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A novel data‐driven methodology is presented for developing mathematical models for crystallization processes. The data‐driven approach is based on the sparse identification of nonlinear dynamics (SINDy) method, which iterates between a partial least‐squares fit and a sparsity‐promoting step leading to the discovery of sparse interpretable models. The performance of the SINDy methodology is characterized for the identification of crystallization kinetics in a mixed tank operated in a continuous mode, the isothermal crystallization of lysozyme in a batch stirred tank and cooling crystallization of paracetamol. The SINDy method is robust against noise. Good agreement is obtained between the data‐driven model and the data obtained from crystallization experiments. The presented data‐driven approach can be attractive for modeling industrial crystallization processes where process analytical technology tools are available for the measurement of process variables but functional forms of kinetic expressions are unknown. [ABSTRACT FROM AUTHOR]

In water distribution networks (WDN) equipped with pump as turbines (PATs), in addition to water pressure problems, energy production by PATs is also necessary in abnormal conditions. Reliability indices are the most important parameters in determining the efficiency of systems when components fail. In this research, while proving the correlation weakness of a number of previous indices with the energy, a new energy reliability index is introduced, and it's integrated with previous reliability indices. Since checking the performance of networks from different aspects leads to increasing accuracy and reducing design and operation costs, in the following, the correlation of each of the integrated indices with the performance indices (PI) of adequacy, equity, energy, adequacy- equity, adequacy-energy, equity-energy, and total are calculated for two WDNs. Finally, the most critical network pipes for repair and maintenance (for each of the performance indices) are determined. [ABSTRACT FROM AUTHOR]

Genetically modified maize DP202216 was developed to confer tolerance to glufosinate‐ammonium‐containing herbicides and to provide an opportunity for yield enhancement under field conditions. These properties were achieved by introducing the mo‐pat and zmm28 expression cassettes. The molecular characterisation data and bioinformatic analyses do not identify issues requiring food/feed safety assessment. None of the identified differences in the agronomic/phenotypic and compositional characteristics tested between maize DP202216 and its comparator needs further assessment, except for the levels of stearic acid (C18:0), which do not raise nutritional and safety concerns. The GMO Panel does not identify safety concerns regarding the toxicity and allergenicity of the PAT and ZMM28 proteins as expressed in maize DP202216, and finds no evidence that the genetic modification would change the overall allergenicity of maize DP202216. In the context of this application, the consumption of food and feed from maize DP202216 does not represent a nutritional concern in humans and animals. The GMO Panel concludes that maize DP202216 is as safe as the comparator and non‐GM reference varieties tested, and no post‐market monitoring of food/feed is considered necessary. In the case of accidental release of viable maize DP202216 grains into the environment, this would not raise environmental safety concerns. The post‐market environmental monitoring plan and reporting intervals are in line with the intended uses of maize DP202216. The GMO Panel concludes that maize DP202216 is as safe as its comparator and the tested non‐GM reference varieties with respect to potential effects on human and animal health and the environment. [ABSTRACT FROM AUTHOR]

Process Analytical Technologies (PATs) are taking a key role in the run for automatization in the biopharmaceutical industry. Spectroscopic methods such as Raman spectroscopy or mid‐infrared (MIR) spectroscopy are getting more recognition in the recent years for inline monitoring of bioprocesses due to their ability to measure various molecules simultaneously. However, their dependency on laborious model calibration making them a challenge to implement. In this study, a novel one‐point calibration that requires a single reference point prior to the inline monitoring of glucose and lactate in bioprocesses with MIR spectroscopy is assessed with 22 mammalian cell perfusion (PER) processes in two different scales and four different products. Concentrations are predicted over all PERs runs with a root mean square error (RMSE) of 0.29 g/L for glucose and 0.24 g/L for lactate, respectively. For comparison conventional partial least square regression (PLSR) models were used and trained with spectroscopic data from six bioreactor runs in two different scales and three products. The general accuracy of those models (RMSE of 0.41 g/L for glucose and 0.16 g/L for lactate) are in the range of the accuracy of the one‐point calibration. This shows the potential of the one‐point calibration as an approach making spectroscopy more accessible for bioprocess development. [ABSTRACT FROM AUTHOR]

Whey protein denaturation and aggregation have long been areas of research interest to the dairy industry, having significant implications for process performance and final product functionality and quality. As such, a significant number of analytical techniques have been developed or adapted to assess and characterize levels of whey protein denaturation and aggregation, to either maximize processing efficiency or create products with enhanced functionality (both technological and biological). This review aims to collate and critique these approaches based on their analytical principles and outline their application for the assessment of denaturation and aggregation. This review also provides insights into recent developments in process analytical technologies relating to whey protein denaturation and aggregation, whereby some of the analytical methods have been adapted to enable measurements in‐line. Developments in this area will enable more live, in‐process data to be generated, which will subsequently allow more adaptive processing, enabling improved product quality and processing efficiency. Along with the applicability of these techniques for the assessment of whey protein denaturation and aggregation, limitations are also presented to help assess the suitability of each analytical technique for specific areas of interest. [ABSTRACT FROM AUTHOR]

In recent years, Beacon Chain known as the core of Ethereum 2.0, has gained considerable attention since its launch. Many validators have staked billions of Ether in the Proof of Stake (PoS) network. It is a mission critical system and its security and stability rely on the justification and finalization of checkpoints. These are essential elements of the Casper FFG consensus algorithm utilized by the Beacon Chain. This process is critical for establishing a trustworthy foundation and finalizing proposed blocks by confirming agreed upon checkpoints. Hence, ensuring the correctness of checkpoints in the Beacon Chain has significant importance because any bug in it can cause serious implications. To address this challenge, we employ formal methods, a popular mathematical approach used for verifying the correctness of such critical systems. In this work, we have done formal verification of the processes of Beacon Chain state initialization, justification and finalization of checkpoints using the Process Analysis Toolkit (PAT) model checker. The adoption of model checking through the PAT model checker presents a novel contribution of our work, as this approach is not previously utilized in the formal verification of Beacon Chain. The presented work is specified through the Communicating Sequential Programs, formal specification language, and the properties are described through Linear Temporal Logic. The PAT model checker takes the specified formal model and properties as input to assess whether the properties are satisfied. The properties are analyzed with respect to the verification time, visited states, total transitions, and memory used. Through this research, we aim to increase confidence in the correctness and reliability of the Beacon Chain.

