To increase manufacturing flexibility and system understanding in pharmaceutical development, the FDA launched the quality by design (QbD) initiative. Within QbD, the design space is the multidimensional region (of the input variables and process parameters) where product quality is assured. Given the high cost of extensive experimentation, there is a need for computational methods to estimate the probabilistic design space that considers interactions between critical process parameters and critical quality attributes, as well as model uncertainty. In this paper we propose two algorithms that extend the flexibility test and flexibility index formulations to replace simulation-based analysis and identify the probabilistic design space more efficiently. The effectiveness and computational efficiency of these approaches is shown on a small example and an industrial case study.

Innovative biologics, including cell therapeutics, virus-like particles, exosomes, recombinant proteins, and peptides, seem likely to substitute monoclonal antibodies as the main therapeutic entities in manufacturing over the next decades. This molecular variety causes a growing need for a general change of methods as well as mindset in the process development stage, as there are no platform processes available such as those for monoclonal antibodies. Moreover, market competitiveness demands hyper-intensified processes, including accelerated decisions toward batch or continuous operation of dedicated modular plant concepts. This indicates gaps in process comprehension, when operation windows need to be run at the edges of optimization. In this editorial, the authors review and assess potential methods and begin discussing possible solutions throughout the workflow, from process development through piloting to manufacturing operation from their point of view and experience. Especially,... [more]

The objective of this paper is to evaluate and to simulate the cogeneration process applied to an apartment building in the Polanco area (Mexico). Considering the building’s electric, thermal demand and consumption data, the cogeneration process model was simulated using Thermoflow© software (Thermoflow Inc., Jacksonville, FL, USA), in order to cover 1.1 MW of electric demand and to supply the thermal needs of hot water, heating, air conditioning and heating pool. As a result of analyzing various schemes of cogeneration, the most efficient scheme consists of the use of a gas turbine (Siemens model SGT-100-1S), achieving a cycle with efficiency of 84.4% and a heat rate of 14,901 kJ/kWh. The economic results of this evaluation show that it is possible to implement the cogeneration in the building with a natural gas price below US$0.014/kWh. The use of financing schemes makes the economic results more attractive. Furthermore, the percentage of the turbine load effect on the turbine load n... [more]

A major challenge in model-based design of synthetic biochemical circuits is how to address uncertainty in the parameters. A circuit whose behavior is robust to variations in the parameters will have more chances to behave as predicted when implemented in practice, and also to function reliably in presence of fluctuations and noise. Here, we extend our recent work on automated-design based on mixed-integer multi-criteria dynamic optimization to take into account parametric uncertainty. We exploit the intensive sampling of the design space performed by a global optimization algorithm to obtain the robustness of the topologies without significant additional computational effort. Our procedure provides automatically topologies that best trade-off performance and robustness against parameter fluctuations. We illustrate our approach considering the automated design of gene circuits achieving adaptation.

In order to obtain high-purity flavonoid products, the extracts from mulberry leaves were separated and purified via high-speed counter-current chromatography (HSCCC). Moreover, the product was detected via high-performance liquid chromatography (HPLC). The characteristic absorption wavelength of the rutin standard for HSCCC detection and HPLC analysis at 257 nm was tested by ultraviolet scanning analysis. The effect of solvent systems and mobile phase flow rate on the separation efficiency were then researched. Finally, the solvent system of V(ethyl acetate):V(n-butanol):V(water) = 4:1:5 was selected as the operating system for HSCCC. This work theoretically analyzed the impact of the molecular structure and polarity of flavonoids on the choice of solvent systems. The results showed that the mobile phase flow rate had a great influence on the separation efficiency. Furthermore, the separation efficiency increased as the mobile phase flow rate decreased. When the mobile phase flow rate... [more]

