Iterative design of dynamic experiments in modeling for optimization of innovative bioprocesses

Finding optimal operating conditions fast with a scarce budget of experimental runs is a key problem to speed up the development and scaling up of innovative bioprocesses. In this paper, a novel iterative methodology for the model-based design of dynamic experiments in modeling for optimization is developed and successfully applied to the optimization of a fed-batch bioreactor related to the production of r-interleukin-11 (rIL-11) whose DNA sequence has been cloned in an Escherichia coli strain. At each iteration, the proposed methodology resorts to a library of tendency models to increasingly bias bioreactor operating conditions towards an optimum. By selecting the ‘most informative’ tendency model in the sequel, the next dynamic experiment is defined by re-optimizing the input policy and calculating optimal sampling times. Model selection is based on minimizing an error measure which distinguishes between parametric and structural uncertainty to selectively bias data gathering towards improved operating conditions. The parametric uncertainty of tendency models is iteratively reduced using Global Sensitivity Analysis (GSA) to pinpoint which parameters are keys for estimating the objective function. Results obtained after just a few iterations are very promising.Fil: Cristaldi, Mariano Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Desarrollo y Diseño. Universidad Tecnológica Nacional. Facultad Regional Santa Fe. Instituto de Desarrollo y Diseño; ArgentinaFil: Grau, Ricardo José Antonio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Desarrollo Tecnológico para la Industria Química. Universidad Nacional del Litoral. Instituto de Desarrollo Tecnológico para la Industria Química; ArgentinaFil: Martínez, Ernesto Carlos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Desarrollo y Diseño. Universidad Tecnológica Nacional. Facultad Regional Santa Fe. Instituto de Desarrollo y Diseño; Argentin

Model-based run-to-run optimization for process development

Research and development of new processes is a fundamental part of any innovative industry. For process engineers, finding optimal operating conditions for new processes from the early stages is a main issue, since it improves economic viability, helps others areas of R&D by avoiding product bottlenecks and shortens the time-to-market period. Model-based optimization strategies are helpful in doing so, but imperfect models with parametric or structural errors can lead to suboptimal operating conditions. In this work, a methodology that uses probabilistic tendency models that are constantly updated through experimental feedback is proposed in order to rapidly and efficiently find improved operating conditions. Characterization of the uncertainty is used to make safe predictions even with scarce data, which is typical in this early stage of process development. The methodology is tested with an example from the traditional innovative pharmaceutical industry.Fil: Luna, Martín Francisco. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Desarrollo y Diseño. Universidad Tecnológica Nacional. Facultad Regional Santa Fe. Instituto de Desarrollo y Diseño; ArgentinaFil: Martínez, Ernesto Carlos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Desarrollo y Diseño. Universidad Tecnológica Nacional. Facultad Regional Santa Fe. Instituto de Desarrollo y Diseño; Argentin

Bayesian optimization of crystallization processes to guarantee end-use product properties

For pharmaceutical solid products, the issue of reproducibly obtaining their desired end-use properties depending on crystal size and form is the main problem to be addressed and solved in process development. Lacking a reliable first-principles model of a crystallization process, a Bayesian optimization algorithm is proposed. On this basis, a short sequence of experimental runs for pinpointing operating conditions that maximize the probability of successfully complying with end-use product properties is defined. Bayesian optimization can take advantage of the full information provided by the sequence of experiments made using a probabilistic model of the probability of success based on a one-class classification method. The proposed algorithm's performance is tested in silico using the crystallization and formulation of an API product where success is about fulfilling a dissolution profile as required by the FDA. Results obtained demonstrate that the sequence of generated experiments allows pinpointing operating conditions for reproducible quality.Fil: Luna, Martín Francisco. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Desarrollo y Diseño. Universidad Tecnológica Nacional. Facultad Regional Santa Fe. Instituto de Desarrollo y Diseño; ArgentinaFil: Martínez, Ernesto Carlos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Desarrollo y Diseño. Universidad Tecnológica Nacional. Facultad Regional Santa Fe. Instituto de Desarrollo y Diseño; Argentin

Propriedades psicométricas de uma escala para medir a gestão da vergonha em adolescentes (Moss-Sast)