The semi and fully continuous production of monoclonal antibodies (mAbs) has been gaining traction as a lower cost, and efficient production of mAbs to broaden patient access. To be truly flexible and adaptive to process demands, the industry has lacked sufficient advanced control strategies. The variation of the upstream product concentration typically cannot be handled by the downstream capture step, which is configured for a constant feed concentration and fixed binding capacity. This inflexibility leads to losses of efficiency and product yield. This study shows that these challenges can be overcome by a novel advanced control strategy concept that includes dynamic control throughout a perfusion bioreactor, with cell retention by alternating tangential flow, integrated with simulated moving bed (SMB) multi‐column chromatography. The automation workflow and advanced control strategy were implemented through the use of a visual programming development environment. This enabled dynamic flow control across the upstream and downstream process integrated with a dynamic column loading of the SMB. A sensor prototype, based on continuous biolayer interferometry measurements was applied to detect mAb breakthrough within the last column flow‐through to manage column switching. This novel approach provided higher specificity and lower background signal compared to commonly used spectroscopy methods, resulting in an optimized resin utilization while simultaneously avoiding product loss. The dynamic loading was found to provide a twofold increase of the mAb concentration in the eluate compared to a conservative approach with a predefined recipe with similar impurity removal. This concept shows that advanced control strategies can lead to significant process efficiency and yield improvement. [ABSTRACT FROM AUTHOR]

The world's water infrastructures suffer from inefficiencies, such as high energy consumption and water losses due to inadequate management practices and feeble pressure regulation, leading to frequent water and energy losses. This strains vital water and energy resources, especially in the face of the worsening challenges of climate change and population growth. A novel method is presented that integrates micro-hydropower plants, with pumps as turbines (PATs), in the water network in the city of Funchal. Sensitivity analyses evaluated the microgrid's response to variations in the cost of energy components, showing favorable outcomes with positive net present value (NPV). PV solar and micro-wind turbines installed exclusively at the selected PRV sites within the Funchal hydro grid generate a combined 153 and 55 MWh/year, respectively, supplementing the 406 MWh/year generated by PATs. It should be noted that PATs consistently have the lowest cost of electricity (LCOE), confirming their economic viability and efficiency across different scenarios, even after accounting for reductions in alternative energy sources and grid infrastructure costs. [ABSTRACT FROM AUTHOR]

BACKGROUND: Intensified ethanol fermentation produces higher ethanol concentrations while reducing water and energy requirements. Nevertheless, the inhibitory and detrimental effect of the cellular stress barriers in this process further complicates the nonlinear dynamic relationship between the variables that directly reflect the fermentation quality. These key variables are hard to measure in real time and therefore cannot be directly controlled. RESULTS: This work presents the development of a soft sensor that predicts in real time the ethanol and substrate concentrations of an intensified fermentation. The soft sensor uses feedforward neural networks (FNNs) with easily measurable process analytical technology (PAT) tools. The application of advanced PAT tools such as redox potential and capacitance, in addition to temperature and pH are explored as input variables. The complex kinetic relationship between the studied variables was captured with FNN architectures with a single hidden layer and between 95 and 175 hidden neurons for the different cases studied. Acceptable predictions are achieved for the concentration of ethanol (RMSE = 9.5 and R2 = 0.97) and substrate (RMSE = 17.02 and R2 = 0.92). CONCLUSIONS: The results confirm that the proposed soft sensor can accurately predict the ethanol and substrate concentrations. Collectively, capacitance, redox potential, temperature and pH provide a powerful platform of PAT tools that can directly infer key variables showing the fermentation quality in real time. This study provides a significant step towards the systematic development of a reliable soft sensor with integration of advanced PAT tools. © 2023 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Degumming is an oil refinement process in which the naturally occurring phospholipids in crude vegetable oils are removed. Enzymatic degumming results in higher oil yield and more cost-efficient processing compared to traditional degumming processes using only water or acid. Phospholipase C hydrolyses phospholipids into diglycerides and phosphate groups during degumming. The diglyceride content can therefore be considered a good indicator of the state of the enzymatic reaction. This study investigates the use of near-infrared (NIR) spectroscopy and chemometrics to monitor the degumming process by quantifying diglycerides in soybean oil in both off-line and on-line settings. Fifteen enzymatic degumming lab scale batches originating from a definitive screening design (with varying water, acid, and enzyme dosages) were investigated with the aim to develop a NIR spectroscopy prediction method. By applying tailored preprocessing and variable selection methods, the diglyceride content can be predicted with a root mean square error of prediction of 0.06% (w/w) for the off-line set-up and 0.07% (w/w) for the on-line set-up. The results show that the diglyceride content is a good indicator of the enzyme performance and that NIR spectroscopy is a suitable analytical technique for robust real-time diglyceride quantification. Graphical abstract This is a visual representation of the abstract. [ABSTRACT FROM AUTHOR]