In this study, we attempted the preparation of gac oil-loaded solid lipid nanoparticles (SLNs) by the high-speed homogenization method using Naterol SE solid lipid, a cosmetic self-emulsifying base, and surfactant and investigated the effects of different conditions on the characteristics of the resulting nanoparticles. The suspensions containing 5% active agents (gac-oil, w/w) were dispersed in a surfactant concentration of 5% (w/w) (Span 80:Tween 80 ratio of 28:72 w/w) and 2.5% (w/w) of solid lipid (Naterol SE) concentration. Suitable conditions for hot homogenization were 13,000 rpm, 60 min and 60 °C for speed, time and temperature, respectively. The suitable conditions for the subsequent cold homogenization were 25 min of homogenization time and 5 °C of temperature. The results showed that the mean size of SLNs-gac oil was 107 nm (measured by laser diffraction spectrometry, LDS), and dried size of SLNs-gac oil ranged from 50 to 80 nm (measured by transmission electron microscope, T... [more]

With the rapid development of computer science and information and communication technology (ICT), increasingly intelligent, and complex systems have been applied to industries as well as human life. Fault-tolerant control (FTC) has, therefore, become one of the most important topics attracting attention from both engineers and researchers to maintain system performances when faults occur. The ultimate goal of this study was to develop a sensor fault-tolerant control (SFTC) to enhance the robust position tracking control of a class of electro-hydraulic actuators called mini motion packages (MMPs), which are widely used for applications requiring large force-displacement ratios. First, a mathematical model of the MMP system is presented, which is then applied in the position control process of the MMP system. Here, a well-known proportional, integrated and derivative (PID) control algorithm is employed to ensure the positional response to the reference position. Second, an unknown input... [more]

Melissa Officinalis L. (MOL) domestic preparations appropriate for consumption were studied by monitoring content in Na, K, Ca, Li, phenolic bioactives (total phenols, hydroxycinnamic acid derivatives and flavonols), and antioxidant activity (1,1-diphenyl-2-picrylhydrazyl radical inhibition (DPPH) and ferric reducing ability (FRAP)). The effects of practice applied, material to solvent ratio, time of preparation, and solvent were studied. MOL decoctions and infusions, commonly prepared at home, were better or of equal nutritional value to preparations upon ultrasounds or maceration concerning the studied parameters. Aqueous MOL preparations were richer in total phenols (704⁻1949 mg per 250 mL) and the examined macroelements (1.1⁻2.9, 30.5⁻288.4 and 50.1⁻176.1 mg Na, K and Ca per 250 mL, respectively) and showed better antioxidant activity compared to ethanol counterparts. The 25% w/v hydroethanolic MOL preparations, suitable for consumption, presented a significant content in phenolic... [more]

Thailand’s economy is developing rapidly, with energy being a significant factor in this development. This study uses a variety of models to assess the performance of Thailand’s energy industry in two different phases, the first being from 2013 to 2017 and the second from 2018 to 2020. The Malmquist model-one of data envelopment required input and output data that showed Thailand’s productivity index and the rate-of-change ratio, which is used to assess technical changes, change efficiency, and productivity changes of the 12 listed companies in energetic generation and distribution in Thailand. To calculate future indicators, the forecast data are generated by applying the Grey model (1,1) GM(1,1). Accuracy prediction is determined by the mean absolute percentage error (MAPE). The results show that the magnitude of the change in efficiency during the first period is stable, and some major changes in the technical level of some companies may be observed. In the future, the performance o... [more]

This work investigates the environmental and economic performances of a membrane reactor for hydrogen production from raw biogas. Potential benefits of the innovative technology are compared against reference hydrogen production processes based on steam (or autothermal) reforming, water gas shift reactors and a pressure swing adsorption unit. Both biogas produced by landfill and anaerobic digestion are considered to evaluate the impact of biogas composition. Starting from the thermodynamic results, the environmental analysis is carried out using environmental Life cycle assessment (LCA). Results show that the adoption of the membrane reactor increases the system efficiency by more than 20 percentage points with respect to the reference cases. LCA analysis shows that the innovative BIONICO system performs better than reference systems when biogas becomes a limiting factor for hydrogen production to satisfy market demand, as a higher biogas conversion efficiency can potentially substitut... [more]

