Antibody glycation during a CHO fed-batch process is following a constrained second order reaction

Glycation on lysine side chains of recombinant monoclonal antibodies (mAb) is a well known phenomenon in manufacturing processes of biopharmaceuticals that potentially alter the efficacy of the therapeutic protein. Previously, we reported a method to quantify the level of glycation formation directly from cell culture supernatants using boronate affinity chromatography (BAC). In this study, we report kinetic studies of glycation formation of the model protein Adalimumab, related to glucose and non-glycated protein in six CHO fed batch cultivations. An in-vivo model was demonstrated from glycation kinetic studies that is capable of estimating the reaction rate constant in static and dynamic bioprocesses, respectively. As anticipated, pseudo first order reactions with respect to present glucose concentration or non-glycated mAb were not sufficient to describe the glycation formation during the bioprocesses. However, second order reactions did not reveal linear relationship of glycated mAb to the product of glucose and non-glycated mAb, suggesting a reconsideration of kinetic equation. With the introduction of a constraint using only the newly formed product, i.e., the nascent protein, the second-order reaction was successfully implemented. These results show that the process knowledge derived from dynamic can be transferred to static experiments and vice versa. Hence, intensified DoE can be an applicable and useful tool in product quality studies in cell culture processes.

Dynamic transitions and bifurcations of 1D reaction-diffusion equations: The Self-adjoint case

This paper deals with the classification of transition phenomena in the most basic dissipative system possible, namely the 1D reaction diffusion equation. The emphasis is on the relation between the linear and nonlinear terms and the effect of the boundaries which influence the first transitions. We consider the cases where the linear part is self-adjoint with 2nd order and 4th order derivatives which is the case which most often arises in applications. We assume that the nonlinear term depends on the function and its first derivative which is basically the semilinear case for the second order reaction-diffusion system. As for the boundary conditions, we consider the typical Dirichlet, Neumann and periodic boundary settings. In all the cases, the equations admit a trivial steady state which loses stability at a critical parameter. We aim to classify all possible transitions and bifurcations that take place. Our analysis shows that these systems display all three types of transitions: continuous, jump and mixed and display transcritical, supercritical bifurcations with bifurcated states such as finite equilibria, circle of equilibria, and slowly rotating limit cycle. Many applications found in the literature are basically corollaries of our main results. We apply our results to classify the first transitions of the Chaffee-Infante equation, the Fisher-KPP equation, the Kuramoto Sivashinsky equation and the Swift-Hohenberg equation.

Oxidative hydrolysis of Fe(Ⅱ) in the process of hydrothermal synthesis of hematite

Iron removal is an important step in zinc hydrometallurgy, and hematite process not only can effectively remove iron, but also is environmentally friendly and has certain economic benefits, so it has great application potential in zinc hydrometallurgy. The oxidative hydrolysis of Fe(Ⅱ) was studied by the change of ions in solution with different initial ferrous ion concentration. Meanwhile, the oxidation rates of Fe(Ⅱ) at different initial Zn(Ⅱ) concentrations were also studied. The results show that temperature has an important influence on the oxidative hydrolysis of Fe(Ⅱ). Increasing the temperature can inhibit the formation of complex and make more Fe(Ⅱ) precipitate directly in the form of hematite, which is not limited by the hydrolysis rate of Fe(Ⅲ). The oxidation reaction of Fe(Ⅱ) approximately conforms to the second order reaction rate. Zinc sulfate can promote the oxidation of Fe(Ⅱ). When the initial Zn(Ⅱ) concentration was 20, 40, 60 and 80 g/L, the oxidation kinetic constants of Fe(Ⅱ) were 2.433, 4.492, 10.106 and 14.857 L·mol−1·min−1, respectively.

Phosphorus Retention in Lakes: A Critical Reassessment of Hypotheses and Static Models