The aim of this study was to probe an unexpected relationship between the ice nucleation temperature (T IN), process efficiency and product attributes in a controlled ice nucleation (CIN) lyophilization process. An amorphous product was lyophilized with (CIN-5 °C, CIN-7 °C or CIN-10 °C) or without (NOCIN) control of ice nucleation. Process parameters and product attributes were monitored and compared using a series of advanced in-line and off-line process analytical technology (PAT) tools. Unexpectedly, an indirect relationship was observed between T IN and primary drying efficiency for the CIN processes. Further, the CIN-5 °C process was associated with higher product resistance to mass flow than corresponding CIN-7 °C and CIN-10 °C processes. Surprisingly, the air voids in some NOCIN products were larger than CIN-5 °C products but comparable to CIN-7 °C. Heat flux analysis revealed an indirect relationship between T IN and the minimum hold time required to complete solidification. The heat flux analysis also revealed all products underwent complete solidification prior to primary drying. The order of homogeneity in water activity of the products was CIN-5 °C ≥NOCIN>CIN-7 °C. The higher homogeneity in water activity of CIN-5 °C than corresponding CIN-7 °C processes indicated that the lower process efficiency of CIN-5 °C could not be attributed to unsuccessful induction of ice nucleation during CIN-5 °C. High resolution micro-CT imaging and Artificial Intelligence Image analysis revealed cake wall deformation in CIN-7 °C and NOCIN products but not in CIN-5 °C. In addition, NOCIN products had bimodal distribution in air voids with median size range of 4–5 µm and 151.9–309 µm, respectively, hence the lower process efficiency of NOCIN despite the higher D90. Thus, the observed relationship between T IN and process efficiency may be attributed to microstructural changes post freezing. This hypothesis was corroborated by visible macroscopic cake collapse in NOCIN products but not in CIN products after lyophilization at a higher shelf temperature. In conclusion, the advantages of controlling the ice nucleation temperature of a lyophilization process may only be attained through a robust process design that takes into consideration the primary and secondary drying process parameters. Further, combined use of advanced in-line and off-line PAT tools for process and product characterization may hasten the at scale adoption of advance techniques such as CIN. [ABSTRACT FROM AUTHOR]

Abstract Genetically modified maize DP202216 was developed to confer tolerance to glufosinate‐ammonium‐containing herbicides and to provide an opportunity for yield enhancement under field conditions. These properties were achieved by introducing the mo‐pat and zmm28 expression cassettes. The molecular characterisation data and bioinformatic analyses do not identify issues requiring food/feed safety assessment. None of the identified differences in the agronomic/phenotypic and compositional characteristics tested between maize DP202216 and its comparator needs further assessment, except for the levels of stearic acid (C18:0), which do not raise nutritional and safety concerns. The GMO Panel does not identify safety concerns regarding the toxicity and allergenicity of the PAT and ZMM28 proteins as expressed in maize DP202216, and finds no evidence that the genetic modification would change the overall allergenicity of maize DP202216. In the context of this application, the consumption of food and feed from maize DP202216 does not represent a nutritional concern in humans and animals. The GMO Panel concludes that maize DP202216 is as safe as the comparator and non‐GM reference varieties tested, and no post‐market monitoring of food/feed is considered necessary. In the case of accidental release of viable maize DP202216 grains into the environment, this would not raise environmental safety concerns. The post‐market environmental monitoring plan and reporting intervals are in line with the intended uses of maize DP202216. The GMO Panel concludes that maize DP202216 is as safe as its comparator and the tested non‐GM reference varieties with respect to potential effects on human and animal health and the environment.

Abstract Process Analytical Technologies (PATs) are taking a key role in the run for automatization in the biopharmaceutical industry. Spectroscopic methods such as Raman spectroscopy or mid‐infrared (MIR) spectroscopy are getting more recognition in the recent years for inline monitoring of bioprocesses due to their ability to measure various molecules simultaneously. However, their dependency on laborious model calibration making them a challenge to implement. In this study, a novel one‐point calibration that requires a single reference point prior to the inline monitoring of glucose and lactate in bioprocesses with MIR spectroscopy is assessed with 22 mammalian cell perfusion (PER) processes in two different scales and four different products. Concentrations are predicted over all PERs runs with a root mean square error (RMSE) of 0.29 g/L for glucose and 0.24 g/L for lactate, respectively. For comparison conventional partial least square regression (PLSR) models were used and trained with spectroscopic data from six bioreactor runs in two different scales and three products. The general accuracy of those models (RMSE of 0.41 g/L for glucose and 0.16 g/L for lactate) are in the range of the accuracy of the one‐point calibration. This shows the potential of the one‐point calibration as an approach making spectroscopy more accessible for bioprocess development.

Spaceborne data can be seamlessly handled using a laser-communication system that enables super-high-speed data transfers, greater than or equal to 1 Gbps, and provides size, weight, and power (SWaP) efficiencies at low costs. Laser-communication systems have garnered attention owing to their ability to enhance SWaP efficiencies, and thus they may complement or potentially replace traditional radio frequency (RF) systems in future space networks. Here, we propose a novel space-to-space laser communication system, called very-high-speed inter-satellite link system using infrared optical terminal and nanosatellite (VISION). This study aims to establish and validate laser-crosslink systems and advanced space technologies using two 6U nanosatellites in formation flying. The payload is a laser-communication terminal (LCT) containing a deployable space telescope. The LCT shares beam paths for communication as well as pointing, acquisition, and tracking (PAT) with a single aperture, thereby providing feedback control for the PAT and help mitigate steady-state beam pointing errors. The nanosatellites include a precise formation-flying guidance, navigation, and control system with an S-band RF crosslink and propulsion system. Each nanosatellite is equipped with a propulsion system that can change its inter-satellite ranges rapidly and accurately based on the mission operation scenarios. LCT payload prototypes are constructed, and the PAT system is evaluated using a testbed. Additionally, the components of the nanosatellite bus are electrically integrated for flatsat testing. The proposed laser-crosslink systems are anticipated to contribute to the establishment of high-speed and secure space-to-space networks at low costs in the forthcoming years. • Proposed a novel space-to-space laser communication system called VISION. • Preliminary design of laser-crosslink and advanced space optics systems with two 6U nanosatellites. • Nanosatellites in formation flying included control and propulsion systems. • Constructed a laser-communication terminal payload prototype and evaluated PAT. • VISION system enables development of low-cost super-high-speed space networks. [ABSTRACT FROM AUTHOR]

An efficient monitoring and control strategy is the basis for a reliable production process. Conventional optical density (OD) measurements involve superpositions of light absorption and scattering, and the results are only given in arbitrary units. In contrast, photon density wave (PDW) spectroscopy is a dilution‐free method that allows independent quantification of both effects with defined units. For the first time, PDW spectroscopy was evaluated as a novel optical process analytical technology tool for real‐time monitoring of biomass formation in Escherichia coli high‐cell‐density fed‐batch cultivations. Inline PDW measurements were compared to a commercially available inline turbidity probe and with offline measurements of OD and cell dry weight (CDW). An accurate correlation of the reduced PDW scattering coefficient µs′ with CDW was observed in the range of 5–69 g L−1 (R2 = 0.98). The growth rates calculated based on µs′ were comparable to the rates determined with all reference methods. Furthermore, quantification of the reduced PDW scattering coefficient µs′ as a function of the absorption coefficient µa allowed direct detection of unintended process trends caused by overfeeding and subsequent acetate accumulation. Inline PDW spectroscopy can contribute to more robust bioprocess monitoring and consequently improved process performance. [ABSTRACT FROM AUTHOR]