This paper proposes a microelectric power grid that includes wind and fuel cell power generation units, as well as a water electrolyzer for producing hydrogen gas. The grid is loaded by an induction motor (IM) as a dynamic load and constant impedance load. An optimal control algorithm using the Mine Blast Algorithm (MBA) is designed to improve the performance of the proposed renewable energy system. Normally, wind power is adapted to feed the loads at normal circumstances. Nevertheless, the fuel cell compensates extra load power demand. An optimal controller is applied to regulate the load voltage and frequency of the main power inverter. Also, optimal vector control is applied to the IM speed control. The response of the microgrid with the proposed optimal control is obtained under step variation in wind speed, load impedance, IM rotor speed, and motor mechanical load torque. The simulation results indicate that the proposed renewable generation system supplies the system loads perfec... [more]

In this study, the patterns of chloride ion erosion of unsaturated concrete subjected to the coupling action of cyclic loading and salt spray corrosion were experimentally studied, and Fick’s Second Law was used to fit the variation patterns of chloride concentration to obtain the chloride diffusion coefficient. Accordingly, we have established a mathematical model that describes chloride transport in unsaturated concrete and accounts for the effects of gas flow, water migration, convection diffusion, and capillary action. This model is composed of three equations—the gas flow equation, the solution flow equation, and the solute convection⁻diffusion equation. The COMSOL numerical analysis software was subsequently used to obtain solutions for this model, based on parameters such as porosity and the chloride diffusion coefficient. Subsequently, the saturation, relative permeability, and the chloride ion concentration during the first corrosion cycle were analyzed. The numerical results... [more]

With the rapid increase in production of lithium-ion batteries (LIBs) and environmental issues arising around the world, cathode materials, as the key component of all LIBs, especially need to be environmentally sustainable. However, a variety of life cycle assessment (LCA) methods increase the difficulty of environmental sustainability assessment. Three authoritative LCAs, IMPACT 2002+, Eco-indicator 99(EI-99), and ReCiPe, are used to assess three traditional marketization cathode materials, compared with a new cathode model, FeF₃(H₂O)₃/C. They all show that four cathode models are ranked by a descending sequence of environmental sustainable potential: FeF₃(H₂O)₃/C, LiFe0.98Mn0.02PO₄/C, LiFePO₄/C, and LiCoO₂/C in total values. Human health is a common issue regarding these four cathode materials. Lithium is the main contributor to the environmental impact of the latter three cathode materials. At the midpoint level in different LCAs, the toxicity and land issues for LiCoO₂/C, the non-... [more]

The current competitive environment demands companies to be more and more efficient. In order to increase manufacturing efficiency, two apparently independent approaches have emerged: lean strategies, focusing on identifying and minimizing non-added value activities, identifying wastes in the system and their elimination, and information tools for planning and controlling activities. In this paper, a manufacturing system was considered for which it was necessary to increase the production capacity in order to respond to the customer’s increased demand. A practical case study in the automotive industry for a medium-sized enterprise was considered. In order to investigate the production process parameters and to implement lean principles, Value Stream Mapping (current analysis and optimized solution) and Anylogic agent-based simulations were carried out. Based on this, the lean performances, specific for the target VSM, were evaluated in terms of key performance indicators. The benefits... [more]

Reduction of carbon dioxide emission from natural and industrial flue gases is paramount to help mitigate its effect on global warming. Efforts are continuously deployed worldwide to develop efficient technologies for CO₂ capture. The use of environment friendly amino acids as rate promoters in the present amine systems has attracted the attention of many researchers recently. In this work, the reaction kinetics of carbon dioxide with blends of N-methyldiethanolamine and L-Arginine was investigated using stopped flow technique. The experiments were performed over a temperature range of 293 to 313 K and solution concentration up to one molar of different amino acid/amine ratios. The overall reaction rate constant (kov) was found to increase with increasing temperature and amine concentration as well as with increased proportion of L-Arginine concentration in the mixture. The experimental data were fitted to the zwitterion and termolecular mechanisms using a nonlinear regression techniqu... [more]

