Kinetic Parameter Estimation from Spectroscopic Data for a Multi-Stage Solid-Liquid Pharmaceutical Process

Laboratory and process measurements from spectroscopic instruments are ubiquitous in pharma processes, and directly using the data can pose a number of challenges for kinetic model building. Moreover, scaling up from laboratory to industrial level requires predictive models with accurate parameter values. This means that process identification implies not only kinetic parameter estimation but also the identification of the absorbing species and estimation of variances for both the data and parameters. The recently developed, open-source toolkit KIPET (Short, M.; Schenk, C.; Thierry, D.; Rodriguez, J. S.; Biegler, L. T.; Garcı́a-Muñoz, S. Proceedings of the 9th International Conference on Foundations of Computer-Aided Process Design, 2019, 47, 299; Schenk, C.; Short, M.; Thierry, D.; Rodriguez, J. S.; Biegler, L. T.; Garcı́a-Muñoz, S.; Chen, W. Comput. Chem. Eng.2020, 134, 106716) addresses these topics and provides an alternative to standard parameter estimation packages, in particular for spectroscopic data problems. Moreover, batch processes commonly used in the chemical and pharmaceutical industries involve multiple stages to carry out synthesis operations in a step-by-step manner, often dealing with heterogeneous mixtures, wide operating temperatures, and constant additions and removals of product and waste. For such cases novel modeling approaches are required, as the structure of the kinetic model may vary with time, with model switches that are state dependent. This study presents a new modeling approach and methodology that deals with these practical issues. In developing kinetic models, it approximates the solid dissolution process and deals with multiple stages with different reactor temperatures. Moreover, variances, parameters, concentration, and absorbance profiles are estimated for the process stages using the approach presented by Chen et al. (Chen, W.; Biegler, L. T.; Garcı́a Muñoz, S. J. Chemom.2016, 30, 506). The application of these developed concepts results in realistic profiles as well as reliable kinetic parameter values. The outcomes of this work show that KIPET is a useful toolkit for dealing with pharmaceutical processes with capabilities for dealing with challenging kinetic modeling problems.Funded by Pfizer Inc

Micromechanics of liquid-phase exfoliation of a layered 2D material: A hydrodynamic peeling model

We present a micromechanical analysis of flow-induced peeling of a layered 2D material suspended in a liquid, for the first time accounting for realistic hydrodynamic loads. In our model, fluid forces trigger a fracture of the inter-layer interface by lifting a flexible “flap” of nanomaterial from the surface of a suspended microparticle. We show that the so far ignored dependence of the hydrodynamic load on the wedge angle produces a transition in the curve relating the critical fluid shear rate for peeling to the non-dimensional adhesion energy. For intermediate values of the non-dimensional adhesion energy, the critical shear rate saturates, yielding critical shear rate values that are drastically smaller than those predicted by a constant load assumption. Our results highlight the importance of accounting for realistic hydrodynamic loads in fracture mechanics models of liquid-phase exfoliation.Green Open Access added to TU Delft Institutional Repository 'You share, we take care!' - Taverne project https://www.openaccess.nl/en/you-share-we-take-care Otherwise as indicated in the copyright section: the publisher is the copyright holder of this work and the author uses the Dutch legislation to make this work public.Energy Technolog

European Citizens’ Initiative: A Tool for Engagement and Active Citizenship

This publication gathers contributions to understand better and further develop the European Citizens’ Initiative. This participatory and agenda-setting tool introduced into the Treaty of Lisbon has not yet reached its full potential of citizen engagement, nor has it driven the significant policy changes initially expected. Bearing this in mind, the project ECI: From A to Z aimed to promote the knowledge and use of the European Citizens’ Initiative within the higher education arena by engaging investigators and students from four different Universities (University of Coimbra; Georg-August University of Göttingen; Alexandru Ioan Cuza University of Iaşi and the University of Vigo) to work together to share their concerns and common views on the European Union role and policies. This publication describes the methodology followed and results reached under the project, but more than that, it is a practical toolkit for all who wish to know more about the European Citizens’ Initiative and how to put it in motion

Análisis in vitro de la inhibición “por clorhexidina” de la actividad mmp-2 y mmp-9 en dentina cariada

Versión original del auto

Análisis in vitro de la inhibición "por clorhexidina" de la actividad MMP-2 y MMP-9 en dentina cariada

Las metaloproteinasas (MMPs) de la matriz dentinaria, MMP-2 y MMP-9, están involucradas en la destrucción de la dentina después de la desmineralización por ácidos bacterianos, y la Clorhexidina (CHX) es capaz de inhibir estas MMPs en muy bajas concentraciones. Sin embargo, no existe evidencia experimental sobre la capacidad de este antimicrobiano para inhibir a las MMPs activadas del tejido dentinario cariado. Por tanto, el propósito de este estudio fue determinar si las formas activas de MMP-2 y/o MMP-9 presentes en dentina cariada, podían ser inhibidas mediante el uso de Clorhexidina en concentraciones clínicamente aceptadas. Para esto, se realizó análisis de Western blot utilizando anticuerpos específicos para ambas metaloproteinasas, se evaluó la actividad gelatinolítica y se determinó el efecto inhibitorio de esta actividad mediante el uso de CHX (0,001%, 0,04%, 0,01%, 1%) a través de zimografía. Se detectó actividad gelatinolítica identificada como MMP-9 y MMP 2 en dentina cariada, evidenciándose una mayor actividad enzimática de la MMP-2 y que concentraciones de Clorexhidina de 0,04% son suficientes para inhibir la actividad enzimática tanto de MMP-2 como de MMP-9 presentes en dentina cariada.Versión original del auto

Radiographic assessment of proximal surface carious lesion progression in Chilean young adults

Objective: To investigate the rate and associations of interproximal carious lesion progression. Methods: Retrospective data were analysed from 125 young adults (age range: 18-29 years) with repeated bitewing radiographs collected over a 6-year period. Participants were submitted to different protocols of radiographic examination frequency. Transitions from outer enamel to outer dentine (OE-to-OD) and from outer dentine to dentine (OD-to-D) were selected because of their clinical relevance. Factors associated with each transition were assessed in Cox regression models. Results: One hundred seven (85.6%) and 52 (41.6%) participants experienced OE-to-OD and OD-to-D transitions, respectively. In addition, 16.8% of 537 eligible surfaces progressed from OE-to-OD whereas 59.4% of 128 eligible surfaces progressed from OD-to-D. Incidence rates were 6.6 and 44.1 per 100 tooth surface-years, respectively. Mean survival time for OE-to-OD transition was 6.4 years (95% confidence interval: 6.0-6.9) and the median survival time for OD-to-D transition was 1.6 years (95%CI: 1.3-1.7). In adjusted Cox regression models, location in the lower jaw (hazard ratio: 0.34; 95% CI: 0.21-0.57) was inversely associated with OE-to-OD progression. In addition, proximal DMFS at baseline (HR: 0.93; 95%CI: 0.87-0.99) and location in the lower jaw (HR: 0.51; 95%CI: 0.26-0.99) were inversely associated with OD-to-D progression. Conclusions: This group of Chilean young adults has a high progression rate of proximal caries lesions. Location of the caries lesion and proximal DMFS were the only factors associated with caries progression. © 2020 John Wiley & Sons A/S. Published by John Wiley & Sons LtdUniversidad Autónoma de Chil