Biologics manufacturing is increasingly moving toward intensified processes that require novel control strategies in order to achieve higher titers in shorter periods of time compared to traditional fed-batch cultures. In order to implement these strategies for intensified processes, continuous process monitoring is often required. To this end, inline Raman spectroscopy was used to develop partial least squares models to monitor changes in residual concentrations of glucose, phenylalanine and methionine during the culture of five different glutamine synthetase piggyBac® Chinese hamster ovary clones cultured using an intensified high inoculation density fed-batch platform process. Continuous monitoring of residual metabolite concentrations facilitated automated feed-rate adjustment of three supplemental feeds to maintain glucose, phenylalanine, and methionine at desired setpoints, while maintaining other nutrient concentrations at acceptable levels across all clones cultured on the high inoculation density platform process. Furthermore, all clones cultured on this process achieved high viable cell concentrations over the course of culture, indicating no detrimental impacts from the proposed feeding strategy. Finally, the automated control strategy sustained cultures inoculated at high cell densities to achieve product concentrations between 5 and 8.3 g/L over the course of 12 days of culture. [ABSTRACT FROM AUTHOR]

In this work, the performance of two fast chemical imaging techniques, Raman and near-infrared (NIR) imaging is compared by utilizing these methods to predict the rate of drug release from sustained-release tablets. Sustained release is provided by adding hydroxypropyl methylcellulose (HPMC), as its concentration and particle size determine the dissolution rate of the drug. The chemical images were processed using classical least squares; afterwards, a convolutional neural network was applied to extract information regarding the particle size of HPMC. The chemical images were reduced to an average HPMC concentration and a predicted particle size value; these were used as inputs in an artificial neural network with a single hidden layer to predict the dissolution profile of the tablets. Both NIR and Raman imaging yielded accurate predictions. As the instrumentation of NIR imaging allows faster measurements than Raman imaging, this technique is a better candidate for implementing a real-time technique. The introduction of chemical imaging in the routine quality control of pharmaceutical products would profoundly change quality assurance in the pharmaceutical industry. [ABSTRACT FROM AUTHOR]

The need for electrical energy increases yearly; this study aims to analyze the feasibility of constructing a pico-hydro power plant in remote villages that do not yet have a power grid using a centrifugal pump as a turbine. The results of the analysis of technical aspects get information that there are about 25 houses that require electrical energy. The electrical power requirement of each house is about 100 W, which is used for lighting with five energy-efficient LED lamps of 20 W each. After adding street lighting and power losses to the network of about 500 W, the total electrical power needed is around 3000 W. A pico-hydro power generation system can meet the 3000 W power with a potential power of 5 kW and an effective turbine power of 3.51 kW. The water discharge requirement for the turbine is 104 liters/s, the turbine rotational speed is 543 rpm, the generator rotation speed is 1500 rpm, the specific speed is 133, the PAT runner diameter is 8 inches, and the distance from the power plant to the resident's house is 150 m, network losses 8 V, and the household electricity voltage is 210.45 V. The results of the technical aspect analysis show that the pico-hydro power plant is considered feasible to be built. The results of this analysis are the initial stage of feasibility study activities and can be continued with analysis from other aspects such as financial, economic, social, and environmental aspects. [ABSTRACT FROM AUTHOR]

Background: This work performs a literature review of photoacoustic imaging (PAI) in dentistry and discusses the development of PAI in relation to oral health. Methods: A search method was used to locate papers published between 2011 and 2023 in Google Scholar and PubMed databases, and 25 studies were selected. Reports on PAI in dentistry were included. Articles not written in English or whose full text could not be accessed were excluded. The remaining publications were checked and evaluated to determine whether they contain supportive materials for PAI in dentistry. Results: The majority of articles about PAI in dentistry are associated with caries studies. Photoacoustic microscopy is the most commonly utilized PAI system. PAI studies generally focus on ex-vivo investigations using extracted human teeth. The acoustic signal obtained from carious teeth is greater than that obtained from normal teeth. In addition to imaging oral soft tissues from animal models and the periodontal pocket depth in human volunteers, PAI is applied to evaluate dental implants and oral biofilms. Conclusion: There have been numerous investigation on PAI in dentistry, but it is not yet applicable in dental practice. In the future, PAI studies are expected to contribute to the invention of an alternative non-ionizing imaging technology that is comfortable for patients, user friendly, and capable of providing reliable information at a reasonable cost.

This work performs a literature review of photoacoustic imaging (PAI) in dentistry and discusses the development of PAI in relation to oral health. A search method was used to locate papers published between 2011 and 2023 in Google Scholar and PubMed databases, and 25 studies were selected. Reports on PAI in dentistry were included. Articles not written in English or whose full text could not be accessed were excluded. The remaining publications were checked and evaluated to determine whether they contain supportive materials for PAI in dentistry. The majority of articles about PAI in dentistry are associated with caries studies. Photoacoustic microscopy is the most commonly utilized PAI system. PAI studies generally focus on ex-vivo investigations using extracted human teeth. The acoustic signal obtained from carious teeth is greater than that obtained from normal teeth. In addition to imaging oral soft tissues from animal models and the periodontal pocket depth in human volunteers, PAI is applied to evaluate dental implants and oral biofilms. There have been numerous investigation on PAI in dentistry, but it is not yet applicable in dental practice. In the future, PAI studies are expected to contribute to the invention of an alternative non-ionizing imaging technology that is comfortable for patients, user friendly, and capable of providing reliable information at a reasonable cost. [ABSTRACT FROM AUTHOR]

