Optimal economic design and operation of single- and multi-column chromatographic processes

Single-column chromatography is widely used in the biopharmaceutical industries, although multi-column alternatives in the form of simulated moving bed (SMB) processes are now emerging. It may be difficult, however, to determine which column alternative will be best suited for a given application, and this work sets out to address this issue. A systematic approach is presented that is based on a full economic appraisal of each process alternative based on an optimization of the net annual profit. Single-column processes with and without recycling are considered, as are both the SMB and the Varicol process. The cyclic steady state for the SMB and Varicol processes is determined directly by complete discretization. The approach is applied to a case study based on a linear isotherm where it is found that for this particular system, a recycling policy is not necessary for the single column. When comparing the single-column process with the multi-column alternatives, the single column is the most economical provided the life time of the project is short; however, the economic benefits of the more capital-intensive multi-column processes are greater if the life time of the project is over 5 years. The SMB process is found to perform marginally better than the Varicol process over 15 years; however, this may be because not all extra degrees of freedom for the Varicol process were considered.     

Melatonin and aging

Although many theories relating the pineal secretory product melatonin to aging have been put forward, the role of this agent in the aging process is not clear. However, there are several reasons to postulate a role for melatonin in this process. Melatonin levels fall gradually over the life-span. Melatonin is a potent free radical scavenger. Melatonin deficiency is related to suppressed immunocompetence. In at least one animal model melatonin supplementation increased life-span although several other studies have failed. The aging process is multifactorial, and no single element seems to be of basic importance. It seems, however, that although melatonin can not be univocally recognized as a substance delaying aging, some of its actions may be beneficial for the process of aging. However, the precise role of melatonin in the aging process remains to be determined.     

Process development and evaluation for algal glycerol production

This article and develops a process for large-scale production of glycerol by means of a hemophilic algae. The process is shown to be economically and technically feasible. Although the proposed process is extremely capital intensive, the total production cost is competitive with existing glycerol process. In addition, the overall energy requirement is much lower than that of the petrochemical process. This proposed process provides an alternative route for glycerol production that is minimally dependent on fossil fuels and is therefore, less sensitive to crude oil availability and price. The primary raw material carbon dioxide from stack gas, is an inexpensive and renewable resource. Maximal Utilization of solar energy is made not only in the glycerol synthesis steps but also in the product recovery system. Significant improvement in the process economics can be realized through further development of large-scale cultivation technology, and biomass distribution and collection machinery. Due to the labor intensive nature of the proposed algal process, it is particularly suitable for less developed nations with limited fossil fuel resources and lower labor costs.     

Industrial glucoamylase fed-batch benefits from oxygen limitation and high osmolarity

The market for glucoamylase is large and very competitive and the production process has been optimized through several decades. So far a thorough characterization of the process has not been published, but previous academic reports suggest that the process suffers from severe byproduct formation. In this study we have carried out a thorough characterization of a process as close as possible to the industrial reality. The results show that the oxygen-limited phases of the process have the highest glucoamylase yields on carbon and that the byproducts are efficiently reused in late phases of the process. An alternative process with low glucose concentration show that high osmolarity is beneficial for the process, and we conclude that oxygen limitation, high osmolarity, and the associated byproduct metabolism are important for the efficiency of the process.     

A system control framework for the self-fertilization and selection process of breeding

The self-fertilization and selection process is the main method for speeding up the purifying course of a hybrid population in breeding. This is a complex combinatorial random process with large time delay. To raise the control effectiveness and efficiency of the process, we try, in this paper, to construct a mathematical model of the process by means of effective factors. Then, a control framework for the process is presented which can be used as a guide by breeders for helping them in selecting appropriate control actions.     

Extractive fermentation-integrated reaction and product recovery

Summary Refinements have been made to a prototype process for the production of ethanol by extractive fermentation. The process is characterized by thein situ extraction of ethanol from a 7 L continuous stirred tank fermenter and the thermal recovery of ethanol from the extracting solvent, which is circulated in a closed loop through the process. Data are provided to show the efficacy and stability of the process under various operating conditions, and the near complete (>96%) continuous conversion of a 300 g/L glucose feed.     

