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111.
Online control of cell culture redox potential prevents antibody interchain disulfide bond reduction
Michael W. Handlogten Jihong Wang Sanjeev Ahuja 《Biotechnology and bioengineering》2020,117(5):1329-1336
The phenomenon of monoclonal antibody (mAb) interchain disulfide bond reduction during manufacturing processes continues to be a focus of the biotechnology industry due to the potential for loss of product, increased complexity of purification processes, and reduced stability of the drug product. We hypothesized that antibody reduction can be mitigated by controlling the cell culture redox potential and subsequently established a threshold redox potential above which the mAb remained intact and below which there were significant and highly variable amounts of reduced mAb. Using this knowledge, we developed three control schemes to prevent mAb reduction in the bioreactor by controlling the cell culture redox potential via an online redox probe. These control methodologies functioned by increasing the concentration of dissolved oxygen (DO), copper (II) (Cu), or both DO and Cu to maintain the redox potential above the threshold value. Using these methods, we were able to demonstrate successful control of antibody reduction. Importantly, the redox control strategies did not significantly impact the cell growth, viability, mAb production, or product quality attributes including aggregates, C-terminal lysine, high mannose, deamidation, and glycation. Our results demonstrate that controlling the cell culture redox potential is a simple and effective method to prevent mAb reduction. 相似文献
112.
This paper addresses the building of stochastic models that adequately describe dynamic phenomena and, in particular, those that occur in the Biosciences. In this context, the empirical fitting of a Gaussian diffusion process from sample data of a dynamic growth phenomenon is considered. In order to do this, a methodology based on approximations to its mean and variance functions is presented. Finally, several applications based on simulated and real data have been carried out. 相似文献
113.
Stanislaus J. Schymanski Carsten F. Dormann Juliano Cabral Isabelle Chuine Catherine H. Graham Florian Hartig Michael Kearney Xavier Morin Christine Römermann Boris Schröder Alexander Singer 《Journal of Biogeography》2013,40(3):612-613
In a recent article (Dormann et al., 2012, Journal of Biogeography, 39, 2119–2131), we compared different approaches to species distribution modelling and depicted modelling approaches along an axis from purely ‘correlative’ to ‘forward process‐based’ models. In their correspondence, Kriticos et al. (2013, Journal of Biogeography, doi: 10.1111/j.1365‐2699.2012.02791.x ) challenge this view, claiming that our continuum representation neglects differences among models and does not consider the ability of fitted process‐based models to combine the advantages of both process‐based and correlative modelling approaches. Here we clarify that the continuum view resulted from recognition of the manifold differences between models. We also reinforce the point that the current trend towards combining different modelling approaches may lead not only to the desired combination of the advantages but also to the accumulation of the disadvantages of those approaches. This point has not been made sufficiently clear previously. 相似文献
114.
A. M. Babu N. B. Chowdary V. Kumar M. V. Rajan S. B. Dandin 《Archives Of Phytopathology And Plant Protection》2013,46(4):290-295
Abstract The pre-penetration and infection process of Colletotrichum dematium on mulberry leaf was investigated by scanning electron microscope. Conidia produced on germination appressoria directly or at the end of short germ tubes. Appressoria were formed mostly over cuticle, but sometimes over stomata also. At 72 h post-inoculation, an extensive network of sub-cuticular runner hyphae (RH) was produced. The RH were traceable by the cuticular bulgings on leaf surface. The RH emerged to leaf surface through ruptured cuticle to form secondary infection hyphae (SIH). The SIH re-entered the leaf tissue by sending penetration branches through stomata. Conidia were formed singly on short conidiophores from the RH and SIH, at short intervals. The conidia developed on RH were exposed to leaf surface through ruptured cuticle. Some times conidia were released through stomata also. The RH and SIH had thick knots from which hyphal branches and conidia were developed. Definite acervuli were not developed. 相似文献
115.
116.