3D printing technology can be used to develop individualized medicines in hospitals and pharmacies, allowing a high degree of personalization and the possibility to adjust the dose of the API based on the quantity of material extruded. The main goal of incorporating this technology is to have a stock of API-load print cartridges that could be used at different storage times and for different patients. However, it is necessary to study the extrudability, stability, and buildability of these print cartridges during storage time. A paste-like formulation containing hydrochlorothiazide as a model drug was prepared and distributed in five print cartridges, each of which was studied for different storage times (0 h–72 h) and conditions, for repeated use on different days. For each print cartridge, an extrudability analysis was performed, and subsequently, 100 unit forms of 10 mg hydrochlorothiazide were printed. Finally, various dosage units containing different doses were printed, taking into account the optimized printing parameters based on the results of the extrudability analysis carried out previously. An appropriate methodology for the rapid development of appropriate SSE 3DP inks for pediatrics was established and evaluated. The extrudability analysis and several parameters allowed the detection of changes in the mechanical behavior of the printing inks, the pressure interval of the steady flow, and the selection of the volume of ink to be extruded to obtain each of the required doses. The print cartridges were stable for up to 72 h after processing, and orodispersible printlets containing 6 mg to 24 mg of hydrochlorothiazide can be produced using the same print cartridge and during the same printing process with guaranteed content and chemical stability. The proposed workflow for the development of new printing inks containing APIs will allow the optimization of feedstock material and human resources in pharmacy or hospital pharmacy services, thus speeding up their development and reducing costs. [ABSTRACT FROM AUTHOR]

The world’s water infrastructures suffer from inefficiencies, such as high energy consumption and water losses due to inadequate management practices and feeble pressure regulation, leading to frequent water and energy losses. This strains vital water and energy resources, especially in the face of the worsening challenges of climate change and population growth. A novel method is presented that integrates micro-hydropower plants, with pumps as turbines (PATs), in the water network in the city of Funchal. Sensitivity analyses evaluated the microgrid’s response to variations in the cost of energy components, showing favorable outcomes with positive net present value (NPV). PV solar and micro-wind turbines installed exclusively at the selected PRV sites within the Funchal hydro grid generate a combined 153 and 55 MWh/year, respectively, supplementing the 406 MWh/year generated by PATs. It should be noted that PATs consistently have the lowest cost of electricity (LCOE), confirming their economic viability and efficiency across different scenarios, even after accounting for reductions in alternative energy sources and grid infrastructure costs.

Pointing, acquisition, and tracking (PAT) is a major technical challenge of laser inter-satellite links (ISLs). For the fast establishment of laser link and the maximization of communication time, it is of importance to minimize the acquisition time. Satellite vibrations affect the PAT procedure adversely, and thus serve to increase the acquisition time. In this paper, we investigate through theoretical analysis the average acquisition time of laser ISLs in the presence of satellite vibrations. The analytic expression about the time taken from the beginning of spiral scan to the acquisition of the scan beam is provided in the presence of the pointing errors caused by vibrations. We also derive the optimum beam divergence angle for the acquisition time. The analyses are validated by Monte-Carlo computer simulations and a proof-of-concept experiment. The results show that the acquisition time can be minimized by adjusting the beam divergence angle adaptively to the link conditions.

The use of nondestructive techniques that can guarantee in situ monitoring of the quality of food products during drying processes can promote improvements in industrial processes. In this context, digital imaging and near infrared spectroscopy can play an important role. Red beet moisture content, betalain content, shrinkage, and color were measured during drying. The digital images showed changes in color, which intensified with increasing temperature and correlated with betalain content through multivariate linear regression (R2 of 0.90). In addition, sample shrinkage was identified by digital images. The volumetric shrinkage increased proportionally to the drying air temperature, with a shrinkage of 85.4 ± 0.3% at 70 °C. Spectral data were obtained by a low-cost portable near infrared spectrometer. Partial least square regression was used to predict the product moisture content ( R P 2 = 0.89 ; RMSEP = 0.79 %) and total betalain content ( R P 2 = 0.79 ; RMSEP = 0.30 m g g d. b.) during drying. These tools can be used for the in situ control of red beet drying. [ABSTRACT FROM AUTHOR]

In this study, we developed a method to build Raman calibration models without culture data for cell culture monitoring. First, Raman spectra were collected and then analyzed for the signals of all the mentioned analytes: glucose, lactate, glutamine, glutamate, ammonia, antibody, viable cells, media, and feed agent. Using these spectral data, the specific peak positions and intensities for each factor were detected. Next, according to the design of the experiment method, samples were prepared by mixing the above-mentioned factors. Raman spectra of these samples were collected and were used to build calibration models. Several combinations of spectral pretreatments and wavenumber regions were compared to optimize the calibration model for cell culture monitoring without culture data. The accuracy of the developed calibration model was evaluated by performing actual cell culture and fitting the in-line measured spectra to the developed calibration model. As a result, the calibration model achieved sufficiently good accuracy for the three components, glucose, lactate, and antibody (root mean square errors of prediction, or RMSEP = 0.23, 0.29, and 0.20 g/L, respectively). This study has presented innovative results in developing a culture monitoring method without using culture data, while using a basic conventional method of investigating the Raman spectra of each component in the culture media and then utilizing a design of experiment approach. Graphical Abstract This is a visual representation of the abstract. [ABSTRACT FROM AUTHOR]

Spatially offset Raman spectroscopy (SORS) is a subset of Raman spectroscopy devised for probing subsurface compositions in non-homogenous media. An example of such media is the wet filter cake during pharmaceutical drying. This non-homogeneity poses a challenge for process monitoring as it could render the determined solvent content during drying, and the end point, inaccurate. In this study, a SORS probe was developed for the monitoring of pharmaceutical drying. The probe includes a 45° illumination point and 0–5 mm equidistant collection offsets. Using the SORS probe, solvent signal detection through variable thicknesses of dry paracetamol was examined. The solvent content during the drying of paracetamol in anisole was then monitored using the SORS probe. Partial least squares regression (PLSR) analysis was applied to evaluate the performance of offset configurations in monitoring the solvent content during drying. The results showed that the solvent signal is detected through thicknesses beyond 6 mm of paracetamol from the larger offsets of 4–5 mm. A more accurate prediction of the solvent content was obtained from larger offsets. PLSR models using offset spectra showed a decrease in estimation error up to 50 % compared to backscattering spectra, with a further decrease upon using standard normal variate pre-processing. This suggests that SORS could offer improved monitoring of pharmaceutical drying processes. • A spatially offset Raman spectroscopy probe was developed for in-line process monitoring. • SORS probe characteristics include 45° illumination and 0–5 mm offsets. • Spatial offsets of 4–5 mm could probe samples up to a depth of 6 mm. • Partial least squares regression analysis of offset spectra showed a decreased estimation error up to 50 % compared to backscattering spectra. • Spatially offset Raman spectroscopy offers improved monitoring of solvent content during pharmaceutical drying. [ABSTRACT FROM AUTHOR]