(Ahmed, 1999) to measure shame management in adolescents in situations of aggression toward peers. The study was conducted with a sample of 700 students from public secondary schools (N= 700) located in a northwestern state municipality of Mexico. Results enabled to obtain an empirically sustainable measuring model formed by two factors: Acknowledgment and Displacement (X2 = 5.16, p= 0.27; CMIN= 1.29; GFI= .98; CFI= .99; NFI= .97; RMSEA= .05). Evidence was obtained to show that the instrument has criterion validity since it is capable to differentiate between subgroups of students with and without reports of bullying in both factors, Acknowledgment (t= 3.49, gl= 137, p< .001) and Displacement (t= 3.63, gl= 137, p< .001). It was concluded that the results strengthen the original factorial structure of the scale and show the usefulness of the same, both for inquiring about emotions related to moral development and for identifying students involved as aggressors in bullying situations.Se establecieron las evidencias de validez y confiabilidad de la adaptación del cuestionario MOSS-SAST (Ahmed, 1999) para medir el manejo de la vergüenza en adolescentes ante situaciones de agresión hacia los pares. El estudio se realizó en una muestra de estudiantes de escuelas secundarias públicas (N= 700) ubicadas en un municipio de un estado del noroeste de México. Los resultados permitieron obtener un modelo de medición empíricamente sustentable formado por nueve ítems agrupados en dos factores: Reconocimiento y Desplazamiento (c2 = 5.16, p= 0.27; CMIN= 1.29; GFI= .98; CFI= .99; NFI= .97; RMSEA= .05). El instrumento cuenta con evidencias de validez de criterio, ya que establece la diferencia en los factores de reconocimiento (t= 3.49, gl= 137, p< .001) y desplazamiento (t= 3.63, gl= 137, p< .001) en subgrupos de estudiantes con y sin reportes de bullying. Se concluyó que los resultados fortalecen la estructura factorial original de la escala y muestran su utilidad, tanto en la indagación de emociones relacionadas con el del desarrollo moral, como en la identificación de estudiantes involucrados como agresores en situaciones de bullying.Foram estabelecidas as evidências de validade e confiabilidade da adaptação do Questionário MOSS-SAST (Ahmed, 1999) para medir a gestão da vergonha em adolescentes ante situações de agressão contra os pares. O estudo foi realizado com uma amostra de estudantes do ensino fundamental e médio (N=700) de um município do noroeste do México. Os resultados permitiram obter um modelo de medição empiricamente sustentável, formado por nove itens agrupados em dois fatores: reconhecimento e deslocamento (c2 = 5.16, p= 0.27; CMIN= 1.29; GFI= .98; CFI= .99; NFI= .97; RMSEA= .05). O instrumento conta com evidências de validade de critério já que estabelece a diferença nos fatores de reconhecimento (t= 3.49, gl= 137, p< .001) e deslocamento (t= 3.63, gl= 137, p< .001) em subgrupos de estudantes com e sem relatos de bullying. Conclui-se que os resultados fortalecem a estrutura fatorial original da escala e mostram sua utilidade, tanto na indagação de emoções relacionadas com o desenvolvimento moral quanto na identificação de estudantes envolvidos como agressores em situações de bullying

ANALISIS DE LA CADENA PRODUCTIVA DEL PULQUE DEL ESTADO DE MÉXICO Y TLAXCALA

Durante la historia de México ha existido una vasta diversidad de productos alimenticios, algunos han desaparecido, otros lograron perdurar hasta nuestros dias con gran dificultad, un claro ejemplo es la bebida alcohólica llamada pulque, obtenida a partir de aguamiel extraído del maguey pulquero y sometido a un proceso de fermentación; el consumo de esta bebida es tradicional en el centro del país, principalmente en los Estados de Hidalgo, México, Puebla y Tlaxcala. No obstante a pesar de ser aparentemente la misma bebida en cada uno de los estados, existen diferencias marcadas entre ellos en los aspectos de superficie sembrada, rendimiento de litros por hectárea, costo por litro y ganancias obtenidas por esta actividad; a partir de estas diferencias es que se plantea el estudio de la cadena productiva del pulque en los Estados de México y Tlaxcala, siendo el primero el de mayor superficie plantada, pero el que recibe la menor cantidad de ingresos en contraste con el segundo que recibe la mayor cantidad de ingresos en una superficie cuatro veces menor (SIAP, 2010); para apoyar esta comparación se utilizó el método Delphi que contempla la aplicación de cuestionarios a expertos del tema (Scott, 2001) y el posterior procesamiento de los datos. Al término del análisis de datos se identificaron las variables que determinan la diferencia entre ambas cadenas mediante una tabla que concentra y señala los contrastes de ambos estados y de la cual se generaron las conclusiones