Measurement of Diversity and Dissimilarity for Stochastic Populations

The existing measures of diversity within a population and of dissimilarity between two populations postulate a static population with unchanging probabilistic structure. We assume that the measurements associated with an individual change with time according to a stochastic process. General measures of diversity and of dissimilarity when the underlying process is a finite Markov chain are developed. An aportionment of these measures based on a partition of the state-space is provided. Their asymptotic behaviour is investigated. The spectral analysis of measures of diversity is carried out. Some specific measures of diversity and dissimilarity are obtained when the underlying stochastic process is a general vector-valued process. An indication of directions for future work is provided.     

Saturable and nonsaturable process of sugar uptake: effect of oncogenic transformation in transport and uptake of nutrients.

Uptake of sugars into cells by a saturable process increased enormously during and after transformation, and uptake by a nonsaturable process increased significantly but less remarkably compared to controls. The drastic change of uptake rates, observed at around 5 x 10(-3) M sugar during and after transformation, emphasizes the significant observation that transition of the sugar uptake system from a saturable to a nonsaturable process occurs near the physiological concentration of D-glucose normally seen in animal blood. At concentrations below higher than 5 x 10(-3) M, where a saturable process is barely involved, nonsaturable uptakes of D-glucose, D-mannose, D-galactose, 2-deoxy-D-glucose and 3-O-methyl-D-glucose proceed tens to hundreds fold faster than the rate of simple diffusion of L-glucose. These findings suggest that nonsaturable uptake of the sugars known to be substrates for the saturable transport carrier system may not be a physical process or simple diffusion, as observed for L-glucose uptake. Rather, the nonsaturable uptake might be part of the total physiological process which, along with the saturable process, is controlled by a membrane-coordination mechanism. A plausible mechanism is discussed in which negative cooperativity of nutrient uptake, such as that found in bacteria, is involved.     

Diversity and Evolution of the Marsupial Mandibular Angular Process

A medial inflection of the mandibular angular process is present in most marsupials. The few living marsupials that lack this trait either are very specialized forms (e.g., Tarsipes) or show a medial inflection at some point in development that is lost in later ontogenetic stages (cf. Dactylopsila and Phascolarctos). A medially inflected angular process is not present in any known extant or extinct placental (including all Cretaceous taxa that preserve the back of the dentary bone). Some extant placentals with enlarged auditory bullae evolved a medial flange of the angular process as a strategy to increase gape, but this is not homologous to the marsupial condition. We conclude that the medially inflected angular process is a shared derived trait of extant and extinct marsupials. The significant diversity in the form of the medially inflected mandibular angular process in marsupials, documented here for 53 taxa, shows a general relation to dietary adaptations. Herbivores (with well-developed masseter and medial pterygoid muscles) tend to have a shelf-like angular process, while small, insectivorous marsupials generally have a rod-like angular process. A close connection between the angular process and the ectotympanic is maintained during early postnatal development in all marsupials examined, a relation not seen in the placentals examined. A previous hypothesis suggested that the angular process plays a role in hearing in pouch-young Monodelphis. Data on the maturation of the auditory system does not support this hypothesis. Currently there are no data on differences in muscular anatomy or mastication between marsupials and placentals that could serve as a causal explanation for the difference in adult form of the angular process between the two groups.     

Dynamic modeling and analyses of simultaneous saccharification and fermentation process to produce bio-ethanol from rice straw

The rice straw, an agricultural waste from Asians’ main provision, was collected as feedstock to convert cellulose into ethanol through the enzymatic hydrolysis and followed by the fermentation process. When the two process steps are performed sequentially, it is referred to as separate hydrolysis and fermentation (SHF). The steps can also be performed simultaneously, i.e., simultaneous saccharification and fermentation (SSF). In this research, the kinetic model parameters of the cellulose saccharification process step using the rice straw as feedstock is obtained from real experimental data of cellulase hydrolysis. Furthermore, this model can be combined with a fermentation model at high glucose and ethanol concentrations to form a SSF model. The fermentation model is based on cybernetic approach from a paper in the literature with an extension of including both the glucose and ethanol inhibition terms to approach more to the actual plants. Dynamic effects of the operating variables in the enzymatic hydrolysis and the fermentation models will be analyzed. The operation of the SSF process will be compared to the SHF process. It is shown that the SSF process is better in reducing the processing time when the product (ethanol) concentration is high. The means to improve the productivity of the overall SSF process, by properly using aeration during the batch operation will also be discussed.     

