scholarly journals Challenges in transfer of gas-liquid reactions from batch to continuous operation: dimensional analysis and simulations for aerobic oxidation

2021 ◽  
Author(s):  
Jens Friedland ◽  
Robert Güttel
Keyword(s):  
Mass Transfer ◽  
Reaction Kinetics ◽  
Early Phase ◽  
Process Development ◽  
Early Stage ◽  
Aerobic Oxidation ◽  
Operation Mode ◽  
Continuous Operation ◽  
Batch Operation ◽  
Main Challenge

AbstractThe transfer of gas-liquid reactions from conventional batch processes into continuous operation using milli and micro reactors is claimed as an important step towards process intensification. Importantly, this transfer step should be realized in an early phase of process development, already, in order to minimize research efforts towards the undesired operation strategy. The main challenge of this approach, therefore, arises from lack of knowledge in the early stage of process development and the resulting system with high degrees of freedom. This contribution presents an approach to tackle this challenge by means of mathematical modelling and simulation for the aerobic oxidation of 9,10-dihydroanthracene (DHA) catalyzed by polyoxometalates (POMs) being used as example for gas-liquid reactions. The reaction was chosen as it provides sufficient complexity, since it consists of three consecutive oxidation steps of DHA and a parallel catalytic redox-cycle according to a Mars-van-Krevelen mechanism. It also provides the challenge of unknown reaction kinetics, which have been estimated in this contribution. The dimensionless balance equations for reactor modeling are derived and parametrized based on early stage experimental results obtained in batch operation mode. The discrimination between batch and continuous operation was performed by means of characteristic dimensionless numbers using the identical mathematical model for comparability reasons. The model was used to perform sensitivity studies with emphasis on the interplay between mass transfer characteristics and reaction kinetics for both the batch and continuous operation mode. The simulation results show that the performance of both operation modes mainly depend on the oxidation state of the POM catalyst, which is caused by the differences in oxygen availability. Therefore, results obtained in batch operation mode are prone to be masked by mass transfer issues, which affects catalyst and reactor development at the same time and may thus cause maldevelopments. With respect to process development it can thus be concluded that the transfer from batch to continuous operation together with mathematical modeling is important in an early phase, already, in order to detect limitations misleading the development. Finally, even simple models with roughly estimated parameters from preliminary experiments are shown to be sufficient in the early phase and can systematically be improved, in the subsequent phases. Graphical abstract

scholarly journals High-throughput microbioreactor provides a capable tool for early stage bioprocess development

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Mathias Fink ◽  
Monika Cserjan-Puschmann ◽  
Daniela Reinisch ◽  
Gerald Striedner
Keyword(s):  
High Throughput ◽  
Process Development ◽  
Early Stage ◽  
Explanatory Power ◽  
Batch Mode ◽  
E Coli ◽  
Speed Up ◽  
Bioreactor System ◽  
Cell Densities ◽  
Microbial Systems

AbstractTremendous advancements in cell and protein engineering methodologies and bioinformatics have led to a vast increase in bacterial production clones and recombinant protein variants to be screened and evaluated. Consequently, an urgent need exists for efficient high-throughput (HTP) screening approaches to improve the efficiency in early process development as a basis to speed-up all subsequent steps in the course of process design and engineering. In this study, we selected the BioLector micro-bioreactor (µ-bioreactor) system as an HTP cultivation platform to screen E. coli expression clones producing representative protein candidates for biopharmaceutical applications. We evaluated the extent to which generated clones and condition screening results were transferable and comparable to results from fully controlled bioreactor systems operated in fed-batch mode at moderate or high cell densities. Direct comparison of 22 different production clones showed great transferability. We observed the same growth and expression characteristics, and identical clone rankings except one host-Fab-leader combination. This outcome demonstrates the explanatory power of HTP µ-bioreactor data and the suitability of this platform as a screening tool in upstream development of microbial systems. Fast, reliable, and transferable screening data significantly reduce experiments in fully controlled bioreactor systems and accelerate process development at lower cost.

scholarly journals Impact of SARS-CoV-2 infection on the recovery of peripheral blood mononuclear cells by density gradient