Various hypotheses and models for phosphorus (P) retention in lakes are reviewed and 39 predictive models are assessed in three categories, namely mechanistic, semi-mechanistic, and strictly-empirical models. A large database consisting of 738 data points is gathered for the analyses. Assessing four pairs of competing hypotheses used in mechanistic models, we found that (i) simulating lakes as mixed-flow reactor is superior to plug-flow reactor hypothesis; (ii) modeling P loss as a second-order reaction outperforms the first-order reaction; (iii) P loss is better explained as a removal process throughout the lake volume than as a settling process across the sediments; and (iv) considering a fraction of P loading is associated with fast settling particles enhances lake total phosphorus (TP) predictions. Due to the systematic approach used for combining the hypotheses, some models are for the first time developed and assessed. For instance, the preeminent mechanistic model combines, for the first time, the second-order reaction hypothesis with the hypothesis that a specific proportion of P loading settles rapidly at the lake entrance. Results also showed that semi-mechanistic models outperform both mechanistic and strictly-empirical models since they take the form of a mechanistic model based on the physical representation of the lakes and utilize statistically acquired equations for unknown parameters. The best-fit model is a semi-mechanistic model that adopts the mixed-flow reactor hypothesis with a second-order volumetric reaction rate that is calculated as a non-linear function of inflow TP concentration, lake average depth, and water retention time. This model predicts 77.8% of the variability of log10-transformed lake TP concentration, which is 4.2% higher than the best mechanistic model and 0.8% higher than the best strictly-empirical model. The findings of this study not only shed light on the understanding of P retention in lakes but also can be useful for assessment of data-limited lakes and large-scale hydrological models to simulate the P cycle.

Photochemical reaction of superoxide radicals with 1-naphthol

he photochemical reactions between 1-naphthol (1-NP) and superoxide anion radical (O2•−) were investigated in detail by using 365 nm UV irradiation. The results showed that the conversion rate of 1-naphthol decreased with the increase of the initial concentration of 1-naphthol, while the raising pH and riboflavin concentration accelerated the photochemical reaction. The second-order reaction rate constant was estimated to be (3.64 ± 0.17) × 108 L mol−1 s−1. The major photolysis products identified by using gas chromatography-mass spectrum (GC-MS) were 1, 4-naphquinone and 2, 3-epoxyresin-2, 3-dihydro-1, 4-naphquinone, and their reaction pathways were also discussed. An atmospheric model showed that both bulk water reaction and heterogeneous surface reaction deserved attentions in atmospheric aqueous chemistry.

Kinetic Studies of the Glycerolysis of Urea to Glycerol Carbonate in the Presence of Amberlyst-15 as Catalyst

Amberlyst-15, a strong acidic ion-exchange resin, has showed as a potential and an effective catalyst for the glycerolysis process of urea to glycerol carbonate. In this work, the kinetic model of the urea glycerolysis over Amberlyst-15 catalyst was investigated. The kinetic model was developed by considering simultaneous steps of urea dissolution in glycerol, mass transfer of urea and glycerol from the bulk of the liquid into the outer part of the catalyst, diffusion of urea and glycerol into the inner part of the particle through the catalyst pores, and irreversible second order reaction of urea and glycerol on the active sites. The irreversibility of second order reaction of urea glycerolysis was validated and proven. The proposed kinetic model was simulated and validated with the experimental data. The kinetic studies show that mechanism proposed works well. Furthermore, the activation energy was found to be 145.58 kJ.mol−1 and the collision factor was in 8.00×1010 (m3)2.kg−1.mol−1.s−1. The simulation result shows that the predicted liquid temperatures were close to the experimental temperature data. It also gave glycerol concentration profile inside the catalyst particle as a function of glycerolysis time and position. Copyright © 2021 by Authors, Published by BCREC Group. This is an open access article under the CC BY-SA License (https://creativecommons.org/licenses/by-sa/4.0).

Theoretical derivation and clinical dose-response quantification of a unified multi-activation (UMA) model of cell survival from a logistic equation

Objective: To theoretically derive a unified multiactivation (UMA) model of cell survival after ionising radiation that can accurately assess doses and responses in radiotherapy and X-ray imaging. Methods: A unified formula with only two parameters in fitting of a cell survival curve (CSC) is first derived from an assumption that radiation-activated cell death pathways compose the first- and second-order reaction kinetics. A logit linear regression of CSC data is used for precise determination of the two model parameters. Intrinsic radiosensitivity, biologically effective dose (BED), equivalent dose to the traditional 2 Gy fractions (EQD2), tumour control probability, normal-tissue complication probability, BED50 and steepness (Γ50) at 50% of tumour control probability (or normal-tissue complication probability) are analytical functions of the model and treatment (or imaging) parameters. Results: The UMA model has almost perfectly fit typical CSCs over the entire dose range with R2≥0.99. Estimated quantities for stereotactic body radiotherapy of early stage lung cancer and the skin reactions from X-ray imaging agree with clinical results. Conclusion: The proposed UMA model has theoretically resolved the catastrophes of the zero slope at zero dose for multiple target model and the bending curve at high dose for the linear quadratic model. More importantly, it analytically predicts dose–responses to various dose–fraction schemes in radiotherapy and to low dose X-ray imaging based on these preclinical CSCs. Advances in knowledge: The discovery of a unified formula of CSC over the entire dose range may reveal a common mechanism of the first- and second-order reaction kinetics among multiple CD pathways activated by ionising radiation at various dose levels.

