An in silico evaluation of data‐driven optimization of biopharmaceutical processes

Two methodological improvements of the design of dynamic experiments (C. Georgakis, Ind Eng Chem Res. 2013) for the modeling and optimization of (semi‐) batch processes are proposed. Their effectiveness is evaluated in two representative classes of biopharmaceutical processes. First, we incorporate prior process knowledge in the design of the experiments. Many batch processes and, in particular, biopharmaceutical processes are usually not understood completely to enable the development of an accurate knowledge‐driven model. However, partial process knowledge is often available and should not be ignored. We demonstrate here how to incorporate such knowledge. Second, we introduce an evolutionary modeling and optimization approach to minimize the initial number of experiments in the face of budgetary and time constraints. The proposed approach starts with the estimation of only a linear Response Surface Model, which requires the minimum number of experiments. Accounting for the model's uncertainty, the proposed approach calculates a process optimum that meets a maximum uncertainty constraint. © 2017 American Institute of Chemical Engineers AIChE J, 63: 2796–2805, 2017     

CONTINUITY BETWEEN DISORDER AND ORDER IN THE SEQUENTIAL DEPOSITION OF PARTICLES

In previous work we pointed out that clusters of particles built through sequential quenching show increasing degrees of order as the temperature is lowered. In the low-temperature limit, a two-dimensional model system with a nondegenerate ground state would result in a perfect crystal. The opposite, high-temperature, limit corresponds to the case of random sequential addition (RSA). In the present work we study the continuous evolution from disorder to order at intermediate states using a triangular well potential to represent particle interactions. We investigate radial and bond-orientation correlation functions and the bond order parameter as measures of the degree of crystallinity of the structures up to a reduced number density of 0.65, which is close to the jamming limit of RSA.     

U-Statistics in Sequential Tests and Change Detection

Abstract

Research on U-statistics within the general framework of sequential and change-point literature is surveyed. Some recent developments are discussed and extended. New sequential testing strategies based on Wiener process approximations are proposed, and empirical studies explore the finite sample performance of these tests. It allows users to choose one that is appropriate for their application.     

Multistage decission problems

K treatments that yield dichotomous responses are considered in a multistage clinical trial. The total number of patients to be involved in the trial is N, which is random. The optimal length for each treatment at each stage is to be decided. The objective is to maximize the expected total number of successes of the trial. Two cases are considered: (1) Two stages. It is shown that the rate of the optimal length of the first stage is no greater than √E(N) as E(N) goes to infinity, when the distribution of N, Q, yields a regular discount sequence. The rate may be smaller than √E(N) which depends on the distribution of N and the prior distributions on the probabilities of success of the treatments. Under certain conditions, the rate is exactly √E(N). Nevertheless, the rate may be greater than E(N) without the regularity of Q. (2) r stages. It is shown that M^?/E(N) converges to zero in probability as E(N) goes to infinity when Q has the regularity, where M^? is the sum of the optimal lengths for the first r - 1 stages.     

Multicomponent anion exchange with a resin having weakly and strongly basic groups

Multicomponent anion exchange with a resin having both weakly and strongly basic groups was investigated by means of modelling and column experiments. Our objective was to develop a model able to predict the evolution of the composition of a water treated by such a resin. The studied resin was Purolite S108, used for boron removal from water, on which ternary and quaternary amines were attached (additionally to boron complexing groups). Column dynamics were modelled with the computer code IMPACT, devoted to reactive transport in porous media. A reaction scheme was proposed to represent anion exchange on the two types of groups, with a quaternary anionic system including hydroxide, chloride, sulphate and nitrate at a given ionic concentration. This reaction scheme needed eight parameters: concentrations of weak and strong-base groups and the anion exchange selectivities. These parameters were measured through binary anion exchange, without or with pH step. The breakthrough curves of the binary experiments were in very good agreement with the experimental one. The model was then used to predict the results of a more complex experiment in which the column had been fed by a mixture of acids. The main features of the experimental behaviour were fairly well predicted, even if the agreement was not perfect. These discrepancies were attributed to the model assumptions, mainly to the expressions of anion exchange selectivities. These results enabled us to predict almost quantitatively the evolution of the water composition during its treatment. This point is an improvement in the prediction of the dynamics of an anion exchange with two types of groups. In the future, the model would have to be extended to take into account different expressions of the exchange selectivities, and nonequilibrium conditions.     

MONTE CARLO SIMULATION OF AGGREGATION PROCESSES STRUCTURAL PROPERTIES OF DEPOSITIONAL AGGREGATES

The usefulness of Monte Carlo simulation of aggregation phenomena is discussed and applied in analysis of the structure of particle deposits. The structural properties of depositional aggregates in single and multiparticle regimes are obtained and expressed in terms of fractal geometrical concepts. These properties are related to the Peclet number and to the concentration in the non-aggregate (vapour) phase. The topological properties of the aggregates are obtained from random walk simulation, thus confirming the anomalous properties of these structures, even in the case of multiparticle simulations, i.e. for high values of the concentration in the vapour phase.     

