence complementarity led to enhanced replication rates, suggesting a potential bias for selection. The interplay of synergistic dynamics and competition between replicators was then simulated, under conditions that are not easily accessible with experiments, in an open reactor parametrized and constrained with the unprecedentedly complete experimental kinetic data obtained for our replicative network. Interestingly, the simulations show bistability, as a selective amplification of different species depending on the initial mixture composition. Overall, this network configuration can favor a collective adaptability to changes in the availability of feedstock molecules, with disulfide exchange reactions serving as 'wires' that connect the different individual auto- and cross-catalytic pathways.

Low Salt Treatment Results in Plant Growth Enhancement in Tomato Seedlings.

Climate change together with excessive fertilization and poor water quality can affect soil quality and salinization. In plants, high salinity causes osmotic stress, ionic toxicity, and oxidative stress. Consequently, salt stress limits plant development, growth, productivity, and yield. Tomatoes are a very common agricultural product, and some cultivars can partially tolerate salinity. However, most studies are focused on salt excess, which does not necessarily extrapolate on how plants develop in soils with low concentrations of salts. Thus, this study characterizes plant growth and the development of different salt concentrations from 25 to 200 mM in Solanum lycopersicum cv. Moneymaker. Tomato seedlings grown in Murashige and Skoog medium supplied with different NaCl concentrations (0, 25, 50, 75, 100, 125, 150, 175, and 200 mM) showed that low salt concentrations (25 and 50 mM) have a positive impact on lateral root development. This was further observed in physiological parameters such as shoot length, primary root length, and proliferation of lateral roots versus controls. Interestingly, no significant changes in Na+ concentration were observed in 25 mM NaCl in roots or shoots versus controls. Overall, our results suggest that non-toxic salt concentrations can have a positive impact on plant development.

Encapsulation of Ionic Liquids with an Aprotic Heterocyclic Anion (AHA-IL) for CO2 Capture: Preserving the Favorable Thermodynamics and Enhancing the Kinetics of Absorption.

The performance of an ionic liquid with an aprotic heterocyclic anion (AHA-IL), trihexyl(tetradecyl)phosphonium 2-cyanopyrrolide ([P66614][2-CNPyr]), for CO2 capture has been evaluated considering both the thermodynamics and the kinetics of the phenomena. Absorption gravimetric measurements of the gas-liquid equilibrium isotherms of CO2-AHA-IL systems were carried out from 298 to 333 K and at pressures up to 15 bar, analyzing the role of both chemical and physical absorption phenomena in the overall CO2 solubility in the AHA-IL, as has been done previously. In addition, the kinetics of the CO2 chemical absorption process was evaluated by in situ Fourier transform infrared spectroscopy-attenuated total reflection, following the characteristic vibrational signals of the reactants and products over the reaction time. A chemical absorption model was used to describe the time-dependent concentration of species involved in the reactive absorption, obtaining kinetic parameters (such as chemical reaction kinetic constants and diffusion coefficients) as a function of temperatures and pressures. As expected, the results demonstrate that the CO2 absorption rate is mass-transfer-controlled because of the relatively high viscosity of AHA-IL. The AHA-IL was encapsulated in a porous carbon sphere (Encapsulated Ionic Liquid, ENIL) to improve the kinetic performance of the AHA-IL for CO2 capture. The newly synthesized AHA-ENIL material was evaluated as a CO2 sorbent with gravimetric absorption measurements. AHA-ENIL systems preserve the good CO2 absorption capacity of the AHA-IL but drastically enhance the CO2 absorption rate because of the increased gas-liquid surface contact area achieved by solvent encapsulation.

Encapsulated Ionic Liquids for CO2 Capture: Using 1-Butyl-methylimidazolium Acetate for Quick and Reversible CO2 Chemical Absorption.