Background/aim: Allergic rhinitis (AR) is characterized by chronic inflammation of the nasal mucosa. Under the influence of exogenous factors - allergens, reactive oxygen species (ROS) are released during cellular metabolism. They induce a series of pathological changes in the mucosa. Oxidative stress is а result of an imbalance between the production of ROS and the ability to neutralize them. The aim of this study is to compare the levels of oxidative stress between healthy children and children with allergic rhinitis. Material and methods: A total number of 60 children were included (30 healthy children and 30 children with AR). The oxidative stress index was determined by using the FRAS 5 (Free Radical Analytical System) Bravo system. Demographic characteristics, medical history, children's living conditions and eating habits were obtained from the questionnaire. Anthropometric measurements and the absolute number of eosinophils in the peripheral smear were performed on each child. Results: This study showed high oxidative stress index and a significantly higher value of the absolute number of eosinophils in the peripheral smear in children with AR in comparison to healthy children (p<0.05). The group of children with AR had more atopic characteristics and was more exposed to passive smoking than healthy children. Conclusion: Compared to healthy children, children with AR have a high index of oxidative stress, despite of the very high mean value of the concentration of water-soluble antioxidants in serum (PAT test) in the group of children with AR. [ABSTRACT FROM AUTHOR]

In this work, the performance of two fast chemical imaging techniques, Raman and near-infrared (NIR) imaging is compared by utilizing these methods to predict the rate of drug release from sustained-release tablets. Sustained release is provided by adding hydroxypropyl methylcellulose (HPMC), as its concentration and particle size determine the dissolution rate of the drug. The chemical images were processed using classical least squares; afterwards, a convolutional neural network was applied to extract information regarding the particle size of HPMC. The chemical images were reduced to an average HPMC concentration and a predicted particle size value; these were used as inputs in an artificial neural network with a single hidden layer to predict the dissolution profile of the tablets. Both NIR and Raman imaging yielded accurate predictions. As the instrumentation of NIR imaging allows faster measurements than Raman imaging, this technique is a better candidate for implementing a real-time technique. The introduction of chemical imaging in the routine quality control of pharmaceutical products would profoundly change quality assurance in the pharmaceutical industry.

The pharmaceutical industry has begun incorporating continuous manufacturing technology in synthetic routes toward active pharmaceutical ingredients (APIs). The development of smart manufacturing routes can be accelerated by utilizing digitalization, process analytical technology (PAT), and data-rich experimentation from an early stage. Here, we present the key aspects of implementing automated flow chemistry reactor platforms with real-time process analytics. Based on our experiences in this field, we aim to highlight the potential of these platforms to conduct self-optimization, automated reaction model building, dynamic experiments and to implement advanced process control strategies

Intervals of low-quality photoplethysmogram (PPG) signals might lead to significant inaccuracies in estimation of pulse arrival time (PAT) during polysomnography (PSG) studies. While PSG is considered to be a "gold standard" test for diagnosing obstructive sleep apnea (OSA), it also enables tracking apnea-related nocturnal blood pressure fluctuations correlated with PAT. Since the electrocardiogram (ECG) is recorded synchronously with the PPG during PSG, it makes sense to use the ECG signal for PPG signal-quality assessment. (1) Objective: to develop a PPG signal-quality assessment algorithm for robust PAT estimation, and investigate the influence of signal quality on PAT during various sleep stages and events such as OSA. (2) Approach: the proposed algorithm uses R and T waves from the ECG to determine approximate locations of PPG pulse onsets. The MESA database of 2055 PSG recordings was used for this study. (3) Results: the proportions of high-quality PPG were significantly lower in apnea-related oxygen desaturation (matched-pairs r c = 0.88 and r c = 0.97, compared to OSA and hypopnea, respectively, when p < 0.001) and arousal ( r c = 0.93 and r c = 0.98, when p < 0.001) than in apnea events. The significantly large effect size of interquartile ranges of PAT distributions was between low- and high-quality PPG (p < 0.001, r c = 0.98), and regular and irregular pulse waves (p < 0.001, r c = 0.74), whereas a lower quality of the PPG signal was found to be associated with a higher interquartile range of PAT across all subjects. Suggested PPG signal quality-based PAT evaluation reduced deviations (e.g., r c = 0.97, r c = 0.97, r c = 0.99 in hypopnea, oxygen desaturation, and arousal stages, respectively, when p < 0.001) and allowed obtaining statistically larger differences between different sleep stages and events. (4) Significance: the implemented algorithm has the potential to increase the robustness of PAT estimation in PSG studies related to nocturnal blood pressure monitoring. [ABSTRACT FROM AUTHOR]

Monitoring the protein concentration and buffer composition during the Ultrafiltration/Diafiltration (UF/DF) step enables the further automation of biopharmaceutical production and supports Real-time Release Testing (RTRT). Previously, in-line Ultraviolet (UV) and Infrared (IR) measurements have been used to successfully monitor the protein concentration over a large range. The progress of the diafiltration step has been monitored with density measurements and Infrared Spectroscopy (IR). Raman spectroscopy is capable of measuring both the protein and excipient concentration while being more robust and suitable for production measurements in comparison to Infrared Spectroscopy (IR). Regardless of the spectroscopic sensor used, the low concentration of excipients poses a challenge for the sensors. By combining sensor measurements with a semi-mechanistic model through an Extended Kalman Filter (EKF), the sensitivity to determine the progress of the diafiltration can be improved. In this study, Raman measurements are combined with an EKF for three case studies. The advantages of Kalman-filtered Raman measurements for excipient monitoring are shown in comparison to density measurements. Furthermore, Raman measurements showed a higher measurement speed in comparison to Variable Pathlength (VP) UV measurement at the trade-off of a slightly worse prediction accuracy for the protein concentration. However, the Raman-based protein concentration measurements relied mostly on an increase in the background signal during the process and not on proteinaceous features, which could pose a challenge due to the potential influence of batch variability on the background signal. Overall, the combination of Raman spectroscopy and EKF is a promising tool for monitoring the UF/DF step and enables process automation by using adaptive process control. [ABSTRACT FROM AUTHOR]