Erythrocytes have an environment of continuous pro-oxidant generation due to the presence of hemoglobin (Hb), which represents an additional and quantitatively significant source of superoxide (O2−) generation in biological systems. To counteract oxidative stress, erythrocytes have a self-sustaining antioxidant defense system. Thus, red blood cells uniquely function to protect Hb via a selective barrier allowing gaseous and other ligand transport as well as providing antioxidant protection not only to themselves but also to other tissues and organs in the body. Sickle hemoglobin molecules suffer repeated polymerization/depolymerization generating greater amounts of reactive oxygen species, which can lead to a cyclic cascade characterized by blood cell adhesion, hemolysis, vaso-occlusion, and ischemia–reperfusion injury. In other words, sickle cell disease is intimately linked to a pathophysiologic condition of multiple sources of pro-oxidant processes with consequent chronic and systemic oxidative stress. For this reason, newer therapeutic agents that can target oxidative stress may constitute a valuable means for preventing or delaying the development of organ complications. 相似文献
117.
Abstract Actually, in modern process simulators, more than 75% of the code implemented is dedicated to physical properties estimation, calculation and predictions. Data banks storing pure component parameters and binary interaction parameters for phase equilibrium calculations are extensively used and continuously implemented in actual process simulators. This gives an idea of the important role physical properties availability plays in process simulation. In this paper we propose a new way for coupling molecular and process simulation. The basic machinery is to resort to molecular/quantum mechanics and molecular dynamics simulation techniques for generating the parameters of some equations of state that will subsequently be used for the prediction of phase equilibria and PVT behavior of small and polymeric molecules as well. This information, in turn, will be used as input in the process simulator, thus creating a final and well-defined bridge between molecular and process simulations in chemical engineering. 相似文献
118.
E. A. Castro D. A. J. Barbiric C. S. Nascimento W. B. De Almeida H. F. Dos Santos E. Coscarello 《Molecular simulation》2013,39(8):623-631
The complexation processes of 1 and 2-adamantanol with l-tryptophan-β-cyclodextrin have been studied using ab initio Hartree–Fock and density functional theory levels. For the host: guest inclusion processes, the up mode with the OH group of the alcohol oriented towards the secondary rim, is found to be in qualitative agreement with the experimental finding. A molecular recognition mechanism is proposed based on the host: guest relative dipole orientation. For the complex with the 2-Ada isomer the host and guest the dipoles are parallels favoring the interaction energy and. This mechanism can explain the small energy difference for the processes involving the adamantanol isomers and modified cyclodextrins. 相似文献
119.
DSP is an important by-product of alumina production via the Bayer process. Under Western Australian processing conditions, the DSP has a sodalite-type structure that can incorporate anions within its framework. This is particularly useful for removal of impurity anions from liquor recycled in the circuit. As a first step to gaining a fundamental understanding of the incorporation process, we have undertaken molecular mechanics calculations to examine the interaction energy between a series of anions and the sodalite framework, as a measure of the affinity of the anions for the sodalite cage. Our calculations predict that the ions have an increased affinity for the cage along the series aluminate, chloride, carbonate, sulfate and hydroxide. These calculations have successfully predicted the trends that we observe from competitive-uptake experiments in our laboratory. 相似文献
120.
《Critical reviews in biotechnology》2013,33(4):281-299
AbstractThe emergence of the biopharmaceutical industry represented a major revolution for modern medicine, through the development of recombinant therapeutic proteins that brought new hope for many patients with previously untreatable diseases. There is a ever-growing demand for these therapeutics that forces a constant technological evolution to increase product yields while simultaneously reducing costs. However, the process changes made for this purpose may also affect the quality of the product, a factor that was initially overlooked but which is now a major focus of concern. Of the many properties determining product quality, glycosylation is regarded as one of the most important, influencing, for example, the biological activity, serum half-life and immunogenicity of the protein. Consequently, monitoring and control of glycosylation is now critical in biopharmaceutical manufacturing and a requirement of regulatory agencies. A rapid evolution is being observed in this context, concerning the influence of glycosylation in the efficacy of different therapeutic proteins, the impact on glycosylation of a diversity of parameters/processes involved in therapeutic protein production, the analytical methodologies employed for glycosylation monitoring and control, as well as strategies that are being explored to use this property to improve therapeutic protein efficacy (glycoengineering). This work reviews the main findings on these subjects, providing an up-to-date source of information to support further studies. 相似文献