STUDY ON THE PRECIPITATION KINETICS OF ORDERED PHASE IN Ni-10 at% Cr ALLOY

The precipitation phenomenon of Ni3Cr phase in Ni-10 at% Cr alloy was studied through the isothermal annealing at different high temperatures. It was found that a metastable microstructure is formed during isothermal annealing at 850 ºC. The precipitation of ordered Ni3Cr phase was obtained during isothermal annealing at 950 and 975 ºC. Both processes increase the microstress in the matrix and consequently seemed to impose a heavily pinning action on the magnetic domain walls. The precipitation process was found to be controlled by a second order reaction, activated by an energy of 1.3 eV.

KINETIKA FOTODEGRADASI METHYLENE BLUE MENGGUNAKAN KOMPOSIT Ag3PO4/Ag/HAp TULANG IKAN KAKAP MERAH (Lutjanus sp.)

ABSTRAKTujuan dari penelitian ini untuk mengkaji kinetika fotodegradasi methylene blue (MB) menggunakan komposit Ag3PO4/Ag/HAp tulang ikan kakap merah (Lutjanus sp.). Serbuk tulang ikan yang dikalsinasi hingga 1000ºC dan direaksikan dengan AgNO3 dengan rasio mol 5:1 (Ag:HAp) dan dihasilkan komposit Ag3PO4/Ag/HAp. Larutan MB diinteraksikan dengan komposit dengan variasi waktu 5-180 menit dibawah radiasi cahaya tampak. Konsentrasi MB yang tersisa ditentukan ditentukan dengan spektrofotometer UV-Vis dan data yang diperoleh dianalisis dengan model kinetika reaksi orde ke-1 dan ke-2. Hasil penelitian menunjukkan bahwa fotodegradasi MB oleh komposit Ag3PO4/Ag/HAp mengikuti model kinetika fotodegradasi orde ke-2. ABSTRACT The purpose of this research was to study the kinetics of methylene blue (MB) photodegradation using composite Ag3PO4/Ag/HAp bone fish of red snapper (Lutjanus sp.). Fish bone powder which was calcined to 1000ºC and reacted with AgNO3 with mole ratio of 5 : 1 (Ag: HAp) and produced Ag3PO4/Ag/HAp composite. MB solution was interacted with composites with variation of time 5-180 minutes under visible light radiation. The remaining MB concentrations determined were determined by a UV-Vis spectrophotometer and the data obtained were analyzed with first and second order reaction kinetics model. The results showed that MB photodegradation by Ag3PO4/Ag/HAp composites followed the 2nd order photodegradation kinetics model.

Sulfate radical-based oxidation of an alcohol ethoxylate (Brij30®) by the PS/UV-C process

In this study, sulfate radical-based oxidation of an alcohol ethoxylate (AE) was explored by the persulfate (PS)/UV-C process. Poly(oxyethylene)(4)laurylether, commercially known as Brij30®, was used as a model AE. PS/UV-C oxidation of aqueous Brij30® (8–20 mg/L) was performed at initial PS concentrations varying between 0.50 and 6.50 mM and at initial pH values of 3.0 and 6.0. Results indicated that an increase in both initial PS and Brij30® concentrations did not have a significant effect on Brij30® removal efficiency and that Brij30® abatements of more than 90% could be achieved after 60 min of treatment time. Total organic carbon (TOC) removals were significantly improved with increasing initial PS concentrations for both initial pH values. On the other hand, an increase in initial Brij30® concentration had a negative effect on mineralization. By employing the competitive kinetic method, the second-order reaction rate coefficient of Brij30® with the sulfate radical (SO4•−) was determined as 1.62 × 109 ± 3.5 × 107 M−1s−1. The second-order reaction rate constant of TOC, originating from Brij30® and reaction intermediates, was found to be 9.09 × 105 ± 2.91 × 105 M−1s−1 and 1.13 × 106 ± 0.46 × 106 M−1s−1 for pH values of 6.0 and 3.0, respectively. Toxicity of PS/UV-C treated aqueous Brij30® solutions towards Vibrio fischeri was also investigated to determine the possible toxic behavior of oxidation products.