Multi-agent Learning by Trial and Error for Resource Leveling during Multi-Project (Re)scheduling

In a multi-project context within enterprise networks, reaching feasible solutions to the (re)scheduling problem represents a major challenge, mainly when scarce resources are shared among projects. The multi-project (re)scheduling must achieve the most efficient possible resource usage without increasing the prescribed project constraints, considering the Resource Leveling Problem (RLP), whose objective is to level the consumption of resources shared in order to minimize their idle times and to avoid overallocation conflicts. In this work, a multi-agent solution that allows solving the Resource Constrained Multi-project Scheduling Problem (RCMPSP) and the Resource Investment Problem is extended to incorporate indicators on agents? payoff functions to address the Resource Leveling Problem in a decentralized and autonomous way, through decoupled rules based on Trial-and-Error approach. The proposed agent-based simulation model is tested through a set of project instances that vary in their structure, parameters, number of resources shared, etc. Results obtained are assessed through different scheduling goals, such as project total duration, project total cost and leveling resource usage. Our results are far better compared to the ones obtained with alternative approaches. This proposal shows that the interacting agents that implement decoupled learning rules find a solution which can be understood as a Nash equilibrium.Fil: Tosselli, Laura. Universidad Tecnológica Nacional; ArgentinaFil: Bogado, Verónica Soledad. Universidad Tecnológica Nacional; ArgentinaFil: Martínez, Ernesto Carlos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Desarrollo y Diseño. Universidad Tecnológica Nacional. Facultad Regional Santa Fe. Instituto de Desarrollo y Diseño; Argentin

Evaluación de las propiedades físicas - químicas de Eucalyptus urograndis Eeucalipto), en el sector de Fumisa, cantón Buena Fe, provincia de Los Ríos

La presente investigación propuso: evaluar las propiedades físicas - químicas de Eucalyptus urograndis (Eucalipto), en el sector Fumisa, cantón Buena Fe, provincia de Los Ríos; donde se realizó la georreferenciación del área de estudio para la selección de las parcelas considerando los diámetros promedio y máximo de cada una de las cinco procedencias; las trozas se obtuvieron a la altura del DAP y altura comercial, posteriormente se realizó probetas de 3x4x7 (cm), resultando ocho probetas por cada árbol de las cuales se utilizaron 4 para contenido de humedad seco al horno el cual se realizó a una temperatura 103°C con intervalos de 3 horas, dando un total de 6 mediciones hasta que la diferencia entre medidas no varíe significativamente, las mediciones se realizaron cuando las probetas alcanzaban la temperatura ambiente; y 4 para seco al aire las mismas que se colocaron a temperatura ambiente por 60 días. Se determinó la densidad en verde, seca al horno, seca al aire y la densidad básica. Para la determinación del pH se recogió el aserrín mismo que fue mezclado con agua destilada y para su lectura en el pH metro. Además, se realizó una comparación entre la densidad obtenida por inmersión y medida con pie de rey digital. Obteniendo resultados significativos en la procedencia 2 para contenido de humedad, densidad y pH Palabras clave: PROPIEDADES FÍSICAS - QUÍMICAS - CONTENIDO DE HUMEDAD DE LA MADERA- TECNOLOGÍA DE LA MADERA.The current research work proposed to evaluate the physical-chemical properties of Eucalyptus urograndis (Eucalyptus) of Fumisa, located in the Buena Fe County, Los Ríos Province through the georeferencing about the study area for the selection of plots considering the average and maximum diameters of each of the five provenances. The pieces of wood were obtained at the height of the DAP and commercial height. After that, it made samples of 3x4x7 (cm), obtaining eight test tubes for each tree of which, 4 were used for drying moisture content in the furnace that was made at a temperature of 103°C with intervals of 3 hours, giving a total of 6 measurements until the difference between measurements does not vary significantly. The measurements were made when the test tubes reached room temperature for 60 days. On the other hand, it determined the density in green, dried in the furnace, air dried and basic density. To determine the pH, it collected the wood sawdust which was mixed with distilled water and for its reading at the pH meter. In addition, it made a comparison between the density obtained by immersion and measured with digital measuring caliper obtaining results in provenance 2 for moisture content, density and pH. Key words: PHYSICAL-CHEMICAL PROPERTIES, WOOD MOISTURE CONTENT, WOOD TECHNOLOG