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Maria D. I. Manunta ◽  
Giuseppe Lamorte ◽  
Francesca Ferrari ◽  
Elena Trombetta ◽  
Mario Tirone ◽  
...  
Keyword(s):  
Density Gradient ◽  
Peripheral Blood Mononuclear Cells ◽  
Peripheral Blood ◽  
Early Phase ◽  
Mononuclear Cells ◽  
Early Stage ◽  
Gradient Centrifugation ◽  
Peripheral Blood Mononuclear ◽  
Blood Mononuclear Cells ◽  
Circulating Lymphocytes

AbstractSARS-CoV-2 virus infection is responsible for coronavirus disease (COVID-19), which is characterised by a hyperinflammatory response that plays a major role in determining the respiratory and immune-mediated complications of this condition. While isolating peripheral blood mononuclear cells (PBMCs) from whole blood of COVID-19 patients by density gradient centrifugation, we noticed some changes in the floating properties and in the sedimentation of the cells on density medium. Investigating this further, we found that in early phase COVID-19 patients, characterised by reduced circulating lymphocytes and monocytes, the PBMC fraction contained surprisingly high levels of neutrophils. Furthermore, the neutrophil population exhibited alterations in the cell size and in the internal complexity, consistent with the presence of low density neutrophils (LDNs) and immature forms, which may explain the shift seen in the floating abilities and that may be predictive of the severity of the disease. The percentage of this subset of neutrophils found in the PBMC band was rather spread (35.4 ± 27.2%, with a median 28.8% and IQR 11.6–56.1, Welch’s t-test early phase COVID-19 versus blood donor healthy controls P < 0.0001). Results confirm the presence of an increased number of LDNs in patients with early stage COVID-19, which correlates with disease severity and may be recovered by centrifugation on a density gradient together with PBMCs.

scholarly journals To Swab or Not to Swab? The Lesson Learned in Italy in the Early Stage of the COVID-19 Pandemic

2021 ◽  
Vol 11 (9) ◽  
pp. 4042
Author(s):  
Paola Berchialla ◽  
Maria Teresa Giraudo ◽  
Carmen Fava ◽  
Andrea Ricotti ◽  
Giuseppe Saglio ◽  
...  
Keyword(s):  
Early Phase ◽  
Early Stage ◽  
Respiratory Illness ◽  
Explanatory Variables ◽  
Daily Number ◽  
Testing Strategies ◽  
Serious Infections ◽  
The Impact ◽  
Epidemiological Link ◽  
Severe Respiratory Illness

Testing for the SARS-CoV-2 infection is critical for tracking the spread of the virus and controlling the transmission dynamics. In the early phase of the pandemic in Italy, the decentralized healthcare system allowed regions to adopt different testing strategies. The objective of this paper is to assess the impact of the extensive testing of symptomatic individuals and their contacts on the number of hospitalizations against a more stringent testing strategy limited to suspected cases with severe respiratory illness and an epidemiological link to a COVID-19 case. A Poisson regression modelling approach was adopted. In the first model developed, the cumulative daily number of positive cases and a temporal trend were considered as explanatory variables. In the second, the cumulative daily number of swabs was further added. The explanatory variable, given by the number of swabs over time, explained most of the observed differences in the number of hospitalizations between the two strategies. The percentage of the expected error dropped from 70% of the first, simpler model to 15%. Increasing testing to detect and isolate infected individuals in the early phase of an outbreak improves the capability to reduce the spread of serious infections, lessening the burden of hospitals.

scholarly journals Uwarunkowania procesu pojednania w Kambodży

2020 ◽  
Vol 14 ◽  
pp. 267-280
Author(s):  
Radosław Zarzecki
Keyword(s):  
Early Stage ◽  
Khmer Rouge ◽  
State Level ◽  
Political Life ◽  
Historical Background ◽  
Difficult Situation ◽  
Main Challenge ◽  
Long Time ◽  
History Of ◽  
Culture Of Silence