Source-sink landscape theory and its ecological significance

Exploring the relatiouships between landscape pattern and ecological processes is the key topic of landscape ecology,for which,a large number of indices as well as landscape pattern analysis model were developed.However,one problem faced by landscape ecologists is that it is hard to link the landscape indices with a specific ecological process.Linking landscape pattern and ecological processes has become a challenge for landscape ecologists."Source" and "sink" are common concepts used in air pollution research,by which the movement direction and pattern of different pollutants in air can be clearly identified.In fact,for any ecological process,the research can be considered as a balance between the source and the sink in space.Thus,the concepts of "source" and "sink" could be implemented to the research of landscape pattern and ecological processes.In this paper,a theory of sourcesink landscape was proposed,which include:(1) In the research of landscape pattern and ecological process,all landscape types can be divided into two groups,"source"landscape and "sink" landscape."Source" landscape contributes positively to the ecological process,while "sink" landscape is unhelpful to the ecological process.(2) Both landscapes are recognized with regard to the specific ecological process."Source" landscape in a target ecological process may change into a "sink"landscape as in another ecological process.Therefore,the ecological process should be determined before "source"or "sink" landscape were defined.(3) The key point to distinguish "source" landscape from "sink" landscape is to quantify the effect of landscape on ecological process.The positive effect is made by "source" landscape,and the negative effect by "sink" landscape.(4) For the same ecological process,the contribution of "source" landscapes may vary,and it is the same to the "sink"landscapes.It is required to determine the weight of each landscape type on ecological processes.(5) The sourcesink principle can be applied to non-point source pollution control,biologic diversity protection,urban heat island effect mitigation,etc.However,the landscape evaluation models need to be calibrated respectively,because different ecological processes correspond with different source-sink landscapes and evaluation models for the different study areas.This theory is helpful to further study landscape pattern and ecological process,and offers a basis for new landscape index design.     

Enhanced process understanding and multivariate prediction of the relationship between cell culture process and monoclonal antibody quality

This work investigates the insights and understanding which can be deduced from predictive process models for the product quality of a monoclonal antibody based on designed high‐throughput cell culture experiments performed at milliliter (ambr‐15^®) scale. The investigated process conditions include various media supplements as well as pH and temperature shifts applied during the process. First, principal component analysis (PCA) is used to show the strong correlation characteristics among the product quality attributes including aggregates, fragments, charge variants, and glycans. Then, partial least square regression (PLS1 and PLS2) is applied to predict the product quality variables based on process information (one by one or simultaneously). The comparison of those two modeling techniques shows that a single (PLS2) model is capable of revealing the interrelationship of the process characteristics to the large set product quality variables. In order to show the dynamic evolution of the process predictability separate models are defined at different time points showing that several product quality attributes are mainly driven by the media composition and, hence, can be decently predicted from early on in the process, while others are strongly affected by process parameter changes during the process. Finally, by coupling the PLS2 models with a genetic algorithm first the model performance can be further improved and, most importantly, the interpretation of the large‐dimensioned process–product‐interrelationship can be significantly simplified. The generally applicable toolset presented in this case study provides a solid basis for decision making and process optimization throughout process development. © 2017 American Institute of Chemical Engineers Biotechnol. Prog., 33:1368–1380, 2017     

Thinking and Ways of Investigating It

The thought process, of course, breaks down into different elements. Thus, in problem solving, analysis articulates what is given (known) and what unknown; and analysis of information in accordance with the requirements of the particular problem leads to identification of the conditions constituting what is known and what is unknown. Each element of the thought process, viewed from the perspective of the result achieved, is a unitary act (a mental action, an operation). However, in studying thought we must not forget that what makes each element a unitary act is the objectively determined and explicit end result of the thought process. What is initial and primary are not these operations, but the integral thought process of which they are discrete constituents.     