A microgrid is a group of many small-scale distributed energy resources, such as solar/wind energy sources, diesel generators, energy storage units, and electric loads. As a small-scale power grid, it can be operated independently or within an existing power grid(s). The microgrid energy management system is a system that controls these components to achieve optimized operation in terms of price by reducing costs and maximizing efficiency in energy consumption. A post-Industry-4.0 consumer requires an optimal design and control of energy storage based on a demand forecast, using big data to stably supply clean, new, and renewable energy when necessary while maintaining a consistent level of quality. Thus, this study focused on software technology through which an optimized operation schedule for energy storage in a microgrid is derived. This energy storage operation schedule minimizes the costs involved in electricity use. For this, an optimization technique is used that sets an object... [more]

The Microbiome Regression-based Kernel Association Test (MiRKAT) is widely used in testing for the association between microbiome compositions and an outcome of interest. The MiRKAT statistic is derived as a variance-component score test in a kernel machine regression-based generalized linear mixed model. In this brief report, we show that the MiRKAT statistic is proportional to the R 2 (coefficient of determination) statistic in a similarity matrix regression, which characterizes the fraction of variability in outcome similarity, explained by microbiome similarity (up to a constant).

The increase of CO₂ concentration in the atmosphere is in strong relation with the human-induced warming up due to industrial processes, transportation, etc. In order to reduce the CO₂ content, end of pipe post-combustion methods can be used in addition to other methods and techniques. The CO₂ capture by absorption in potassium carbonate⁻bicarbonate activated solutions remains a viable method. In this study, a mathematical model for a packed bed reactor has been developed and tested. The mathematical model is tested for an industrial reactor based on CO₂ absorption in Carsol solutions. The proposed model was validated by resolving for CO₂ and water content, carbonate⁻bicarbonate, concentrations etc. For each operational parameter the error was calculated. The error for CO₂ concentration is up to 4%. The height of the packed reactor is calculated as function of CO₂ concentration in the final gas phase. The validated model can also be used for absorbing other CO₂ streams taking into acco... [more]

Implementation of energy-efficient train driving strategy is an effective method to save train traction energy consumption, which has attracted much attention from both researchers and practitioners in recent years. Reducing the unnecessary braking during the journey and increasing the coasting distance are efficient to save energy in urban rail transit systems. In the steep downhill segment, the train speed will continue to increase without applying traction due to the ramp force. A high initial speed before stepping into the steep downhill segment will bring partial braking to prevent trains from overspeeding. Optimization of the driving strategy of urban rail trains can avoid the partial braking such that the potential energy is efficiently used and the traction energy is reduced. This paper presents an energy-efficient driving strategy optimization model for the segment with the steep downhill slopes. A numerical method is proposed to calculate the corresponding energy-efficient dr... [more]

Aquaporins are water channel proteins in cell membrane, highly specific for water molecules while restricting the passage of contaminants and small molecules, such as urea and boric acid. Cysteine functional groups were installed on aquaporin Z for covalent attachment to the polymer membrane matrix so that the proteins could be immobilized to the membranes and aligned in the direction of the flow. Depth profiling using x-ray photoelectron spectrometer (XPS) analysis showed the presence of functional groups corresponding to aquaporin Z modified with cysteine (Aqp-SH). Aqp-SH modified membranes showed a higher salt rejection as compared to unmodified membranes. For 2 M NaCl and CaCl₂ solutions, the rejection obtained from Aqp-SH membranes was 49.3 ± 7.5% and 59.1 ± 5.1%. On the other hand, the rejections obtained for 2 M NaCl and CaCl₂ solutions from unmodified membranes were 0.8 ± 0.4% and 1.3 ± 0.2% respectively. Furthermore, Aqp-SH membranes did not show a significant decrease in salt... [more]