The potential advantages of applying encapsulated ionic liquid (ENIL) to CO2 capture by chemical absorption with 1-butyl-3-methylimidazolium acetate [bmim][acetate] are evaluated. The [bmim][acetate]-ENIL is a particle material with solid appearance and 70 % w/w in ionic liquid (IL). The performance of this material as CO2 sorbent was evaluated by gravimetric and fixed-bed sorption experiments at different temperatures and CO2 partial pressures. ENIL maintains the favourable thermodynamic properties of the neat IL regarding CO2 absorption. Remarkably, a drastic increase of CO2 sorption rates was achieved using ENIL, related to much higher contact area after discretization. In addition, experiments demonstrate reversibility of the chemical reaction and the efficient ENIL regeneration, mainly hindered by the unfavourable transport properties. The common drawback of ILs as CO2 chemical absorbents (low absorption rate and difficulties in solvent regeneration) are overcome by using ENIL systems.

Inmunogenicidad de los concentrados de Factor VIII doblemente inactivados producidos en UNC-Hemoderivados / Immunogenecity of double inactivation FVIII concentrates manufactures by UNC-Hemoderivados

El tratamiento de elección en la hemofilia A es la administración de concentrados de factor VIII y hasta un 33 % de estos pacientes pueden desarrollar inhibidores dirigidos contra el factor infundido. Varias causas pueden estar involucradas en este proceso inmune siendo la intensidad de la terapia y tipo de concentrados empleados uno de los más estudiados. Por lo tanto, el análisis cuali / cuantitativo de diferentes proteínas que hacen a un concentrado más inmunogénico que otros cobra vital importancia. En este trabajo se evaluaron los niveles de factor VIII antígeno (FVIII:Ag), factor von Willebrand (FvW) funcional e inmunológico, factor de crecimiento transformador ß1 (TGF-ß1), fibrinógeno e inmunoglobulinas G, A y M en diferentes lotes de concentrados de factor VIII manufacturados en UNC-Hemoderivados y fueron comparados con otros productos comerciales de similares características. Se estudiaron 6 lotes de 250 UI y 2 de 500 UI producidos en UNC-Hemoderivados, dos lotes de 250 UI producidos por las firmas A y B y un lote de 500 UI comercializado por la firma C. Para las determinaciones de factor VIII/factor de von Willebrand, funcional y antigénico, se emplearon métodos estándares y para el TGF-ß1 se utilizó un ELlSA comercial. Los resultados obtenidos mostraron que las relaciones entre FVIII:C/FVIII:Ag y FVIII:C/FvW funcional fueron en promedio 0.60 y 0.52 para el producto de UNC-Hemoderivados y 0.50 y 0.38 para los productos de origen comercial. Los valores TGF­ß1 y la actividad específica arrojaron mejores resultados en el producto de UNC-Hemoderivados que los productos A, B y C y en las otras proteínas analizadas no hubo diferencias. Por lo tanto podemos concluir que los concentrados de FVIII producidos en UNC-­Hemoderivados presentan propiedades que potencialmente indicarían una menor respuesta inmune contra el FVIII infundido.

Replacement therapy using plasma factor VIII (FVIII) concentrates is currently the major mean of preventing and controlling bleeding in hemophilia A patients. However. approximately a 33% of these patients may develop inhibitors to the substituted FVIII. Several causes may be involved in the immune process being the intensity of therapy and type of concentrate used one of the most studied. Therefore. the study quali/quantitative analysis of different proteins which make a concentrated more immunogenic than other takes a vital importance. In this study we evaluated FVIII antigen (FVIII: Ag), von Willebrand factor (vWF) functional and immunological, TGF-Beta1, fibrinogen and immunoglobulins G, A and M levels in FVIII concentrates manufactured in UNC-Hemoderivados and compared with other commercial products of similar characteristics. We studied 6 lots of 250 IU and 2 lots of 500 IU manufactured in UNC-Hemoderivados, 2 lots of 250 IU produced by two pharmaceutical companies named A and B and 1 batch of 500 IU marketed by C. For the determinations of F VIII/FvW functional and antigenic we used standards methods and the TGF-ß1 was assayed by ELlSA test. The results show that the relationship between FVIII/FVIII:Ag and FVIII/vWF functional were in average 0.6 and 0.52 for the product of UNC-Hemoderivados and 0.5 and 0.38 for products from commercial sources. TGF-ß1 levels and the specific activity showed upper values in UNC-Hemoderivados compared to commercial products and none difference was observed in the other proteins assayed. Therefore we can conclude that FVIII concentrates produced at UNC-Hemoderivados have properties that indicate a potentially lower immune response against the infused FVIII.