L-band SAR co-polarized phase difference modeling for corn fields

This research aims at modeling the microwave backscatter of corn fields by coupling an incoherent, interaction-based scattering model with a semi-empirical bulk vegetation dielectric model. The scattering model is fitted to co-polarized phase difference measurements over several corn fields imaged with fully polarimetric synthetic aperture radar (SAR) images with incidence angles ranging from 20° to 60°. The dataset comprised two field campaigns, one over Canada with the Uninhabited Aerial Vehicle Synthetic Aperture Radar (UAVSAR, 1.258 GHz) and the other one over Argentina with Advanced Land Observing Satellite 2 (ALOS-2) Phased Array type L-band Synthetic Aperture Radar (PALSAR-2) (ALOS-2/PALSAR-2, 1.236 GHz), totaling 60 data measurements over 28 grown corn fields at peak biomass with stalk gravimetric moisture larger than 0.8 g/g. Co-polarized phase differences were computed using a maximum likelihood estimation technique from each field’s measured speckled sample histograms. After minimizing the difference between the model and data measurements for varying incidence angles by a nonlinear least-squares fitting, well agreement was found with a root mean squared error of 24.3° for co-polarized phase difference measurements in the range of -170.3° to -19.13°. Model parameterization by stalk gravimetric moisture instead of its complex dielectric constant is also addressed. Further validation was undertaken for the UAVSAR dataset on earlier corn stages, where overall sensitivity to stalk height, stalk gravimetric moisture, and stalk area density agreed with ground data, with the sensitivity to stalk diameter being the weakest. This study provides a new perspective on the use of co-polarized phase differences in retrieving corn stalk features through inverse modeling techniques from space.This research was partially funded by the Argentinean National Scientific and Technical Research Council (CONICET, project PICT 2015 N◦3689), by the Spanish Ministry of Science and Innovation (project CICYT RTI2018-099008-B-C21/AEI/10.13039/501100011033 “Sensing with pioneering opportunistic techniques”) and by the grant to “CommSensLab-UPC” Excellence Research Unit Maria de Maeztu (MINECO grant).Peer ReviewedPostprint (published version

A hierarchical two-tier approach to hyper-parameter optimization in reinforcement learning

Optimization of hyper-parameters in real-world applications of reinforcement learning (RL) is a key issue, because their settings determine how fast the agent will learn its policy by interacting with its environment due to the information content of data gathered. In this work, an approach that uses Bayesian optimization to perform an autonomous two-tier optimization of both representation decisions and algorithm hyper-parameters is proposed: first, categorical / structural RL hyper-parameters are taken as binary variables and optimized with an acquisition function tailored for such type of variables. Then, at a lower level of abstraction, solution-level hyper-parameters are optimized by resorting to the expected improvement acquisition function, whereas the categorical hyper-parameters found in the optimization at the upperlevelof abstraction are fixed. This two-tier approach is validated with a tabular and neural network setting of the value function, in a classic simulated control task. Results obtained are promising and open the way for more user-independent applications of reinforcement learning.Fil: Barsce, Juan Cruz. Universidad Tecnologica Nacional. Facultad Regional Villa Maria; ArgentinaFil: Palombarini, Jorge Andrés. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Centro de Investigaciones y Transferencia de Villa María. Universidad Nacional de Villa María. Centro de Investigaciones y Transferencia de Villa María; Argentina. Universidad Tecnologica Nacional. Facultad Regional Villa Maria; ArgentinaFil: Martínez, Ernesto Carlos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Desarrollo y Diseño. Universidad Tecnológica Nacional. Facultad Regional Santa Fe. Instituto de Desarrollo y Diseño; Argentin

A language for modeling the morphogenesis process of biological system using MAS

The biological systems are Complex Adaptive Systems that can build a complex structure using interaction between cell and its environment. The process is called morphogenesis, it is study by developmental biology and applied by tissue engineering and regenerative medicine. Computational models are used by researchers to organize and communicate ideas, test hypotheses and abstractly represent behaviors, etc. Although, Agent Based Models are used in biological systems, it is necessary appropriate domain-oriented language. This work shows the progress made in the definition of a language for modeling and simulation of such systems, in order to hide details of implementation and execution of a simulation. The language concepts are demonstrated using, as study case, the morphogenesis of a heart valve in vitro.Sociedad Argentina de Informática e Investigación Operativa (SADIO