Quality by Design (QbD) is one of the most important tools for the implementation of Process Analytical Technology (PAT) in biopharmaceutical production. For optimal characterization of a monoclonal antibody (mAb) upstream process a stepwise approach was implemented. The upstream was divided into three process stages, namely inoculum expansion, production, and primary recovery, which were investigated individually. This approach enables analysis of process parameters and associated intermediate quality attributes as well as systematic knowledge transfer to subsequent process steps. Following previous research, this study focuses on the primary recovery of the mAb and thereby marks the final step toward a holistic characterization of the upstream process. Based on gained knowledge during the production process evaluation, the cell viability and density were determined as critical parameters for the primary recovery. Directed cell viability adjustment was achieved using cytotoxic camptothecin in a novel protocol. Additionally, the cell separation method was added to the Design of Experiments (DoE) as a qualitative factor and varied between filtration and centrifugation. To assess the quality attributes after cell separation, the bioactivity of the mAb was analyzed using a cell‐based assay and the purity of the supernatant was evaluated by measurement of process related impurities (host cell protein proportion, residual DNA). Multivariate data analysis of the compiled data confirmed the hypothesis that the upstream process has no significant influence on the bioactivity of the mAb. Therefore, process control must be tuned towards high mAb titers and purity after the primary recovery, enabling optimal downstream processing of the product. To minimize amounts of host cell proteins and residual DNA the cell viability should be maintained above 85% and the cell density should be controlled around 15 × 106 cells/ml during the cell removal. Thereby, this study shows the importance of QbD for the characterization of the primary recovery of mAbs and highlights the useful implementation of the stepwise approach over subsequent process stages. [ABSTRACT FROM AUTHOR]

The correct definition and application of face confinement pressure is one of the main challenges for urban tunnels, where soil perturbation can affect the surrounding structures with undesirable or even severe consequences. The choice of this parameter needs to comply not only with minimal geotechnical performances, such as volume loss control, water pressure balance, and front stability, but also with optimization criteria (impact on production rate and Tunnel Boring Machine (TBM) components wear). The Grand Paris Line 14 South tunnel has emphasized this concept especially on the 1.5 km section below the Orly International Airport, with two constraints: the limitation of deformations on sensitive airport structures and the tight schedule due to the Olympic Games of 2024. The 8.83 m‐diameter Earth Pressure Balance (EPB) TBM 'Koumba' successfully performed the excavation at 20 m depth. The design face pressure profile, varying between 0.8 and 2.6 bar, was studied. A complex monitoring system was also provided to validate design expectations and to update the TBM‐soil interaction prediction model. This article focuses on the experience acquired on the EPB face confinement pressure management along this long, highly sensitive section. The first part presents the comparison between reference values and thresholds given by the designer and the real TBM drive oscillation. The second part is dedicated to the observed influence of the face pressure on the geotechnical aspect, machine mechanical parameters, and production rates. [ABSTRACT FROM AUTHOR]

Genetically modified maize MON 87419 was developed to confer tolerance to dicamba‐ and glufosinate‐based herbicides. These properties were achieved by introducing the dmo and pat expression cassettes. The molecular characterisation data and bioinformatic analyses do not identify issues requiring food/feed safety assessment. None of the identified differences in the agronomic/phenotypic and compositional characteristics tested between maize MON 87419 and its conventional counterpart needed further assessment, except for the levels of arginine and protein in grains which did not raise safety and nutritional concerns. The GMO Panel does not identify safety concerns regarding the toxicity and allergenicity of the dicamba mono‐oxygenase (DMO) and phosphinothricin N‐acetyltransferase (PAT) proteins as expressed in maize MON 87419. The GMO Panel finds no evidence that the genetic modification impacts the overall safety of maize MON 87419. In the context of this application, the consumption of food and feed from maize MON 87419 does not represent a nutritional concern in humans and animals. The GMO Panel concludes that maize MON 87419 is as safe as the conventional counterpart and non‐GM maize varieties tested, and no post‐market monitoring of food/feed is considered necessary. In the case of accidental release of viable maize MON 87419 grains into the environment, this would not raise environmental safety concerns. The post‐market environmental monitoring plan and reporting intervals are in line with the intended uses of maize MON 87419. The GMO Panel concludes that maize MON 87419 is as safe as its conventional counterpart and the tested non‐GM maize varieties with respect to potential effects on human and animal health and the environment. [ABSTRACT FROM AUTHOR]

Genetically modified maize GA21 × T25 was developed by crossing to combine two single events: GA21 and T25. The GMO Panel previously assessed the two single maize events and did not identify safety concerns. No new data on the single maize events were identified that could lead to modification of the original conclusions on their safety. The molecular characterisation, comparative analysis (agronomic, phenotypic and compositional characteristics) and the outcome of the toxicological, allergenicity and nutritional assessment indicate that the combination of the single maize events and of the newly expressed proteins in maize GA21 × T25 does not give rise to food and feed safety and nutritional concerns. The GMO Panel concludes that maize GA21 × T25, as described in this application, is as safe as its conventional counterpart and the non‐GM reference varieties tested, and no post‐market monitoring of food and feed is considered necessary. In the case of accidental release of viable maize GA21 × T25 grains into the environment, this would not raise environmental safety concerns. The post‐market environmental monitoring plan and reporting intervals are in line with the intended uses of maize GA21 × T25. Post‐market monitoring of food and feed is not considered necessary. The GMO Panel concludes that maize GA21 × T25 is as safe as its conventional counterpart and the non‐GM reference varieties tested, with respect to potential effects on human and animal health and the environment. [ABSTRACT FROM AUTHOR]