Evaluación de neoantígenos en concentrados de factor VIII analizados por enzimoinmunoensayo / Neoantigens evaluation on F VIII concentrates analyzed by enzymeimmunoassay (EIA)

El propósito de este estudio fue evaluar la inmunogenicidad de concentrados de factor VIII producidos en UNC-Hemoderivados antes y después del tratamiento térmico empleando un enzimoinmunoensayo (EIE) desarrollado en nuestro laboratorio. Materiales y método: Para ese propósito se obtuvieron anticuerpos contra factor VIII calentado y no-calentado por inmunización de conejos y la inmunoglobulina G específica fue aislada por afinidad a Proteína A-Sepharosa. El EIE fue realizado empleando como antígeno de captura el factor VIII con o sin tratamiento térmico (0.5 ug/pocillo), los sitios inespecíficos bloqueados con albúmina al 2 por ciento y el anticuerpo revelado con un anti-IgG de conejo conjugada a peroxidasa. La presencia de neoantígenos fue estudiada por incubar durante 2 hs a 37°C y luego a 4°C toda la noche, con cantidades crecientes de factor VIII antes y después del tratamiento térmico (0.03 a 600 ug de proteínas), con cantidades adecuadas de IgG anti-factor VIII calentado y no-calentado. Luego de centrifugar la muestra para la separación de los inmunocomplejos, se valoró la presencia de anticuerpos en el sobrenadante por EIE tanto para factor VIII calentado y no calentado. Resultados: Los resultados obtenidos permitieron observar que para ambos anticuerpos (calentado y no calentado) se neutralizaba la misma cantidad de factor VIII calentado y no calentado (0.30 ug) y además, se pudo comprobar que esta conducta se repetía cuando se empleaban en el EIE como antígeno de captura, factor VIII con y sin tratamiento térmico. Conclusiones: Los datos obtenidos de este estudio nos permiten concluir que el tratamiento térmico aplicado a los concentrados de factor VIII elaborados en la UNC-Hemoderivados no producen ninguna formación de neoantígenos. A juzgar por el sensible y específico EIE desarrollado en nuestro laboratorio.

Introduction: with the purpose of improving viral security, plasma-derived products are generally subjects of solvent/detergent and heating (100°C for 30 minutes) treatment which are introduced during the manufacturing process. The formation of neoantigens in factor VIII concentrates produced after the heat treatment could trigger an immune response against the modified protein and the native protein. Objetives: the purpose of this study was to evaluate the immunogenicity of factor VIII concentrates produced in UNC-Hemoderivados before and after heat treatment, using an EIA developed in our laboratory. Materials and methods: antibodies against factor VIII with and without heating treatment were obtained by rabbit immunization. The specific IgG was isolated by protein-A-Sepharose affinity chromatograpy. Two EIA plates were coated (0.5 ug/well) one with factor VIII heated (H) and the other one with factor VIII no-heat (no-H) and the antibodies detection were performed using rabbit anti-lgG peroxidase conjugated. The neoantigens were studied by incubation of increasing concentrations of factor VIII (0.03-600 ug of proteins) before and after heating treatment during 2 hours at 37 °C and overnight at 4 °C with adequate concentrations of anti-factor VIII IgG (with and without treatment). The immunocomplexes were removed by centrifugation and the free antibodies in the supernatant were measured by EIA in plates H and no-H. Results: the EIA showed a linear behavior between antibodies dilution ranged from 1/8000 to 1/512000. With these results we can conclude that the same concentration of factor VIII heated and unheated (0.30 ug) were neutralized with either antibodies (heated and unheated). These results were similar in both EIA plates coated with factor VIII H and no-H...