The computation and modeling of extents has been proposed to handle the complexity of large-scale model identification tasks. Unfortunately, the existing extent-based framework only applies when certain conditions apply. Most typically, it is required that a unique value for each extent can be computed. This severely limits the applicability of this approach. In this work, we propose a novel procedure for parameter estimation inspired by the existing extent-based framework. A key difference with prior work is that the proposed procedure combines structural observability labeling, matrix factorization, and graph-based system partitioning to split the original model parameter estimation problem into parameter estimation problems with the least number of parameters. The value of the proposed method is demonstrated with an extensive simulation study and a study based on a historical data set collected to characterize the isomerization of α -pinene. Most importantly, the obtained resul... [more]

Microwave drying is a promising and effective way to drying and upgrading lignite. The influence of temperature (100⁻140 °C) and microwave power levels (500⁻800 W) on thin-layer drying characteristics of Zhaotong lignite under microwave irradiation were investigated. Fourteen thin-layer drying models were used to analyze the microwave drying process while six thin-layer drying models were used to analyze the hot-air drying process. The microwave drying processes at all temperature (100⁻140 °C) or low microwave power levels (500⁻700 W) exhibited four periods: a warm-up period, a short constant period, the first and second falling rate period, while one falling rate period was found during hot-air drying. The effective diffusion coefficient of lignite were calculated and it increases with increasing temperature and microwave power levels. During microwave drying, the two-term exponential model is the most suitable model for all applied conditions, while the Modified Page model is the mos... [more]

In order to effectively prevent coal mine accidents, we selected the most serious type of accident in coal mines—gas explosions—as the research object. Based on the accident causation model (24Model), we propose an action path and analysis steps of accidents caused by different employees in the organization. A gas explosion coal mine accident was analyzed using the 24Model and the proposed action path, and 12 unsafe actions, 3 unsafe states, 4 habitual behaviors, 10 safety management systems, and 10 safety cultures were obtained. Case analysis results show that by using the 24Model and path analysis the proposed effect can help employees to clearly identify the cause of the accident, to better understand the logical relationship with the causes of the accident, improve the effectiveness of training, and effectively prevent similar accidents. The 24Model and the proposed path can be used to comprehensively analyze the reasons for and help to effectively prevent coal mine gas explosion a... [more]

Coal mass is deformed and fractured under stress to generate electrical potential (EP) signals. The mechanical properties of coal change with the adsorption of gas. To investigate the EP response characteristics of gas-bearing coal during deformation and fracture, a test system to monitor multi-parameters of gas-bearing coal under load was designed. The results showed that abundant EP signals were generated during the loading process and the EP response corresponded well with the stress change and crack expansion, and validated this with the results from acoustic emission (AE) and high-speed photography. The higher stress level and the greater the sudden stress change led to the greater EP abnormal response. With the increase of gas pressure, the confining action and erosion effect are promoted, causing the damage evolution impacted and failure characteristics changes. As a result, the EP response is similar while the characteristics were promoted. The EP response was generated due to... [more]

In Southwest China large-scale hydropower projects, the hydraulic conductivity and fracture aperture within the rock mass of a reservoir bank slope has dramatically undergone a time series of evolution during dam abutment excavation, reservoir impounding and fluctuation operation, and discharge atomization. Accordingly, seepage control measures by hydro-structures such as drainage or water insulation curtains should be guided by scientific foundation with a dynamic process covering life-cycle performance. In this paper, the up-to-date status of studying the evolution mechanism of seepage characteristics relating to fractured rock hydraulics from experimental samples to the engineering scale of the rock mass is reviewed for the first time. Then, the experimental findings and improved practice method on nonlinear seepage flow under intensive pressure drives are introduced. Finally, the scientific progress made in fractured rock seepage control theory and optimization of the design techno... [more]