The objective of the present work was to develop an artificial neural network (ANN) model to accurately predict the dissolution profile of immediate release tablets based on non-destructive spectral data. Six different tablet formulations with varying API (caffeine) and disintegrant (potato starch) concentrations were prepared. The near-infrared (NIR) and Raman spectra of each tablet were collected in both reflection and transmission modes, then principal component analysis (PCA) was conducted. The training of the ANN was performed at each hidden neuron number from 1 to 10 in order to determine the optimal number of neurons in the hidden layer. The best results were obtained when a small number of neurons (1-3) was used. In the case of all four spectroscopic methods, the average similarity values (f2) of the optimized ANN models were above 59 for the validation tablets, indicating that the predicted dissolution profiles were similar to the measured dissolution curves. The optimized model based on reflection Raman spectra exhibited the best predictive ability. The results demonstrated the potential of ANN models in the implementation of the real-time release testing of tablet dissolution. [ABSTRACT FROM AUTHOR]

International tourism bodies consider rural tourism as a lever for economic development that contributes to the reduction of rural poverty and the stability of this population and the revitalization of rural areas. Like tourist countries, Morocco is committed to several tourism strategies insofar as it presents resources in natural environment and biodiversity as well as cultural riches and remarkable traditions. However, the tourist offer that is concentrated on the coast is almost absent in the hinterland and rural destinations. This strategic choice has produced shortfalls and particularly in times of the covid-19 pandemic for tourism operators and for Morocco, whose Fez-Meknes Region is a good example for the consequences of the concentration of supply on seaside tourism. [ABSTRACT FROM AUTHOR]

Root development and plasticity are assessed via diverse endogenous and environmental cues, including phytohormones, nutrition, and stress. In this study, we observed that roots in model plant Arabidopsis thaliana exhibited waving and oscillating phenotypes under normal conditions but lost this pattern when subjected to alkaline stress. We later showed that alkaline treatment disturbed the auxin gradient in roots and increased auxin signal in columella cells. We further demonstrated that the auxin efflux transporter PINFORMED 7 (PIN7) but not PIN3 was translocated to vacuole lumen under alkaline stress. This process is essential for root response to alkaline stress because the pin7 knockout mutants retained the root waving phenotype. Moreover, we provided evidence that the PIN7 vacuolar transport might not depend on the ARF-GEFs but required the proper function of an ESCRT subunit known as FYVE domain protein required for endosomal sorting 1 (FREE1). Induced silencing of FREE1 disrupted the vacuolar transport of PIN7 and reduced sensitivity to alkaline stress, further highlighting the importance of this cellular process. In conclusion, our work reveals a new role of PIN7 in regulating root morphology under alkaline stress. [ABSTRACT FROM AUTHOR]

Post-traumatic stress symptoms (PTSS) are often experienced by children and family members after pediatric traumatic medical events (PTMEs). Assessing families' psychosocial risk factors is a crucial part of trauma-informed practice as it helps identify risk for PTSS in the aftermath of PTME. Using the Psychosocial Assessment Tool 2.0 (PAT2.0), this study describes the psychosocial risk of families following PTMEs in two ways: 1. Describing the psychosocial risk defined by the PAT2.0 based on three-tiered risk levels; 2. Using latent profile analysis (LPA); identifying psychosocial risk profiles and examining how child- and injury-related factors can affect profile membership. Caregivers of 374 children following PTMEs admitted to a pediatric rehabilitation department in Israel completed the PAT2.0. Total PAT2.0 score and the seven PAT2.0 subscales (family structure/resources, social support, child problems, sibling problems, family problems, caregiver stress reactions, and family beliefs) were included in the first analysis. Mean PAT2.0 scores of three risk categories (universal, targeted, clinical) were calculated; LPA, which allows for cross-sectional latent variable mixture models to identify heterogeneity within a population, and multinomial logistic regressions using six out of the seven PAT2.0 subscales, were used to determine distinct profile differences and predictors of profile membership. The three-tiered risk levels revealed were relatively high, as compared to levels in families of children with other clinical diagnoses. LPA yielded a three-profile solution: low family risk (63.53%); high caregiver stress, above-average levels of family risk (22.5%); and sibling problems, above-average levels of family risk (13.94%). Ethnicity and type of injury predicted group membership. Families of children following PTMEs are at increased psychosocial risk. A clinically useful approach to identifying and preventing PTSS may be to evaluate specific domain patterns rather than just the total PAT2.0 risk level alone, based on the PAT2.0 subscales. Families of children in pediatric rehabilitation are prone to significant psychosocial risk following traumatic medical events. Using latent profile analysis of PAT2.0 psychosocial risk domains in pediatric rehabilitation identified specific patterns of risk factors. Screening for all families of children hospitalised following pediatric medical events may enable the facilitation of early interventions and appropriate allocation of medical support resources to those in greatest need. [ABSTRACT FROM AUTHOR]

The start-up process of a centrifugal pump as turbine (PAT) under gas–liquid two-phase conditions was simulated based on Fluent, and the evolution mechanism of the internal flow field and the variation law of force characteristics were studied in its start-up process under gas–liquid two-phase conditions. The results show that the area with high gas phase concentration corresponds to a strong vortex at the beginning of the start-up. The vortex intensity in the impeller gradually decreases with an increase in rotational speed. The gas volume fraction of the blade suction surface is more significant than that of the blade pressure surface. The higher the inlet gas volume fraction (IGVF) is, the more severely the blade load will fluctuate during the start-up process. As the rotational speed increases, the fluctuation of the blade load gradually weakens, and the maximum load is distributed near the inner edge of the blade after the rotational speed is stable. The periodic unbalanced radial force is produced in the start-up process. From the pure liquid conditions to the gas–liquid two-phase conditions with increasing IGVF, the dominant frequency amplitude of radial force shows a similar trend of decreasing first but then increasing. After the rotational speed tends to be stable, the dominant frequency of radial force is equal to the rotational frequency of the blade. With the increase in rotational speed, the dominant frequency amplitude of axial force decreases gradually. The higher the IGVF, the greater the dominant frequency amplitude of axial force at the same time. [ABSTRACT FROM AUTHOR]