细胞迁移中微丝微管的变化及其信号转导通路研究进展

细胞迁移是一个多步骤协调的过程。在此过程中,细胞骨架蛋白微丝和微管的动态变化提供了细胞运动的主要动力。而迁移的过程又被多种信号分子组成的复杂的网络所调控。本文主要综述了细胞迁移中微丝和微管的变化以及调控此种变化的分子机制。     

Process dynamics, instrumentation and control

A total of 77 references pertaining to the subject were consulted to compose the present review. In addition to their years of publication (1981–1983), the references were selected primarily for their practicality and ability to provide experimental results and confirmation. First, a generalized model illustrating the biochemical reaction engineering considerations is presented. Here the knowledge of reactor and reaction kinetics is emphasized and the need for process instrumentation identified. Recent developments in key process sensors are then discussed in detail along with their utilities in various process situations. Finally, application of control principles and on-line computers to biochemical process operation is given a realistic evaluation by considering the process dynamics and instrumentation capabilities. Future challenges and opportunities from both the reaction engineering and system engineering points of view are carefully assessed. The most recent review relevant to the subject is that by Bull (1983).     

Deer antler regeneration: cells, concepts, and controversies

The periodic replacement of antlers is an exceptional regenerative process in mammals, which in general are unable to regenerate complete body appendages. Antler regeneration has traditionally been viewed as an epimorphic process closely resembling limb regeneration in urodele amphibians, and the terminology of the latter process has also been applied to antler regeneration. More recent studies, however, showed that, unlike urodele limb regeneration, antler regeneration does not involve cell dedifferentiation and the formation of a blastema from these dedifferentiated cells. Rather, these studies suggest that antler regeneration is a stem-cell-based process that depends on the periodic activation of, presumably neural-crest-derived, periosteal stem cells of the distal pedicle. The evidence for this hypothesis is reviewed and as a result, a new concept of antler regeneration as a process of stem-cell-based epimorphic regeneration is proposed that does not involve cell dedifferentiation or transdifferentiation. Antler regeneration illustrates that extensive appendage regeneration in a postnatal mammal can be achieved by a developmental process that differs in several fundamental aspects from limb regeneration in urodeles.     

Reversibility and the age of an allele II. Two-allele models,with selection and mutation

A Markov process with absorbing boundaries may be made recurrent by returning the process to the interior whenever a boundary is reached. The age of such a process may be defined as the length of time since the last return event. Examples drawn from two-allele genetic models are discussed, in which reversibility of the return process means that the age of an allele, whose present frequency in the population is known, has the same probability distribution as its future extinction time. Some discrete models are not reversible, yet if approximated by diffusion processes, the (approximate) age distribution is the same as the future extinction time distribution. Various results in the literature are unified by this viewpoint.     

Life‐cycle and cost of goods assessment of fed‐batch and perfusion‐based manufacturing processes for mAbs

Life‐cycle assessment (LCA) is an environmental assessment tool that quantifies the environmental impact associated with a product or a process (e.g., water consumption, energy requirements, and solid waste generation). While LCA is a standard approach in many commercial industries, its application has not been exploited widely in the bioprocessing sector. To contribute toward the design of more cost‐efficient, robust and environmentally‐friendly manufacturing process for monoclonal antibodies (mAbs), a framework consisting of an LCA and economic analysis combined with a sensitivity analysis of manufacturing process parameters and a production scale‐up study is presented. The efficiency of the framework is demonstrated using a comparative study of the two most commonly used upstream configurations for mAb manufacture, namely fed‐batch (FB) and perfusion‐based processes. Results obtained by the framework are presented using a range of visualization tools, and indicate that a standard perfusion process (with a pooling duration of 4 days) has similar cost of goods than a FB process but a larger environmental footprint because it consumed 35% more water, demanded 17% more energy, and emitted 17% more CO₂ than the FB process. Water consumption was the most important impact category, especially when scaling‐up the processes, as energy was required to produce process water and water‐for‐injection, while CO₂ was emitted from energy generation. The sensitivity analysis revealed that the perfusion process can be made more environmentally‐friendly than the FB process if the pooling duration is extended to 8 days. © 2016 American Institute of Chemical Engineers Biotechnol. Prog., 32:1324–1335, 2016