A Comparison of two sequential tests forµ/σ

Either the sequential probability ratio test or the sequential likelihood ratio test can be used to test one—sided hypotheses regarding the ratio λ = µ/σ, Both tests are functions of the usual t—statistic. I discuss and compare empirical and theoretical properties of these two tests, and provide tables of critical and truncation values for a modified version of the sequential likelihood ratio test     

超声场对化工分离过程的强化

近年来，超声场强化工分离过程的研究十分活跃，本文比较详细地综述了这一领域的研究进展，并结合化工分离过程的特点，探讨了超场强化化工分离过程的附加效应，为该邻域的研究工作提供了有效的途径。     

A joint model-based experimental design approach for the identification of kinetic models in continuous flow laboratory reactors

Continuous flow laboratory reactors are typically used for the development of kinetic models for catalytic reactions. Sequential model-based design of experiments (MBDoE) procedures have been proposed in literature where experiments are optimally designed for discriminating amongst candidate models or for improving the estimation of kinetic parameters. However, the effectiveness of these procedures is strongly affected by the initial model uncertainty, leading to suboptimal design solutions and higher number of experiments to be executed. A joint model-based design of experiments (j-MBDoE) technique, based on multi-objective optimization, is proposed in this paper for the simultaneous solution of the dual problem of discriminating among competitive kinetic models and improving the estimation of the model parameters. The effectiveness of the proposed design methodology is tested and discussed through a simulated case study for the identification of kinetic models of methanol oxidation over silver catalyst.     

RANDOM AGGREGATION OF UNIVARIATE AND MULTIVARIATE LINEAR PROCESSES

Abstract. The paper is devoted to random aggregation of multivariate autoregressive moving-average (ARMA) processes. We derive second-order characteristics of random aggregate models. We show that random aggregation preserves the ARMA structure. Moreover, we specify a functional relation between the initial model poles and aggregate ones. We then examine the case of univariate ARMA processes. Theorem 4 shows that, if the initial process is ARMA( p, q ), the random aggregate process is an ARMA( p*, q* ) model with p* at most equal to p ; * depends, among other things, on the sampling distribution L . This theorem generalizes the well-known results on the topic of time interval aggregation without overlapping.     

Complementary modelling of fluid separation processes

Optimal functioning of numerous technological processes depends primarily on relevant process design, properly selected column internals and sufficient understanding of the process behaviour. This can be achieved only with the help of accurate and reliable process models capable of considering process rates in a rigorous way, with respect to both transport phenomena and chemistry. In this article, a new modelling concept called complementary modelling is suggested for a large class of fluid separation processes. Since the conditions and criteria for these processes vary considerably, it is impossible to develop a unified modelling approach. Instead, a reasonable and effective combination of different modelling approaches provides solutions to many present and future tasks. The complementary modelling is discussed in detail and illustrated with several case studies.     

Drying of Fresh and Rewetted Shelled Corn in Microwave Fields

ABSTRACT

Drying of freshly harvested and artificially rewetted yellow dent shelled corn was studied experimentally under microwave conditions. The dehydration rate of rewetted corn was found to be higher than that of freshly harvested corn; the deviation in the dehydration rates was found to be a power law function of the moisture content. under similar conditions, freshly harvested corn has a lower drying rate relative to the rewetted samples. The difference between these drying rates varies by a power law relationship with kernel moisture content.     

中药制剂分析综合性设计性实验教学探讨

《中药制剂分析》课是中药学相关专业的中药专业课,开设综合性、设计性实验,培养学生的创新能力和综合素质是当前中药制剂分析教学改革的重要内容。文章对中药制剂分析综合性设计性实验的开设比例和开展模式做了介绍,并谈了开设综合性设计性实验的体会,以期对完善中药制剂分析的实验教学,提高实验教学质量提供参考。     

粉煤灰泡沫陶瓷浆料的稳定机制

通过不同组分浆料的沉降实验,研究了固含量、分散剂（淀粉、硅酸钠、柠檬酸三铵）对浆料稳定性能的影响。实验过程中测量了1#～12#浆料浑浊液和上清液的高度,进而得到浆料的相对沉降高度（RSH）值。通过测量10#、13#、14#浆料在沉降过程中上清液高度的变化,研究了13#、14#浆料的稳定性。实验结果分析发现,在含硅酸钠的悬浮浆料中,随着浆料中固含量的增加,淀粉作为分散剂对浆料的稳定性能的影响减小;在不含硅酸钠的浆料中．这一规律只在3#～6#的浆料中出现;淀粉、柠檬酸三铵作分散剂可显著提高浆料的稳定性。硅酸钠对浆料的分散效果较差,保证素坯在低温强度的状态下,应尽量减少硅酸钠的用量。