Determinants of Reconciliation in Cambodia Forty years after Cambodian genocide the reconciliation is still in early stage. Despite such long time there was almost nothing done, especially in 20th century, to make that process happened. The article discusses the determinants, reasons and factors that had impact on reconciliation. Determinants can be divided into different categories. First of all the socio-historical background. Circumstances in which Khmer Rouge come to power, their revolutionary approach to economy, implemented reforms, use of children, displacements of people and categorization of citizens had great impact on post-1979 Cambodia. Another determinant is a political one. Policy of post-Khmer Rouge Cambodia rulers stunted the reconciliation. There reason of such actions are multidimensional but the most important one is provenance of People’s Republic of Kampuchea leaders. The most important figures in Cambodia politics are ex-Khmer Rouge soldiers, accused by some of taking a part in genocide. What’s even more confusing, the most powerful opposition party in 1980s were perpetrators themselves and their allies. Even after signing Paris Peace Accords in 1991 until early 2000s there was no will to punish Khmer Rouge officials responsible for genocide. The Cambodian culture of silence, the third determinant, only exacerbates a difficult situation. Cambodians rarely speak about atrocities and harsh past because of fear, shame or trauma. Even in school textbooks until 2009 there was almost nothing said about tragic events which happened between 1975 and 1979. History of Democratic Kampuchea still affects the Cambodian society. Despite sentencing few Khmer Rouge officials in 2010s, there’s still lot to be done also on state-level. Reconciliation and coming back to the state of balance is the main challenge for Cambodia in the nearest future, crucially important to social and political life of this nation.

Red Pepper Seed Inhibits Differentiation of 3T3-L1 Cells during the Early Phase of Adipogenesis via the Activation of AMPK

2018 ◽  
Vol 46 (01) ◽  
pp. 107-118 ◽  
Author(s):  
Hwa-Jin Kim ◽  
Mi-Kyoung You ◽  
Ziyun Wang ◽  
Hyeon-A Kim
Keyword(s):  
Fatty Acid ◽  
Early Phase ◽  
Fatty Acid Synthase ◽  
Early Stage ◽  
Binding Protein ◽  
Water Extract ◽  
Red Pepper ◽  
Fatty Acid Binding ◽  
Compound C ◽  
Pepper Seed

Obesity is the main risk factor for metabolic syndromes and there has been an upsurge in demand for effective therapeutic strategies. This study investigated the effect of red pepper seed water extract (RPS) on the process of differentiation in 3T3-L1 adipocytes. RPS treatment significantly suppressed cellular lipid accumulation and reduced the expression of adipocytes-associated proteins, peroxisome proliferator-activated receptor-[Formula: see text] (PPAR-[Formula: see text]), CCAAT/enhancer-binding proteins [Formula: see text] (C/EBP [Formula: see text]), sterol regulatory element binding protein-1c (SREBP-1c), as well as fatty acid synthase (FAS), and fatty acid binding protein 4 (FABP4). The inhibitory effect of RPS on differentiation was mainly through the modulation of the C/EBP [Formula: see text] and C/EBP [Formula: see text] expression at the early phase of differentiation. Moreover, at the early phase of differentiation, RPS markedly increased the phosphorylation of AMP-activated protein kinase (AMPK). Such enhancing effect of RPS was abolished in the presence of compound C. Our results suggest that activation of AMPK at early stage of adipogenesis is involved in the anti-adipogenesis effect of RPS.

Decision Making and Decision Support Within New Product Development

2014 ◽  
pp. 258-279 ◽  
Author(s):  
Bart MacCarthy ◽  
Robert Pasley
Keyword(s):  
Decision Making ◽  
Decision Support ◽  
New Product Development ◽  
Process Development ◽  
Early Stage ◽  
New Product ◽  
Group Decision Support Systems ◽  
Extensive Literature ◽  
Decision Attributes ◽  
Product And Process

There is an extensive literature on new product and process development (NPD). However, the analysis of decision making and decision support requirements in this area is less well researched. Here we discuss decision making in the context of NPD and identify decision types and decision attributes relevant to the NPD context. They illustrate the approach by analyzing NPD decisions in three industrial cases with a focus on early stage NPD decisions. They create a set of attributes with reference to the decision making literature. They find these attributes can be used to codify decisions in order to characterize them. They find the design decisions in these case studies to be creative and brainstorming-led with a low level of structure. The results provide insights both on decision making in NPD in practice and on the requirements for group decision support systems (GDSS) in this area. The authors suggest that an argumentation-based GDSS that allows structure to be developed may be suitable for these decisions. The cases are used to illustrate the application of the approach and show an interesting set of example decision types, but do not cover the range of NPD decisions that may be evident in a larger set of companies.

CFD Simulation of the Particle Dispersion Behavior and Mass Transfer–Reaction Kinetics in non-Newton Fluid with High Viscosity

2019 ◽  
Vol 17 (7) ◽  
Author(s):  
Le Xie ◽  
Qi-An Wang ◽  
Xian-Jin Luo ◽  
Zheng-Hong Luo
Keyword(s):  
Mass Transfer ◽  
Reaction Kinetics ◽  
Transfer Reaction ◽  
High Viscosity ◽  
Particle Dispersion ◽  
Agitation Speed ◽  
Fluid Viscosity ◽  
Condensation Polymerization ◽  
Cross Model ◽  
Dispersion Behavior

Abstract Solid particle dispersion and chemical reactions in high-viscosity non-Newtonian fluid are commonly encountered in polymerization systems. In this study, an interphase mass transfer model and a finite-rate/eddy-dissipation formulation were integrated into a computational fluid dynamics model to simulate the dispersion behavior of particles and the mass transfer–reaction kinetics in a condensation polymerization-stirred tank reactor. Turbulence fields were obtained using the standard k–ε model and employed to calculate the mixing rate. Cross model was used to characterize the rheological property of the non-Newton fluid. The proposed model was first validated by experimental data in terms of input power. Then, several key operating variables (i.e. agitation speed, viscosity, and particle size) were investigated to evaluate the dispersive mixing performance of the stirred vessel. Simulation showed that a high agitation speed and a low fluid viscosity favored particle dispersions. This study provided useful guidelines for industrial-scale high-viscosity polymerization reactors.

scholarly journals Industrial Production of Poly-β-hydroxybutyrate from CO2: Can Cyanobacteria Meet this Challenge?

Processes ◽  
2020 ◽  
Vol 8 (3) ◽  
pp. 323 ◽  
Author(s):  
Roberta Carpine ◽  
Giuseppe Olivieri ◽  
Klaas J. Hellingwerf ◽  
Antonino Pollio ◽  
Antonio Marzocchella
Keyword(s):  
Low Cost ◽  
Operation Mode ◽  
Commercial Production ◽  
Continuous Operation ◽  
Attractive Alternative ◽  
Bacterial Fermentation ◽  
Plastic Materials ◽  
Phb Production ◽  
Global Concern ◽  
Environmentally Friendly Process

The increasing impact of plastic materials on the environment is a growing global concern. In regards to this circumstance, it is a major challenge to find new sources for the production of bioplastics. Poly-β-hydroxybutyrate (PHB) is characterized by interesting features that draw attention for research and commercial ventures. Indeed, PHB is eco-friendly, biodegradable, and biocompatible. Bacterial fermentation processes are a known route to produce PHB. However, the production of PHB through the chemoheterotrophic bacterial system is very expensive due to the high costs of the carbon source for the growth of the organism. On the contrary, the production of PHB through the photoautotrophic cyanobacterium system is considered an attractive alternative for a low-cost PHB production because of the inexpensive feedstock (CO2 and light). This paper regards the evaluation of four independent strategies to improve the PHB production by cyanobacteria: (i) the design of the medium; (ii) the genetic engineering to improve the PHB accumulation; (iii) the development of robust models as a tool to identify the bottleneck(s) of the PHB production to maximize the production; and (iv) the continuous operation mode in a photobioreactor for PHB production. The synergic effect of these strategies could address the design of the optimal PHB production process by cyanobacteria. A further limitation for the commercial production of PHB via the biotechnological route are the high costs related to the recovery of PHB granules. Therefore, a further challenge is to select a low-cost and environmentally friendly process to recover PHB from cyanobacteria.

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